Mixing of Chromatic and Luminance Retinal Signals in Primate Area V1.

PubMed

Li, Xiaobing; Chen, Yao; Lashgari, Reza; Bereshpolova, Yulia; Swadlow, Harvey A; Lee, Barry B; Alonso, Jose Manuel

2015-07-01

Vision emerges from activation of chromatic and achromatic retinal channels whose interaction in visual cortex is still poorly understood. To investigate this interaction, we recorded neuronal activity from retinal ganglion cells and V1 cortical cells in macaques and measured their visual responses to grating stimuli that had either luminance contrast (luminance grating), chromatic contrast (chromatic grating), or a combination of the two (compound grating). As with parvocellular or koniocellular retinal ganglion cells, some V1 cells responded mostly to the chromatic contrast of the compound grating. As with magnocellular retinal ganglion cells, other V1 cells responded mostly to the luminance contrast and generated a frequency-doubled response to equiluminant chromatic gratings. Unlike magnocellular and parvocellular retinal ganglion cells, V1 cells formed a unimodal distribution for luminance/color preference with a 2- to 4-fold bias toward luminance. V1 cells associated with positive local field potentials in deep layers showed the strongest combined responses to color and luminance and, as a population, V1 cells encoded a diverse combination of luminance/color edges that matched edge distributions of natural scenes. Taken together, these results suggest that the primary visual cortex combines magnocellular and parvocellular retinal inputs to increase cortical receptive field diversity and to optimize visual processing of our natural environment. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The effect of strenuous exercise and beta-adrenergic blockade on the visual performance of juvenile rainbow trout, Oncorhynchus mykiss.

PubMed

Herbert, N A; Wells, R M G

2002-12-01

It is hypothesised that the visual performance of rainbow trout, Oncorhynchus mykiss, will be impaired by strenuous exercise as a result of metabolic stress (blood lactacidosis) that activates the Root effect and limits the oxygen-carrying capacity of blood flowing to the eye. The ability to resolve high contrast objects on a moving background, as a measure of visual performance, was quantified pre- and post-exercise using the optomotor response. Strenuous exercise induced a metabolic acidosis (8.0 mmol l(-1) blood lactate) and a significant red cell swelling response but no change in the optomotor response threshold (120 min of arc) was observed. Beta-adrenergic blockade (propranolol) abolished post-exercise red cell swelling but optomotor response thresholds were still maintained at 120 min of arc despite a significant blood lactate load (7.8 mmol l(-1)). The choroid rete mirabile of the trout is extremely well developed (rete area:eye area = 0.39) and may maintain visual performance by ensuring a relatively direct supply of oxygen to the central regions of the avascular retina. Exercised fish under beta-adrenergic blockade exhibited an enhanced optomotor response at 240-300 min of arc. Assuming that these responses reflect "tunnel vision", adrenergic regulation of red cell function may preserve a high ocular PO(2) gradient that satisfies the oxygen demand of peripheral retinal cells.

Photoreceptor Cells With Profound Structural Deficits Can Support Useful Vision in Mice

PubMed Central

Thompson, Stewart; Blodi, Frederick R.; Lee, Swan; Welder, Chris R.; Mullins, Robert F.; Tucker, Budd A.; Stasheff, Steven F.; Stone, Edwin M.

2014-01-01

Purpose. In animal models of degenerative photoreceptor disease, there has been some success in restoring photoreception by transplanting stem cell–derived photoreceptor cells into the subretinal space. However, only a small proportion of transplanted cells develop extended outer segments, considered critical for photoreceptor cell function. The purpose of this study was to determine whether photoreceptor cells that lack a fully formed outer segment could usefully contribute to vision. Methods. Retinal and visual function was tested in wild-type and Rds mice at 90 days of age (RdsP90). Photoreceptor cells of mice homozygous for the Rds mutation in peripherin 2 never develop a fully formed outer segment. The electroretinogram and multielectrode recording of retinal ganglion cells were used to test retinal responses to light. Three distinct visual behaviors were used to assess visual capabilities: the optokinetic tracking response, the discrimination-based visual water task, and a measure of the effect of vision on wheel running. Results. RdsP90 mice had reduced but measurable electroretinogram responses to light, and exhibited light-evoked responses in multiple types of retinal ganglion cells, the output neurons of the retina. In optokinetic and discrimination-based tests, acuity was measurable but reduced, most notably when contrast was decreased. The wheel running test showed that RdsP90 mice needed 3 log units brighter luminance than wild type to support useful vision (10 cd/m2). Conclusions. Photoreceptors that lack fully formed outer segments can support useful vision. This challenges the idea that normal cellular structure needs to be completely reproduced for transplanted cells to contribute to useful vision. PMID:24569582

Digital Museum of Retinal Ganglion Cells with Dense Anatomy and Physiology.

PubMed

Bae, J Alexander; Mu, Shang; Kim, Jinseop S; Turner, Nicholas L; Tartavull, Ignacio; Kemnitz, Nico; Jordan, Chris S; Norton, Alex D; Silversmith, William M; Prentki, Rachel; Sorek, Marissa; David, Celia; Jones, Devon L; Bland, Doug; Sterling, Amy L R; Park, Jungman; Briggman, Kevin L; Seung, H Sebastian

2018-05-17

When 3D electron microscopy and calcium imaging are used to investigate the structure and function of neural circuits, the resulting datasets pose new challenges of visualization and interpretation. Here, we present a new kind of digital resource that encompasses almost 400 ganglion cells from a single patch of mouse retina. An online "museum" provides a 3D interactive view of each cell's anatomy, as well as graphs of its visual responses. The resource reveals two aspects of the retina's inner plexiform layer: an arbor segregation principle governing structure along the light axis and a density conservation principle governing structure in the tangential plane. Structure is related to visual function; ganglion cells with arbors near the layer of ganglion cell somas are more sustained in their visual responses on average. Our methods are potentially applicable to dense maps of neuronal anatomy and physiology in other parts of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

Vision's Brain.

ERIC Educational Resources Information Center

Miller, Julie Ann

1978-01-01

The functional architecture of the primary visual cortex has been explored by monitoring the responses of individual brain cells to visual stimuli. A combination of anatomical and physiological techniques reveals groups of functionally related cells, juxtaposed and superimposed, in a sometimes complex, but presumably efficient, structure. (BB)

Roles of ON Cone Bipolar Cell Subtypes in Temporal Coding in the Mouse Retina

PubMed Central

Fyk-Kolodziej, Bozena; Cohn, Jesse

2014-01-01

In the visual system, diverse image processing starts with bipolar cells, which are the second-order neurons of the retina. Thirteen subtypes of bipolar cells have been identified, which are thought to encode different features of image signaling and to initiate distinct signal-processing streams. Although morphologically identified, the functional roles of each bipolar cell subtype in visual signal encoding are not fully understood. Here, we investigated how ON cone bipolar cells of the mouse retina encode diverse temporal image signaling. We recorded bipolar cell voltage changes in response to two different input functions: sinusoidal light and step light stimuli. Temporal tuning in ON cone bipolar cells was diverse and occurred in a subtype-dependent manner. Subtypes 5s and 8 exhibited low-pass filtering property in response to a sinusoidal light stimulus, and responded with sustained fashion to step-light stimulation. Conversely, subtypes 5f, 6, 7, and XBC exhibited bandpass filtering property in response to sinusoidal light stimuli, and responded transiently to step-light stimuli. In particular, subtypes 7 and XBC were high-temporal tuning cells. We recorded responses in different ways to further examine the underlying mechanisms of temporal tuning. Current injection evoked low-pass filtering, whereas light responses in voltage-clamp mode produced bandpass filtering in all ON bipolar cells. These findings suggest that cone photoreceptor inputs shape bandpass filtering in bipolar cells, whereas intrinsic properties of bipolar cells shape low-pass filtering. Together, our results demonstrate that ON bipolar cells encode diverse temporal image signaling in a subtype-dependent manner to initiate temporal visual information-processing pathways. PMID:24966376

Processing of single-photon responses in the mammalian On and Off retinal pathways at the sensitivity limit of vision

PubMed Central

2017-01-01

Visually guided behaviour at its sensitivity limit relies on single-photon responses originating in a small number of rod photoreceptors. For decades, researchers have debated the neural mechanisms and noise sources that underlie this striking sensitivity. To address this question, we need to understand the constraints arising from the retinal output signals provided by distinct retinal ganglion cell types. It has recently been shown in the primate retina that On and Off parasol ganglion cells, the cell types likely to underlie light detection at the absolute visual threshold, differ fundamentally not only in response polarity, but also in the way they handle single-photon responses originating in rods. The On pathway provides the brain with a thresholded, low-noise readout and the Off pathway with a noisy, linear readout. We outline the mechanistic basis of these different coding strategies and analyse their implications for detecting the weakest light signals. We show that high-fidelity, nonlinear signal processing in the On pathway comes with costs: more single-photon responses are lost and their propagation is delayed compared with the Off pathway. On the other hand, the responses of On ganglion cells allow better intensity discrimination compared with the Off ganglion cell responses near visual threshold. This article is part of the themed issue ‘Vision in dim light’. PMID:28193818

Processing of single-photon responses in the mammalian On and Off retinal pathways at the sensitivity limit of vision.

PubMed

Takeshita, Daisuke; Smeds, Lina; Ala-Laurila, Petri

2017-04-05

Visually guided behaviour at its sensitivity limit relies on single-photon responses originating in a small number of rod photoreceptors. For decades, researchers have debated the neural mechanisms and noise sources that underlie this striking sensitivity. To address this question, we need to understand the constraints arising from the retinal output signals provided by distinct retinal ganglion cell types. It has recently been shown in the primate retina that On and Off parasol ganglion cells, the cell types likely to underlie light detection at the absolute visual threshold, differ fundamentally not only in response polarity, but also in the way they handle single-photon responses originating in rods. The On pathway provides the brain with a thresholded, low-noise readout and the Off pathway with a noisy, linear readout. We outline the mechanistic basis of these different coding strategies and analyse their implications for detecting the weakest light signals. We show that high-fidelity, nonlinear signal processing in the On pathway comes with costs: more single-photon responses are lost and their propagation is delayed compared with the Off pathway. On the other hand, the responses of On ganglion cells allow better intensity discrimination compared with the Off ganglion cell responses near visual threshold.This article is part of the themed issue 'Vision in dim light'. © 2017 The Authors.

Differences in Visual-Spatial Input May Underlie Different Compression Properties of Firing Fields for Grid Cell Modules in Medial Entorhinal Cortex

PubMed Central

Raudies, Florian; Hasselmo, Michael E.

2015-01-01

Firing fields of grid cells in medial entorhinal cortex show compression or expansion after manipulations of the location of environmental barriers. This compression or expansion could be selective for individual grid cell modules with particular properties of spatial scaling. We present a model for differences in the response of modules to barrier location that arise from different mechanisms for the influence of visual features on the computation of location that drives grid cell firing patterns. These differences could arise from differences in the position of visual features within the visual field. When location was computed from the movement of visual features on the ground plane (optic flow) in the ventral visual field, this resulted in grid cell spatial firing that was not sensitive to barrier location in modules modeled with small spacing between grid cell firing fields. In contrast, when location was computed from static visual features on walls of barriers, i.e. in the more dorsal visual field, this resulted in grid cell spatial firing that compressed or expanded based on the barrier locations in modules modeled with large spacing between grid cell firing fields. This indicates that different grid cell modules might have differential properties for computing location based on visual cues, or the spatial radius of sensitivity to visual cues might differ between modules. PMID:26584432

Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on spatial response properties of relay cells

PubMed Central

Martínez-Cañada, Pablo; Halnes, Geir; Fyhn, Marianne

2018-01-01

Despite half-a-century of research since the seminal work of Hubel and Wiesel, the role of the dorsal lateral geniculate nucleus (dLGN) in shaping the visual signals is not properly understood. Placed on route from retina to primary visual cortex in the early visual pathway, a striking feature of the dLGN circuit is that both the relay cells (RCs) and interneurons (INs) not only receive feedforward input from retinal ganglion cells, but also a prominent feedback from cells in layer 6 of visual cortex. This feedback has been proposed to affect synchronicity and other temporal properties of the RC firing. It has also been seen to affect spatial properties such as the center-surround antagonism of thalamic receptive fields, i.e., the suppression of the response to very large stimuli compared to smaller, more optimal stimuli. Here we explore the spatial effects of cortical feedback on the RC response by means of a a comprehensive network model with biophysically detailed, single-compartment and multicompartment neuron models of RCs, INs and a population of orientation-selective layer 6 simple cells, consisting of pyramidal cells (PY). We have considered two different arrangements of synaptic feedback from the ON and OFF zones in the visual cortex to the dLGN: phase-reversed (‘push-pull’) and phase-matched (‘push-push’), as well as different spatial extents of the corticothalamic projection pattern. Our simulation results support that a phase-reversed arrangement provides a more effective way for cortical feedback to provide the increased center-surround antagonism seen in experiments both for flashing spots and, even more prominently, for patch gratings. This implies that ON-center RCs receive direct excitation from OFF-dominated cortical cells and indirect inhibitory feedback from ON-dominated cortical cells. The increased center-surround antagonism in the model is accompanied by spatial focusing, i.e., the maximum RC response occurs for smaller stimuli when feedback is present. PMID:29377888

Versatile functional roles of horizontal cells in the retinal circuit.

PubMed

Chaya, Taro; Matsumoto, Akihiro; Sugita, Yuko; Watanabe, Satoshi; Kuwahara, Ryusuke; Tachibana, Masao; Furukawa, Takahisa

2017-07-17

In the retinal circuit, environmental light signals are converted into electrical signals that can be decoded properly by the brain. At the first synapse of the visual system, information flow from photoreceptors to bipolar cells is modulated by horizontal cells (HCs), however, their functional contribution to retinal output and individual visual function is not fully understood. In the current study, we investigated functional roles for HCs in retinal ganglion cell (RGC) response properties and optokinetic responses by establishing a HC-depleted mouse line. We observed that HC depletion impairs the antagonistic center-surround receptive field formation of RGCs, supporting a previously reported HC function revealed by pharmacological approaches. In addition, we found that HC loss reduces both the ON and OFF response diversities of RGCs, impairs adjustment of the sensitivity to ambient light at the retinal output level, and alters spatial frequency tuning at an individual level. Taken together, our current study suggests multiple functional aspects of HCs crucial for visual processing.

Area 21a of cat visual cortex strongly modulates neuronal activities in the superior colliculus

PubMed Central

Hashemi-Nezhad, M; Wang, C; Burke, W; Dreher, B

2003-01-01

We have examined the influence of cortico-tectal projections from one of the pattern-processing extrastriate visual cortical areas, area 21a, on the responses to visual stimuli of single neurones in the superior colliculi of adult cats. For this purpose area 21a was briefly inactivated by cooling to 10 °C using a Peltier device. Responses to visual stimuli before and during cooling as well as after rewarming ipsilateral area 21a were compared. In addition, in a subpopulation of collicular neurones we have studied the effects of reversible inactivation of ipsilateral striate cortex (area 17, area V1). When area 21a was cooled, the temperature of area 17 was kept at 36 °C and vice versa. In the majority of cases (41/65; 63 %), irrespective of the velocity response profiles of collicular neurones, inactivation of area 21a resulted in a significant decrease in magnitude of responses of neurones in the ipsilateral colliculus and only in a small proportion of cells (2/65; 3.1 %) was there a significant increase in the magnitude of responses. Inactivation of area 21a resulted in significant changes in the magnitude of responses of collicular cells located not only in the retino-recipient layers but also in the stratum griseum intermediale. In most cases, reversible inactivation of area 17 resulted in a greater reduction in the magnitude of responses of collicular cells than inactivation of area 21a. Reversible inactivation of area 21a also affected the direction selectivity indices and length tuning of most collicular cells tested. PMID:12794178

Synaptic physiology of the flow of information in the cat's visual cortex in vivo

PubMed Central

Hirsch, Judith A; Martinez, Luis M; Alonso, José-Manuel; Desai, Komal; Pillai, Cinthi; Pierre, Carhine

2002-01-01

Each stage of the striate cortical circuit extracts novel information about the visual environment. We asked if this analytic process reflected laminar variations in synaptic physiology by making whole-cell recording with dye-filled electrodes from the cat's visual cortex and thalamus; the stimuli were flashed spots. Thalamic afferents terminate in layer 4, which contains two types of cell, simple and complex, distinguished by the spatial structure of the receptive field. Previously, we had found that the postsynaptic and spike responses of simple cells reliably followed the time course of flash-evoked thalamic activity. Here we report that complex cells in layer 4 (or cells intermediate between simple and complex) similarly reprised thalamic activity (response/trial, 99 ± 1.9 %; response duration 159 ± 57 ms; latency 25 ± 4 ms; average ± standard deviation; n = 7). Thus, all cells in layer 4 share a common synaptic physiology that allows secure integration of thalamic input. By contrast, at the second cortical stage (layer 2+3), where layer 4 directs its output, postsynaptic responses did not track simple patterns of antecedent activity. Typical responses to the static stimulus were intermittent and brief (response/trial, 31 ± 40 %; response duration 72 ± 60 ms, latency 39 ± 7 ms; n = 11). Only richer stimuli like those including motion evoked reliable responses. All told, the second level of cortical processing differs markedly from the first. At that later stage, ascending information seems strongly gated by connections between cortical neurons. Inputs must be combined in newly specified patterns to influence intracortical stages of processing. PMID:11927691

Response-dependent dynamics of cell-specific inhibition in cortical networks in vivo

PubMed Central

El-Boustani, Sami; Sur, Mriganka

2014-01-01

In the visual cortex, inhibitory neurons alter the computations performed by target cells via combination of two fundamental operations, division and subtraction. The origins of these operations have been variously ascribed to differences in neuron classes, synapse location or receptor conductances. Here, by utilizing specific visual stimuli and single optogenetic probe pulses, we show that the function of parvalbumin-expressing and somatostatin-expressing neurons in mice in vivo is governed by the overlap of response timing between these neurons and their targets. In particular, somatostatin-expressing neurons respond at longer latencies to small visual stimuli compared with their target neurons and provide subtractive inhibition. With large visual stimuli, however, they respond at short latencies coincident with their target cells and switch to provide divisive inhibition. These results indicate that inhibition mediated by these neurons is a dynamic property of cortical circuits rather than an immutable property of neuronal classes. PMID:25504329

Receptive Field Vectors of Genetically-Identified Retinal Ganglion Cells Reveal Cell-Type-Dependent Visual Functions

PubMed Central

Katz, Matthew L.; Viney, Tim J.; Nikolic, Konstantin

2016-01-01

Sensory stimuli are encoded by diverse kinds of neurons but the identities of the recorded neurons that are studied are often unknown. We explored in detail the firing patterns of eight previously defined genetically-identified retinal ganglion cell (RGC) types from a single transgenic mouse line. We first introduce a new technique of deriving receptive field vectors (RFVs) which utilises a modified form of mutual information (“Quadratic Mutual Information”). We analysed the firing patterns of RGCs during presentation of short duration (~10 second) complex visual scenes (natural movies). We probed the high dimensional space formed by the visual input for a much smaller dimensional subspace of RFVs that give the most information about the response of each cell. The new technique is very efficient and fast and the derivation of novel types of RFVs formed by the natural scene visual input was possible even with limited numbers of spikes per cell. This approach enabled us to estimate the 'visual memory' of each cell type and the corresponding receptive field area by calculating Mutual Information as a function of the number of frames and radius. Finally, we made predictions of biologically relevant functions based on the RFVs of each cell type. RGC class analysis was complemented with results for the cells’ response to simple visual input in the form of black and white spot stimulation, and their classification on several key physiological metrics. Thus RFVs lead to predictions of biological roles based on limited data and facilitate analysis of sensory-evoked spiking data from defined cell types. PMID:26845435

A Novel Ex Vivo Method for Visualizing Live-Cell Calcium Response Behavior in Intact Human Tumors.

PubMed

Koh, James; Hogue, Joyce A; Sosa, Julie A

2016-01-01

The functional impact of intratumoral heterogeneity has been difficult to assess in the absence of a means to interrogate dynamic, live-cell biochemical events in the native tissue context of a human tumor. Conventional histological methods can reveal morphology and static biomarker expression patterns but do not provide a means to probe and evaluate tumor functional behavior and live-cell responsiveness to experimentally controlled stimuli. Here, we describe an approach that couples vibratome-mediated viable tissue sectioning with live-cell confocal microscopy imaging to visualize human parathyroid adenoma tumor cell responsiveness to extracellular calcium challenge. Tumor sections prepared as 300 micron-thick tissue slices retain viability throughout a >24 hour observation period and retain the native architecture of the parental tumor. Live-cell observation of biochemical signaling in response to extracellular calcium challenge in the intact tissue slices reveals discrete, heterogeneous kinetic waveform categories of calcium agonist reactivity within each tumor. Plotting the proportion of maximally responsive tumor cells as a function of calcium concentration yields a sigmoid dose-response curve with a calculated calcium EC50 value significantly elevated above published reference values for wild-type calcium-sensing receptor (CASR) sensitivity. Subsequent fixation and immunofluorescence analysis of the functionally evaluated tissue specimens allows alignment and mapping of the physical characteristics of individual cells within the tumor to specific calcium response behaviors. Evaluation of the relative abundance of intracellular PTH in tissue slices challenged with variable calcium concentrations demonstrates that production of the hormone can be dynamically manipulated ex vivo. The capability of visualizing live human tumor tissue behavior in response to experimentally controlled conditions opens a wide range of possibilities for personalized ex vivo therapeutic testing. This highly adaptable system provides a unique platform for live-cell ex vivo provocative testing of human tumor responsiveness to a range of physiological agonists or candidate therapeutic compounds.

Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells’ activities

PubMed Central

Jing, Wei; Liu, Wen-Zhong; Gong, Xin-Wei; Gong, Hai-Qing

2010-01-01

Neural information is processed based on integrated activities of relevant neurons. Concerted population activity is one of the important ways for retinal ganglion cells to efficiently organize and process visual information. In the present study, the spike activities of bullfrog retinal ganglion cells in response to three different visual patterns (checker-board, vertical gratings and horizontal gratings) were recorded using multi-electrode arrays. A measurement of subsequence distribution discrepancy (MSDD) was applied to identify the spatio-temporal patterns of retinal ganglion cells’ activities in response to different stimulation patterns. The results show that the population activity patterns were different in response to different stimulation patterns, such difference in activity pattern was consistently detectable even when visual adaptation occurred during repeated experimental trials. Therefore, the stimulus pattern can be reliably discriminated according to the spatio-temporal pattern of the neuronal activities calculated using the MSDD algorithm. PMID:21886670

Crizotinib-Induced Abnormal Signal Processing in the Retina

PubMed Central

Ishii, Toshiyuki; Iwasawa, Shunichiro; Kurimoto, Ryota; Maeda, Akemi; Takiguchi, Yuichi; Kaneda, Makoto

2015-01-01

Molecular target therapy for cancer is characterized by unique adverse effects that are not usually observed with cytotoxic chemotherapy. For example, the anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor crizotinib causes characteristic visual disturbances, whereas such effects are rare when another ALK-tyrosine kinase inhibitor, alectinib, is used. To elucidate the mechanism responsible for these visual disturbances, the responses to light exhibited by retinal ganglion cells treated with these agents were evaluated using a C57BL6 mouse ex vivo model. Both crizotinib and alectinib changed the firing rate of ON and OFF type retinal ganglion cells. However, the ratio of alectinib-affected cells (15.7%) was significantly lower than that of crizotinib-affected cells (38.6%). Furthermore, these drugs changed the response properties to light stimuli of retinal ganglion cells in some of the affected cells, i.e., OFF cells responded to both ON and OFF stimuli, etc. Finally, the expressions of ALK (a target receptor of both crizotinib and alectinib) and of MET and ROS1 (additional target receptors of crizotinib) were observed at the mRNA level in the retina. Our findings suggest that these drugs might target retinal ganglion cells and that the potency of the drug actions on the light responses of retinal ganglion cells might be responsible for the difference in the frequencies of visual disturbances observed between patients treated with crizotinib and those treated with alectinib. The present experimental system might be useful for screening new molecular target agents prior to their use in clinical trials. PMID:26271036

Dissection of Drosophila Visual Circuits Implicative in Figure Motion

NASA Astrophysics Data System (ADS)

Kelley, Ross G.

The Drosophila visual system offers a model to study the foundations of how motion signals are computed from raw visual input and transformed into behavioral output. My studies focus on how specific cells in the Drosophila nervous system implement this input-output transformation. The individual cell types are known from classical studies using Golgi impregnations, but the assembly of motion processing circuits and the behavioral outputs remain poorly understood. Using an electronic flight simulator for flies and a white-noise analysis developed by Aptekar et al., I screen specific neurons in the optic lobes for behavioral ramifications. This approach produces wing responses to both the spatial and temporal dynamics of motion signals. The results of these experiments give Spatiotemporal Action Fields (STAFs) across the entire visual panorama. Genetically inactivating a distinct grouping of cells in the third optic ganglion, the Lobula Plate, the Horizontal System (HS) cell group, produced a robust phenotype through STAF analysis. Using the Gal4-UAS transgene expression system, we selectively inactivated the HS cells by expressing in their membrane inward rectifying potassium channels (Kir2.1) to hyperpolarize these cells, preventing their role in synaptic signaling. The results of the experiments show mutants lose steering responses to several distinct categories of figure motion and reduced behavioral responses to figure motion set against a contrasting moving background, highlighting their role in figure tracking behavior. Finally, a synapse inactivating protein, tetanus toxin (TNT), expressed in the HS cell group, produces a different behavioral phenotype than overexpressing inward rectifier. TNT, a bacterial neurotoxin, cleaves SNARE proteins resulting in loss of synaptic output of the cell, but the dendrites are intact and signal normally, preserving dendro-dendritic interactions known to sculpt the visual receptive fields of these cells. The two distinct phenotypes to each genetically targeted silencer differentiate the functional role of dendritic integration versus axonal output in this important cell group.

Segregation of Form, Color, Movement, and Depth: Anatomy, Physiology, and Perception

NASA Astrophysics Data System (ADS)

Livingstone, Margaret; Hubel, David

1988-05-01

Anatomical and physiological observations in monkeys indicate that the primate visual system consists of several separate and independent subdivisions that analyze different aspects of the same retinal image: cells in cortical visual areas 1 and 2 and higher visual areas are segregated into three interdigitating subdivisions that differ in their selectivity for color, stereopsis, movement, and orientation. The pathways selective for form and color seem to be derived mainly from the parvocellular geniculate subdivisions, the depth- and movement-selective components from the magnocellular. At lower levels, in the retina and in the geniculate, cells in these two subdivisions differ in their color selectivity, contrast sensitivity, temporal properties, and spatial resolution. These major differences in the properties of cells at lower levels in each of the subdivisions led to the prediction that different visual functions, such as color, depth, movement, and form perception, should exhibit corresponding differences. Human perceptual experiments are remarkably consistent with these predictions. Moreover, perceptual experiments can be designed to ask which subdivisions of the system are responsible for particular visual abilities, such as figure/ground discrimination or perception of depth from perspective or relative movement--functions that might be difficult to deduce from single-cell response properties.

Visuomotor properties of corticotectal cells in area 17 and posteromedial lateral suprasylvian (PMLS) cortex of the cat.

PubMed

Weyand, T G; Gafka, A C

2001-01-01

We studied the visuomotor activity of corticotectal (CT) cells in two visual cortical areas [area 17 and the posteromedial lateral suprasylvian cortex (PMLS)] of the cat. The cats were trained in simple oculomotor tasks, and head position was fixed. Most CT cells in both cortical areas gave a vigorous discharge to a small stimulus used to control gaze when it fell within the retinotopically defined visual field. However, the vigor of the visual response did not predict latency to initiate a saccade, saccade velocity, amplitude, or even if a saccade would be made, minimizing any potential role these cells might have in premotor or attentional processes. Most CT cells in both areas were selective for direction of stimulus motion, and cells in PMLS showed a direction preference favoring motion away from points of central gaze. CT cells did not discharge with eye movements in the dark. During eye movements in the light, many CT cells in area 17 increased their activity. In contrast, cells in PMLS, including CT cells, were generally unresponsive during saccades. Paradoxically, cells in PMLS responded vigorously to stimuli moving at saccadic velocities, indicating that the oculomotor system suppresses visual activity elicited by moving the retina across an illuminated scene. Nearly all CT cells showed oscillatory activity in the frequency range of 20-90 Hz, especially in response to visual stimuli. However, this activity was capricious; strong oscillations in one trial could disappear in the next despite identical stimulus conditions. Although the CT cells in both of these regions share many characteristics, the direction anisotropy and the suppression of activity during eye movements which characterize the neurons in PMLS suggests that these two areas have different roles in facilitating perceptual/motor processes at the level of the superior colliculus.

Stimulus selectivity and response latency in putative inhibitory and excitatory neurons of the primate inferior temporal cortex

PubMed Central

Mruczek, Ryan E. B.

2012-01-01

The cerebral cortex is composed of many distinct classes of neurons. Numerous studies have demonstrated corresponding differences in neuronal properties across cell types, but these comparisons have largely been limited to conditions outside of awake, behaving animals. Thus the functional role of the various cell types is not well understood. Here, we investigate differences in the functional properties of two widespread and broad classes of cells in inferior temporal cortex of macaque monkeys: inhibitory interneurons and excitatory projection cells. Cells were classified as putative inhibitory or putative excitatory neurons on the basis of their extracellular waveform characteristics (e.g., spike duration). Consistent with previous intracellular recordings in cortical slices, putative inhibitory neurons had higher spontaneous firing rates and higher stimulus-evoked firing rates than putative excitatory neurons. Additionally, putative excitatory neurons were more susceptible to spike waveform adaptation following very short interspike intervals. Finally, we compared two functional properties of each neuron's stimulus-evoked response: stimulus selectivity and response latency. First, putative excitatory neurons showed stronger stimulus selectivity compared with putative inhibitory neurons. Second, putative inhibitory neurons had shorter response latencies compared with putative excitatory neurons. Selectivity differences were maintained and latency differences were enhanced during a visual search task emulating more natural viewing conditions. Our results suggest that short-latency inhibitory responses are likely to sculpt visual processing in excitatory neurons, yielding a sparser visual representation. PMID:22933717

Biophysical Network Modelling of the dLGN Circuit: Different Effects of Triadic and Axonal Inhibition on Visual Responses of Relay Cells.

PubMed

Heiberg, Thomas; Hagen, Espen; Halnes, Geir; Einevoll, Gaute T

2016-05-01

Despite its prominent placement between the retina and primary visual cortex in the early visual pathway, the role of the dorsal lateral geniculate nucleus (dLGN) in molding and regulating the visual signals entering the brain is still poorly understood. A striking feature of the dLGN circuit is that relay cells (RCs) and interneurons (INs) form so-called triadic synapses, where an IN dendritic terminal can be simultaneously postsynaptic to a retinal ganglion cell (GC) input and presynaptic to an RC dendrite, allowing for so-called triadic inhibition. Taking advantage of a recently developed biophysically detailed multicompartmental model for an IN, we here investigate putative effects of these different inhibitory actions of INs, i.e., triadic inhibition and standard axonal inhibition, on the response properties of RCs. We compute and investigate so-called area-response curves, that is, trial-averaged visual spike responses vs. spot size, for circular flashing spots in a network of RCs and INs. The model parameters are grossly tuned to give results in qualitative accordance with previous in vivo data of responses to such stimuli for cat GCs and RCs. We particularly investigate how the model ingredients affect salient response properties such as the receptive-field center size of RCs and INs, maximal responses and center-surround antagonisms. For example, while triadic inhibition not involving firing of IN action potentials was found to provide only a non-linear gain control of the conversion of input spikes to output spikes by RCs, axonal inhibition was in contrast found to substantially affect the receptive-field center size: the larger the inhibition, the more the RC center size shrinks compared to the GC providing the feedforward excitation. Thus, a possible role of the different inhibitory actions from INs to RCs in the dLGN circuit is to provide separate mechanisms for overall gain control (direct triadic inhibition) and regulation of spatial resolution (axonal inhibition) of visual signals sent to cortex.

Responses of single cells in cat visual cortex to prolonged stimulus movement: neural correlates of visual aftereffects.

PubMed

Vautin, R G; Berkley, M A

1977-09-01

1. The activity of single cortical cells in area 17 of anesthetized and unanesthetized cats was recorded in response to prolonged stimulation with moving stimuli. 2. Under the appropriate conditions, all cells observed showed a progressive response decrement during the stimulation period, regardless of cell classification, i.e., simple, complex, or hypercomplex. 3. The observed response decrement was shown to be largely cortical in origin and could be adequately described with an exponential function of the form R = Rf +(R1-Rf)e-t/T. Time constants derived from such calculations yielded values ranging from 1.92 to 12.45 s under conditions of optimal-stimulation. 4. Most cells showed poststimulation effects, usually a brief period of reduced responsiveness that recovered exponentially. Recovery was essentially complete in about 5-35 s. 5. The degree to which stimuli were effective at inducing response was shown to have significant effects on the magnitude of the response decrement. 6. Several cells showed neural patterns of response and recovery that suggested the operation of intracortical inhibitory mechanisms. 7. A simple two-process model that adequately describes the behavior of all the studied cells is presented. 8. Because the properties of the cells studied correlate well with human psychophysical measures of contour and movement adaptation and recovery, a causal relationship to similar neural mechanisms in humans is suggested.

Brain State Effects on Layer 4 of the Awake Visual Cortex

PubMed Central

Zhuang, Jun; Bereshpolova, Yulia; Stoelzel, Carl R.; Huff, Joseph M.; Hei, Xiaojuan; Alonso, Jose-Manuel

2014-01-01

Awake mammals can switch between alert and nonalert brain states hundreds of times per day. Here, we study the effects of alertness on two cell classes in layer 4 of primary visual cortex of awake rabbits: presumptive excitatory “simple” cells and presumptive fast-spike inhibitory neurons (suspected inhibitory interneurons). We show that in both cell classes, alertness increases the strength and greatly enhances the reliability of visual responses. In simple cells, alertness also increases the temporal frequency bandwidth, but preserves contrast sensitivity, orientation tuning, and selectivity for direction and spatial frequency. Finally, alertness selectively suppresses the simple cell responses to high-contrast stimuli and stimuli moving orthogonal to the preferred direction, effectively enhancing mid-contrast borders. Using a population coding model, we show that these effects of alertness in simple cells—enhanced reliability, higher gain, and increased suppression in orthogonal orientation—could play a major role at increasing the speed of cortical feature detection. PMID:24623767

Neural mechanism for sensing fast motion in dim light.

PubMed

Li, Ran; Wang, Yi

2013-11-07

Luminance is a fundamental property of visual scenes. A population of neurons in primary visual cortex (V1) is sensitive to uniform luminance. In natural vision, however, the retinal image often changes rapidly. Consequently the luminance signals visual cells receive are transiently varying. How V1 neurons respond to such luminance changes is unknown. By applying large static uniform stimuli or grating stimuli altering at 25 Hz that resemble the rapid luminance changes in the environment, we show that approximately 40% V1 cells responded to rapid luminance changes of uniform stimuli. Most of them strongly preferred luminance decrements. Importantly, when tested with drifting gratings, the preferred speeds of these cells were significantly higher than cells responsive to static grating stimuli but not to uniform stimuli. This responsiveness can be accounted for by the preferences for low spatial frequencies and high temporal frequencies. These luminance-sensitive cells subserve the detection of fast motion under the conditions of dim illumination.

Cross-modality Sharpening of Visual Cortical Processing through Layer 1-Mediated Inhibition and Disinhibition

PubMed Central

Ibrahim, Leena A.; Mesik, Lukas; Ji, Xu-ying; Fang, Qi; Li, Hai-fu; Li, Ya-tang; Zingg, Brian; Zhang, Li I.; Tao, Huizhong Whit

2016-01-01

Summary Cross-modality interaction in sensory perception is advantageous for animals’ survival. How cortical sensory processing is cross-modally modulated and what are the underlying neural circuits remain poorly understood. In mouse primary visual cortex (V1), we discovered that orientation selectivity of layer (L)2/3 but not L4 excitatory neurons was sharpened in the presence of sound or optogenetic activation of projections from primary auditory cortex (A1) to V1. The effect was manifested by decreased average visual responses yet increased responses at the preferred orientation. It was more pronounced at lower visual contrast, and was diminished by suppressing L1 activity. L1 neurons were strongly innervated by A1-V1 axons and excited by sound, while visual responses of L2/3 vasoactive intestinal peptide (VIP) neurons were suppressed by sound, both preferentially at the cell's preferred orientation. These results suggest that the cross-modality modulation is achieved primarily through L1 neuron and L2/3 VIP-cell mediated inhibitory and disinhibitory circuits. PMID:26898778

Live-cell visualization of gasdermin D-driven pyroptotic cell death.

PubMed

Rathkey, Joseph K; Benson, Bryan L; Chirieleison, Steven M; Yang, Jie; Xiao, Tsan S; Dubyak, George R; Huang, Alex Y; Abbott, Derek W

2017-09-01

Pyroptosis is a form of cell death important in defenses against pathogens that can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, GSDMD (gasdermin D), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has complicated our ability to understand the biology of this protein. Studies aimed at visualizing GSDMD have relied on expression of GSDMD fragments in epithelial cell lines that naturally lack GSDMD expression and also lack the proteases necessary to cleave GSDMD. In this work, we performed mutagenesis and molecular modeling to strategically place tags and fluorescent proteins within GSDMD that support native pyroptosis and facilitate live-cell imaging of pyroptotic cell death. Here, we demonstrate that these fusion proteins are cleaved by caspases-1 and -11 at Asp-276. Mutations that disrupted the predicted p30-p20 autoinhibitory interface resulted in GSDMD aggregation, supporting the oligomerizing activity of these mutations. Furthermore, we show that these novel GSDMD fusions execute inflammasome-dependent pyroptotic cell death in response to multiple stimuli and allow for visualization of the morphological changes associated with pyroptotic cell death in real time. This work therefore provides new tools that not only expand the molecular understanding of pyroptosis but also enable its direct visualization. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A Nonlinear Model for Transient Responses from Light-Adapted Wolf Spider Eyes

PubMed Central

DeVoe, Robert D.

1967-01-01

A quantitative model is proposed to test the hypothesis that the dynamics of nonlinearities in retinal action potentials from light-adapted wolf spider eyes may be due to delayed asymmetries in responses of the visual cells. For purposes of calculation, these delayed asymmetries are generated in an analogue by a time-variant resistance. It is first shown that for small incremental stimuli, the linear behavior of such a resistance describes peaking and low frequency phase lead in frequency responses of the eye to sinusoidal modulations of background illumination. It also describes the overshoots in linear step responses. It is next shown that the analogue accounts for nonlinear transient and short term DC responses to large positive and negative step stimuli and for the variations in these responses with changes in degree of light adaptation. Finally, a physiological model is proposed in which the delayed asymmetries in response are attributed to delayed rectification by the visual cell membrane. In this model, cascaded chemical reactions may serve to transduce visual stimuli into membrane resistance changes. PMID:6056011

Vestibular responses in the macaque pedunculopontine nucleus and central mesencephalic reticular formation

PubMed Central

Aravamuthan, Bhooma R.; Angelaki, Dora E.

2012-01-01

The pedunculopontine nucleus (PPN) and central mesencephalic reticular formation (cMRF) both send projections and receive input from areas with known vestibular responses. Noting their connections with the basal ganglia, the locomotor disturbances that occur following lesions of the PPN or cMRF, and the encouraging results of PPN deep brain stimulation in Parkinson’s disease patients, both the PPN and cMRF have been linked to motor control. In order to determine the existence of and characterize vestibular responses in the PPN and cMRF, we recorded single neurons from both structures during vertical and horizontal rotation, translation, and visual pursuit stimuli. The majority of PPN cells (72.5%) were vestibular-only cells that responded exclusively to rotation and translation stimuli but not visual pursuit. Visual pursuit responses were much more prevalent in the cMRF (57.1%) though close to half of cMRF cells were vestibular-only cells (41.1%). Directional preferences also differed between the PPN, which was preferentially modulated during nose-down pitch, and cMRF, which was preferentially modulated during ipsilateral yaw rotation. Finally, amplitude responses were similar between the PPN and cMRF during rotation and pursuit stimuli, but PPN responses to translation were of higher amplitude than cMRF responses. Taken together with their connections to the vestibular circuit, these results implicate the PPN and cMRF in the processing of vestibular stimuli and suggest important roles for both in responding to motion perturbations like falls and turns. PMID:22864184

Variability of visual responses of superior colliculus neurons depends on stimulus velocity.

PubMed

Mochol, Gabriela; Wójcik, Daniel K; Wypych, Marek; Wróbel, Andrzej; Waleszczyk, Wioletta J

2010-03-03

Visually responding neurons in the superficial, retinorecipient layers of the cat superior colliculus receive input from two primarily parallel information processing channels, Y and W, which is reflected in their velocity response profiles. We quantified the time-dependent variability of responses of these neurons to stimuli moving with different velocities by Fano factor (FF) calculated in discrete time windows. The FF for cells responding to low-velocity stimuli, thus receiving W inputs, increased with the increase in the firing rate. In contrast, the dynamics of activity of the cells responding to fast moving stimuli, processed by Y pathway, correlated negatively with FF whether the response was excitatory or suppressive. These observations were tested against several types of surrogate data. Whereas Poisson description failed to reproduce the variability of all collicular responses, the inclusion of secondary structure to the generating point process recovered most of the observed features of responses to fast moving stimuli. Neither model could reproduce the variability of low-velocity responses, which suggests that, in this case, more complex time dependencies need to be taken into account. Our results indicate that Y and W channels may differ in reliability of responses to visual stimulation. Apart from previously reported morphological and physiological differences of the cells belonging to Y and W channels, this is a new feature distinguishing these two pathways.

Cortical Double-Opponent Cells in Color Perception: Perceptual Scaling and Chromatic Visual Evoked Potentials.

PubMed

Nunez, Valerie; Shapley, Robert M; Gordon, James

2018-01-01

In the early visual cortex V1, there are currently only two known neural substrates for color perception: single-opponent and double-opponent cells. Our aim was to explore the relative contributions of these neurons to color perception. We measured the perceptual scaling of color saturation for equiluminant color checkerboard patterns (designed to stimulate double-opponent neurons preferentially) and uniformly colored squares (designed to stimulate only single-opponent neurons) at several cone contrasts. The spatially integrative responses of single-opponent neurons would produce the same response magnitude for checkerboards as for uniform squares of the same space-averaged cone contrast. However, perceived saturation of color checkerboards was higher than for the corresponding squares. The perceptual results therefore imply that double-opponent cells are involved in color perception of patterns. We also measured the chromatic visual evoked potential (cVEP) produced by the same stimuli; checkerboard cVEPs were much larger than those for corresponding squares, implying that double-opponent cells also contribute to the cVEP response. The total Fourier power of the cVEP grew sublinearly with cone contrast. However, the 6-Hz Fourier component's power grew linearly with contrast-like saturation perception. This may also indicate that cortical coding of color depends on response dynamics.

Cortical Double-Opponent Cells in Color Perception: Perceptual Scaling and Chromatic Visual Evoked Potentials

PubMed Central

Shapley, Robert M.; Gordon, James

2018-01-01

In the early visual cortex V1, there are currently only two known neural substrates for color perception: single-opponent and double-opponent cells. Our aim was to explore the relative contributions of these neurons to color perception. We measured the perceptual scaling of color saturation for equiluminant color checkerboard patterns (designed to stimulate double-opponent neurons preferentially) and uniformly colored squares (designed to stimulate only single-opponent neurons) at several cone contrasts. The spatially integrative responses of single-opponent neurons would produce the same response magnitude for checkerboards as for uniform squares of the same space-averaged cone contrast. However, perceived saturation of color checkerboards was higher than for the corresponding squares. The perceptual results therefore imply that double-opponent cells are involved in color perception of patterns. We also measured the chromatic visual evoked potential (cVEP) produced by the same stimuli; checkerboard cVEPs were much larger than those for corresponding squares, implying that double-opponent cells also contribute to the cVEP response. The total Fourier power of the cVEP grew sublinearly with cone contrast. However, the 6-Hz Fourier component’s power grew linearly with contrast-like saturation perception. This may also indicate that cortical coding of color depends on response dynamics. PMID:29375753

Causal evidence for retina dependent and independent visual motion computations in mouse cortex

PubMed Central

Hillier, Daniel; Fiscella, Michele; Drinnenberg, Antonia; Trenholm, Stuart; Rompani, Santiago B.; Raics, Zoltan; Katona, Gergely; Juettner, Josephine; Hierlemann, Andreas; Rozsa, Balazs; Roska, Botond

2017-01-01

How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity – either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells – and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an overrepresentation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward. In mice with disrupted retinal direction selectivity, the overrepresentation of posterior-motion-preferring cortical cells disappeared, and their response at higher stimulus speeds was reduced. This work reveals the existence of two functionally distinct, sensory-periphery-dependent and -independent computations of visual motion in the cortex. PMID:28530661

What Are the Shapes of Response Time Distributions in Visual Search?

ERIC Educational Resources Information Center

Palmer, Evan M.; Horowitz, Todd S.; Torralba, Antonio; Wolfe, Jeremy M.

2011-01-01

Many visual search experiments measure response time (RT) as their primary dependent variable. Analyses typically focus on mean (or median) RT. However, given enough data, the RT distribution can be a rich source of information. For this paper, we collected about 500 trials per cell per observer for both target-present and target-absent displays…

Projection-specific visual feature encoding by layer 5 cortical subnetworks

PubMed Central

Lur, Gyorgy; Vinck, Martin A.; Tang, Lan; Cardin, Jessica A.; Higley, Michael J.

2016-01-01

Summary Primary neocortical sensory areas act as central hubs, distributing afferent information to numerous cortical and subcortical structures. However, it remains unclear whether each downstream target receives distinct versions of sensory information. We used in vivo calcium imaging combined with retrograde tracing to monitor visual response properties of three distinct subpopulations of projection neurons in primary visual cortex. While there is overlap across the groups, on average corticotectal (CT) cells exhibit lower contrast thresholds and broader tuning for orientation and spatial frequency in comparison to corticostriatal (CS) cells, while corticocortical (CC) cells have intermediate properties. Noise correlational analyses support the hypothesis that CT cells integrate information across diverse layer 5 populations, whereas CS and CC cells form more selectively interconnected groups. Overall, our findings demonstrate the existence of functional subnetworks within layer 5 that may differentially route visual information to behaviorally relevant downstream targets. PMID:26972011

A neural model of motion processing and visual navigation by cortical area MST.

PubMed

Grossberg, S; Mingolla, E; Pack, C

1999-12-01

Cells in the dorsal medial superior temporal cortex (MSTd) process optic flow generated by self-motion during visually guided navigation. A neural model shows how interactions between well-known neural mechanisms (log polar cortical magnification, Gaussian motion-sensitive receptive fields, spatial pooling of motion-sensitive signals and subtractive extraretinal eye movement signals) lead to emergent properties that quantitatively simulate neurophysiological data about MSTd cell properties and psychophysical data about human navigation. Model cells match MSTd neuron responses to optic flow stimuli placed in different parts of the visual field, including position invariance, tuning curves, preferred spiral directions, direction reversals, average response curves and preferred locations for stimulus motion centers. The model shows how the preferred motion direction of the most active MSTd cells can explain human judgments of self-motion direction (heading), without using complex heading templates. The model explains when extraretinal eye movement signals are needed for accurate heading perception, and when retinal input is sufficient, and how heading judgments depend on scene layouts and rotation rates.

Broad Thorny Ganglion Cells: A Candidate for Visual Pursuit Error Signaling in the Primate Retina

PubMed Central

Manookin, Michael B.; Neitz, Jay; Rieke, Fred

2015-01-01

Functional analyses exist only for a few of the morphologically described primate ganglion cell types, and their correlates in other mammalian species remain elusive. Here, we recorded light responses of broad thorny cells in the whole-mounted macaque retina. They showed ON-OFF-center light responses that were strongly suppressed by stimulation of the receptive field surround. Spike responses were delayed compared with parasol ganglion cells and other ON-OFF cells, including recursive bistratified ganglion cells and A1 amacrine cells. The receptive field structure was shaped by direct excitatory synaptic input and strong presynaptic and postsynaptic inhibition in both ON and OFF pathways. The cells responded strongly to dark or bright stimuli moving either in or out of the receptive field, independent of the direction of motion. However, they did not show a maintained spike response either to a uniform background or to a drifting plaid pattern. These properties could be ideally suited for guiding movements involved in visual pursuit. The functional characteristics reported here permit the first direct cross-species comparison of putative homologous ganglion cell types. Based on morphological similarities, broad thorny ganglion cells have been proposed to be homologs of rabbit local edge detector ganglion cells, but we now show that the two cells have quite distinct physiological properties. Thus, our data argue against broad thorny cells as the homologs of local edge detector cells. PMID:25834063

Visual-servoing optical microscopy

DOEpatents

Callahan, Daniel E.; Parvin, Bahram

2009-06-09

The present invention provides methods and devices for the knowledge-based discovery and optimization of differences between cell types. In particular, the present invention provides visual servoing optical microscopy, as well as analysis methods. The present invention provides means for the close monitoring of hundreds of individual, living cells over time: quantification of dynamic physiological responses in multiple channels; real-time digital image segmentation and analysis; intelligent, repetitive computer-applied cell stress and cell stimulation; and the ability to return to the same field of cells for long-term studies and observation. The present invention further provides means to optimize culture conditions for specific subpopulations of cells.

Visual-servoing optical microscopy

DOEpatents

Callahan, Daniel E [Martinez, CA; Parvin, Bahram [Mill Valley, CA

2011-05-24

The present invention provides methods and devices for the knowledge-based discovery and optimization of differences between cell types. In particular, the present invention provides visual servoing optical microscopy, as well as analysis methods. The present invention provides means for the close monitoring of hundreds of individual, living cells over time; quantification of dynamic physiological responses in multiple channels; real-time digital image segmentation and analysis; intelligent, repetitive computer-applied cell stress and cell stimulation; and the ability to return to the same field of cells for long-term studies and observation. The present invention further provides means to optimize culture conditions for specific subpopulations of cells.

Visual-servoing optical microscopy

DOEpatents

Callahan, Daniel E; Parvin, Bahram

2013-10-01

The present invention provides methods and devices for the knowledge-based discovery and optimization of differences between cell types. In particular, the present invention provides visual servoing optical microscopy, as well as analysis methods. The present invention provides means for the close monitoring of hundreds of individual, living cells over time; quantification of dynamic physiological responses in multiple channels; real-time digital image segmentation and analysis; intelligent, repetitive computer-applied cell stress and cell stimulation; and the ability to return to the same field of cells for long-term studies and observation. The present invention further provides means to optimize culture conditions for specific subpopulations of cells.

Computational models of cortical visual processing.

PubMed Central

Heeger, D J; Simoncelli, E P; Movshon, J A

1996-01-01

The visual responses of neurons in the cerebral cortex were first adequately characterized in the 1960s by D. H. Hubel and T. N. Wiesel [(1962) J. Physiol. (London) 160, 106-154; (1968) J. Physiol. (London) 195, 215-243] using qualitative analyses based on simple geometric visual targets. Over the past 30 years, it has become common to consider the properties of these neurons by attempting to make formal descriptions of these transformations they execute on the visual image. Most such models have their roots in linear-systems approaches pioneered in the retina by C. Enroth-Cugell and J. R. Robson [(1966) J. Physiol. (London) 187, 517-552], but it is clear that purely linear models of cortical neurons are inadequate. We present two related models: one designed to account for the responses of simple cells in primary visual cortex (V1) and one designed to account for the responses of pattern direction selective cells in MT (or V5), an extrastriate visual area thought to be involved in the analysis of visual motion. These models share a common structure that operates in the same way on different kinds of input, and instantiate the widely held view that computational strategies are similar throughout the cerebral cortex. Implementations of these models for Macintosh microcomputers are available and can be used to explore the models' properties. PMID:8570605

Role of feedforward geniculate inputs in the generation of orientation selectivity in the cat's primary visual cortex

PubMed Central

Viswanathan, Sivaram; Jayakumar, Jaikishan; Vidyasagar, Trichur R

2011-01-01

Abstract Neurones of the mammalian primary visual cortex have the remarkable property of being selective for the orientation of visual contours. It has been controversial whether the selectivity arises from intracortical mechanisms, from the pattern of afferent connectivity from lateral geniculate nucleus (LGN) to cortical cells or from the sharpening of a bias that is already present in the responses of many geniculate cells. To investigate this, we employed a variation of an electrical stimulation protocol in the LGN that has been claimed to suppress intracortical inputs and isolate the raw geniculocortical input to a striate cortical cell. Such stimulation led to a sharpening of the orientation sensitivity of geniculate cells themselves and some broadening of cortical orientation selectivity. These findings are consistent with the idea that non-specific inhibition of the signals from LGN cells which exhibit an orientation bias can generate the sharp orientation selectivity of primary visual cortical cells. This obviates the need for an excitatory convergence from geniculate cells whose receptive fields are arranged along a row in visual space as in the classical model and provides a framework for orientation sensitivity originating in the retina and getting sharpened through inhibition at higher levels of the visual pathway. PMID:21486788

Vestibular responses in the macaque pedunculopontine nucleus and central mesencephalic reticular formation.

PubMed

Aravamuthan, B R; Angelaki, D E

2012-10-25

The pedunculopontine nucleus (PPN) and central mesencephalic reticular formation (cMRF) both send projections and receive input from areas with known vestibular responses. Noting their connections with the basal ganglia, the locomotor disturbances that occur following lesions of the PPN or cMRF, and the encouraging results of PPN deep brain stimulation in Parkinson's disease patients, both the PPN and cMRF have been linked to motor control. In order to determine the existence of and characterize vestibular responses in the PPN and cMRF, we recorded single neurons from both structures during vertical and horizontal rotation, translation, and visual pursuit stimuli. The majority of PPN cells (72.5%) were vestibular-only (VO) cells that responded exclusively to rotation and translation stimuli but not visual pursuit. Visual pursuit responses were much more prevalent in the cMRF (57.1%) though close to half of cMRF cells were VO cells (41.1%). Directional preferences also differed between the PPN, which was preferentially modulated during nose-down pitch, and cMRF, which was preferentially modulated during ipsilateral yaw rotation. Finally, amplitude responses were similar between the PPN and cMRF during rotation and pursuit stimuli, but PPN responses to translation were of higher amplitude than cMRF responses. Taken together with their connections to the vestibular circuit, these results implicate the PPN and cMRF in the processing of vestibular stimuli and suggest important roles for both in responding to motion perturbations like falls and turns. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Spatiotemporal characteristics of retinal response to network-mediated photovoltaic stimulation.

PubMed

Ho, Elton; Smith, Richard; Goetz, Georges; Lei, Xin; Galambos, Ludwig; Kamins, Theodore I; Harris, James; Mathieson, Keith; Palanker, Daniel; Sher, Alexander

2018-02-01

Subretinal prostheses aim at restoring sight to patients blinded by photoreceptor degeneration using electrical activation of the surviving inner retinal neurons. Today, such implants deliver visual information with low-frequency stimulation, resulting in discontinuous visual percepts. We measured retinal responses to complex visual stimuli delivered at video rate via a photovoltaic subretinal implant and by visible light. Using a multielectrode array to record from retinal ganglion cells (RGCs) in the healthy and degenerated rat retina ex vivo, we estimated their spatiotemporal properties from the spike-triggered average responses to photovoltaic binary white noise stimulus with 70-μm pixel size at 20-Hz frame rate. The average photovoltaic receptive field size was 194 ± 3 μm (mean ± SE), similar to that of visual responses (221 ± 4 μm), but response latency was significantly shorter with photovoltaic stimulation. Both visual and photovoltaic receptive fields had an opposing center-surround structure. In the healthy retina, ON RGCs had photovoltaic OFF responses, and vice versa. This reversal is consistent with depolarization of photoreceptors by electrical pulses, as opposed to their hyperpolarization under increasing light, although alternative mechanisms cannot be excluded. In degenerate retina, both ON and OFF photovoltaic responses were observed, but in the absence of visual responses, it is not clear what functional RGC types they correspond to. Degenerate retina maintained the antagonistic center-surround organization of receptive fields. These fast and spatially localized network-mediated ON and OFF responses to subretinal stimulation via photovoltaic pixels with local return electrodes raise confidence in the possibility of providing more functional prosthetic vision. NEW & NOTEWORTHY Retinal prostheses currently in clinical use have struggled to deliver visual information at naturalistic frequencies, resulting in discontinuous percepts. We demonstrate modulation of the retinal ganglion cells (RGC) activity using complex spatiotemporal stimuli delivered via subretinal photovoltaic implant at 20 Hz in healthy and in degenerate retina. RGCs exhibit fast and localized ON and OFF network-mediated responses, with antagonistic center-surround organization of their receptive fields.

Physiological and morphological characterization of ganglion cells in the salamander retina

PubMed Central

Wang, Jing; Jacoby, Roy; Wu, Samuel M.

2016-01-01

Retinal ganglion cells (RGCs) integrate visual information from the retina and transmit collective signals to the brain. A systematic investigation of functional and morphological characteristics of various types of RGCs is important to comprehensively understand how the visual system encodes and transmits information via various RGC pathways. This study evaluated both physiological and morphological properties of 67 RGCs in dark-adapted flat-mounted salamander retina by examining light-evoked cation and chloride current responses via voltage-clamp recordings and visualizing morphology by Lucifer yellow fluorescence with a confocal microscope. Six groups of RGCs were described: asymmetrical ON–OFF RGCs, symmetrical ON RGCs, OFF RGCs, and narrow-, medium- and wide-field ON–OFF RGCs. Dendritic field diameters of RGCs ranged 102–490 µm: narrow field (<200 µm, 31% of RGCs), medium field (200–300 µm, 45%) and wide field (>300 µm, 24%). Dendritic ramification patterns of RGCs agree with the sub-lamina A/B rule. 34% of RGCs were monostratified, 24% bistratified and 42% diffusely stratified. 70% of ON RGCs and OFF RGCs were monostratified. Wide-field RGCs were diffusely stratified. 82% of RGCs generated light-evoked ON–OFF responses, while 11% generated ON responses and 7% OFF responses. Response sensitivity analysis suggested that some RGCs obtained separated rod/cone bipolar cell inputs whereas others obtained mixed bipolar cell inputs. 25% of neurons in the RGC layer were displaced amacrine cells. Although more types may be defined by more refined classification criteria, this report is to incorporate more physiological properties into RGC classification. PMID:26731645

Activity of neurons in area 6 of the cat during fixation and eye movements.

PubMed

Weyand, T G; Gafka, A C

1998-01-01

We studied the visuomotor properties of 645 neurons in area 6 of five cats trained in oculomotor tasks. The area we recorded from corresponds well with territories believed to contain the feline homologue of the frontal eye fields observed in primates. Despite an expectation that cells with pre-saccadic activity would be common, only a small fraction (approximately 5%) of the cells displayed activity that could be linked to subsequent saccadic eye movements. These pre-motor cells appeared to be distributed over a broad region of cortex mixed in with other cell types. As in primates, saccade-related activity tended to occur only during "purposeful" saccades. At least 30% (208/645) of the neurons were visual, with many of these cells possessing huge receptive fields that appeared to include the entire contralateral visual field. Visual responsiveness was generally attenuated by fixation during the oculomotor tasks. Although attentional mechanisms may play a role in this attenuation, this cortical area also exhibits powerful lateral interactions in which spatially displaced visual stimuli suppress each other. Most cells, visually responsive or not, were affected by fixation. Nearly equal proportions of cells showed increases or decreases in activity during fixation. For many of the cells affected by fixation, the source of this modulation appears to reflect cognitive, rather than sensory or motor processes. This included cells that showed anticipatory activity, and cells that responded to the reward only when it was presented in the context of the task. Based on the paucity of pre-saccadic neurons, it would be difficult to conclude that this region of cortex in the cat is homologous to the frontal eye fields of the monkey. However, when considered in the context of differences in the oculomotor habits of these two animals, we believe the homology fits. In addition to pre-motor neurons, the properties of several other cell types found in this area could contribute to the control of gaze.

Walking modulates speed sensitivity in Drosophila motion vision.

PubMed

Chiappe, M Eugenia; Seelig, Johannes D; Reiser, Michael B; Jayaraman, Vivek

2010-08-24

Changes in behavioral state modify neural activity in many systems. In some vertebrates such modulation has been observed and interpreted in the context of attention and sensorimotor coordinate transformations. Here we report state-dependent activity modulations during walking in a visual-motor pathway of Drosophila. We used two-photon imaging to monitor intracellular calcium activity in motion-sensitive lobula plate tangential cells (LPTCs) in head-fixed Drosophila walking on an air-supported ball. Cells of the horizontal system (HS)--a subgroup of LPTCs--showed stronger calcium transients in response to visual motion when flies were walking rather than resting. The amplified responses were also correlated with walking speed. Moreover, HS neurons showed a relatively higher gain in response strength at higher temporal frequencies, and their optimum temporal frequency was shifted toward higher motion speeds. Walking-dependent modulation of HS neurons in the Drosophila visual system may constitute a mechanism to facilitate processing of higher image speeds in behavioral contexts where these speeds of visual motion are relevant for course stabilization. Copyright 2010 Elsevier Ltd. All rights reserved.

Modulation of Temporal Precision in Thalamic Population Responses to Natural Visual Stimuli

PubMed Central

Desbordes, Gaëlle; Jin, Jianzhong; Alonso, Jose-Manuel; Stanley, Garrett B.

2010-01-01

Natural visual stimuli have highly structured spatial and temporal properties which influence the way visual information is encoded in the visual pathway. In response to natural scene stimuli, neurons in the lateral geniculate nucleus (LGN) are temporally precise – on a time scale of 10–25 ms – both within single cells and across cells within a population. This time scale, established by non stimulus-driven elements of neuronal firing, is significantly shorter than that of natural scenes, yet is critical for the neural representation of the spatial and temporal structure of the scene. Here, a generalized linear model (GLM) that combines stimulus-driven elements with spike-history dependence associated with intrinsic cellular dynamics is shown to predict the fine timing precision of LGN responses to natural scene stimuli, the corresponding correlation structure across nearby neurons in the population, and the continuous modulation of spike timing precision and latency across neurons. A single model captured the experimentally observed neural response, across different levels of contrasts and different classes of visual stimuli, through interactions between the stimulus correlation structure and the nonlinearity in spike generation and spike history dependence. Given the sensitivity of the thalamocortical synapse to closely timed spikes and the importance of fine timing precision for the faithful representation of natural scenes, the modulation of thalamic population timing over these time scales is likely important for cortical representations of the dynamic natural visual environment. PMID:21151356

Fyn kinase genetic ablation causes structural abnormalities in mature retina and defective Müller cell function.

PubMed

Chavez-Solano, Marbella; Ibarra-Sanchez, Alfredo; Treviño, Mario; Gonzalez-Espinosa, Claudia; Lamas, Monica

2016-04-01

Fyn kinase is widely expressed in neuronal and glial cells of the brain, where it exerts multiple functional roles that affect fundamental physiological processes. The aim of our study was to investigate the, so far unknown, functional role of Fyn in the retina. We report that Fyn is expressed, in vivo, in a subpopulation of Müller glia. We used a mouse model of Fyn genetic ablation and Müller-enriched primary cultures to demonstrate that Fyn deficiency induces morphological alterations in the mature retina, a reduction in the thickness of the outer and inner nuclear layers and alterations in postnatal Müller cell physiology. These include shortening of Müller cell processes, a decrease in cell proliferation, inactivation of the Akt signal transduction pathway, a reduced number of focal adhesions points and decreased adhesion of these cells to the ECM. As abnormalities in Müller cell physiology have been previously associated to a compromised retinal function we evaluated behavioral responses to visual stimulation. Our results associate Fyn deficiency with impaired visual optokinetic responses under scotopic and photopic light conditions. Our study reveals novel roles for Fyn kinase in retinal morphology and Müller cell physiology and suggests that Fyn is required for optimal visual processing. Copyright © 2016 Elsevier Inc. All rights reserved.

Neocortical Rebound Depolarization Enhances Visual Perception

PubMed Central

Funayama, Kenta; Ban, Hiroshi; Chan, Allen W.; Matsuki, Norio; Murphy, Timothy H.; Ikegaya, Yuji

2015-01-01

Animals are constantly exposed to the time-varying visual world. Because visual perception is modulated by immediately prior visual experience, visual cortical neurons may register recent visual history into a specific form of offline activity and link it to later visual input. To examine how preceding visual inputs interact with upcoming information at the single neuron level, we designed a simple stimulation protocol in which a brief, orientated flashing stimulus was subsequently coupled to visual stimuli with identical or different features. Using in vivo whole-cell patch-clamp recording and functional two-photon calcium imaging from the primary visual cortex (V1) of awake mice, we discovered that a flash of sinusoidal grating per se induces an early, transient activation as well as a long-delayed reactivation in V1 neurons. This late response, which started hundreds of milliseconds after the flash and persisted for approximately 2 s, was also observed in human V1 electroencephalogram. When another drifting grating stimulus arrived during the late response, the V1 neurons exhibited a sublinear, but apparently increased response, especially to the same grating orientation. In behavioral tests of mice and humans, the flashing stimulation enhanced the detection power of the identically orientated visual stimulation only when the second stimulation was presented during the time window of the late response. Therefore, V1 late responses likely provide a neural basis for admixing temporally separated stimuli and extracting identical features in time-varying visual environments. PMID:26274866

Modeling the impact of common noise inputs on the network activity of retinal ganglion cells

PubMed Central

Ahmadian, Yashar; Shlens, Jonathon; Pillow, Jonathan W.; Kulkarni, Jayant; Litke, Alan M.; Chichilnisky, E. J.; Simoncelli, Eero; Paninski, Liam

2013-01-01

Synchronized spontaneous firing among retinal ganglion cells (RGCs), on timescales faster than visual responses, has been reported in many studies. Two candidate mechanisms of synchronized firing include direct coupling and shared noisy inputs. In neighboring parasol cells of primate retina, which exhibit rapid synchronized firing that has been studied extensively, recent experimental work indicates that direct electrical or synaptic coupling is weak, but shared synaptic input in the absence of modulated stimuli is strong. However, previous modeling efforts have not accounted for this aspect of firing in the parasol cell population. Here we develop a new model that incorporates the effects of common noise, and apply it to analyze the light responses and synchronized firing of a large, densely-sampled network of over 250 simultaneously recorded parasol cells. We use a generalized linear model in which the spike rate in each cell is determined by the linear combination of the spatio-temporally filtered visual input, the temporally filtered prior spikes of that cell, and unobserved sources representing common noise. The model accurately captures the statistical structure of the spike trains and the encoding of the visual stimulus, without the direct coupling assumption present in previous modeling work. Finally, we examined the problem of decoding the visual stimulus from the spike train given the estimated parameters. The common-noise model produces Bayesian decoding performance as accurate as that of a model with direct coupling, but with significantly more robustness to spike timing perturbations. PMID:22203465

Functional divisions for visual processing in the central brain of flying Drosophila

PubMed Central

Weir, Peter T.; Dickinson, Michael H.

2015-01-01

Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to behavioral context. We imaged panneuronal responses to visual stimuli in a highly conserved central brain region in the fruit fly, Drosophila, during flight. In one substructure, the fan-shaped body, automated analysis revealed three layers that were unresponsive in quiescent flies but became responsive to visual stimuli when the animal was flying. The responses of these regions to a broad suite of visual stimuli suggest that they are involved in the regulation of flight heading. To identify the cell types that underlie these responses, we imaged activity in sets of genetically defined neurons with arborizations in the targeted layers. The responses of this collection during flight also segregated into three sets, confirming the existence of three layers, and they collectively accounted for the panneuronal activity. Our results provide an atlas of flight-gated visual responses in a central brain circuit. PMID:26324910

Mouse V1 population correlates of visual detection rely on heterogeneity within neuronal response patterns

PubMed Central

Montijn, Jorrit S; Goltstein, Pieter M; Pennartz, Cyriel MA

2015-01-01

Previous studies have demonstrated the importance of the primary sensory cortex for the detection, discrimination, and awareness of visual stimuli, but it is unknown how neuronal populations in this area process detected and undetected stimuli differently. Critical differences may reside in the mean strength of responses to visual stimuli, as reflected in bulk signals detectable in functional magnetic resonance imaging, electro-encephalogram, or magnetoencephalography studies, or may be more subtly composed of differentiated activity of individual sensory neurons. Quantifying single-cell Ca2+ responses to visual stimuli recorded with in vivo two-photon imaging, we found that visual detection correlates more strongly with population response heterogeneity rather than overall response strength. Moreover, neuronal populations showed consistencies in activation patterns across temporally spaced trials in association with hit responses, but not during nondetections. Contrary to models relying on temporally stable networks or bulk signaling, these results suggest that detection depends on transient differentiation in neuronal activity within cortical populations. DOI: http://dx.doi.org/10.7554/eLife.10163.001 PMID:26646184

Functional divisions for visual processing in the central brain of flying Drosophila.

PubMed

Weir, Peter T; Dickinson, Michael H

2015-10-06

Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to behavioral context. We imaged panneuronal responses to visual stimuli in a highly conserved central brain region in the fruit fly, Drosophila, during flight. In one substructure, the fan-shaped body, automated analysis revealed three layers that were unresponsive in quiescent flies but became responsive to visual stimuli when the animal was flying. The responses of these regions to a broad suite of visual stimuli suggest that they are involved in the regulation of flight heading. To identify the cell types that underlie these responses, we imaged activity in sets of genetically defined neurons with arborizations in the targeted layers. The responses of this collection during flight also segregated into three sets, confirming the existence of three layers, and they collectively accounted for the panneuronal activity. Our results provide an atlas of flight-gated visual responses in a central brain circuit.

Synchronous activity in cat visual cortex encodes collinear and cocircular contours.

PubMed

Samonds, Jason M; Zhou, Zhiyi; Bernard, Melanie R; Bonds, A B

2006-04-01

We explored how contour information in primary visual cortex might be embedded in the simultaneous activity of multiple cells recorded with a 100-electrode array. Synchronous activity in cat visual cortex was more selective and predictable in discriminating between drifting grating and concentric ring stimuli than changes in firing rate. Synchrony was found even between cells with wholly different orientation preferences when their receptive fields were circularly aligned, and membership in synchronous groups was orientation and curvature dependent. The existence of synchrony between cocircular cells reinforces its role as a general mechanism for contour integration and shape detection as predicted by association field concepts. Our data suggest that cortical synchrony results from common and synchronous input from earlier visual areas and that it could serve to shape extrastriate response selectivity.

Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex

PubMed Central

Muthukumaraswamy, Suresh D; Myers, Jim F M; Wilson, Sue J; Nutt, David J; Hamandi, Khalid; Lingford-Hughes, Anne; Singh, Krish D

2013-01-01

The electroencephalographic/magnetoencephalographic (EEG/MEG) signal is generated primarily by the summation of the postsynaptic currents of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons. Here we investigated the relative sensitivity of visual evoked and induced responses to altered levels of endogenous GABAergic inhibition. To do this, we pharmacologically manipulated the GABA system using tiagabine, which blocks the synaptic GABA transporter 1, and so increases endogenous GABA levels. In a single-blinded and placebo-controlled crossover study of 15 healthy participants, we administered either 15 mg of tiagabine or a placebo. We recorded whole-head MEG, while participants viewed a visual grating stimulus, before, 1, 3 and 5 h post tiagabine ingestion. Using beamformer source localization, we reconstructed responses from early visual cortices. Our results showed no change in either stimulus-induced gamma-band amplitude increases or stimulus-induced alpha amplitude decreases. However, the same data showed a 45% reduction in the evoked response component at ∼80 ms. These data demonstrate that, in early visual cortex the evoked response shows a greater sensitivity compared with induced oscillations to pharmacologically increased endogenous GABA levels. We suggest that previous studies correlating GABA concentrations as measured by magnetic resonance spectroscopy to gamma oscillation frequency may reflect underlying variations such as interneuron/inhibitory synapse density rather than functional synaptic GABA concentrations. PMID:23361120

Feature extraction inspired by V1 in visual cortex

NASA Astrophysics Data System (ADS)

Lv, Chao; Xu, Yuelei; Zhang, Xulei; Ma, Shiping; Li, Shuai; Xin, Peng; Zhu, Mingning; Ma, Hongqiang

2018-04-01

Target feature extraction plays an important role in pattern recognition. It is the most complicated activity in the brain mechanism of biological vision. Inspired by high properties of primary visual cortex (V1) in extracting dynamic and static features, a visual perception model was raised. Firstly, 28 spatial-temporal filters with different orientations, half-squaring operation and divisive normalization were adopted to obtain the responses of V1 simple cells; then, an adjustable parameter was added to the output weight so that the response of complex cells was got. Experimental results indicate that the proposed V1 model can perceive motion information well. Besides, it has a good edge detection capability. The model inspired by V1 has good performance in feature extraction and effectively combines brain-inspired intelligence with computer vision.

Contrast Sensitivity With a Subretinal Prosthesis and Implications for Efficient Delivery of Visual Information

PubMed Central

Goetz, Georges; Smith, Richard; Lei, Xin; Galambos, Ludwig; Kamins, Theodore; Mathieson, Keith; Sher, Alexander; Palanker, Daniel

2015-01-01

Purpose To evaluate the contrast sensitivity of a degenerate retina stimulated by a photovoltaic subretinal prosthesis, and assess the impact of low contrast sensitivity on transmission of visual information. Methods We measure ex vivo the full-field contrast sensitivity of healthy rat retina stimulated with white light, and the contrast sensitivity of degenerate rat retina stimulated with a subretinal prosthesis at frequencies exceeding flicker fusion (>20 Hz). Effects of eye movements on retinal ganglion cell (RGC) activity are simulated using a linear–nonlinear model of the retina. Results Retinal ganglion cells adapt to high frequency stimulation of constant intensity, and respond transiently to changes in illumination of the implant, exhibiting responses to ON-sets, OFF-sets, and both ON- and OFF-sets of light. The percentage of cells with an OFF response decreases with progression of the degeneration, indicating that OFF responses are likely mediated by photoreceptors. Prosthetic vision exhibits reduced contrast sensitivity and dynamic range, with 65% contrast changes required to elicit responses, as compared to the 3% (OFF) to 7% (ON) changes with visible light. The maximum number of action potentials elicited with prosthetic stimulation is at most half of its natural counterpart for the ON pathway. Our model predicts that for most visual scenes, contrast sensitivity of prosthetic vision is insufficient for triggering RGC activity by fixational eye movements. Conclusions Contrast sensitivity of prosthetic vision is 10 times lower than normal, and dynamic range is two times below natural. Low contrast sensitivity and lack of OFF responses hamper delivery of visual information via a subretinal prosthesis. PMID:26540657

Diversification of non-visual photopigment parapinopsin in spectral sensitivity for diverse pineal functions.

PubMed

Koyanagi, Mitsumasa; Wada, Seiji; Kawano-Yamashita, Emi; Hara, Yuichiro; Kuraku, Shigehiro; Kosaka, Shigeaki; Kawakami, Koichi; Tamotsu, Satoshi; Tsukamoto, Hisao; Shichida, Yoshinori; Terakita, Akihisa

2015-09-15

Recent genome projects of various animals have uncovered an unexpectedly large number of opsin genes, which encode protein moieties of photoreceptor molecules, in most animals. In visual systems, the biological meanings of this diversification are clear; multiple types of visual opsins with different spectral sensitivities are responsible for color vision. However, the significance of the diversification of non-visual opsins remains uncertain, in spite of the importance of understanding the molecular mechanism and evolution of varied non-visual photoreceptions. Here, we investigated the diversification of the pineal photopigment parapinopsin, which serves as the UV-sensitive photopigment for the pineal wavelength discrimination in the lamprey, linking it with other pineal photoreception. Spectroscopic analyses of the recombinant pigments of the two teleost parapinopsins PP1 and PP2 revealed that PP1 is a UV-sensitive pigment, similar to lamprey parapinopsin, but PP2 is a blue-sensitive pigment, with an absorption maximum at 460-480 nm, showing the diversification of non-visual pigment with respect to spectral sensitivity. We also found that PP1 and PP2 exhibit mutually exclusive expressions in the pineal organs of three teleost species. By using transgenic zebrafish in which these parapinopsin-expressing cells are labeled, we found that PP1-expressing cells basically possess neuronal processes, which is consistent with their involvement in wavelength discrimination. Interestingly, however, PP2-expressing cells rarely possess neuronal processes, raising the possibility that PP2 could be involved in non-neural responses rather than neural responses. Furthermore, we found that PP2-expressing cells contain serotonin and aanat2, the key enzyme involved in melatonin synthesis from serotonin, whereas PP1-expressing cells do not contain either, suggesting that blue-sensitive PP2 is instead involved in light-regulation of melatonin secretion. In this paper, we have clearly shown the different molecular properties of duplicated non-visual opsins by demonstrating the diversification of parapinopsin with respect to spectral sensitivity. Moreover, we have shown a plausible link between the diversification and its physiological impact by discovering a strong candidate for the underlying pigment in light-regulated melatonin secretion in zebrafish; the diversification could generate a new contribution of parapinopsin to pineal photoreception. Current findings could also provide an opportunity to understand the "color" preference of non-visual photoreception.

Impact of stride-coupled gaze shifts of walking blowflies on the neuronal representation of visual targets

PubMed Central

Kress, Daniel; Egelhaaf, Martin

2014-01-01

During locomotion animals rely heavily on visual cues gained from the environment to guide their behavior. Examples are basic behaviors like collision avoidance or the approach to a goal. The saccadic gaze strategy of flying flies, which separates translational from rotational phases of locomotion, has been suggested to facilitate the extraction of environmental information, because only image flow evoked by translational self-motion contains relevant distance information about the surrounding world. In contrast to the translational phases of flight during which gaze direction is kept largely constant, walking flies experience continuous rotational image flow that is coupled to their stride-cycle. The consequences of these self-produced image shifts for the extraction of environmental information are still unclear. To assess the impact of stride-coupled image shifts on visual information processing, we performed electrophysiological recordings from the HSE cell, a motion sensitive wide-field neuron in the blowfly visual system. This cell has been concluded to play a key role in mediating optomotor behavior, self-motion estimation and spatial information processing. We used visual stimuli that were based on the visual input experienced by walking blowflies while approaching a black vertical bar. The response of HSE to these stimuli was dominated by periodic membrane potential fluctuations evoked by stride-coupled image shifts. Nevertheless, during the approach the cell’s response contained information about the bar and its background. The response components evoked by the bar were larger than the responses to its background, especially during the last phase of the approach. However, as revealed by targeted modifications of the visual input during walking, the extraction of distance information on the basis of HSE responses is much impaired by stride-coupled retinal image shifts. Possible mechanisms that may cope with these stride-coupled responses are discussed. PMID:25309362

Nonlinear Y-Like Receptive Fields in the Early Visual Cortex: An Intermediate Stage for Building Cue-Invariant Receptive Fields from Subcortical Y Cells.

PubMed

Gharat, Amol; Baker, Curtis L

2017-01-25

Many of the neurons in early visual cortex are selective for the orientation of boundaries defined by first-order cues (luminance) as well as second-order cues (contrast, texture). The neural circuit mechanism underlying this selectivity is still unclear, but some studies have proposed that it emerges from spatial nonlinearities of subcortical Y cells. To understand how inputs from the Y-cell pathway might be pooled to generate cue-invariant receptive fields, we recorded visual responses from single neurons in cat Area 18 using linear multielectrode arrays. We measured responses to drifting and contrast-reversing luminance gratings as well as contrast modulation gratings. We found that a large fraction of these neurons have nonoriented responses to gratings, similar to those of subcortical Y cells: they respond at the second harmonic (F2) to high-spatial frequency contrast-reversing gratings and at the first harmonic (F1) to low-spatial frequency drifting gratings ("Y-cell signature"). For a given neuron, spatial frequency tuning for linear (F1) and nonlinear (F2) responses is quite distinct, similar to orientation-selective cue-invariant neurons. Also, these neurons respond to contrast modulation gratings with selectivity for the carrier (texture) spatial frequency and, in some cases, orientation. Their receptive field properties suggest that they could serve as building blocks for orientation-selective cue-invariant neurons. We propose a circuit model that combines ON- and OFF-center cortical Y-like cells in an unbalanced push-pull manner to generate orientation-selective, cue-invariant receptive fields. A significant fraction of neurons in early visual cortex have specialized receptive fields that allow them to selectively respond to the orientation of boundaries that are invariant to the cue (luminance, contrast, texture, motion) that defines them. However, the neural mechanism to construct such versatile receptive fields remains unclear. Using multielectrode recording, we found a large fraction of neurons in early visual cortex with receptive fields not selective for orientation that have spatial nonlinearities like those of subcortical Y cells. These are strong candidates for building cue-invariant orientation-selective neurons; we present a neural circuit model that pools such neurons in an imbalanced "push-pull" manner, to generate orientation-selective cue-invariant receptive fields. Copyright © 2017 the authors 0270-6474/17/370998-16$15.00/0.

Features and functions of nonlinear spatial integration by retinal ganglion cells.

PubMed

Gollisch, Tim

2013-11-01

Ganglion cells in the vertebrate retina integrate visual information over their receptive fields. They do so by pooling presynaptic excitatory inputs from typically many bipolar cells, which themselves collect inputs from several photoreceptors. In addition, inhibitory interactions mediated by horizontal cells and amacrine cells modulate the structure of the receptive field. In many models, this spatial integration is assumed to occur in a linear fashion. Yet, it has long been known that spatial integration by retinal ganglion cells also incurs nonlinear phenomena. Moreover, several recent examples have shown that nonlinear spatial integration is tightly connected to specific visual functions performed by different types of retinal ganglion cells. This work discusses these advances in understanding the role of nonlinear spatial integration and reviews recent efforts to quantitatively study the nature and mechanisms underlying spatial nonlinearities. These new insights point towards a critical role of nonlinearities within ganglion cell receptive fields for capturing responses of the cells to natural and behaviorally relevant visual stimuli. In the long run, nonlinear phenomena of spatial integration may also prove important for implementing the actual neural code of retinal neurons when designing visual prostheses for the eye. Copyright © 2012 Elsevier Ltd. All rights reserved.

Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision

PubMed Central

Hovhannisyan, Anahit; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel

2017-01-01

Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring. SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration. PMID:28373392

EQUILUMINANCE CELLS IN VISUAL CORTICAL AREA V4

PubMed Central

Bushnell, Brittany N.; Harding, Philip J.; Kosai, Yoshito; Bair, Wyeth; Pasupathy, Anitha

2011-01-01

We report a novel class of V4 neuron in the macaque monkey that responds selectively to equiluminant colored form. These "equiluminance" cells stand apart because they violate the well established trend throughout the visual system that responses are minimal at low luminance contrast and grow and saturate as contrast increases. Equiluminance cells, which compose about 22% of V4, exhibit the opposite behavior: responses are greatest near zero contrast and decrease as contrast increases. While equilumiance cells respond preferentially to equiluminant colored stimuli, strong hue tuning is not their distinguishing feature—some equilumiance cells do exhibit strong unimodal hue tuning but many show little or no tuning for hue. We find that equiluminance cells are color and shape selective to a degree comparable to other classes of V4 cells with more conventional contrast response functions. Those more conventional cells respond equally well to achromatic luminance and equiluminant color stimuli, analogous to color-luminance cells described in V1. The existence of equiluminance cells, which have not been reported in V1 or V2, suggests that chromatically-defined boundaries and shapes are given special status in V4 and raises the possibility that form at equiluminance and form at higher contrasts are processed in separate channels in V4. PMID:21880901

An egalitarian network model for the emergence of simple and complex cells in visual cortex

PubMed Central

Tao, Louis; Shelley, Michael; McLaughlin, David; Shapley, Robert

2004-01-01

We explain how simple and complex cells arise in a large-scale neuronal network model of the primary visual cortex of the macaque. Our model consists of ≈4,000 integrate-and-fire, conductance-based point neurons, representing the cells in a small, 1-mm2 patch of an input layer of the primary visual cortex. In the model the local connections are isotropic and nonspecific, and convergent input from the lateral geniculate nucleus confers cortical cells with orientation and spatial phase preference. The balance between lateral connections and lateral geniculate nucleus drive determines whether individual neurons in this recurrent circuit are simple or complex. The model reproduces qualitatively the experimentally observed distributions of both extracellular and intracellular measures of simple and complex response. PMID:14695891

Improved CORF model of simple cell combined with non-classical receptive field and its application on edge detection

NASA Astrophysics Data System (ADS)

Sun, Xiao; Chai, Guobei; Liu, Wei; Bao, Wenzhuo; Zhao, Xiaoning; Ming, Delie

2018-02-01

Simple cells in primary visual cortex are believed to extract local edge information from a visual scene. In this paper, inspired by different receptive field properties and visual information flow paths of neurons, an improved Combination of Receptive Fields (CORF) model combined with non-classical receptive fields was proposed to simulate the responses of simple cell's receptive fields. Compared to the classical model, the proposed model is able to better imitate simple cell's physiologic structure with consideration of facilitation and suppression of non-classical receptive fields. And on this base, an edge detection algorithm as an application of the improved CORF model was proposed. Experimental results validate the robustness of the proposed algorithm to noise and background interference.

Identification of non-visual photomotor response cells in the vertebrate hindbrain

PubMed Central

Kokel, David; Dunn, Timothy W.; Ahrens, Misha B.; Alshut, Rüdiger; Cheung, Chung Yan J.; Saint-Amant, Louis; Bruni, Giancarlo; Mateus, Rita; van Ham, Tjakko J.; Shiraki, Tomoya; Fukada, Yoshitaka; Kojima, Daisuke; Yeh, Jing-Ruey J.; Mikut, Ralf; von Lintig, Johannes; Engert, Florian; Peterson, Randall T.

2013-01-01

Non-visual photosensation enables animals to sense light without sight. However, the cellular and molecular mechanisms of non-visual photobehaviors are poorly understood, especially in vertebrate animals. Here, we describe the photomotor response (PMR), a robust and reproducible series of motor behaviors in zebrafish that is elicited by visual wavelengths of light, but does not require the eyes, pineal gland or other canonical deep-brain photoreceptive organs. Unlike the relatively slow effects of canonical non-visual pathways, motor circuits are strongly and quickly (seconds) recruited during the PMR behavior. We find that the hindbrain is both necessary and sufficient to drive these behaviors. Using in vivo calcium imaging, we identify a discrete set of neurons within the hindbrain whose responses to light mirror the PMR behavior. Pharmacological inhibition of the visual cycle blocks PMR behaviors, suggesting that opsin-based photoreceptors control this behavior. These data represent the first known light-sensing circuit in the vertebrate hindbrain. PMID:23447595

Disinhibition outside receptive fields in the visual cortex.

PubMed

Walker, Gary A; Ohzawa, Izumi; Freeman, Ralph D

2002-07-01

By definition, the region outside the classical receptive field (CRF) of a neuron in the visual cortex does not directly activate the cell. However, the response of a neuron can be influenced by stimulation of the surrounding area. In previous work, we showed that this influence is mainly suppressive and that it is generally limited to a local region outside the CRF. In the experiments reported here, we investigate the mechanisms of the suppressive effect. Our approach is to find the position of a grating patch that is most effective in suppressing the response of a cell. We then use a masking stimulus at different contrasts over the grating patch in an attempt to disinhibit the response. We find that suppressive effects may be partially or completely reversed by use of the masking stimulus. This disinhibition suggests that effects from outside the CRF may be local. Although they do not necessarily underlie the perceptual analysis of a figure-ground visual scene, they may provide a substrate for this process.

The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

PubMed

Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

2016-03-01

Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

PubMed Central

Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C.; Roelfsema, Pieter R.

2016-01-01

Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons’ receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

Contralateral Bias of High Spatial Frequency Tuning and Cardinal Direction Selectivity in Mouse Visual Cortex

PubMed Central

Zeitoun, Jack H.; Kim, Hyungtae

2017-01-01

Binocular mechanisms for visual processing are thought to enhance spatial acuity by combining matched input from the two eyes. Studies in the primary visual cortex of carnivores and primates have confirmed that eye-specific neuronal response properties are largely matched. In recent years, the mouse has emerged as a prominent model for binocular visual processing, yet little is known about the spatial frequency tuning of binocular responses in mouse visual cortex. Using calcium imaging in awake mice of both sexes, we show that the spatial frequency preference of cortical responses to the contralateral eye is ∼35% higher than responses to the ipsilateral eye. Furthermore, we find that neurons in binocular visual cortex that respond only to the contralateral eye are tuned to higher spatial frequencies. Binocular neurons that are well matched in spatial frequency preference are also matched in orientation preference. In contrast, we observe that binocularly mismatched cells are more mismatched in orientation tuning. Furthermore, we find that contralateral responses are more direction-selective than ipsilateral responses and are strongly biased to the cardinal directions. The contralateral bias of high spatial frequency tuning was found in both awake and anesthetized recordings. The distinct properties of contralateral cortical responses may reflect the functional segregation of direction-selective, high spatial frequency-preferring neurons in earlier stages of the central visual pathway. Moreover, these results suggest that the development of binocularity and visual acuity may engage distinct circuits in the mouse visual system. SIGNIFICANCE STATEMENT Seeing through two eyes is thought to improve visual acuity by enhancing sensitivity to fine edges. Using calcium imaging of cellular responses in awake mice, we find surprising asymmetries in the spatial processing of eye-specific visual input in binocular primary visual cortex. The contralateral visual pathway is tuned to higher spatial frequencies than the ipsilateral pathway. At the highest spatial frequencies, the contralateral pathway strongly prefers to respond to visual stimuli along the cardinal (horizontal and vertical) axes. These results suggest that monocular, and not binocular, mechanisms set the limit of spatial acuity in mice. Furthermore, they suggest that the development of visual acuity and binocularity in mice involves different circuits. PMID:28924011

Parvalbumin-expressing interneurons can act solo while somatostatin-expressing interneurons act in chorus in most cases on cortical pyramidal cells.

PubMed

Safari, Mir-Shahram; Mirnajafi-Zadeh, Javad; Hioki, Hiroyuki; Tsumoto, Tadaharu

2017-10-06

Neural circuits in the cerebral cortex consist primarily of excitatory pyramidal (Pyr) cells and inhibitory interneurons. Interneurons are divided into several subtypes, in which the two major groups are those expressing parvalbumin (PV) or somatostatin (SOM). These subtypes of interneurons are reported to play distinct roles in tuning and/or gain of visual response of pyramidal cells in the visual cortex. It remains unclear whether there is any quantitative and functional difference between the PV → Pyr and SOM → Pyr connections. We compared unitary inhibitory postsynaptic currents (uIPSCs) evoked by electrophysiological activation of single presynaptic interneurons with population IPSCs evoked by photo-activation of a mass of interneurons in vivo and in vitro in transgenic mice in which PV or SOM neurons expressed channelrhodopsin-2, and found that at least about 14 PV neurons made strong connections with a postsynaptic Pyr cell while a much larger number of SOM neurons made weak connections. Activation or suppression of single PV neurons modified visual responses of postsynaptic Pyr cells in 6 of 7 pairs whereas that of single SOM neurons showed no significant modification in 8 of 11 pairs, suggesting that PV neurons can act solo whereas most of SOM neurons may act in chorus on Pyr cells.

Synaptology of physiologically identified ganglion cells in the cat retina: a comparison of retinal X- and Y-cells.

PubMed

Weber, A J; Stanford, L R

1994-05-15

It has long been known that a number of functionally different types of ganglion cells exist in the cat retina, and that each responds differently to visual stimulation. To determine whether the characteristic response properties of different retinal ganglion cell types might reflect differences in the number and distribution of their bipolar and amacrine cell inputs, we compared the percentages and distributions of the synaptic inputs from bipolar and amacrine cells to the entire dendritic arbors of physiologically characterized retinal X- and Y-cells. Sixty-two percent of the synaptic input to the Y-cell was from amacrine cell terminals, while the X-cells received approximately equal amounts of input from amacrine and bipolar cells. We found no significant difference in the distributions of bipolar or amacrine cell inputs to X- and Y-cells, or ON-center and OFF-center cells, either as a function of dendritic branch order or distance from the origin of the dendritic arbor. While, on the basis of these data, we cannot exclude the possibility that the difference in the proportion of bipolar and amacrine cell input contributes to the functional differences between X- and Y-cells, the magnitude of this difference, and the similarity in the distributions of the input from the two afferent cell types, suggest that mechanisms other than a simple predominance of input from amacrine or bipolar cells underlie the differences in their response properties. More likely, perhaps, is that the specific response features of X- and Y-cells originate in differences in the visual responses of the bipolar and amacrine cells that provide their input, or in the complex synaptic arrangements found among amacrine and bipolar cell terminals and the dendrites of specific types of retinal ganglion cells.

Model-based analysis of pattern motion processing in mouse primary visual cortex

PubMed Central

Muir, Dylan R.; Roth, Morgane M.; Helmchen, Fritjof; Kampa, Björn M.

2015-01-01

Neurons in sensory areas of neocortex exhibit responses tuned to specific features of the environment. In visual cortex, information about features such as edges or textures with particular orientations must be integrated to recognize a visual scene or object. Connectivity studies in rodent cortex have revealed that neurons make specific connections within sub-networks sharing common input tuning. In principle, this sub-network architecture enables local cortical circuits to integrate sensory information. However, whether feature integration indeed occurs locally in rodent primary sensory areas has not been examined directly. We studied local integration of sensory features in primary visual cortex (V1) of the mouse by presenting drifting grating and plaid stimuli, while recording the activity of neuronal populations with two-photon calcium imaging. Using a Bayesian model-based analysis framework, we classified single-cell responses as being selective for either individual grating components or for moving plaid patterns. Rather than relying on trial-averaged responses, our model-based framework takes into account single-trial responses and can easily be extended to consider any number of arbitrary predictive models. Our analysis method was able to successfully classify significantly more responses than traditional partial correlation (PC) analysis, and provides a rigorous statistical framework to rank any number of models and reject poorly performing models. We also found a large proportion of cells that respond strongly to only one stimulus class. In addition, a quarter of selectively responding neurons had more complex responses that could not be explained by any simple integration model. Our results show that a broad range of pattern integration processes already take place at the level of V1. This diversity of integration is consistent with processing of visual inputs by local sub-networks within V1 that are tuned to combinations of sensory features. PMID:26300738

Analysis of mitosis and antimitotic drug responses in tumors by in vivo microscopy and single-cell pharmacodynamics.

PubMed

Orth, James D; Kohler, Rainer H; Foijer, Floris; Sorger, Peter K; Weissleder, Ralph; Mitchison, Timothy J

2011-07-01

Cancer relies upon frequent or abnormal cell division, but how the tumor microenvironment affects mitotic processes in vivo remains unclear, largely due to the technical challenges of optical access, spatial resolution, and motion. We developed high-resolution in vivo microscopy methods to visualize mitosis in a murine xenograft model of human cancer. Using these methods, we determined whether the single-cell response to the antimitotic drug paclitaxel (Ptx) was the same in tumors as in cell culture, observed the impact of Ptx on the tumor response as a whole, and evaluated the single-cell pharmacodynamics (PD) of Ptx (by in vivo PD microscopy). Mitotic initiation was generally less frequent in tumors than in cell culture, but subsequently it proceeded normally. Ptx treatment caused spindle assembly defects and mitotic arrest, followed by slippage from mitotic arrest, multinucleation, and apoptosis. Compared with cell culture, the peak mitotic index in tumors exposed to Ptx was lower and the tumor cells survived longer after mitotic arrest, becoming multinucleated rather than dying directly from mitotic arrest. Thus, the tumor microenvironment was much less proapoptotic than cell culture. The morphologies associated with mitotic arrest were dose and time dependent, thereby providing a semiquantitative, single-cell measure of PD. Although many tumor cells did not progress through Ptx-induced mitotic arrest, tumor significantly regressed in the model. Our findings show that in vivo microscopy offers a useful tool to visualize mitosis during tumor progression, drug responses, and cell fate at the single-cell level. ©2011 AACR.

Visual motion integration by neurons in the middle temporal area of a New World monkey, the marmoset

PubMed Central

Solomon, Selina S; Tailby, Chris; Gharaei, Saba; Camp, Aaron J; Bourne, James A; Solomon, Samuel G

2011-01-01

Abstract The middle temporal area (MT/V5) is an anatomically distinct region of primate visual cortex that is specialized for the processing of image motion. It is generally thought that some neurons in area MT are capable of signalling the motion of complex patterns, but this has only been established in the macaque monkey. We made extracellular recordings from single units in area MT of anaesthetized marmosets, a New World monkey. We show through quantitative analyses that some neurons (35 of 185; 19%) are capable of signalling pattern motion (‘pattern cells’). Across several dimensions, the visual response of pattern cells in marmosets is indistinguishable from that of pattern cells in macaques. Other neurons respond to the motion of oriented contours in a pattern (‘component cells’) or show intermediate properties. In addition, we encountered a subset of neurons (22 of 185; 12%) insensitive to sinusoidal gratings but very responsive to plaids and other two-dimensional patterns and otherwise indistinguishable from pattern cells. We compared the response of each cell class to drifting gratings and dot fields. In pattern cells, directional selectivity was similar for gratings and dot fields; in component cells, directional selectivity was weaker for dot fields than gratings. Pattern cells were more likely to have stronger suppressive surrounds, prefer lower spatial frequencies and prefer higher speeds than component cells. We conclude that pattern motion sensitivity is a feature of some neurons in area MT of both New and Old World monkeys, suggesting that this functional property is an important stage in motion analysis and is likely to be conserved in humans. PMID:21946851

Partially converted stereoscopic images and the effects on visual attention and memory

NASA Astrophysics Data System (ADS)

Kim, Sanghyun; Morikawa, Hiroyuki; Mitsuya, Reiko; Kawai, Takashi; Watanabe, Katsumi

2015-03-01

This study contained two experimental examinations of the cognitive activities such as visual attention and memory in viewing stereoscopic (3D) images. For this study, partially converted 3D images were used with binocular parallax added to a specific region of the image. In Experiment 1, change blindness was used as a presented stimulus. The visual attention and impact on memory were investigated by measuring the response time to accomplish the given task. In the change blindness task, an 80 ms blank was intersected between the original and altered images, and the two images were presented alternatingly for 240 ms each. Subjects were asked to temporarily memorize the two switching images and to compare them, visually recognizing the difference between the two. The stimuli for four conditions (2D, 3D, Partially converted 3D, distracted partially converted 3D) were randomly displayed for 20 subjects. The results of Experiment 1 showed that partially converted 3D images tend to attract visual attention and are prone to remain in viewer's memory in the area where moderate negative parallax has been added. In order to examine the impact of a dynamic binocular disparity on partially converted 3D images, an evaluation experiment was conducted that applied learning, distraction, and recognition tasks for 33 subjects. The learning task involved memorizing the location of cells in a 5 × 5 matrix pattern using two different colors. Two cells were positioned with alternating colors, and one of the gray cells was moved up, down, left, or right by one cell width. Experimental conditions was set as a partially converted 3D condition in which a gray cell moved diagonally for a certain period of time with a dynamic binocular disparity added, a 3D condition in which binocular disparity was added to all gray cells, and a 2D condition. The correct response rates for recognition of each task after the distraction task were compared. The results of Experiment 2 showed that the correct response rate in the partial 3D condition was significantly higher with the recognition task than in the other conditions. These results showed that partially converted 3D images tended to have a visual attraction and affect viewer's memory.

Visual Information Present in Infragranular Layers of Mouse Auditory Cortex.

PubMed

Morrill, Ryan J; Hasenstaub, Andrea R

2018-03-14

The cerebral cortex is a major hub for the convergence and integration of signals from across the sensory modalities; sensory cortices, including primary regions, are no exception. Here we show that visual stimuli influence neural firing in the auditory cortex of awake male and female mice, using multisite probes to sample single units across multiple cortical layers. We demonstrate that visual stimuli influence firing in both primary and secondary auditory cortex. We then determine the laminar location of recording sites through electrode track tracing with fluorescent dye and optogenetic identification using layer-specific markers. Spiking responses to visual stimulation occur deep in auditory cortex and are particularly prominent in layer 6. Visual modulation of firing rate occurs more frequently at areas with secondary-like auditory responses than those with primary-like responses. Auditory cortical responses to drifting visual gratings are not orientation-tuned, unlike visual cortex responses. The deepest cortical layers thus appear to be an important locus for cross-modal integration in auditory cortex. SIGNIFICANCE STATEMENT The deepest layers of the auditory cortex are often considered its most enigmatic, possessing a wide range of cell morphologies and atypical sensory responses. Here we show that, in mouse auditory cortex, these layers represent a locus of cross-modal convergence, containing many units responsive to visual stimuli. Our results suggest that this visual signal conveys the presence and timing of a stimulus rather than specifics about that stimulus, such as its orientation. These results shed light on both how and what types of cross-modal information is integrated at the earliest stages of sensory cortical processing. Copyright © 2018 the authors 0270-6474/18/382854-09$15.00/0.

LRRTM1 underlies synaptic convergence in visual thalamus

PubMed Central

Monavarfeshani, Aboozar; Stanton, Gail; Van Name, Jonathan; Su, Kaiwen; Mills, William A; Swilling, Kenya; Kerr, Alicia; Huebschman, Natalie A; Su, Jianmin

2018-01-01

It has long been thought that the mammalian visual system is organized into parallel pathways, with incoming visual signals being parsed in the retina based on feature (e.g. color, contrast and motion) and then transmitted to the brain in unmixed, feature-specific channels. To faithfully convey feature-specific information from retina to cortex, thalamic relay cells must receive inputs from only a small number of functionally similar retinal ganglion cells. However, recent studies challenged this by revealing substantial levels of retinal convergence onto relay cells. Here, we sought to identify mechanisms responsible for the assembly of such convergence. Using an unbiased transcriptomics approach and targeted mutant mice, we discovered a critical role for the synaptic adhesion molecule Leucine Rich Repeat Transmembrane Neuronal 1 (LRRTM1) in the emergence of retinothalamic convergence. Importantly, LRRTM1 mutant mice display impairment in visual behaviors, suggesting a functional role of retinothalamic convergence in vision. PMID:29424692

Curtailing effect of awakening on visual responses of cortical neurons by cholinergic activation of inhibitory circuits.

PubMed

Kimura, Rui; Safari, Mir-Shahram; Mirnajafi-Zadeh, Javad; Kimura, Rie; Ebina, Teppei; Yanagawa, Yuchio; Sohya, Kazuhiro; Tsumoto, Tadaharu

2014-07-23

Visual responsiveness of cortical neurons changes depending on the brain state. Neural circuit mechanism underlying this change is unclear. By applying the method of in vivo two-photon functional calcium imaging to transgenic rats in which GABAergic neurons express fluorescent protein, we analyzed changes in visual response properties of cortical neurons when animals became awakened from anesthesia. In the awake state, the magnitude and reliability of visual responses of GABAergic neurons increased whereas the decay of responses of excitatory neurons became faster. To test whether the basal forebrain (BF) cholinergic projection is involved in these changes, we analyzed effects of electrical and optogenetic activation of BF on visual responses of mouse cortical neurons with in vivo imaging and whole-cell recordings. Electrical BF stimulation in anesthetized animals induced the same direction of changes in visual responses of both groups of neurons as awakening. Optogenetic activation increased the frequency of visually evoked action potentials in GABAergic neurons but induced the delayed hyperpolarization that ceased the late generation of action potentials in excitatory neurons. Pharmacological analysis in slice preparations revealed that photoactivation-induced depolarization of layer 1 GABAergic neurons was blocked by a nicotinic receptor antagonist, whereas non-fast-spiking layer 2/3 GABAergic neurons was blocked only by the application of both nicotinic and muscarinic receptor antagonists. These results suggest that the effect of awakening is mediated mainly through nicotinic activation of layer 1 GABAergic neurons and mixed nicotinic/muscarinic activation of layer 2/3 non-fast-spiking GABAergic neurons, which together curtails the visual responses of excitatory neurons. Copyright © 2014 the authors 0270-6474/14/3410122-12$15.00/0.

Drug/Cell-line Browser: interactive canvas visualization of cancer drug/cell-line viability assay datasets.

PubMed

Duan, Qiaonan; Wang, Zichen; Fernandez, Nicolas F; Rouillard, Andrew D; Tan, Christopher M; Benes, Cyril H; Ma'ayan, Avi

2014-11-15

Recently, several high profile studies collected cell viability data from panels of cancer cell lines treated with many drugs applied at different concentrations. Such drug sensitivity data for cancer cell lines provide suggestive treatments for different types and subtypes of cancer. Visualization of these datasets can reveal patterns that may not be obvious by examining the data without such efforts. Here we introduce Drug/Cell-line Browser (DCB), an online interactive HTML5 data visualization tool for interacting with three of the recently published datasets of cancer cell lines/drug-viability studies. DCB uses clustering and canvas visualization of the drugs and the cell lines, as well as a bar graph that summarizes drug effectiveness for the tissue of origin or the cancer subtypes for single or multiple drugs. DCB can help in understanding drug response patterns and prioritizing drug/cancer cell line interactions by tissue of origin or cancer subtype. DCB is an open source Web-based tool that is freely available at: http://www.maayanlab.net/LINCS/DCB CONTACT: avi.maayan@mssm.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Stimulus relevance modulates contrast adaptation in visual cortex

PubMed Central

Keller, Andreas J; Houlton, Rachael; Kampa, Björn M; Lesica, Nicholas A; Mrsic-Flogel, Thomas D; Keller, Georg B; Helmchen, Fritjof

2017-01-01

A general principle of sensory processing is that neurons adapt to sustained stimuli by reducing their response over time. Most of our knowledge on adaptation in single cells is based on experiments in anesthetized animals. How responses adapt in awake animals, when stimuli may be behaviorally relevant or not, remains unclear. Here we show that contrast adaptation in mouse primary visual cortex depends on the behavioral relevance of the stimulus. Cells that adapted to contrast under anesthesia maintained or even increased their activity in awake naïve mice. When engaged in a visually guided task, contrast adaptation re-occurred for stimuli that were irrelevant for solving the task. However, contrast adaptation was reversed when stimuli acquired behavioral relevance. Regulation of cortical adaptation by task demand may allow dynamic control of sensory-evoked signal flow in the neocortex. DOI: http://dx.doi.org/10.7554/eLife.21589.001 PMID:28130922

Imaging light responses of foveal ganglion cells in the living macaque eye.

PubMed

Yin, Lu; Masella, Benjamin; Dalkara, Deniz; Zhang, Jie; Flannery, John G; Schaffer, David V; Williams, David R; Merigan, William H

2014-05-07

The fovea dominates primate vision, and its anatomy and perceptual abilities are well studied, but its physiology has been little explored because of limitations of current physiological methods. In this study, we adapted a novel in vivo imaging method, originally developed in mouse retina, to explore foveal physiology in the macaque, which permits the repeated imaging of the functional response of many retinal ganglion cells (RGCs) simultaneously. A genetically encoded calcium indicator, G-CaMP5, was inserted into foveal RGCs, followed by calcium imaging of the displacement of foveal RGCs from their receptive fields, and their intensity-response functions. The spatial offset of foveal RGCs from their cone inputs makes this method especially appropriate for fovea by permitting imaging of RGC responses without excessive light adaptation of cones. This new method will permit the tracking of visual development, progression of retinal disease, or therapeutic interventions, such as insertion of visual prostheses.

Visual-Motor Transformations Within Frontal Eye Fields During Head-Unrestrained Gaze Shifts in the Monkey.

PubMed

Sajad, Amirsaman; Sadeh, Morteza; Keith, Gerald P; Yan, Xiaogang; Wang, Hongying; Crawford, John Douglas

2015-10-01

A fundamental question in sensorimotor control concerns the transformation of spatial signals from the retina into eye and head motor commands required for accurate gaze shifts. Here, we investigated these transformations by identifying the spatial codes embedded in visually evoked and movement-related responses in the frontal eye fields (FEFs) during head-unrestrained gaze shifts. Monkeys made delayed gaze shifts to the remembered location of briefly presented visual stimuli, with delay serving to dissociate visual and movement responses. A statistical analysis of nonparametric model fits to response field data from 57 neurons (38 with visual and 49 with movement activities) eliminated most effector-specific, head-fixed, and space-fixed models, but confirmed the dominance of eye-centered codes observed in head-restrained studies. More importantly, the visual response encoded target location, whereas the movement response mainly encoded the final position of the imminent gaze shift (including gaze errors). This spatiotemporal distinction between target and gaze coding was present not only at the population level, but even at the single-cell level. We propose that an imperfect visual-motor transformation occurs during the brief memory interval between perception and action, and further transformations from the FEF's eye-centered gaze motor code to effector-specific codes in motor frames occur downstream in the subcortical areas. © The Author 2014. Published by Oxford University Press.

A dual-color marker system for in vivo visualization of cell cycle progression in Arabidopsis.

PubMed

Yin, Ke; Ueda, Minako; Takagi, Hitomi; Kajihara, Takehiro; Sugamata Aki, Shiori; Nobusawa, Takashi; Umeda-Hara, Chikage; Umeda, Masaaki

2014-11-01

Visualization of the spatiotemporal pattern of cell division is crucial to understand how multicellular organisms develop and how they modify their growth in response to varying environmental conditions. The mitotic cell cycle consists of four phases: S (DNA replication), M (mitosis and cytokinesis), and the intervening G1 and G2 phases; however, only G2/M-specific markers are currently available in plants, making it difficult to measure cell cycle duration and to analyze changes in cell cycle progression in living tissues. Here, we developed another cell cycle marker that labels S-phase cells by manipulating Arabidopsis CDT1a, which functions in DNA replication origin licensing. Truncations of the CDT1a coding sequence revealed that its carboxy-terminal region is responsible for proteasome-mediated degradation at late G2 or in early mitosis. We therefore expressed this region as a red fluorescent protein fusion protein under the S-specific promoter of a histone 3.1-type gene, HISTONE THREE RELATED2 (HTR2), to generate an S/G2 marker. Combining this marker with the G2/M-specific CYCB1-GFP marker enabled us to visualize both S to G2 and G2 to M cell cycle stages, and thus yielded an essential tool for time-lapse imaging of cell cycle progression. The resultant dual-color marker system, Cell Cycle Tracking in Plant Cells (Cytrap), also allowed us to identify root cells in the last mitotic cell cycle before they entered the endocycle. Our results demonstrate that Cytrap is a powerful tool for in vivo monitoring of the plant cell cycle, and thus for deepening our understanding of cell cycle regulation in particular cell types during organ development. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Dynamic Imaging of CD8(+) T cells and dendritic cells during infection with Toxoplasma gondii.

PubMed

John, Beena; Harris, Tajie H; Tait, Elia D; Wilson, Emma H; Gregg, Beth; Ng, Lai Guan; Mrass, Paulus; Roos, David S; Dzierszinski, Florence; Weninger, Wolfgang; Hunter, Christopher A

2009-07-01

To better understand the initiation of CD8(+) T cell responses during infection, the primary response to the intracellular parasite Toxoplasma gondii was characterized using 2-photon microscopy combined with an experimental system that allowed visualization of dendritic cells (DCs) and parasite specific CD8(+) T cells. Infection with T. gondii induced localization of both these populations to the sub-capsular/interfollicular region of the draining lymph node and DCs were required for the expansion of the T cells. Consistent with current models, in the presence of cognate antigen, the average velocity of CD8(+) T cells decreased. Unexpectedly, infection also resulted in modulation of the behavior of non-parasite specific T cells. This TCR-independent process correlated with the re-modeling of the lymph node micro-architecture and changes in expression of CCL21 and CCL3. Infection also resulted in sustained interactions between the DCs and CD8(+) T cells that were visualized only in the presence of cognate antigen and were limited to an early phase in the response. Infected DCs were rare within the lymph node during this time frame; however, DCs presenting the cognate antigen were detected. Together, these data provide novel insights into the earliest interaction between DCs and CD8(+) T cells and suggest that cross presentation by bystander DCs rather than infected DCs is an important route of antigen presentation during toxoplasmosis.

Dynamic Imaging of CD8+ T Cells and Dendritic Cells during Infection with Toxoplasma gondii

PubMed Central

John, Beena; Harris, Tajie H.; Tait, Elia D.; Wilson, Emma H.; Gregg, Beth; Ng, Lai Guan; Mrass, Paulus; Roos, David S.; Dzierszinski, Florence; Weninger, Wolfgang; Hunter, Christopher A.

2009-01-01

To better understand the initiation of CD8+ T cell responses during infection, the primary response to the intracellular parasite Toxoplasma gondii was characterized using 2-photon microscopy combined with an experimental system that allowed visualization of dendritic cells (DCs) and parasite specific CD8+ T cells. Infection with T. gondii induced localization of both these populations to the sub-capsular/interfollicular region of the draining lymph node and DCs were required for the expansion of the T cells. Consistent with current models, in the presence of cognate antigen, the average velocity of CD8+ T cells decreased. Unexpectedly, infection also resulted in modulation of the behavior of non-parasite specific T cells. This TCR-independent process correlated with the re-modeling of the lymph node micro-architecture and changes in expression of CCL21 and CCL3. Infection also resulted in sustained interactions between the DCs and CD8+ T cells that were visualized only in the presence of cognate antigen and were limited to an early phase in the response. Infected DCs were rare within the lymph node during this time frame; however, DCs presenting the cognate antigen were detected. Together, these data provide novel insights into the earliest interaction between DCs and CD8+ T cells and suggest that cross presentation by bystander DCs rather than infected DCs is an important route of antigen presentation during toxoplasmosis. PMID:19578440

Virally delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness

PubMed Central

Doroudchi, M Mehdi; Greenberg, Kenneth P; Liu, Jianwen; Silka, Kimberly A; Boyden, Edward S; Lockridge, Jennifer A; Arman, A Cyrus; Janani, Ramesh; Boye, Shannon E; Boye, Sanford L; Gordon, Gabriel M; Matteo, Benjamin C; Sampath, Alapakkam P; Hauswirth, William W; Horsager, Alan

2011-01-01

Previous work established retinal expression of channelrhodopsin-2 (ChR2), an algal cation channel gated by light, restored physiological and behavioral visual responses in otherwise blind rd1 mice. However, a viable ChR2-based human therapy must meet several key criteria: (i) ChR2 expression must be targeted, robust, and long-term, (ii) ChR2 must provide long-term and continuous therapeutic efficacy, and (iii) both viral vector delivery and ChR2 expression must be safe. Here, we demonstrate the development of a clinically relevant therapy for late stage retinal degeneration using ChR2. We achieved specific and stable expression of ChR2 in ON bipolar cells using a recombinant adeno-associated viral vector (rAAV) packaged in a tyrosine-mutated capsid. Targeted expression led to ChR2-driven electrophysiological ON responses in postsynaptic retinal ganglion cells and significant improvement in visually guided behavior for multiple models of blindness up to 10 months postinjection. Light levels to elicit visually guided behavioral responses were within the physiological range of cone photoreceptors. Finally, chronic ChR2 expression was nontoxic, with transgene biodistribution limited to the eye. No measurable immune or inflammatory response was observed following intraocular vector administration. Together, these data indicate that virally delivered ChR2 can provide a viable and efficacious clinical therapy for photoreceptor disease-related blindness. PMID:21505421

Representation of vestibular and visual cues to self-motion in ventral intraparietal (VIP) cortex

PubMed Central

Chen, Aihua; Deangelis, Gregory C.; Angelaki, Dora E.

2011-01-01

Convergence of vestibular and visual motion information is important for self-motion perception. One cortical area that combines vestibular and optic flow signals is the ventral intraparietal area (VIP). We characterized unisensory and multisensory responses of macaque VIP neurons to translations and rotations in three dimensions. Approximately half of VIP cells show significant directional selectivity in response to optic flow, half show tuning to vestibular stimuli, and one-third show multisensory responses. Visual and vestibular direction preferences of multisensory VIP neurons could be congruent or opposite. When visual and vestibular stimuli were combined, VIP responses could be dominated by either input, unlike medial superior temporal area (MSTd) where optic flow tuning typically dominates or the visual posterior sylvian area (VPS) where vestibular tuning dominates. Optic flow selectivity in VIP was weaker than in MSTd but stronger than in VPS. In contrast, vestibular tuning for translation was strongest in VPS, intermediate in VIP, and weakest in MSTd. To characterize response dynamics, direction-time data were fit with a spatiotemporal model in which temporal responses were modeled as weighted sums of velocity, acceleration, and position components. Vestibular responses in VIP reflected balanced contributions of velocity and acceleration, whereas visual responses were dominated by velocity. Timing of vestibular responses in VIP was significantly faster than in MSTd, whereas timing of optic flow responses did not differ significantly among areas. These findings suggest that VIP may be proximal to MSTd in terms of vestibular processing but hierarchically similar to MSTd in terms of optic flow processing. PMID:21849564

Integration of auditory and visual communication information in the primate ventrolateral prefrontal cortex.

PubMed

Sugihara, Tadashi; Diltz, Mark D; Averbeck, Bruno B; Romanski, Lizabeth M

2006-10-25

The integration of auditory and visual stimuli is crucial for recognizing objects, communicating effectively, and navigating through our complex world. Although the frontal lobes are involved in memory, communication, and language, there has been no evidence that the integration of communication information occurs at the single-cell level in the frontal lobes. Here, we show that neurons in the macaque ventrolateral prefrontal cortex (VLPFC) integrate audiovisual communication stimuli. The multisensory interactions included both enhancement and suppression of a predominantly auditory or a predominantly visual response, although multisensory suppression was the more common mode of response. The multisensory neurons were distributed across the VLPFC and within previously identified unimodal auditory and visual regions (O'Scalaidhe et al., 1997; Romanski and Goldman-Rakic, 2002). Thus, our study demonstrates, for the first time, that single prefrontal neurons integrate communication information from the auditory and visual domains, suggesting that these neurons are an important node in the cortical network responsible for communication.

Integration of Auditory and Visual Communication Information in the Primate Ventrolateral Prefrontal Cortex

PubMed Central

Sugihara, Tadashi; Diltz, Mark D.; Averbeck, Bruno B.; Romanski, Lizabeth M.

2009-01-01

The integration of auditory and visual stimuli is crucial for recognizing objects, communicating effectively, and navigating through our complex world. Although the frontal lobes are involved in memory, communication, and language, there has been no evidence that the integration of communication information occurs at the single-cell level in the frontal lobes. Here, we show that neurons in the macaque ventrolateral prefrontal cortex (VLPFC) integrate audiovisual communication stimuli. The multisensory interactions included both enhancement and suppression of a predominantly auditory or a predominantly visual response, although multisensory suppression was the more common mode of response. The multisensory neurons were distributed across the VLPFC and within previously identified unimodal auditory and visual regions (O’Scalaidhe et al., 1997; Romanski and Goldman-Rakic, 2002). Thus, our study demonstrates, for the first time, that single prefrontal neurons integrate communication information from the auditory and visual domains, suggesting that these neurons are an important node in the cortical network responsible for communication. PMID:17065454

Distinct learning-induced changes in stimulus selectivity and interactions of GABAergic interneuron classes in visual cortex.

PubMed

Khan, Adil G; Poort, Jasper; Chadwick, Angus; Blot, Antonin; Sahani, Maneesh; Mrsic-Flogel, Thomas D; Hofer, Sonja B

2018-06-01

How learning enhances neural representations for behaviorally relevant stimuli via activity changes of cortical cell types remains unclear. We simultaneously imaged responses of pyramidal cells (PYR) along with parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP) inhibitory interneurons in primary visual cortex while mice learned to discriminate visual patterns. Learning increased selectivity for task-relevant stimuli of PYR, PV and SOM subsets but not VIP cells. Strikingly, PV neurons became as selective as PYR cells, and their functional interactions reorganized, leading to the emergence of stimulus-selective PYR-PV ensembles. Conversely, SOM activity became strongly decorrelated from the network, and PYR-SOM coupling before learning predicted selectivity increases in individual PYR cells. Thus, learning differentially shapes the activity and interactions of multiple cell classes: while SOM inhibition may gate selectivity changes, PV interneurons become recruited into stimulus-specific ensembles and provide more selective inhibition as the network becomes better at discriminating behaviorally relevant stimuli.

Protein-Coupled Fluorescent Probe To Visualize Potassium Ion Transition on Cellular Membranes.

PubMed

Hirata, Tomoya; Terai, Takuya; Yamamura, Hisao; Shimonishi, Manabu; Komatsu, Toru; Hanaoka, Kenjiro; Ueno, Tasuku; Imaizumi, Yuji; Nagano, Tetsuo; Urano, Yasuteru

2016-03-01

K(+) is the most abundant metal ion in cells, and changes of [K(+)] around cell membranes play important roles in physiological events. However, there is no practical method to selectively visualize [K(+)] at the surface of cells. To address this issue, we have developed a protein-coupled fluorescent probe for K(+), TLSHalo. TLSHalo is responsive to [K(+)] in the physiological range, with good selectivity over Na(+) and retains its K(+)-sensing properties after covalent conjugation with HaloTag protein. By using cells expressing HaloTag on the plasma membrane, we successfully directed TLSHalo specifically to the outer surface of target cells. This enabled us to visualize localized extracellular [K(+)] change with TLSHalo under a fluorescence microscope in real time. To confirm the experimental value of this system, we used TLSHalo to monitor extracellular [K(+)] change induced by K(+) ionophores or by activation of a native Ca(2+)-dependent K(+) channel (BK channel). Further, we show that K(+) efflux via BK channel induced by electrical stimulation at the bottom surface of the cells can be visualized with TLSHalo by means of total internal reflection fluorescence microscope (TIRFM) imaging. Our methodology should be useful to analyze physiological K(+) dynamics with high spatiotemporal resolution.

Emerging category representation in the visual forebrain hierarchy of pigeons (Columba livia).

PubMed

Azizi, Amir Hossein; Pusch, Roland; Koenen, Charlotte; Klatt, Sebastian; Bröcker, Franziska; Thiele, Samuel; Kellermann, Janosch; Güntürkün, Onur; Cheng, Sen

2018-06-06

Recognizing and categorizing visual stimuli are cognitive functions vital for survival, and an important feature of visual systems in primates as well as in birds. Visual stimuli are processed along the ventral visual pathway. At every stage in the hierarchy, neurons respond selectively to more complex features, transforming the population representation of the stimuli. It is therefore easier to read-out category information in higher visual areas. While explicit category representations have been observed in the primate brain, less is known on equivalent processes in the avian brain. Even though their brain anatomies are radically different, it has been hypothesized that visual object representations are comparable across mammals and birds. In the present study, we investigated category representations in the pigeon visual forebrain using recordings from single cells responding to photographs of real-world objects. Using a linear classifier, we found that the population activity in the visual associative area mesopallium ventrolaterale (MVL) distinguishes between animate and inanimate objects, although this distinction is not required by the task. By contrast, a population of cells in the entopallium, a region that is lower in the hierarchy of visual areas and that is related to the primate extrastriate cortex, lacked this information. A model that pools responses of simple cells, which function as edge detectors, can account for the animate vs. inanimate categorization in the MVL, but performance in the model is based on different features than in MVL. Therefore, processing in MVL cells is very likely more abstract than simple computations on the output of edge detectors. Copyright © 2018. Published by Elsevier B.V.

Predictions of the spontaneous symmetry-breaking theory for visual code completeness and spatial scaling in single-cell learning rules.

PubMed

Webber, C J

2001-05-01

This article shows analytically that single-cell learning rules that give rise to oriented and localized receptive fields, when their synaptic weights are randomly and independently initialized according to a plausible assumption of zero prior information, will generate visual codes that are invariant under two-dimensional translations, rotations, and scale magnifications, provided that the statistics of their training images are sufficiently invariant under these transformations. Such codes span different image locations, orientations, and size scales with equal economy. Thus, single-cell rules could account for the spatial scaling property of the cortical simple-cell code. This prediction is tested computationally by training with natural scenes; it is demonstrated that a single-cell learning rule can give rise to simple-cell receptive fields spanning the full range of orientations, image locations, and spatial frequencies (except at the extreme high and low frequencies at which the scale invariance of the statistics of digitally sampled images must ultimately break down, because of the image boundary and the finite pixel resolution). Thus, no constraint on completeness, or any other coupling between cells, is necessary to induce the visual code to span wide ranges of locations, orientations, and size scales. This prediction is made using the theory of spontaneous symmetry breaking, which we have previously shown can also explain the data-driven self-organization of a wide variety of transformation invariances in neurons' responses, such as the translation invariance of complex cell response.

SU-E-J-274: Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Molecular Imaging Program at Stanford, Stanford, CA; Bio-X Program, Stanford, CA

2015-06-15

Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs). Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/minmore » was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses. Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells. Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based-dose re-optimization.« less

Adaptations for vision in dim light: impulse responses and bumps in nocturnal spider photoreceptor cells (Cupiennius salei Keys).

PubMed

Pirhofer-Walzl, Karin; Warrant, Eric; Barth, Friedrich G

2007-10-01

The photoreceptor cells of the nocturnal spider Cupiennius salei were investigated by intracellular electrophysiology. (1) The responses of photoreceptor cells of posterior median (PM) and anterior median (AM) eyes to short (2 ms) light pulses showed long integration times in the dark-adapted and shorter integration times in the light-adapted state. (2) At very low light intensities, the photoreceptors responded to single photons with discrete potentials, called bumps, of high amplitude (2-20 mV). When measured in profoundly dark-adapted photoreceptor cells of the PM eyes these bumps showed an integration time of 128 +/- 35 ms (n = 7) whereas in dark-adapted photoreceptor cells of AM eyes the integration time was 84 +/- 13 ms (n = 8), indicating that the AM eyes are intrinsically faster than the PM eyes. (3) Long integration times, which improve visual reliability in dim light, and large responses to single photons in the dark-adapted state, contribute to a high visual sensitivity in Cupiennius at night. This conclusion is underlined by a calculation of sensitivity that accounts for both anatomical and physiological characteristics of the eye.

Response properties of ON-OFF retinal ganglion cells to high-order stimulus statistics.

PubMed

Xiao, Lei; Gong, Han-Yan; Gong, Hai-Qing; Liang, Pei-Ji; Zhang, Pu-Ming

2014-10-17

The visual stimulus statistics are the fundamental parameters to provide the reference for studying visual coding rules. In this study, the multi-electrode extracellular recording experiments were designed and implemented on bullfrog retinal ganglion cells to explore the neural response properties to the changes in stimulus statistics. The changes in low-order stimulus statistics, such as intensity and contrast, were clearly reflected in the neuronal firing rate. However, it was difficult to distinguish the changes in high-order statistics, such as skewness and kurtosis, only based on the neuronal firing rate. The neuronal temporal filtering and sensitivity characteristics were further analyzed. We observed that the peak-to-peak amplitude of the temporal filter and the neuronal sensitivity, which were obtained from either neuronal ON spikes or OFF spikes, could exhibit significant changes when the high-order stimulus statistics were changed. These results indicate that in the retina, the neuronal response properties may be reliable and powerful in carrying some complex and subtle visual information. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response.

PubMed

Xue, Qiong; Bettini, Emily; Paczkowski, Patrick; Ng, Colin; Kaiser, Alaina; McConnell, Timothy; Kodrasi, Olja; Quigley, Máire F; Heath, James; Fan, Rong; Mackay, Sean; Dudley, Mark E; Kassim, Sadik H; Zhou, Jing

2017-11-21

It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads. The enriched CAR-T cells were stimulated with anti-CAR or control IgG beads, stained with anti-CD4 RPE and anti-CD8 Alexa Fluor 647 antibodies, and incubated for 16 h in a single-cell barcode chip (SCBC). Each SCBC contains ~12,000 microchambers, covered with a glass slide that was pre-patterned with a complete copy of a 16-plex antibody array. Protein secretions from single CAR-T cells were captured and subsequently analyzed using proprietary software and new visualization methods. We demonstrate a new method for single-cell profiling of CD19 CAR-T pre-infusion products prepared from 4 healthy donors. CAR-T single cells exhibited a marked heterogeneity of cytokine secretions and polyfunctional (2+ cytokine) subsets specific to anti-CAR bead stimulation. The breadth of responses includes anti-tumor effector (Granzyme B, IFN-γ, MIP-1α, TNF-α), stimulatory (GM-CSF, IL-2, IL-8), regulatory (IL-4, IL-13, IL-22), and inflammatory (IL-6, IL-17A) functions. Furthermore, we developed two new bioinformatics tools for more effective polyfunctional subset visualization and comparison between donors. Single-cell, multiplexed, proteomic profiling of CD19 CAR-T product reveals a diverse landscape of immune effector response of CD19 CAR-T cells to antigen-specific challenge, providing a new platform for capturing CAR-T product data for correlative analysis. Additionally, such high dimensional data requires new visualization methods to further define precise polyfunctional response differences in these products. The presented biomarker capture and analysis system provides a more sensitive and comprehensive functional assessment of CAR-T pre-infusion products and may provide insights into the safety and efficacy of CAR-T cell therapy.

Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision.

PubMed

Beier, Corinne; Hovhannisyan, Anahit; Weiser, Sydney; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel; Sher, Alexander

2017-04-26

Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring. SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration. Copyright © 2017 the authors 0270-6474/17/374635-10$15.00/0.

Cholinergic suppression of visual responses in primate V1 is mediated by GABAergic inhibition

PubMed Central

Aoki, Chiye; Hawken, Michael J.

2012-01-01

Acetylcholine (ACh) has been implicated in selective attention. To understand the local circuit action of ACh, we iontophoresed cholinergic agonists into the primate primary visual cortex (V1) while presenting optimal visual stimuli. Consistent with our previous anatomical studies showing that GABAergic neurons in V1 express ACh receptors to a greater extent than do excitatory neurons, we observed suppressed visual responses in 36% of recorded neurons outside V1's primary thalamorecipient layer (4c). This suppression is blocked by the GABAA receptor antagonist gabazine. Within layer 4c, ACh release produces a response gain enhancement (Disney AA, Aoki C, Hawken MJ. Neuron 56: 701–713, 2007); elsewhere, ACh suppresses response gain by strengthening inhibition. Our finding contrasts with the observation that the dominant mechanism of suppression in the neocortex of rats is reduced glutamate release. We propose that in primates, distinct cholinergic receptor subtypes are recruited on specific cell types and in specific lamina to yield opposing modulatory effects that together increase neurons' responsiveness to optimal stimuli without changing tuning width. PMID:22786955

Cholinergic suppression of visual responses in primate V1 is mediated by GABAergic inhibition.

PubMed

Disney, Anita A; Aoki, Chiye; Hawken, Michael J

2012-10-01

Acetylcholine (ACh) has been implicated in selective attention. To understand the local circuit action of ACh, we iontophoresed cholinergic agonists into the primate primary visual cortex (V1) while presenting optimal visual stimuli. Consistent with our previous anatomical studies showing that GABAergic neurons in V1 express ACh receptors to a greater extent than do excitatory neurons, we observed suppressed visual responses in 36% of recorded neurons outside V1's primary thalamorecipient layer (4c). This suppression is blocked by the GABA(A) receptor antagonist gabazine. Within layer 4c, ACh release produces a response gain enhancement (Disney AA, Aoki C, Hawken MJ. Neuron 56: 701-713, 2007); elsewhere, ACh suppresses response gain by strengthening inhibition. Our finding contrasts with the observation that the dominant mechanism of suppression in the neocortex of rats is reduced glutamate release. We propose that in primates, distinct cholinergic receptor subtypes are recruited on specific cell types and in specific lamina to yield opposing modulatory effects that together increase neurons' responsiveness to optimal stimuli without changing tuning width.

Motion perception: behavior and neural substrate.

PubMed

Mather, George

2011-05-01

Visual motion perception is vital for survival. Single-unit recordings in primate primary visual cortex (V1) have revealed the existence of specialized motion sensing neurons; perceptual effects such as the motion after-effect demonstrate their importance for motion perception. Human psychophysical data on motion detection can be explained by a computational model of cortical motion sensors. Both psychophysical and physiological data reveal at least two classes of motion sensor capable of sensing motion in luminance-defined and texture-defined patterns, respectively. Psychophysical experiments also reveal that motion can be seen independently of motion sensor output, based on attentive tracking of visual features. Sensor outputs are inherently ambiguous, due to the problem of univariance in neural responses. In order to compute stimulus direction and speed, the visual system must compare the responses of many different sensors sensitive to different directions and speeds. Physiological data show that this computation occurs in the visual middle temporal (MT) area. Recent psychophysical studies indicate that information about spatial form may also play a role in motion computations. Adaptation studies show that the human visual system is selectively sensitive to large-scale optic flow patterns, and physiological studies indicate that cells in the middle superior temporal (MST) area derive this sensitivity from the combined responses of many MT cells. Extraretinal signals used to control eye movements are an important source of signals to cancel out the retinal motion responses generated by eye movements, though visual information also plays a role. A number of issues remain to be resolved at all levels of the motion-processing hierarchy. WIREs Cogni Sci 2011 2 305-314 DOI: 10.1002/wcs.110 For further resources related to this article, please visit the WIREs website Additional Supporting Information may be found in http://www.lifesci.sussex.ac.uk/home/George_Mather/Motion/index.html. Copyright © 2010 John Wiley & Sons, Ltd.

Quantitative visualization of synchronized insulin secretion from 3D-cultured cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Takahiro; Kanamori, Takao; Inouye, Satoshi

Quantitative visualization of synchronized insulin secretion was performed in an isolated rat pancreatic islet and a spheroid of rat pancreatic beta cell line using a method of video-rate bioluminescence imaging. Video-rate images of insulin secretion from 3D-cultured cells were obtained by expressing the fusion protein of insulin and Gaussia luciferase (Insulin-GLase). A subclonal rat INS-1E cell line stably expressing Insulin-GLase, named iGL, was established and a cluster of iGL cells showed oscillatory insulin secretion that was completely synchronized in response to high glucose. Furthermore, we demonstrated the effect of an antidiabetic drug, glibenclamide, on synchronized insulin secretion from 2D- andmore » 3D-cultured iGL cells. The amount of secreted Insulin-GLase from iGL cells was also determined by a luminometer. Thus, our bioluminescence imaging method could generally be used for investigating protein secretion from living 3D-cultured cells. In addition, iGL cell line would be valuable for evaluating antidiabetic drugs. - Highlights: • An imaging method for protein secretion from 3D-cultured cells was established. • The fused protein of insulin to GLase, Insulin-GLase, was used as a reporter. • Synchronous insulin secretion was visualized in rat islets and spheroidal beta cells. • A rat beta cell line stably expressing Insulin-GLase, named iGL, was established. • Effect of an antidiabetic drug on insulin secretion was visualized in iGL cells.« less

Comparison of visual receptive fields in the dorsolateral prefrontal cortex and ventral intraparietal area in macaques.

PubMed

Viswanathan, Pooja; Nieder, Andreas

2017-12-01

The concept of receptive field (RF) describes the responsiveness of neurons to sensory space. Neurons in the primate association cortices have long been known to be spatially selective but a detailed characterisation and direct comparison of RFs between frontal and parietal association cortices are missing. We sampled the RFs of a large number of neurons from two interconnected areas of the frontal and parietal lobes, the dorsolateral prefrontal cortex (dlPFC) and ventral intraparietal area (VIP), of rhesus monkeys by systematically presenting a moving bar during passive fixation. We found that more than half of neurons in both areas showed spatial selectivity. Single neurons in both areas could be assigned to five classes according to the spatial response patterns: few non-uniform RFs with multiple discrete response maxima could be dissociated from the vast majority of uniform RFs showing a single maximum; the latter were further classified into full-field and confined foveal, contralateral and ipsilateral RFs. Neurons in dlPFC showed a preference for the contralateral visual space and collectively encoded the contralateral visual hemi-field. In contrast, VIP neurons preferred central locations, predominantly covering the foveal visual space. Putative pyramidal cells with broad-spiking waveforms in PFC had smaller RFs than putative interneurons showing narrow-spiking waveforms, but distributed similarly across the visual field. In VIP, however, both putative pyramidal cells and interneurons had similar RFs at similar eccentricities. We provide a first, thorough characterisation of visual RFs in two reciprocally connected areas of a fronto-parietal cortical network. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Learning invariance from natural images inspired by observations in the primary visual cortex.

PubMed

Teichmann, Michael; Wiltschut, Jan; Hamker, Fred

2012-05-01

The human visual system has the remarkable ability to largely recognize objects invariant of their position, rotation, and scale. A good interpretation of neurobiological findings involves a computational model that simulates signal processing of the visual cortex. In part, this is likely achieved step by step from early to late areas of visual perception. While several algorithms have been proposed for learning feature detectors, only few studies at hand cover the issue of biologically plausible learning of such invariance. In this study, a set of Hebbian learning rules based on calcium dynamics and homeostatic regulations of single neurons is proposed. Their performance is verified within a simple model of the primary visual cortex to learn so-called complex cells, based on a sequence of static images. As a result, the learned complex-cell responses are largely invariant to phase and position.

Luminance, Colour, Viewpoint and Border Enhanced Disparity Energy Model

PubMed Central

Martins, Jaime A.; Rodrigues, João M. F.; du Buf, Hans

2015-01-01

The visual cortex is able to extract disparity information through the use of binocular cells. This process is reflected by the Disparity Energy Model, which describes the role and functioning of simple and complex binocular neuron populations, and how they are able to extract disparity. This model uses explicit cell parameters to mathematically determine preferred cell disparities, like spatial frequencies, orientations, binocular phases and receptive field positions. However, the brain cannot access such explicit cell parameters; it must rely on cell responses. In this article, we implemented a trained binocular neuronal population, which encodes disparity information implicitly. This allows the population to learn how to decode disparities, in a similar way to how our visual system could have developed this ability during evolution. At the same time, responses of monocular simple and complex cells can also encode line and edge information, which is useful for refining disparities at object borders. The brain should then be able, starting from a low-level disparity draft, to integrate all information, including colour and viewpoint perspective, in order to propagate better estimates to higher cortical areas. PMID:26107954

A neural model of the temporal dynamics of figure-ground segregation in motion perception.

PubMed

Raudies, Florian; Neumann, Heiko

2010-03-01

How does the visual system manage to segment a visual scene into surfaces and objects and manage to attend to a target object? Based on psychological and physiological investigations, it has been proposed that the perceptual organization and segmentation of a scene is achieved by the processing at different levels of the visual cortical hierarchy. According to this, motion onset detection, motion-defined shape segregation, and target selection are accomplished by processes which bind together simple features into fragments of increasingly complex configurations at different levels in the processing hierarchy. As an alternative to this hierarchical processing hypothesis, it has been proposed that the processing stages for feature detection and segregation are reflected in different temporal episodes in the response patterns of individual neurons. Such temporal epochs have been observed in the activation pattern of neurons as low as in area V1. Here, we present a neural network model of motion detection, figure-ground segregation and attentive selection which explains these response patterns in an unifying framework. Based on known principles of functional architecture of the visual cortex, we propose that initial motion and motion boundaries are detected at different and hierarchically organized stages in the dorsal pathway. Visual shapes that are defined by boundaries, which were generated from juxtaposed opponent motions, are represented at different stages in the ventral pathway. Model areas in the different pathways interact through feedforward and modulating feedback, while mutual interactions enable the communication between motion and form representations. Selective attention is devoted to shape representations by sending modulating feedback signals from higher levels (working memory) to intermediate levels to enhance their responses. Areas in the motion and form pathway are coupled through top-down feedback with V1 cells at the bottom end of the hierarchy. We propose that the different temporal episodes in the response pattern of V1 cells, as recorded in recent experiments, reflect the strength of modulating feedback signals. This feedback results from the consolidated shape representations from coherent motion patterns and the attentive modulation of responses along the cortical hierarchy. The model makes testable predictions concerning the duration and delay of the temporal episodes of V1 cell responses as well as their response variations that were caused by modulating feedback signals. Copyright 2009 Elsevier Ltd. All rights reserved.

Retinal ganglion cells in diabetes

PubMed Central

Kern, Timothy S; Barber, Alistair J

2008-01-01

Diabetic retinopathy has long been recognized as a vascular disease that develops in most patients, and it was believed that the visual dysfunction that develops in some diabetics was due to the vascular lesions used to characterize the disease. It is becoming increasingly clear that neuronal cells of the retina also are affected by diabetes, resulting in dysfunction and even degeneration of some neuronal cells. Retinal ganglion cells (RGCs) are the best studied of the retinal neurons with respect to the effect of diabetes. Although investigations are providing new information about RGCs in diabetes, including therapies to inhibit the neurodegeneration, critical information about the function, anatomy and response properties of these cells is yet needed to understand the relationship between RGC changes and visual dysfunction in diabetes. PMID:18565995

Asymmetries of Dark and Bright Negative Afterimages Are Paralleled by Subcortical ON and OFF Poststimulus Responses.

PubMed

Li, Hui; Liu, Xu; Andolina, Ian M; Li, Xiaohong; Lu, Yiliang; Spillmann, Lothar; Wang, Wei

2017-02-22

Humans are more sensitive to luminance decrements than increments, as evidenced by lower thresholds and shorter latencies for dark stimuli. This asymmetry is consistent with results of neurophysiological recordings in dorsal lateral geniculate nucleus (dLGN) and primary visual cortex (V1) of cat and monkey. Specifically, V1 population responses demonstrate that darks elicit higher levels of activation than brights, and the latency of OFF responses in dLGN and V1 is shorter than that of ON responses. The removal of a dark or bright disc often generates the perception of a negative afterimage, and here we ask whether there also exist asymmetries for negative afterimages elicited by dark and bright discs. If so, do the poststimulus responses of subcortical ON and OFF cells parallel such afterimage asymmetries? To test these hypotheses, we performed psychophysical experiments in humans and single-cell/S-potential recordings in cat dLGN. Psychophysically, we found that bright afterimages elicited by luminance decrements are stronger and last longer than dark afterimages elicited by luminance increments of equal sizes. Neurophysiologically, we found that ON cells responded to the removal of a dark disc with higher firing rates that were maintained for longer than OFF cells to the removal of a bright disc. The ON and OFF cell asymmetry was most pronounced at long stimulus durations in the dLGN. We conclude that subcortical response strength differences between ON and OFF channels parallel the asymmetries between bright and dark negative afterimages, further supporting a subcortical origin of bright and dark afterimage perception. SIGNIFICANCE STATEMENT Afterimages are physiological aftereffects following stimulation of the eye, the study of which helps us to understand how our visual brain generates visual perception in the absence of physical stimuli. We report, for the first time to our knowledge, asymmetries between bright and dark negative afterimages elicited by luminance decrements and increments, respectively. Bright afterimages are stronger and last longer than dark afterimages. Subcortical neuronal recordings of poststimulus responses of ON and OFF cells reveal similar asymmetries with respect to response strength and duration. Our results suggest that subcortical differences between ON and OFF channels help explain intensity and duration asymmetries between bright and dark afterimages, supporting the notion of a subcortical origin of bright and dark afterimages. Copyright © 2017 the authors 0270-6474/17/371984-13$15.00/0.

Publisher Correction: Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex.

PubMed

Hrvatin, Sinisa; Hochbaum, Daniel R; Nagy, M Aurel; Cicconet, Marcelo; Robertson, Keiramarie; Cheadle, Lucas; Zilionis, Rapolas; Ratner, Alex; Borges-Monroy, Rebeca; Klein, Allon M; Sabatini, Bernardo L; Greenberg, Michael E

2018-05-11

In the version of this article initially published, the x-axis labels in Fig. 3c read Vglut, Gad1/2, Aldh1l1 and Pecam1; they should have read Vglut + , Gad1/2 + , Aldh1l1 + and Pecam1 + . In Fig. 4, the range values were missing from the color scales; they are, from left to right, 4-15, 0-15, 4-15 and 0-15 in Fig. 4a and 4-15, 4-15 and 4-8 in Fig. 4h. In the third paragraph of the main text, the phrase reading "Previous approaches have analyzed a limited number of inhibitory cell types, thus masking the full diversity of excitatory populations" should have read "Previous approaches have analyzed a limited number of inhibitory cell types and masked the full diversity of excitatory populations." In the second paragraph of Results section "Diversity of experience-regulated ERGs," the phrase reading "thus suggesting considerable divergence within the gene expression program responding to early stimuli" should have read "thus suggesting considerable divergence within the early stimulus-responsive gene expression program." In the fourth paragraph of Results section "Excitatory neuronal LRGs," the sentence reading "The anatomical organization of these cell types into sublayers, coupled with divergent transcriptional responses to a sensory stimulus, suggested previously unappreciated functional subdivisions located within the laminae of the mouse visual cortex and resembling the cytoarchitecture in higher mammals" should have read "The anatomical organization of these cell types into sublayers, coupled with divergent transcriptional responses to a sensory stimulus, suggests previously unappreciated functional subdivisions located within the laminae of the mouse visual cortex, resembling the cytoarchitecture in higher mammals." In the last sentence of the Results, "sensory-responsive genes" should have read "sensory-stimulus-responsive genes." The errors have been corrected in the HTML and PDF versions of the article.

The Effects of Nicotinic and Muscarinic Receptor Activation on Patch-Clamped Cells in the Optic Tectum of Rana Pipiens

PubMed Central

Yu, C.-J.; Debski, E. A.

2008-01-01

Both nicotinic and muscarinic cholinergic receptors are present in the optic tectum. To begin to understand how the activation of these receptors affects visual activity patterns, we have determined the types of physiological responses induced by their activation. Using tectal brain slices from the leopard frog, we found that application of nicotine (100 μM) evoked long-lasting responses in 60% of patch-clamped tectal cells. Thirty percent of these responses consisted of an increase in spontaneous postsynaptic currents (sPSCs) and had both a glutamatergic and GABAergic component as determined by the use of 6-cyano-7-nitroquinoxaline-2,3-dione (50 μM) and bicuculline (25 μM), respectively. Remaining response types consisted of an inward membrane current (16%) and an increase in sPSCs combined with an inward membrane current (14%). All responses could be elicited in the presence of tetrodotoxin (0.5 μM). Muscarinic receptor-mediated responses, induced by carbachol (100 μM) application after nicotinic receptor desensitization, produced responses in 70% of tectal cells. In contrast to responses elicited by nicotine, carbachol-induced responses could be evoked multiple times without significant decrement. Responses consisted of either an outward current (57%), a decrease in sPSCs (5%) or an increase in sPSCs, with (almost 6%) or without (almost 3%) an outward current. The response elicited by carbachol was not predicted by the response of the cell to nicotine. Our results suggest that nicotinic receptors are found predominantly at presynaptic locations in the optic tectum while muscarinic receptors are most often present at postsynaptic sites. We conclude that both of these receptor types could substantially modulate visual activity by changing either the input to tectal neurons or the level of their response to that input. PMID:12676145

The effects of nicotinic and muscarinic receptor activation on patch-clamped cells in the optic tectum of Rana pipiens.

PubMed

Yu, C-J; Debski, E A

2003-01-01

Both nicotinic and muscarinic cholinergic receptors are present in the optic tectum. To begin to understand how the activation of these receptors affects visual activity patterns, we have determined the types of physiological responses induced by their activation. Using tectal brain slices from the leopard frog, we found that application of nicotine (100 microM) evoked long-lasting responses in 60% of patch-clamped tectal cells. Thirty percent of these responses consisted of an increase in spontaneous postsynaptic currents (sPSCs) and had both a glutamatergic and GABAergic component as determined by the use of 6-cyano-7-nitroquinoxaline-2,3-dione (50 microM) and bicuculline (25 microM), respectively. Remaining response types consisted of an inward membrane current (16%) and an increase in sPSCs combined with an inward membrane current (14%). All responses could be elicited in the presence of tetrodotoxin (0.5 microM). Muscarinic receptor-mediated responses, induced by carbachol (100 microM) application after nicotinic receptor desensitization, produced responses in 70% of tectal cells. In contrast to responses elicited by nicotine, carbachol-induced responses could be evoked multiple times without significant decrement. Responses consisted of either an outward current (57%), a decrease in sPSCs (5%) or an increase in sPSCs, with (almost 6%) or without (almost 3%) an outward current. The response elicited by carbachol was not predicted by the response of the cell to nicotine. Our results suggest that nicotinic receptors are found predominantly at presynaptic locations in the optic tectum while muscarinic receptors are most often present at postsynaptic sites. We conclude that both of these receptor types could substantially modulate visual activity by changing either the input to tectal neurons or the level of their response to that input.

Bidirectional modulation of visual plasticity by cholinergic receptor subtypes in the frog optic tectum

PubMed Central

Yu, Chuan-Jiang; Butt, Christopher M.; Debski, Elizabeth A.

2008-01-01

Cholinergic input to the optic tectum is necessary for visual map maintenance. To understand why, we examined the effects of activation of the different cholinergic receptor subtypes in tectal brain slices and determined whether the retinotectal map was affected by manipulations of their activity in vivo. Both α-bungarotoxin sensitive and insensitive nicotinic receptor agonists increased spontaneous postsynaptic currents (sPSCs) in a subpopulation of patch-clamped tectal cells; application of subtype selective receptor antagonists reduced nicotine-induced increases in sPSCs. Activation of α-bungarotoxin insensitive nicotinic receptors also induced substantial inward current in some cells. Muscarinic receptor mediated outward current responses were blocked by the M2-like muscarinic receptor antagonists himbacine or AF-DX 384 and mimicked by application of the M2-like agonist oxotremorine. A less frequently observed muscarinic response involving a change in sPSC frequency appeared to be mediated by M1-like muscarinic receptors. In separate experiments, pharmacological manipulation of cholinergic receptor subtype activation led to changes in the activity-dependent visual map created in the tectum by retinal ganglion cell terminals. Chronic exposure of the tectum to either α-bungarotoxin insensitive, α-bungarotoxin sensitive or M1-like receptor antagonists resulted in map disruption. However, treatment with the M2-like receptor antagonist, AF-DX 384, compressed the map. We conclude that nicotinic or M1-like muscarinic receptors control input to tectal cells while α-bungarotoxin insensitive nicotinic receptors and M2-like muscarinic receptors change tectal cell responses to that input. Blockade of the different cholinergic receptor subtypes can have opposing effects on map topography that are consistent with expected effects on tectal cell activity levels. PMID:12670313

The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal Amacrine Cell of the Rabbit Retina.

PubMed

Murphy-Baum, Benjamin L; Taylor, W Rowland

2015-09-30

Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene. Copyright © 2015 the authors 0270-6474/15/3513336-15$15.00/0.

Analytical validation of quantitative immunohistochemical assays of tumor infiltrating lymphocyte biomarkers.

PubMed

Singh, U; Cui, Y; Dimaano, N; Mehta, S; Pruitt, S K; Yearley, J; Laterza, O F; Juco, J W; Dogdas, B

2018-06-04

Tumor infiltrating lymphocytes (TIL), especially T-cells, have both prognostic and therapeutic applications. The presence of CD8+ effector T-cells and the ratio of CD8+ cells to FOXP3+ regulatory T-cells have been used as biomarkers of disease prognosis to predict response to various immunotherapies. Blocking the interaction between inhibitory receptors on T-cells and their ligands with therapeutic antibodies including atezolizumab, nivolumab, pembrolizumab and tremelimumab increases the immune response against cancer cells and has shown significant improvement in clinical benefits and survival in several different tumor types. The improved clinical outcome is presumed to be associated with a higher tumor infiltration; therefore, it is thought that more accurate methods for measuring the amount of TIL could assist prognosis and predict treatment response. We have developed and validated quantitative immunohistochemistry (IHC) assays for CD3, CD8 and FOXP3 for immunophenotyping T-lymphocytes in tumor tissue. Various types of formalin fixed, paraffin embedded (FFPE) tumor tissues were immunolabeled with anti-CD3, anti-CD8 and anti-FOXP3 antibodies using an IHC autostainer. The tumor area of stained tissues, including the invasive margin of the tumor, was scored by a pathologist (visual scoring) and by computer-based quantitative image analysis. Two image analysis scores were obtained for the staining of each biomarker: the percent positive cells in the tumor area and positive cells/mm 2 tumor area. Comparison of visual vs. image analysis scoring methods using regression analysis showed high correlation and indicated that quantitative image analysis can be used to score the number of positive cells in IHC stained slides. To demonstrate that the IHC assays produce consistent results in normal daily testing, we evaluated the specificity, sensitivity and reproducibility of the IHC assays using both visual and image analysis scoring methods. We found that CD3, CD8 and FOXP3 IHC assays met the fit-for-purpose analytical acceptance validation criteria and that they can be used to support clinical studies.

The Effect of PKCα on the Light Response of Rod Bipolar Cells in the Mouse Retina

PubMed Central

Xiong, Wei-Hong; Pang, Ji-Jie; Pennesi, Mark E.; Duvoisin, Robert M.; Wu, Samuel M.; Morgans, Catherine W.

2015-01-01

Purpose Protein kinase C α (PKCα) is abundantly expressed in rod bipolar cells (RBCs) in the retina, yet the physiological function of PKCα in these cells is not well understood. To elucidate the role of PKCα in visual processing in the eye, we examined the effect of genetic deletion of PKCα on the ERG and on RBC light responses in the mouse. Methods Immunofluorescent labeling was performed on wild-type (WT), TRPM1 knockout, and PKCα knockout (PKC-KO) retina. Scotopic and photopic ERGs were recorded from WT and PKC-KO mice. Light responses of RBCs were measured using whole-cell recordings in retinal slices from WT and PKC-KO mice. Results Protein kinase C alpha expression in RBCs is correlated with the activity state of the cell. Rod bipolar cells dendrites are a major site of PKCα phosphorylation. Electroretinogram recordings indicated that loss of PKCα affects the scotopic b-wave, including a larger peak amplitude, longer implicit time, and broader width of the b-wave. There were no differences in the ERG a- or c-wave between PKCα KO and WT mice, indicating no measurable effect of PKCα in photoreceptors or the RPE. The photopic ERG was unaffected consistent with the lack of detectable PKCα in cone bipolar cells. Whole-cell recordings from RBCs in PKC-KO retinal slices revealed that, compared with WT, RBC light responses in the PKC-KO retina are delayed and of longer duration. Conclusions Protein kinase C alpha plays an important modulatory role in RBCs, regulating both the peak amplitude and temporal properties of the RBC light response in the rod visual pathway. PMID:26230760

Distinctive receptive field and physiological properties of a wide-field amacrine cell in the macaque monkey retina

PubMed Central

Puller, Christian; Rieke, Fred; Neitz, Jay; Neitz, Maureen

2015-01-01

At early stages of visual processing, receptive fields are typically described as subtending local regions of space and thus performing computations on a narrow spatial scale. Nevertheless, stimulation well outside of the classical receptive field can exert clear and significant effects on visual processing. Given the distances over which they occur, the retinal mechanisms responsible for these long-range effects would certainly require signal propagation via active membrane properties. Here the physiology of a wide-field amacrine cell—the wiry cell—in macaque monkey retina is explored, revealing receptive fields that represent a striking departure from the classic structure. A single wiry cell integrates signals over wide regions of retina, 5–10 times larger than the classic receptive fields of most retinal ganglion cells. Wiry cells integrate signals over space much more effectively than predicted from passive signal propagation, and spatial integration is strongly attenuated during blockade of NMDA spikes but integration is insensitive to blockade of NaV channels with TTX. Thus these cells appear well suited for contributing to the long-range interactions of visual signals that characterize many aspects of visual perception. PMID:26133804

Rapid steroid influences on visually guided sexual behavior in male goldfish

PubMed Central

Lord, Louis-David; Bond, Julia; Thompson, Richmond R.

2013-01-01

The ability of steroid hormones to rapidly influence cell physiology through nongenomic mechanisms raises the possibility that these molecules may play a role in the dynamic regulation of social behavior, particularly in species in which social stimuli can rapidly influence circulating steroid levels. We therefore tested if testosterone (T), which increases in male goldfish in response to sexual stimuli, can rapidly influence approach responses towards females. Injections of T stimulated approach responses towards the visual cues of females 30–45 min after the injection but did not stimulate approach responses towards stimulus males or affect general activity, indicating that the effect is stimulus-specific and not a secondary consequence of increased arousal. Estradiol produced the same effect 30–45 min and even 10–25 min after administration, and treatment with the aromatase inhibitor fadrozole blocked exogenous T’s behavioral effect, indicating that T’s rapid stimulation of visual approach responses depends on aromatization. We suggest that T surges induced by sexual stimuli, including preovulatory pheromones, rapidly prime males to mate by increasing sensitivity within visual pathways that guide approach responses towards females and/or by increasing the motivation to approach potential mates through actions within traditional limbic circuits. PMID:19751737

Rapid steroid influences on visually guided sexual behavior in male goldfish.

PubMed

Lord, Louis-David; Bond, Julia; Thompson, Richmond R

2009-11-01

The ability of steroid hormones to rapidly influence cell physiology through nongenomic mechanisms raises the possibility that these molecules may play a role in the dynamic regulation of social behavior, particularly in species in which social stimuli can rapidly influence circulating steroid levels. We therefore tested if testosterone (T), which increases in male goldfish in response to sexual stimuli, can rapidly influence approach responses towards females. Injections of T stimulated approach responses towards the visual cues of females 30-45 min after the injection but did not stimulate approach responses towards stimulus males or affect general activity, indicating that the effect is stimulus-specific and not a secondary consequence of increased arousal. Estradiol produced the same effect 30-45 min and even 10-25 min after administration, and treatment with the aromatase inhibitor fadrozole blocked exogenous T's behavioral effect, indicating that T's rapid stimulation of visual approach responses depends on aromatization. We suggest that T surges induced by sexual stimuli, including preovulatory pheromones, rapidly prime males to mate by increasing sensitivity within visual pathways that guide approach responses towards females and/or by increasing the motivation to approach potential mates through actions within traditional limbic circuits.

Visual Analytics approach for Lightning data analysis and cell nowcasting

NASA Astrophysics Data System (ADS)

Peters, Stefan; Meng, Liqiu; Betz, Hans-Dieter

2013-04-01

Thunderstorms and their ground effects, such as flash floods, hail, lightning, strong wind and tornadoes, are responsible for most weather damages (Bonelli & Marcacci 2008). Thus to understand, identify, track and predict lightning cells is essential. An important aspect for decision makers is an appropriate visualization of weather analysis results including the representation of dynamic lightning cells. This work focuses on the visual analysis of lightning data and lightning cell nowcasting which aim to detect and understanding spatial-temporal patterns of moving thunderstorms. Lightnings are described by 3D coordinates and the exact occurrence time of lightnings. The three-dimensionally resolved total lightning data used in our experiment are provided by the European lightning detection network LINET (Betz et al. 2009). In all previous works, lightning point data, detected lightning cells and derived cell tracks are visualized in 2D. Lightning cells are either displayed as 2D convex hulls with or without the underlying lightning point data. Due to recent improvements of lightning data detection and accuracy, there is a growing demand on multidimensional and interactive visualization in particular for decision makers. In a first step lightning cells are identified and tracked. Then an interactive graphic user interface (GUI) is developed to investigate the dynamics of the lightning cells: e.g. changes of cell density, location, extension as well as merging and splitting behavior in 3D over time. In particular a space time cube approach is highlighted along with statistical analysis. Furthermore a lightning cell nowcasting is conducted and visualized. The idea thereby is to predict the following cell features for the next 10-60 minutes including location, centre, extension, density, area, volume, lifetime and cell feature probabilities. The main focus will be set to a suitable interactive visualization of the predicted featured within the GUI. The developed visual exploring tool for the purpose of supporting decision making is investigated for two determined user groups: lightning experts and interested lay public. Betz HD, Schmidt K, Oettinger WP (2009) LINET - An International VLF/LF Lightning Detection Network in Europe. In: Betz HD, Schumann U, Laroche P (eds) Lightning: Principles, Instruments and Applications. Springer Netherlands, Dordrecht, pp 115-140 Bonelli P, Marcacci P (2008) Thunderstorm nowcasting by means of lightning and radar data: algorithms and applications in northern Italy. Nat. Hazards Earth Syst. Sci 8(5):1187-1198

A Feedback Model of Attention Explains the Diverse Effects of Attention on Neural Firing Rates and Receptive Field Structure.

PubMed

Miconi, Thomas; VanRullen, Rufin

2016-02-01

Visual attention has many effects on neural responses, producing complex changes in firing rates, as well as modifying the structure and size of receptive fields, both in topological and feature space. Several existing models of attention suggest that these effects arise from selective modulation of neural inputs. However, anatomical and physiological observations suggest that attentional modulation targets higher levels of the visual system (such as V4 or MT) rather than input areas (such as V1). Here we propose a simple mechanism that explains how a top-down attentional modulation, falling on higher visual areas, can produce the observed effects of attention on neural responses. Our model requires only the existence of modulatory feedback connections between areas, and short-range lateral inhibition within each area. Feedback connections redistribute the top-down modulation to lower areas, which in turn alters the inputs of other higher-area cells, including those that did not receive the initial modulation. This produces firing rate modulations and receptive field shifts. Simultaneously, short-range lateral inhibition between neighboring cells produce competitive effects that are automatically scaled to receptive field size in any given area. Our model reproduces the observed attentional effects on response rates (response gain, input gain, biased competition automatically scaled to receptive field size) and receptive field structure (shifts and resizing of receptive fields both spatially and in complex feature space), without modifying model parameters. Our model also makes the novel prediction that attentional effects on response curves should shift from response gain to contrast gain as the spatial focus of attention drifts away from the studied cell.

Visual detection following retinal damage: predictions of an inhomogeneous retino-cortical model

NASA Astrophysics Data System (ADS)

Arnow, Thomas L.; Geisler, Wilson S.

1996-04-01

A model of human visual detection performance has been developed, based on available anatomical and physiological data for the primate visual system. The inhomogeneous retino- cortical (IRC) model computes detection thresholds by comparing simulated neural responses to target patterns with responses to a uniform background of the same luminance. The model incorporates human ganglion cell sampling distributions; macaque monkey ganglion cell receptive field properties; macaque cortical cell contrast nonlinearities; and a optical decision rule based on ideal observer theory. Spatial receptive field properties of cortical neurons were not included. Two parameters were allowed to vary while minimizing the squared error between predicted and observed thresholds. One parameter was decision efficiency, the other was the relative strength of the ganglion-cell center and surround. The latter was only allowed to vary within a small range consistent with known physiology. Contrast sensitivity was measured for sinewave gratings as a function of spatial frequency, target size and eccentricity. Contrast sensitivity was also measured for an airplane target as a function of target size, with and without artificial scotomas. The results of these experiments, as well as contrast sensitivity data from the literature were compared to predictions of the IRC model. Predictions were reasonably good for grating and airplane targets.

A multichip aVLSI system emulating orientation selectivity of primary visual cortical cells.

PubMed

Shimonomura, Kazuhiro; Yagi, Tetsuya

2005-07-01

In this paper, we designed and fabricated a multichip neuromorphic analog very large scale integrated (aVLSI) system, which emulates the orientation selective response of the simple cell in the primary visual cortex. The system consists of a silicon retina and an orientation chip. An image, which is filtered by a concentric center-surround (CS) antagonistic receptive field of the silicon retina, is transferred to the orientation chip. The image transfer from the silicon retina to the orientation chip is carried out with analog signals. The orientation chip selectively aggregates multiple pixels of the silicon retina, mimicking the feedforward model proposed by Hubel and Wiesel. The chip provides the orientation-selective (OS) outputs which are tuned to 0 degrees, 60 degrees, and 120 degrees. The feed-forward aggregation reduces the fixed pattern noise that is due to the mismatch of the transistors in the orientation chip. The spatial properties of the orientation selective response were examined in terms of the adjustable parameters of the chip, i.e., the number of aggregated pixels and size of the receptive field of the silicon retina. The multichip aVLSI architecture used in the present study can be applied to implement higher order cells such as the complex cell of the primary visual cortex.

Visual–Motor Transformations Within Frontal Eye Fields During Head-Unrestrained Gaze Shifts in the Monkey

PubMed Central

Sajad, Amirsaman; Sadeh, Morteza; Keith, Gerald P.; Yan, Xiaogang; Wang, Hongying; Crawford, John Douglas

2015-01-01

A fundamental question in sensorimotor control concerns the transformation of spatial signals from the retina into eye and head motor commands required for accurate gaze shifts. Here, we investigated these transformations by identifying the spatial codes embedded in visually evoked and movement-related responses in the frontal eye fields (FEFs) during head-unrestrained gaze shifts. Monkeys made delayed gaze shifts to the remembered location of briefly presented visual stimuli, with delay serving to dissociate visual and movement responses. A statistical analysis of nonparametric model fits to response field data from 57 neurons (38 with visual and 49 with movement activities) eliminated most effector-specific, head-fixed, and space-fixed models, but confirmed the dominance of eye-centered codes observed in head-restrained studies. More importantly, the visual response encoded target location, whereas the movement response mainly encoded the final position of the imminent gaze shift (including gaze errors). This spatiotemporal distinction between target and gaze coding was present not only at the population level, but even at the single-cell level. We propose that an imperfect visual–motor transformation occurs during the brief memory interval between perception and action, and further transformations from the FEF's eye-centered gaze motor code to effector-specific codes in motor frames occur downstream in the subcortical areas. PMID:25491118

Synaptic Mechanisms Generating Orientation Selectivity in the ON Pathway of the Rabbit Retina

PubMed Central

Venkataramani, Sowmya

2016-01-01

Neurons that signal the orientation of edges within the visual field have been widely studied in primary visual cortex. Much less is known about the mechanisms of orientation selectivity that arise earlier in the visual stream. Here we examine the synaptic and morphological properties of a subtype of orientation-selective ganglion cell in the rabbit retina. The receptive field has an excitatory ON center, flanked by excitatory OFF regions, a structure similar to simple cell receptive fields in primary visual cortex. Examination of the light-evoked postsynaptic currents in these ON-type orientation-selective ganglion cells (ON-OSGCs) reveals that synaptic input is mediated almost exclusively through the ON pathway. Orientation selectivity is generated by larger excitation for preferred relative to orthogonal stimuli, and conversely larger inhibition for orthogonal relative to preferred stimuli. Excitatory orientation selectivity arises in part from the morphology of the dendritic arbors. Blocking GABAA receptors reduces orientation selectivity of the inhibitory synaptic inputs and the spiking responses. Negative contrast stimuli in the flanking regions produce orientation-selective excitation in part by disinhibition of a tonic NMDA receptor-mediated input arising from ON bipolar cells. Comparison with earlier studies of OFF-type OSGCs indicates that diverse synaptic circuits have evolved in the retina to detect the orientation of edges in the visual input. SIGNIFICANCE STATEMENT A core goal for visual neuroscientists is to understand how neural circuits at each stage of the visual system extract and encode features from the visual scene. This study documents a novel type of orientation-selective ganglion cell in the retina and shows that the receptive field structure is remarkably similar to that of simple cells in primary visual cortex. However, the data indicate that, unlike in the cortex, orientation selectivity in the retina depends on the activity of inhibitory interneurons. The results further reveal the physiological basis for feature detection in the visual system, elucidate the synaptic mechanisms that generate orientation selectivity at an early stage of visual processing, and illustrate a novel role for NMDA receptors in retinal processing. PMID:26985041

Synaptic Mechanisms Generating Orientation Selectivity in the ON Pathway of the Rabbit Retina.

PubMed

Venkataramani, Sowmya; Taylor, W Rowland

2016-03-16

Neurons that signal the orientation of edges within the visual field have been widely studied in primary visual cortex. Much less is known about the mechanisms of orientation selectivity that arise earlier in the visual stream. Here we examine the synaptic and morphological properties of a subtype of orientation-selective ganglion cell in the rabbit retina. The receptive field has an excitatory ON center, flanked by excitatory OFF regions, a structure similar to simple cell receptive fields in primary visual cortex. Examination of the light-evoked postsynaptic currents in these ON-type orientation-selective ganglion cells (ON-OSGCs) reveals that synaptic input is mediated almost exclusively through the ON pathway. Orientation selectivity is generated by larger excitation for preferred relative to orthogonal stimuli, and conversely larger inhibition for orthogonal relative to preferred stimuli. Excitatory orientation selectivity arises in part from the morphology of the dendritic arbors. Blocking GABAA receptors reduces orientation selectivity of the inhibitory synaptic inputs and the spiking responses. Negative contrast stimuli in the flanking regions produce orientation-selective excitation in part by disinhibition of a tonic NMDA receptor-mediated input arising from ON bipolar cells. Comparison with earlier studies of OFF-type OSGCs indicates that diverse synaptic circuits have evolved in the retina to detect the orientation of edges in the visual input. A core goal for visual neuroscientists is to understand how neural circuits at each stage of the visual system extract and encode features from the visual scene. This study documents a novel type of orientation-selective ganglion cell in the retina and shows that the receptive field structure is remarkably similar to that of simple cells in primary visual cortex. However, the data indicate that, unlike in the cortex, orientation selectivity in the retina depends on the activity of inhibitory interneurons. The results further reveal the physiological basis for feature detection in the visual system, elucidate the synaptic mechanisms that generate orientation selectivity at an early stage of visual processing, and illustrate a novel role for NMDA receptors in retinal processing. Copyright © 2016 the authors 0270-6474/16/363336-14$15.00/0.

Edge Detection Based On the Characteristic of Primary Visual Cortex Cells

NASA Astrophysics Data System (ADS)

Zhu, M. M.; Xu, Y. L.; Ma, H. Q.

2018-01-01

Aiming at the problem that it is difficult to balance the accuracy of edge detection and anti-noise performance, and referring to the dynamic and static perceptions of the primary visual cortex (V1) cells, a V1 cell model is established to perform edge detection. A spatiotemporal filter is adopted to simulate the receptive field of V1 simple cells, the model V1 cell is obtained after integrating the responses of simple cells by half-wave rectification and normalization, Then the natural image edge is detected by using static perception of V1 cells. The simulation results show that, the V1 model can basically fit the biological data and has the universality of biology. What’s more, compared with other edge detection operators, the proposed model is more effective and has better robustness

Visual area of the lateral suprasylvian gyrus (Clare—Bishop area) of the cat

PubMed Central

Hubel, David H.; Wiesel, Torsten N.

1969-01-01

On anatomical and physiological grounds a zone of cat cortex deep in the medial bank of the suprasylvian sulcus (the Clare—Bishop area) is known to receive strong visual projections both from the lateral geniculate body and area 17. We have mapped receptive fields of single cells in this area in eight cats. Active responses to visual stimuli were found over most of the medial bank of the suprasylvian sulcus extending to the depths and over to the lowest part of the lateral bank. The area is clearly topographically arranged. The first responsive cells, recorded over the lateral convexity and 2-3 mm down the medial bank, had receptive fields in the far periphery of the contralateral visual fields. The receptive fields tended to be large, but showed considerable variation in size and scatter in their positions. As the electrode advanced down the bank, fields of successively recorded cells gradually tended to move inwards, so that in the depths of the sulcus the inner borders of many of the fields reached the vertical mid line. Here the fields were smaller, though they still varied very much in size. Receptive fields were larger than in 17, 18, or 19, but otherwise were not obviously different from the complex and lower-order hypercomplex fields in those areas. No simple fields, or concentric fields of the retino-geniculate type, were seen. Cells with common receptive-field orientation were grouped together, but whether or not the grouping occurs in columns was not established. Most cells were driven independently by the two eyes. Fields in the two eyes seemed to be identical in organization. Cells dominated by the contralateral eye were much more common than ipsilaterally dominated ones, but when cells with parafoveal and peripheral fields were considered separately, the asymmetry was seen to apply mainly to cells with peripheral fields. PMID:5770897

Spatial resolution, contrast sensitivity, and sensitivity to defocus of chicken retinal ganglion cells in vitro.

PubMed

Diedrich, Erich; Schaeffel, Frank

2009-11-01

The chicken has been extensively studied as an animal model for myopia because its eye growth is tightly controlled by visual experience. It has been found that the retina controls the axial eye growth rates depending on the amount and the sign of defocus imposed in the projected image. Glucagonergic amacrine cells were discovered that appear to encode for the sign of imposed defocus. It is not clear whether the downstream neurons, the retinal ganglion cells, still have access to this information-and whether it ultimately reaches the brain. We have analyzed the spike rates of chicken retinal ganglion cells in vitro using a microelectrode array. For this purpose, we initially defined spatial resolution and contrast sensitivity in vitro. Two classes of chicken retinal ganglions were found, depending on the linearity of their responses with increasing contrast. Responses generally declined with increasing defocus of the visual stimulus. These responses were well predicted by the modulation transfer function for a diffraction-limited defocused optical system, the first Bessel function. Thus, the studied retinal ganglion cells did not distinguish between a loss of contrast at a given spatial frequency due to reduced contrast of the stimulus pattern or because the pattern was presented out of focus. Furthermore, there was no indication that the retinal ganglion cells responded differently to defocus of either sign, at least for the cells that were recorded in this study.

Origin and Function of Tuning Diversity in Macaque Visual Cortex.

PubMed

Goris, Robbe L T; Simoncelli, Eero P; Movshon, J Anthony

2015-11-18

Neurons in visual cortex vary in their orientation selectivity. We measured responses of V1 and V2 cells to orientation mixtures and fit them with a model whose stimulus selectivity arises from the combined effects of filtering, suppression, and response nonlinearity. The model explains the diversity of orientation selectivity with neuron-to-neuron variability in all three mechanisms, of which variability in the orientation bandwidth of linear filtering is the most important. The model also accounts for the cells' diversity of spatial frequency selectivity. Tuning diversity is matched to the needs of visual encoding. The orientation content found in natural scenes is diverse, and neurons with different selectivities are adapted to different stimulus configurations. Single orientations are better encoded by highly selective neurons, while orientation mixtures are better encoded by less selective neurons. A diverse population of neurons therefore provides better overall discrimination capabilities for natural images than any homogeneous population. Copyright © 2015 Elsevier Inc. All rights reserved.

Muscarinic Acetylcholine Receptor Localization and Activation Effects on Ganglion Response Properties

PubMed Central

Renna, Jordan M.; Amthor, Franklin R.; Keyser, Kent T.

2010-01-01

Purpose. The activation and blockade of muscarinic acetylcholine receptors (mAChRs) affects retinal ganglion cell light responses and firing rates. This study was undertaken to identify the full complement of mAChRs expressed in the rabbit retina and to assess mAChR distribution and the functional effects of mAChR activation and blockade on retinal response properties. Methods. RT-PCR, Western blot analysis, and immunohistochemistry were used to identify the complement and distribution of mAChRs in the rabbit retina. Extracellular electrophysiology was used to determine the effects of the activation or blockade of mAChRs on ganglion cell response properties. Results. RT-PCR of whole neural retina resulted in the amplification of mRNA transcripts for the m1 to m5 mAChR subtypes. Western blot and immunohistochemical analyses confirmed that all five mAChR subtypes were expressed by subpopulations of bipolar, amacrine, and ganglion cells in the rabbit retina, including subsets of cells in cholinergic and glycinergic circuits. Nonspecific muscarinic activation and blockade resulted in the class-specific modulation of maintained ganglion cell firing rates and light responses. Conclusions. The expression of mAChR subtypes on subsets of bipolar, amacrine, and ganglion cells provides a substrate for both enhancement and suppression of retinal responses via activation by cholinergic agents. Thus, the muscarinic cholinergic system in the retina may contribute to the modulation of complex stimuli. Understanding the distribution and function of mAChRs in the retina has the potential to provide important insights into the visual changes that are caused by decreased ACh in the retinas of Alzheimer's patients and the potential visual effects of anticholinergic treatments for ocular diseases. PMID:20042645

Orientation-selective Responses in the Mouse Lateral Geniculate Nucleus

PubMed Central

Zhao, Xinyu; Chen, Hui; Liu, Xiaorong

2013-01-01

The dorsal lateral geniculate nucleus (dLGN) receives visual information from the retina and transmits it to the cortex. In this study, we made extracellular recordings in the dLGN of both anesthetized and awake mice, and found that a surprisingly high proportion of cells were selective for stimulus orientation. The orientation selectivity of dLGN cells was unchanged after silencing the visual cortex pharmacologically, indicating that it is not due to cortical feedback. The orientation tuning of some dLGN cells correlated with their elongated receptive fields, while in others orientation selectivity was observed despite the fact that their receptive fields were circular, suggesting that their retinal input might already be orientation selective. Consistently, we revealed orientation/axis-selective ganglion cells in the mouse retina using multielectrode arrays in an in vitro preparation. Furthermore, the orientation tuning of dLGN cells was largely maintained at different stimulus contrasts, which could be sufficiently explained by a simple linear feedforward model. We also compared the degree of orientation selectivity in different visual structures under the same recording condition. Compared with the dLGN, orientation selectivity is greatly improved in the visual cortex, but is similar in the superior colliculus, another major retinal target. Together, our results demonstrate prominent orientation selectivity in the mouse dLGN, which may potentially contribute to visual processing in the cortex. PMID:23904611

Endothelial Ca2+ oscillations reflect VEGFR signaling-regulated angiogenic capacity in vivo

PubMed Central

Yokota, Yasuhiro; Nakajima, Hiroyuki; Wakayama, Yuki; Muto, Akira; Kawakami, Koichi; Fukuhara, Shigetomo; Mochizuki, Naoki

2015-01-01

Sprouting angiogenesis is a well-coordinated process controlled by multiple extracellular inputs, including vascular endothelial growth factor (VEGF). However, little is known about when and how individual endothelial cell (EC) responds to angiogenic inputs in vivo. Here, we visualized endothelial Ca2+ dynamics in zebrafish and found that intracellular Ca2+ oscillations occurred in ECs exhibiting angiogenic behavior. Ca2+ oscillations depended upon VEGF receptor-2 (Vegfr2) and Vegfr3 in ECs budding from the dorsal aorta (DA) and posterior cardinal vein, respectively. Thus, visualizing Ca2+ oscillations allowed us to monitor EC responses to angiogenic cues. Vegfr-dependent Ca2+ oscillations occurred in migrating tip cells as well as stalk cells budding from the DA. We investigated how Dll4/Notch signaling regulates endothelial Ca2+ oscillations and found that it was required for the selection of single stalk cell as well as tip cell. Thus, we captured spatio-temporal Ca2+ dynamics during sprouting angiogenesis, as a result of cellular responses to angiogenic inputs. DOI: http://dx.doi.org/10.7554/eLife.08817.001 PMID:26588168

The neurophysiology of figure-ground segregation in primary visual cortex.

PubMed

Lamme, V A

1995-02-01

The activity of neurons in the primary visual cortex of the awake macaque monkey was recorded while the animals were viewing full screen arrays of either oriented line segments or moving random dots. A square patch of the screen was made to perceptually pop out as a circumscribed figure by virtue of differences between the orientation or the direction of motion of the texture elements within that patch and the surround. The animals were trained to identify the figure patches by making saccadic eye movements towards their positions. Almost every cell gave a significantly larger response to elements belonging to the figure than to similar elements belonging to the background. The figure-ground response enhancement was present along the entire extent of the patch and was absent as soon as the receptive field was outside the patch. The strength of the effect had no relation with classical receptive field properties like orientation or direction selectivity or receptive field size. The response enhancement had a latency of 30-40 msec relative to the onset of the neuronal response itself. The results show that context modulation within primary visual cortex has a highly sophisticated nature, putting the image features the cells are responding to into their fully evaluated perceptual context.

Modeling the Time-Course of Responses for the Border Ownership Selectivity Based on the Integration of Feedforward Signals and Visual Cortical Interactions

PubMed Central

Wagatsuma, Nobuhiko; Sakai, Ko

2017-01-01

Border ownership (BO) indicates which side of a contour owns a border, and it plays a fundamental role in figure-ground segregation. The majority of neurons in V2 and V4 areas of monkeys exhibit BO selectivity. A physiological work reported that the responses of BO-selective cells show a rapid transition when a presented square is flipped along its classical receptive field (CRF) so that the opposite BO is presented, whereas the transition is significantly slower when a square with a clear BO is replaced by an ambiguous edge, e.g., when the square is enlarged greatly. The rapid transition seemed to reflect the influence of feedforward processing on BO selectivity. Herein, we investigated the role of feedforward signals and cortical interactions for time-courses in BO-selective cells by modeling a visual cortical network comprising V1, V2, and posterior parietal (PP) modules. In our computational model, the recurrent pathways among these modules gradually established the visual progress and the BO assignments. Feedforward inputs mainly determined the activities of these modules. Surrounding suppression/facilitation of early-level areas modulates the activities of V2 cells to provide BO signals. Weak feedback signals from the PP module enhanced the contrast gain extracted in V1, which underlies the attentional modulation of BO signals. Model simulations exhibited time-courses depending on the BO ambiguity, which were caused by the integration delay of V1 and V2 cells and the local inhibition therein given the difference in input stimulus. However, our model did not fully explain the characteristics of crucially slow transition: the responses of BO-selective physiological cells indicated the persistent activation several times longer than that of our model after the replacement with the ambiguous edge. Furthermore, the time-course of BO-selective model cells replicated the attentional modulation of response time in human psychophysical experiments. These attentional modulations for time-courses were induced by selective enhancement of early-level features due to interactions between V1 and PP. Our proposed model suggests fundamental roles of surrounding suppression/facilitation based on feedforward inputs as well as the interactions between early and parietal visual areas with respect to the ambiguity dependence of the neural dynamics in intermediate-level vision. PMID:28163688

Modeling the Time-Course of Responses for the Border Ownership Selectivity Based on the Integration of Feedforward Signals and Visual Cortical Interactions.

PubMed

Wagatsuma, Nobuhiko; Sakai, Ko

2016-01-01

Border ownership (BO) indicates which side of a contour owns a border, and it plays a fundamental role in figure-ground segregation. The majority of neurons in V2 and V4 areas of monkeys exhibit BO selectivity. A physiological work reported that the responses of BO-selective cells show a rapid transition when a presented square is flipped along its classical receptive field (CRF) so that the opposite BO is presented, whereas the transition is significantly slower when a square with a clear BO is replaced by an ambiguous edge, e.g., when the square is enlarged greatly. The rapid transition seemed to reflect the influence of feedforward processing on BO selectivity. Herein, we investigated the role of feedforward signals and cortical interactions for time-courses in BO-selective cells by modeling a visual cortical network comprising V1, V2, and posterior parietal (PP) modules. In our computational model, the recurrent pathways among these modules gradually established the visual progress and the BO assignments. Feedforward inputs mainly determined the activities of these modules. Surrounding suppression/facilitation of early-level areas modulates the activities of V2 cells to provide BO signals. Weak feedback signals from the PP module enhanced the contrast gain extracted in V1, which underlies the attentional modulation of BO signals. Model simulations exhibited time-courses depending on the BO ambiguity, which were caused by the integration delay of V1 and V2 cells and the local inhibition therein given the difference in input stimulus. However, our model did not fully explain the characteristics of crucially slow transition: the responses of BO-selective physiological cells indicated the persistent activation several times longer than that of our model after the replacement with the ambiguous edge. Furthermore, the time-course of BO-selective model cells replicated the attentional modulation of response time in human psychophysical experiments. These attentional modulations for time-courses were induced by selective enhancement of early-level features due to interactions between V1 and PP. Our proposed model suggests fundamental roles of surrounding suppression/facilitation based on feedforward inputs as well as the interactions between early and parietal visual areas with respect to the ambiguity dependence of the neural dynamics in intermediate-level vision.

Are neural correlates of visual consciousness retinotopic?

PubMed

ffytche, Dominic H; Pins, Delphine

2003-11-14

Some visual neurons code what we see, their defining characteristic being a response profile which mirrors conscious percepts rather than veridical sensory attributes. One issue yet to be resolved is whether, within a given cortical area, conscious visual perception relates to diffuse activity across the entire population of such cells or focal activity within the sub-population mapping the location of the perceived stimulus. Here we investigate the issue in the human brain with fMRI, using a threshold stimulation technique to dissociate perceptual from non-perceptual activity. Our results point to a retinotopic organisation of perceptual activity in early visual areas, with independent perceptual activations for different regions of visual space.

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel.

PubMed

Bolgioni, Amanda F; Vittoria, Marc A; Ganem, Neil J

2018-05-14

Live-cell imaging is a powerful technique that can be used to directly visualize biological phenomena in single cells over extended periods of time. Over the past decade, new and innovative technologies have greatly enhanced the practicality of live-cell imaging. Cells can now be kept in focus and continuously imaged over several days while maintained under 37 °C and 5% CO2 cell culture conditions. Moreover, multiple fields of view representing different experimental conditions can be acquired simultaneously, thus providing high-throughput experimental data. Live-cell imaging provides a significant advantage over fixed-cell imaging by allowing for the direct visualization and temporal quantitation of dynamic cellular events. Live-cell imaging can also identify variation in the behavior of single cells that would otherwise have been missed using population-based assays. Here, we describe live-cell imaging protocols to assess cell fate decisions following treatment with the anti-mitotic drug paclitaxel. We demonstrate methods to visualize whether mitotically arrested cells die directly from mitosis or slip back into interphase. We also describe how the fluorescent ubiquitination-based cell cycle indicator (FUCCI) system can be used to assess the fraction of interphase cells born from mitotic slippage that are capable of re-entering the cell cycle. Finally, we describe a live-cell imaging method to identify nuclear envelope rupture events.

Four alpha ganglion cell types in mouse retina: Function, structure, and molecular signatures

PubMed Central

Sanes, Joshua R.

2017-01-01

The retina communicates with the brain using ≥30 parallel channels, each carried by axons of distinct types of retinal ganglion cells. In every mammalian retina one finds so-called "alpha" ganglion cells (αRGCs), identified by their large cell bodies, stout axons, wide and mono-stratified dendritic fields, and high levels of neurofilament protein. In the mouse, three αRGC types have been described based on responses to light steps: On-sustained, Off-sustained, and Off-transient. Here we employed a transgenic mouse line that labels αRGCs in the live retina, allowing systematic targeted recordings. We characterize the three known types and identify a fourth, with On-transient responses. All four αRGC types share basic aspects of visual signaling, including a large receptive field center, a weak antagonistic surround, and absence of any direction selectivity. They also share a distinctive waveform of the action potential, faster than that of other RGC types. Morphologically, they differ in the level of dendritic stratification within the IPL, which accounts for their response properties. Molecularly, each type has a distinct signature. A comparison across mammals suggests a common theme, in which four large-bodied ganglion cell types split the visual signal into four channels arranged symmetrically with respect to polarity and kinetics. PMID:28753612

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MedlinePlus

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Correspondence between visual and electrical input filters of ON and OFF mouse retinal ganglion cells

NASA Astrophysics Data System (ADS)

Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

2017-08-01

Objective. Over the past two decades retinal prostheses have made major strides in restoring functional vision to patients blinded by diseases such as retinitis pigmentosa. Presently, implants use single pulses to activate the retina. Though this stimulation paradigm has proved beneficial to patients, an unresolved problem is the inability to selectively stimulate the on and off visual pathways. To this end our goal was to test, using white noise, voltage-controlled, cathodic, monophasic pulse stimulation, whether different retinal ganglion cell (RGC) types in the wild type retina have different electrical input filters. This is an important precursor to addressing pathway-selective stimulation. Approach. Using full-field visual flash and electrical and visual Gaussian noise stimulation, combined with the technique of spike-triggered averaging (STA), we calculate the electrical and visual input filters for different types of RGCs (classified as on, off or on-off based on their response to the flash stimuli). Main results. Examining the STAs, we found that the spiking activity of on cells during electrical stimulation correlates with a decrease in the voltage magnitude preceding a spike, while the spiking activity of off cells correlates with an increase in the voltage preceding a spike. No electrical preference was found for on-off cells. Comparing STAs of wild type and rd10 mice revealed narrower electrical STA deflections with shorter latencies in rd10. Significance. This study is the first comparison of visual cell types and their corresponding temporal electrical input filters in the retina. The altered input filters in degenerated rd10 retinas are consistent with photoreceptor stimulation underlying visual type-specific electrical STA shapes in wild type retina. It is therefore conceivable that existing implants could target partially degenerated photoreceptors that have only lost their outer segments, but not somas, to selectively activate the on and off visual pathways.

Relationship between cortical state and spiking activity in the lateral geniculate nucleus of marmosets

PubMed Central

Pietersen, Alexander N.J.; Cheong, Soon Keen; Munn, Brandon; Gong, Pulin; Solomon, Samuel G.

2017-01-01

Key points How parallel are the primate visual pathways? In the present study, we demonstrate that parallel visual pathways in the dorsal lateral geniculate nucleus (LGN) show distinct patterns of interaction with rhythmic activity in the primary visual cortex (V1).In the V1 of anaesthetized marmosets, the EEG frequency spectrum undergoes transient changes that are characterized by fluctuations in delta‐band EEG power.We show that, on multisecond timescales, spiking activity in an evolutionary primitive (koniocellular) LGN pathway is specifically linked to these slow EEG spectrum changes. By contrast, on subsecond (delta frequency) timescales, cortical oscillations can entrain spiking activity throughout the entire LGN.Our results are consistent with the hypothesis that, in waking animals, the koniocellular pathway selectively participates in brain circuits controlling vigilance and attention. Abstract The major afferent cortical pathway in the visual system passes through the dorsal lateral geniculate nucleus (LGN), where nerve signals originating in the eye can first interact with brain circuits regulating visual processing, vigilance and attention. In the present study, we investigated how ongoing and visually driven activity in magnocellular (M), parvocellular (P) and koniocellular (K) layers of the LGN are related to cortical state. We recorded extracellular spiking activity in the LGN simultaneously with local field potentials (LFP) in primary visual cortex, in sufentanil‐anaesthetized marmoset monkeys. We found that asynchronous cortical states (marked by low power in delta‐band LFPs) are linked to high spike rates in K cells (but not P cells or M cells), on multisecond timescales. Cortical asynchrony precedes the increases in K cell spike rates by 1–3 s, implying causality. At subsecond timescales, the spiking activity in many cells of all (M, P and K) classes is phase‐locked to delta waves in the cortical LFP, and more cells are phase‐locked during synchronous cortical states than during asynchronous cortical states. The switch from low‐to‐high spike rates in K cells does not degrade their visual signalling capacity. By contrast, during asynchronous cortical states, the fidelity of visual signals transmitted by K cells is improved, probably because K cell responses become less rectified. Overall, the data show that slow fluctuations in cortical state are selectively linked to K pathway spiking activity, whereas delta‐frequency cortical oscillations entrain spiking activity throughout the entire LGN, in anaesthetized marmosets. PMID:28116750

Live fate-mapping of joint-associated fibroblasts visualizes expansion of cell contributions during zebrafish fin regeneration.

PubMed

Tornini, Valerie A; Thompson, John D; Allen, Raymond L; Poss, Kenneth D

2017-08-15

The blastema is a mass of progenitor cells responsible for regeneration of amputated salamander limbs and fish fins. Previous studies have indicated that resident cell sources producing the blastema contribute lineage-restricted progeny to regenerating tissue. However, these studies have labeled general cell types rather than granular cell subpopulations, and they do not explain the developmental transitions that must occur for distal structures to arise from cells with proximal identities in the appendage stump. Here, we find that regulatory sequences of tph1b , which encodes an enzyme that synthesizes serotonin, mark a subpopulation of fibroblast-like cells restricted to the joints of uninjured adult zebrafish fins. Amputation stimulates serotonin production in regenerating fin fibroblasts, yet targeted tph1b mutations abrogating this response do not disrupt fin regeneration. In uninjured animals, tph1b -expressing cells contribute fibroblast progeny that remain restricted to joints throughout life. By contrast, upon amputation, tph1b + joint cells give rise to fibroblasts that distribute across the entire lengths of regenerating fin rays. Our experiments visualize and quantify how incorporation into an appendage blastema broadens the progeny contributions of a cellular subpopulation that normally has proximodistal restrictions. © 2017. Published by The Company of Biologists Ltd.

Corticostriatal and corticotectal neurons in area 6 of the cat during fixation and eye movements.

PubMed

Weyand, T G; Gafka, A C

1998-01-01

We studied the visuomotor properties of 54 corticostriatal (CS) and 38 corticotectal (CT) neurons in a region of area 6 that largely corresponds to the cat's frontal eye fields in five cats trained to do simple oculomotor tasks. Overall, these cells were similar to the general population of area 6 neurons described in the previous paper (Weyand & Gafka, 1998), with very few showing pre-saccadic activity. Likewise, CS and CT cells were similar to each other, although only CS cells showed activity exclusively related to the delivery of the reward and CT cells were more likely to be active during saccades. Variability in visual response latencies and the observation that some cells showed initial visual suppression suggest CS and CT cells reflect the output of a variety of intracortical circuits. Despite similar response properties and overlapping laminar origin, CS and CT circuits appear largely independent. Among 32 cells that we could electrically activate (either synaptically or antidromically) from the superior colliculus, only two could also be activated from stimulating electrodes in the striatum. Similarly, 23 of 25 cells electrically activated from the striatum could not be activated from the superior colliculus. Although few of these efferent cells exhibited pre-motor activity, many exhibit properties that could contribute to gaze control.

Method and apparatus for measuring areas of photoelectric cells and photoelectric cell performance parameters

DOEpatents

Osterwald, C.R.; Emery, K.A.

1984-05-29

A laser scanning system for scanning the surface of photovoltaic cell in a precise, stepped raster pattern includes electric current detecting and measuring equipment for sensing the current response of the scanned cell to the laser beam at each stepped irradiated spot or pixel on the cell surface. A computer is used to control and monitor the raster position of the laser scan as well as monitoring the corresponding current responses, storing this data, operating on it, and for feeding the data to a graphical plotter for producing a visual, color-coded image of the current response of the cell to the laser scan. A translation platform driven by stepper motors in precise X and Y distances holds and rasters the cell being scanned under a stationary spot-focused laser beam.

Method and apparatus for measuring areas of photoelectric cells and photoelectric cell performance parameters

DOEpatents

Osterwald, Carl R.; Emery, Keith A.

1987-01-01

A laser scanning system for scanning the surface of a photovoltaic cell in a precise, stepped raster pattern includes electric current detecting and measuring equipment for sensing the current response of the scanned cell to the laser beam at each stepped irradiated spot or pixel on the cell surface. A computer is used to control and monitor the raster position of the laser scan as well as monitoring the corresponding current responses, storing this data, operating on it, and for feeding the data to a graphic plotter for producing a visual, color-coded image of the current response of the cell to the laser scan. A translation platform driven by stepper motors in precise X and Y distances holds and rasters the cell being scanned under a stationary spot-focused laser beam.

Visualization of glucagon secretion from pancreatic α cells by bioluminescence video microscopy: Identification of secretion sites in the intercellular contact regions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yokawa, Satoru; School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650; Suzuki, Takahiro

We have firstly visualized glucagon secretion using a method of video-rate bioluminescence imaging. The fusion protein of proglucagon and Gaussia luciferase (PGCG-GLase) was used as a reporter to detect glucagon secretion and was efficiently expressed in mouse pancreatic α cells (αTC1.6) using a preferred human codon-optimized gene. In the culture medium of the cells expressing PGCG-GLase, luminescence activity determined with a luminometer was increased with low glucose stimulation and KCl-induced depolarization, as observed for glucagon secretion. From immunochemical analyses, PGCG-GLase stably expressed in clonal αTC1.6 cells was correctly processed and released by secretory granules. Luminescence signals of the secreted PGCG-GLase frommore » the stable cells were visualized by video-rate bioluminescence microscopy. The video images showed an increase in glucagon secretion from clustered cells in response to stimulation by KCl. The secretory events were observed frequently at the intercellular contact regions. Thus, the localization and frequency of glucagon secretion might be regulated by cell-cell adhesion. - Highlights: • The fused protein of proglucagon to Gaussia luciferase was used as a reporter. • The fusion protein was highly expressed using a preferred human-codon optimized gene. • Glucagon secretion stimulated by depolarization was determined by luminescence. • Glucagon secretion in α cells was visualized by bioluminescence imaging. • Glucagon secretion sites were localized in the intercellular contact regions.« less

Active listening impairs visual perception and selectivity: an ERP study of auditory dual-task costs on visual attention.

PubMed

Gherri, Elena; Eimer, Martin

2011-04-01

The ability to drive safely is disrupted by cell phone conversations, and this has been attributed to a diversion of attention from the visual environment. We employed behavioral and ERP measures to study whether the attentive processing of spoken messages is, in itself, sufficient to produce visual-attentional deficits. Participants searched for visual targets defined by a unique feature (Experiment 1) or feature conjunction (Experiment 2), and simultaneously listened to narrated text passages that had to be recalled later (encoding condition), or heard backward-played speech sounds that could be ignored (control condition). Responses to targets were slower in the encoding condition, and ERPs revealed that the visual processing of search arrays and the attentional selection of target stimuli were less efficient in the encoding relative to the control condition. Results demonstrate that the attentional processing of visual information is impaired when concurrent spoken messages are encoded and maintained, in line with cross-modal links in selective attention, but inconsistent with the view that attentional resources are modality-specific. The distraction of visual attention by active listening could contribute to the adverse effects of cell phone use on driving performance.

Mechanisms of Neuronal Computation in Mammalian Visual Cortex

PubMed Central

Priebe, Nicholas J.; Ferster, David

2012-01-01

Orientation selectivity in the primary visual cortex (V1) is a receptive field property that is at once simple enough to make it amenable to experimental and theoretical approaches and yet complex enough to represent a significant transformation in the representation of the visual image. As a result, V1 has become an area of choice for studying cortical computation and its underlying mechanisms. Here we consider the receptive field properties of the simple cells in cat V1—the cells that receive direct input from thalamic relay cells—and explore how these properties, many of which are highly nonlinear, arise. We have found that many receptive field properties of V1 simple cells fall directly out of Hubel and Wiesel’s feedforward model when the model incorporates realistic neuronal and synaptic mechanisms, including threshold, synaptic depression, response variability, and the membrane time constant. PMID:22841306

Functional implications of orientation maps in primary visual cortex

NASA Astrophysics Data System (ADS)

Koch, Erin; Jin, Jianzhong; Alonso, Jose M.; Zaidi, Qasim

2016-11-01

Stimulus orientation in the primary visual cortex of primates and carnivores is mapped as iso-orientation domains radiating from pinwheel centres, where orientation preferences of neighbouring cells change circularly. Whether this orientation map has a function is currently debated, because many mammals, such as rodents, do not have such maps. Here we show that two fundamental properties of visual cortical responses, contrast saturation and cross-orientation suppression, are stronger within cat iso-orientation domains than at pinwheel centres. These differences develop when excitation (not normalization) from neighbouring oriented neurons is applied to different cortical orientation domains and then balanced by inhibition from un-oriented neurons. The functions of the pinwheel mosaic emerge from these local intra-cortical computations: Narrower tuning, greater cross-orientation suppression and higher contrast gain of iso-orientation cells facilitate extraction of object contours from images, whereas broader tuning, greater linearity and less suppression of pinwheel cells generate selectivity for surface patterns and textures.

Macaque Parieto-Insular Vestibular Cortex: Responses to self-motion and optic flow

PubMed Central

Chen, Aihua; DeAngelis, Gregory C.; Angelaki, Dora E.

2011-01-01

The parieto-insular vestibular cortex (PIVC) is thought to contain an important representation of vestibular information. Here we describe responses of macaque PIVC neurons to three-dimensional (3D) vestibular and optic flow stimulation. We found robust vestibular responses to both translational and rotational stimuli in the retroinsular (Ri) and adjacent secondary somatosensory (S2) cortices. PIVC neurons did not respond to optic flow stimulation, and vestibular responses were similar in darkness and during visual fixation. Cells in the upper bank and tip of the lateral sulcus (Ri and S2) responded to sinusoidal vestibular stimuli with modulation at the first harmonic frequency, and were directionally tuned. Cells in the lower bank of the lateral sulcus (mostly Ri) often modulated at the second harmonic frequency, and showed either bimodal spatial tuning or no tuning at all. All directions of 3D motion were represented in PIVC, with direction preferences distributed roughly uniformly for translation, but showing a preference for roll rotation. Spatio-temporal profiles of responses to translation revealed that half of PIVC cells followed the linear velocity profile of the stimulus, one-quarter carried signals related to linear acceleration (in the form of two peaks of direction selectivity separated in time), and a few neurons followed the derivative of linear acceleration (jerk). In contrast, mainly velocity-coding cells were found in response to rotation. Thus, PIVC comprises a large functional region in macaque areas Ri and S2, with robust responses to 3D rotation and translation, but is unlikely to play a significant role in visual/vestibular integration for self-motion perception. PMID:20181599

The projective field of a retinal amacrine cell

PubMed Central

de Vries, Saskia E. J.; Baccus, Stephen A.; Meister, Markus

2011-01-01

In sensory systems, neurons are generally characterized by their receptive field, namely the sensitivity to activity patterns at the circuit's input. To assess the neuron's role in the system, one must also know its projective field, namely the spatio-temporal effects the neuron exerts on all the circuit's outputs. We studied both the receptive and projective fields of an amacrine interneuron in the salamander retina. This amacrine type has a sustained OFF response with a small receptive field, but its output projects over a much larger region. Unlike other amacrines, this type is remarkably promiscuous and affects nearly every ganglion cell within reach of its dendrites. Its activity modulates the sensitivity of visual responses in ganglion cells, while leaving their kinetics unchanged. The projective field displays a center-surround structure: Depolarizing a single amacrine suppresses the visual sensitivity of ganglion cells nearby, and enhances it at greater distances. This change in sign is seen even within the receptive field of one ganglion cell; thus the modulation occurs presynaptically on bipolar cell terminals, most likely via GABAB receptors. Such an antagonistic projective field could contribute to the retina's mechanisms for predictive coding. PMID:21653863

Multimap formation in visual cortex

PubMed Central

Jain, Rishabh; Millin, Rachel; Mel, Bartlett W.

2015-01-01

An extrastriate visual area such as V2 or V4 contains neurons selective for a multitude of complex shapes, all sharing a common topographic organization. Simultaneously developing multiple interdigitated maps—hereafter a “multimap”—is challenging in that neurons must compete to generate a diversity of response types locally, while cooperating with their dispersed same-type neighbors to achieve uniform visual field coverage for their response type at all orientations, scales, etc. Previously proposed map development schemes have relied on smooth spatial interaction functions to establish both topography and columnar organization, but by locally homogenizing cells' response properties, local smoothing mechanisms effectively rule out multimap formation. We found in computer simulations that the key requirements for multimap development are that neurons are enabled for plasticity only within highly active regions of cortex designated “learning eligibility regions” (LERs), but within an LER, each cell's learning rate is determined only by its activity level with no dependence on location. We show that a hybrid developmental rule that combines spatial and activity-dependent learning criteria in this way successfully produces multimaps when the input stream contains multiple distinct feature types, or in the degenerate case of a single feature type, produces a V1-like map with “salt-and-pepper” structure. Our results support the hypothesis that cortical maps containing a fine mixture of different response types, whether in monkey extrastriate cortex, mouse V1 or elsewhere in the cortex, rather than signaling a breakdown of map formation mechanisms at the fine scale, are a product of a generic cortical developmental scheme designed to map cells with a diversity of response properties across a shared topographic space. PMID:26641946

Homeostatic plasticity shapes cell-type-specific wiring in the retina

PubMed Central

Tien, Nai-Wen; Soto, Florentina; Kerschensteiner, Daniel

2017-01-01

SUMMARY Convergent input from different presynaptic partners shapes the responses of postsynaptic neurons. Whether developing postsynaptic neurons establish connections with each presynaptic partner independently, or balance inputs to attain specific responses is unclear. Retinal ganglion cells (RGCs) receive convergent input from bipolar cell types with different contrast responses and temporal tuning. Here, using optogenetic activation and pharmacogenetic silencing, we found that type 6 bipolar cells (B6) dominate excitatory input to ONα-RGCs. We generated mice in which B6 cells were selectively removed from developing circuits (B6-DTA). In B6-DTA mice, ONα-RGCs adjusted connectivity with other bipolar cells in a cell-type-specific manner. They recruited new partners, increased synapses with some existing partners, and maintained constant input from others. Patch clamp recordings revealed that anatomical rewiring precisely preserved contrast- and temporal frequency response functions of ONα-RGCs, indicating that homeostatic plasticity shapes cell-type-specific wiring in the developing retina to stabilize visual information sent to the brain. PMID:28457596

Restoration of vision after transplantation of photoreceptors.

PubMed

Pearson, R A; Barber, A C; Rizzi, M; Hippert, C; Xue, T; West, E L; Duran, Y; Smith, A J; Chuang, J Z; Azam, S A; Luhmann, U F O; Benucci, A; Sung, C H; Bainbridge, J W; Carandini, M; Yau, K-W; Sowden, J C; Ali, R R

2012-05-03

Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1−/− mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.

In Vivo Voltage-Sensitive Dye Study of Lateral Spreading of Cortical Activity in Mouse Primary Visual Cortex Induced by a Current Impulse

PubMed Central

Fehérvári, Tamás Dávid; Sawai, Hajime; Yagi, Tetsuya

2015-01-01

In the mammalian primary visual cortex (V1), lateral spreading of excitatory potentials is believed to be involved in spatial integrative functions, but the underlying cortical mechanism is not well understood. Visually-evoked population-level responses have been shown to propagate beyond the V1 initial activation site in mouse, similar to higher mammals. Visually-evoked responses are, however, affected by neuronal circuits prior to V1 (retina, LGN), making the separate analysis of V1 difficult. Intracortical stimulation eliminates these initial processing steps. We used in vivo RH1691 voltage-sensitive dye (VSD) imaging and intracortical microstimulation in adult C57BL/6 mice to elucidate the spatiotemporal properties of population-level signal spreading in V1 cortical circuits. The evoked response was qualitatively similar to that measured in single-cell electrophysiological experiments in rodents: a fast transient fluorescence peak followed by a fast and a slow decrease or hyperpolarization, similar to EPSP and fast and slow IPSPs in single cells. The early cortical response expanded at speeds commensurate with long horizontal projections (at 5% of the peak maximum, 0.08–0.15 m/s) however, the bulk of the VSD signal propagated slowly (at half-peak maximum, 0.05–0.08 m/s) suggesting an important role of regenerative multisynaptic transmission through short horizontal connections in V1 spatial integrative functions. We also found a tendency for a widespread and fast cortical response suppression in V1, which was eliminated by GABAA-antagonists gabazine and bicuculline methiodide. Our results help understand the neuronal circuitry involved in lateral spreading in V1. PMID:26230520

The sequence of cortical activity inferred by response latency variability in the human ventral pathway of face processing.

PubMed

Lin, Jo-Fu Lotus; Silva-Pereyra, Juan; Chou, Chih-Che; Lin, Fa-Hsuan

2018-04-11

Variability in neuronal response latency has been typically considered caused by random noise. Previous studies of single cells and large neuronal populations have shown that the temporal variability tends to increase along the visual pathway. Inspired by these previous studies, we hypothesized that functional areas at later stages in the visual pathway of face processing would have larger variability in the response latency. To test this hypothesis, we used magnetoencephalographic data collected when subjects were presented with images of human faces. Faces are known to elicit a sequence of activity from the primary visual cortex to the fusiform gyrus. Our results revealed that the fusiform gyrus showed larger variability in the response latency compared to the calcarine fissure. Dynamic and spectral analyses of the latency variability indicated that the response latency in the fusiform gyrus was more variable than in the calcarine fissure between 70 ms and 200 ms after the stimulus onset and between 4 Hz and 40 Hz, respectively. The sequential processing of face information from the calcarine sulcus to the fusiform sulcus was more reliably detected based on sizes of the response variability than instants of the maximal response peaks. With two areas in the ventral visual pathway, we show that the variability in response latency across brain areas can be used to infer the sequence of cortical activity.

Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity.

PubMed

Ueno, Akiko; Omori, Yoshihiro; Sugita, Yuko; Watanabe, Satoshi; Chaya, Taro; Kozuka, Takashi; Kon, Tetsuo; Yoshida, Satoyo; Matsushita, Kenji; Kuwahara, Ryusuke; Kajimura, Naoko; Okada, Yasushi; Furukawa, Takahisa

2018-03-27

In the vertebrate retina, cone photoreceptors play crucial roles in photopic vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells. However, the mechanisms underlying selective synapse formation in the cone photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a leucine-rich transmembrane protein, localizes to the photoreceptor synaptic terminal and regulates the synaptic connection between cone photoreceptors and cone ON-bipolar cells. Lrit1-deficient retinas exhibit an aberrant morphology of cone photoreceptor pedicles, as well as an impairment of signal transmission from cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6, an ON-bipolar cell-specific glutamate receptor. Additionally, Lrit1-null mice showed visual acuity impairments in their optokinetic responses. These results suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation in cone photoreceptors and is essential for normal visual function. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Coding of spatial attention priorities and object features in the macaque lateral intraparietal cortex.

PubMed

Levichkina, Ekaterina; Saalmann, Yuri B; Vidyasagar, Trichur R

2017-03-01

Primate posterior parietal cortex (PPC) is known to be involved in controlling spatial attention. Neurons in one part of the PPC, the lateral intraparietal area (LIP), show enhanced responses to objects at attended locations. Although many are selective for object features, such as the orientation of a visual stimulus, it is not clear how LIP circuits integrate feature-selective information when providing attentional feedback about behaviorally relevant locations to the visual cortex. We studied the relationship between object feature and spatial attention properties of LIP cells in two macaques by measuring the cells' orientation selectivity and the degree of attentional enhancement while performing a delayed match-to-sample task. Monkeys had to match both the location and orientation of two visual gratings presented separately in time. We found a wide range in orientation selectivity and degree of attentional enhancement among LIP neurons. However, cells with significant attentional enhancement had much less orientation selectivity in their response than cells which showed no significant modulation by attention. Additionally, orientation-selective cells showed working memory activity for their preferred orientation, whereas cells showing attentional enhancement also synchronized with local neuronal activity. These results are consistent with models of selective attention incorporating two stages, where an initial feature-selective process guides a second stage of focal spatial attention. We suggest that LIP contributes to both stages, where the first stage involves orientation-selective LIP cells that support working memory of the relevant feature, and the second stage involves attention-enhanced LIP cells that synchronize to provide feedback on spatial priorities. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Focal damage to macaque photoreceptors produces persistent visual loss

PubMed Central

Strazzeri, Jennifer M.; Hunter, Jennifer J.; Masella, Benjamin D.; Yin, Lu; Fischer, William S.; DiLoreto, David A.; Libby, Richard T.; Williams, David R.; Merigan, William H.

2014-01-01

Insertion of light-gated channels into inner retina neurons restores neural light responses, light evoked potentials, visual optomotor responses and visually-guided maze behavior in mice blinded by retinal degeneration. This method of vision restoration bypasses damaged outer retina, providing stimulation directly to retinal ganglion cells in inner retina. The approach is similar to that of electronic visual protheses, but may offer some advantages, such as avoidance of complex surgery and direct targeting of many thousands of neurons. However, the promise of this technique for restoring human vision remains uncertain because rodent animal models, in which it has been largely developed, are not ideal for evaluating visual perception. On the other hand, psychophysical vision studies in macaque can be used to evaluate different approaches to vision restoration in humans. Furthermore, it has not been possible to test vision restoration in macaques, the optimal model for human-like vision, because there has been no macaque model of outer retina degeneration. In this study, we describe development of a macaque model of photoreceptor degeneration that can in future studies be used to test restoration of perception by visual prostheses. Our results show that perceptual deficits caused by focal light damage are restricted to locations at which photoreceptors are damaged, that optical coherence tomography (OCT) can be used to track such lesions, and that adaptive optics retinal imaging, which we recently used for in vivo recording of ganglion cell function, can be used in future studies to examine these lesions. PMID:24316158

Gamma oscillation maintains stimulus structure-dependent synchronization in cat visual cortex.

PubMed

Samonds, Jason M; Bonds, A B

2005-01-01

Visual cortical cells demonstrate both oscillation and synchronization, although the underlying causes and functional significance of these behaviors remain uncertain. We simultaneously recorded single-unit activity with microelectrode arrays in supragranular layers of area 17 of cats paralyzed and anesthetized with propofol and N(2)O. Rate-normalized autocorrelograms of 24 cells reveal bursting (100%) and gamma oscillation (63%). Renewal density analysis, used to explore the source of oscillation, suggests a contribution from extrinsic influences such as feedback. However, a bursting refractory period, presumably membrane-based, could also encourage oscillatory firing. When we investigated the source of synchronization for 60 cell pairs we found only moderate correlation of synchrony with bursts and oscillation. We did, nonetheless, discover a possible functional role for oscillation. In all cases of cross-correlograms that exhibited oscillation, the strength of the synchrony was maintained throughout the stimulation period. When no oscillation was apparent, 75% of the cell pairs showed decay in their synchronization. The synchrony between cells is strongly dependent on similar response onset latencies. We therefore propose that structured input, which yields tight organization of latency, is a more likely candidate for the source of synchronization than oscillation. The reliable synchrony at response onset could be driven by spatial and temporal correlation of the stimulus that is preserved through the earlier stages of the visual system. Oscillation then contributes to maintenance of the synchrony to enhance reliable transmission of the information for higher cognitive processing.

Binocular disparity tuning and visual-vestibular congruency of multisensory neurons in macaque parietal cortex

PubMed Central

Yang, Yun; Liu, Sheng; Chowdhury, Syed A.; DeAngelis, Gregory C.; Angelaki, Dora E.

2012-01-01

Many neurons in the dorsal medial superior temporal (MSTd) and ventral intraparietal (VIP) areas of the macaque brain are multisensory, responding to both optic flow and vestibular cues to self-motion. The heading tuning of visual and vestibular responses can be either congruent or opposite, but only congruent cells have been implicated in cue integration for heading perception. Because of the geometric properties of motion parallax, however, both congruent and opposite cells could be involved in coding self-motion when observers fixate a world-fixed target during translation, if congruent cells prefer near disparities and opposite cells prefer far disparities. We characterized the binocular disparity selectivity and heading tuning of MSTd and VIP cells using random-dot stimuli. Most (70%) MSTd neurons were disparity-selective with monotonic tuning, and there was no consistent relationship between depth preference and congruency of visual and vestibular heading tuning. One-third of disparity-selective MSTd cells reversed their depth preference for opposite directions of motion (direction-dependent disparity tuning, DDD), but most of these cells were unisensory with no tuning for vestibular stimuli. Inconsistent with previous reports, the direction preferences of most DDD neurons do not reverse with disparity. By comparison to MSTd, VIP contains fewer disparity-selective neurons (41%) and very few DDD cells. On average, VIP neurons also preferred higher speeds and nearer disparities than MSTd cells. Our findings are inconsistent with the hypothesis that visual/vestibular congruency is linked to depth preference, and also suggest that DDD cells are not involved in multisensory integration for heading perception. PMID:22159105

Area 18 of the cat: the first step in processing visual movement information.

PubMed

Orban, G A

1977-01-01

In cats, responses of area 18 neurons to different moving patterns were measured. The influence of three movement parameters--direction, angular velocity, and amplitude of movement--were tested. The results indicate that in area 18 no ideal movement detector exists, but that simple and complex cells each perform complementary operations of primary visual areas, i.e. analysis and detection of movement.

Biochemical, histological and behavioural aspects of visual function during early development of rainbow trout

USGS Publications Warehouse

Carvalho, Paulo S. M.; Noltie, Douglas B.; Tillitt, D.E.

2004-01-01

Retinal structure and concentration of retinoids involved in phototransduction changed during early development of rainbow trout Oncorhynchus mykiss, correlating with improvements in visual function. A test chamber was used to evaluate the presence of optokinetic or optomotor responses and to assess the functionality of the integrated cellular, physiological and biochemical components of the visual system. The results indicated that in rainbow trout optomotor responses start at 10 days post-hatch, and demonstrated for the first time that increases in acuity, sensitivity to low light as well as in motion detection abilities occur from this stage until exogenous feeding starts. The structure of retinal cells such as cone ellipsoids increased in length as photopic visual acuity improved, and rod densities increased concurrently with improvements in scotopic thresholds (2.2 log10 units). An increase in the concentrations of the chromophore all-trans-retinal correlated with improvements of all behavioural measures of visual function during the same developmental phase. ?? 2004 The Fisheries Society of the British Isles.

In vitro interactions between splenocytes and dansylamide dye-embedded nanoparticles detected by flow cytometry

PubMed Central

Nyland, Jennifer F.; Bai, Jennifer J. K.; Katz, Howard E.; Silbergeld, Ellen K.

2009-01-01

Engineered nanoparticles (NPs) possess a range of biological activity. In vitro methods for assessing toxicity and efficacy would be enhanced by simultaneous quantitative information on the behavior of NPs in culture systems and signals of cell response. We have developed a method for visualizing NPs within cells using standard flow cytometric techniques and uniquely designed spherical siloxane NPs with an embedded (covalently bound) dansylamide dye. This method allowed NP visualization without obscuring detection of relevant biomarkers of cell subtype, activation state, and other events relevant to assessing bioactivity. We determined that NPs penetrated cells and induced a range of biological signals consistent with activation and costimulation. These results indicate that NPs may affect cell function at concentrations below those inducing cytotoxicity or apoptosis and demonstrate a novel method to image both localization of NPs and cell-level effects. PMID:19523425

Lack of the Sodium-Driven Chloride Bicarbonate Exchanger NCBE Impairs Visual Function in the Mouse Retina

PubMed Central

Hilgen, Gerrit; Huebner, Antje K.; Tanimoto, Naoyuki; Sothilingam, Vithiyanjali; Seide, Christina; Garrido, Marina Garcia; Schmidt, Karl-Friedrich; Seeliger, Mathias W.; Löwel, Siegrid; Weiler, Reto

2012-01-01

Regulation of ion and pH homeostasis is essential for normal neuronal function. The sodium-driven chloride bicarbonate exchanger NCBE (Slc4a10), a member of the SLC4 family of bicarbonate transporters, uses the transmembrane gradient of sodium to drive cellular net uptake of bicarbonate and to extrude chloride, thereby modulating both intracellular pH (pHi) and chloride concentration ([Cl−]i) in neurons. Here we show that NCBE is strongly expressed in the retina. As GABAA receptors conduct both chloride and bicarbonate, we hypothesized that NCBE may be relevant for GABAergic transmission in the retina. Importantly, we found a differential expression of NCBE in bipolar cells: whereas NCBE was expressed on ON and OFF bipolar cell axon terminals, it only localized to dendrites of OFF bipolar cells. On these compartments, NCBE colocalized with the main neuronal chloride extruder KCC2, which renders GABA hyperpolarizing. NCBE was also expressed in starburst amacrine cells, but was absent from neurons known to depolarize in response to GABA, like horizontal cells. Mice lacking NCBE showed decreased visual acuity and contrast sensitivity in behavioral experiments and smaller b-wave amplitudes and longer latencies in electroretinograms. Ganglion cells from NCBE-deficient mice also showed altered temporal response properties. In summary, our data suggest that NCBE may serve to maintain intracellular chloride and bicarbonate concentration in retinal neurons. Consequently, lack of NCBE in the retina may result in changes in pHi regulation and chloride-dependent inhibition, leading to altered signal transmission and impaired visual function. PMID:23056253

Strabismus and the Oculomotor System: Insights from Macaque Models

PubMed Central

Das, Vallabh E.

2017-01-01

Disrupting binocular vision in infancy leads to strabismus and oftentimes to a variety of associated visual sensory deficits and oculomotor abnormalities. Investigation of this disorder has been aided by the development of various animal models, each of which has advantages and disadvantages. In comparison to studies of binocular visual responses in cortical structures, investigations of neural oculomotor structures that mediate the misalignment and abnormalities of eye movements have been more recent, and these studies have shown that different brain areas are intimately involved in driving several aspects of the strabismic condition, including horizontal misalignment, dissociated deviations, A and V patterns of strabismus, disconjugate eye movements, nystagmus, and fixation switch. The responses of cells in visual and oculomotor areas that potentially drive the sensory deficits and also eye alignment and eye movement abnormalities follow a general theme of disrupted calibration, lower sensitivity, and poorer specificity compared with the normally developed visual oculomotor system. PMID:28532347

Light and the laboratory mouse.

PubMed

Peirson, Stuart N; Brown, Laurence A; Pothecary, Carina A; Benson, Lindsay A; Fisk, Angus S

2018-04-15

Light exerts widespread effects on physiology and behaviour. As well as the widely-appreciated role of light in vision, light also plays a critical role in many non-visual responses, including regulating circadian rhythms, sleep, pupil constriction, heart rate, hormone release and learning and memory. In mammals, responses to light are all mediated via retinal photoreceptors, including the classical rods and cones involved in vision as well as the recently identified melanopsin-expressing photoreceptive retinal ganglion cells (pRGCs). Understanding the effects of light on the laboratory mouse therefore depends upon an appreciation of the physiology of these retinal photoreceptors, including their differing sens itivities to absolute light levels and wavelengths. The signals from these photoreceptors are often integrated, with different responses involving distinct retinal projections, making generalisations challenging. Furthermore, many commonly used laboratory mouse strains carry mutations that affect visual or non-visual physiology, ranging from inherited retinal degeneration to genetic differences in sleep and circadian rhythms. Here we provide an overview of the visual and non-visual systems before discussing practical considerations for the use of light for researchers and animal facility staff working with laboratory mice. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Visually Evoked 3-5 Hz Membrane Potential Oscillations Reduce the Responsiveness of Visual Cortex Neurons in Awake Behaving Mice.

PubMed

Einstein, Michael C; Polack, Pierre-Olivier; Tran, Duy T; Golshani, Peyman

2017-05-17

Low-frequency membrane potential ( V m ) oscillations were once thought to only occur in sleeping and anesthetized states. Recently, low-frequency V m oscillations have been described in inactive awake animals, but it is unclear whether they shape sensory processing in neurons and whether they occur during active awake behavioral states. To answer these questions, we performed two-photon guided whole-cell V m recordings from primary visual cortex layer 2/3 excitatory and inhibitory neurons in awake mice during passive visual stimulation and performance of visual and auditory discrimination tasks. We recorded stereotyped 3-5 Hz V m oscillations where the V m baseline hyperpolarized as the V m underwent high amplitude rhythmic fluctuations lasting 1-2 s in duration. When 3-5 Hz V m oscillations coincided with visual cues, excitatory neuron responses to preferred cues were significantly reduced. Despite this disruption to sensory processing, visual cues were critical for evoking 3-5 Hz V m oscillations when animals performed discrimination tasks and passively viewed drifting grating stimuli. Using pupillometry and animal locomotive speed as indicators of arousal, we found that 3-5 Hz oscillations were not restricted to unaroused states and that they occurred equally in aroused and unaroused states. Therefore, low-frequency V m oscillations play a role in shaping sensory processing in visual cortical neurons, even during active wakefulness and decision making. SIGNIFICANCE STATEMENT A neuron's membrane potential ( V m ) strongly shapes how information is processed in sensory cortices of awake animals. Yet, very little is known about how low-frequency V m oscillations influence sensory processing and whether they occur in aroused awake animals. By performing two-photon guided whole-cell recordings from layer 2/3 excitatory and inhibitory neurons in the visual cortex of awake behaving animals, we found visually evoked stereotyped 3-5 Hz V m oscillations that disrupt excitatory responsiveness to visual stimuli. Moreover, these oscillations occurred when animals were in high and low arousal states as measured by animal speed and pupillometry. These findings show, for the first time, that low-frequency V m oscillations can significantly modulate sensory signal processing, even in awake active animals. Copyright © 2017 the authors 0270-6474/17/375084-15$15.00/0.

Predictive Feedback Can Account for Biphasic Responses in the Lateral Geniculate Nucleus

PubMed Central

Jehee, Janneke F. M.; Ballard, Dana H.

2009-01-01

Biphasic neural response properties, where the optimal stimulus for driving a neural response changes from one stimulus pattern to the opposite stimulus pattern over short periods of time, have been described in several visual areas, including lateral geniculate nucleus (LGN), primary visual cortex (V1), and middle temporal area (MT). We describe a hierarchical model of predictive coding and simulations that capture these temporal variations in neuronal response properties. We focus on the LGN-V1 circuit and find that after training on natural images the model exhibits the brain's LGN-V1 connectivity structure, in which the structure of V1 receptive fields is linked to the spatial alignment and properties of center-surround cells in the LGN. In addition, the spatio-temporal response profile of LGN model neurons is biphasic in structure, resembling the biphasic response structure of neurons in cat LGN. Moreover, the model displays a specific pattern of influence of feedback, where LGN receptive fields that are aligned over a simple cell receptive field zone of the same polarity decrease their responses while neurons of opposite polarity increase their responses with feedback. This phase-reversed pattern of influence was recently observed in neurophysiology. These results corroborate the idea that predictive feedback is a general coding strategy in the brain. PMID:19412529

Modeling for Visual Feature Extraction Using Spiking Neural Networks

NASA Astrophysics Data System (ADS)

Kimura, Ichiro; Kuroe, Yasuaki; Kotera, Hiromichi; Murata, Tomoya

This paper develops models for “visual feature extraction” in biological systems by using “spiking neural network (SNN)”. The SNN is promising for developing the models because the information is encoded and processed by spike trains similar to biological neural networks. Two architectures of SNN are proposed for modeling the directionally selective and the motion parallax cell in neuro-sensory systems and they are trained so as to possess actual biological responses of each cell. To validate the developed models, their representation ability is investigated and their visual feature extraction mechanisms are discussed from the neurophysiological viewpoint. It is expected that this study can be the first step to developing a sensor system similar to the biological systems and also a complementary approach to investigating the function of the brain.

Molecular signaling in live cells studied by FRET

NASA Astrophysics Data System (ADS)

Chien, Shu; Wang, Yingxiao

2011-11-01

Genetically encoded biosensors based on fluorescence resonance energy transfer (FRET) enables visualization of signaling events in live cells with high spatiotemporal resolution. We have used FRET to assess temporal and spatial characteristics for signaling molecules, including tyrosine kinases Src and FAK, small GTPase Rac, calcium, and a membrane-bound matrix metalloproteinase MT1-MMP. Activations of Src and Rac by platelet derived growth factor (PDGF) led to distinct subcellular patterns during cell migration on micropatterned surface, and these two enzymes interact with each other to form a feedback loop with differential regulations at different subcellular locations. We have developed FRET biosensors to monitor FAK activities at rafts vs. non-raft regions of plasma membrane in live cells. In response to cell adhesion on matrix proteins or stimulation by PDGF, the raft-targeting FAK biosensor showed a stronger FRET response than that at non-rafts. The FAK activation at rafts induced by PDGF is mediated by Src. In contrast, the FAK activation at rafts induced by adhesion is independent of Src activity, but rather is essential for Src activation. Thus, Src is upstream to FAK in response to chemical stimulation (PDGF), but FAK is upstream to Src in response to mechanical stimulation (adhesion). A novel biosensor has been developed to dynamically visualize the activity of membrane type-1-matrix metalloproteinase (MT1-MMP), which proteolytically remodels the extracellular matrix. Epidermal growth factor (EGF) directed active MT1-MMP to the leading edge of migrating live cancer cells with local accumulation of EGF receptor via a process dependent on an intact cytoskeletal network. In summary, FRET-based biosensors enable the elucidation of molecular processes and hierarchies underlying spatiotemporal regulation of biological and pathological processes, thus advancing our knowledge on how cells perceive mechanical/chemical cues in space and time to coordinate molecular/cellular functions.

Molecular signaling in live cells studied by FRET

NASA Astrophysics Data System (ADS)

Chien, Shu; Wang, Yingxiao

2012-03-01

Genetically encoded biosensors based on fluorescence resonance energy transfer (FRET) enables visualization of signaling events in live cells with high spatiotemporal resolution. We have used FRET to assess temporal and spatial characteristics for signaling molecules, including tyrosine kinases Src and FAK, small GTPase Rac, calcium, and a membrane-bound matrix metalloproteinase MT1-MMP. Activations of Src and Rac by platelet derived growth factor (PDGF) led to distinct subcellular patterns during cell migration on micropatterned surface, and these two enzymes interact with each other to form a feedback loop with differential regulations at different subcellular locations. We have developed FRET biosensors to monitor FAK activities at rafts vs. non-raft regions of plasma membrane in live cells. In response to cell adhesion on matrix proteins or stimulation by PDGF, the raft-targeting FAK biosensor showed a stronger FRET response than that at non-rafts. The FAK activation at rafts induced by PDGF is mediated by Src. In contrast, the FAK activation at rafts induced by adhesion is independent of Src activity, but rather is essential for Src activation. Thus, Src is upstream to FAK in response to chemical stimulation (PDGF), but FAK is upstream to Src in response to mechanical stimulation (adhesion). A novel biosensor has been developed to dynamically visualize the activity of membrane type-1-matrix metalloproteinase (MT1-MMP), which proteolytically remodels the extracellular matrix. Epidermal growth factor (EGF) directed active MT1-MMP to the leading edge of migrating live cancer cells with local accumulation of EGF receptor via a process dependent on an intact cytoskeletal network. In summary, FRET-based biosensors enable the elucidation of molecular processes and hierarchies underlying spatiotemporal regulation of biological and pathological processes, thus advancing our knowledge on how cells perceive mechanical/chemical cues in space and time to coordinate molecular/cellular functions.

Contrast invariance of orientation tuning in the lateral geniculate nucleus of the feline visual system.

PubMed

Viswanathan, Sivaram; Jayakumar, Jaikishan; Vidyasagar, Trichur R

2015-09-01

Responses of most neurons in the primary visual cortex of mammals are markedly selective for stimulus orientation and their orientation tuning does not vary with changes in stimulus contrast. The basis of such contrast invariance of orientation tuning has been shown to be the higher variability in the response for low-contrast stimuli. Neurons in the lateral geniculate nucleus (LGN), which provides the major visual input to the cortex, have also been shown to have higher variability in their response to low-contrast stimuli. Parallel studies have also long established mild degrees of orientation selectivity in LGN and retinal cells. In our study, we show that contrast invariance of orientation tuning is already present in the LGN. In addition, we show that the variability of spike responses of LGN neurons increases at lower stimulus contrasts, especially for non-preferred orientations. We suggest that such contrast- and orientation-sensitive variability not only explains the contrast invariance observed in the LGN but can also underlie the contrast-invariant orientation tuning seen at the level of the primary visual cortex. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Effects of Antipsychotic Drugs Haloperidol and Clozapine on Visual Responses of Retinal Ganglion Cells in a Rat Model of Retinitis Pigmentosa.

PubMed

Jensen, Ralph J

2016-12-01

In the P23H rat model of retinitis pigmentosa, the dopamine D2 receptor antagonists sulpiride and eticlopride appear to improve visual responses of retinal ganglion cells (RGCs) by increasing light sensitivity of RGCs and transforming abnormal, long-latency ON-center RGCs into OFF-center cells. Antipsychotic drugs are believed to mediate their therapeutic benefits by blocking D2 receptors. This investigation was conducted to test whether haloperidol (a typical antipsychotic drug) and clozapine (an atypical antipsychotic drug) could similarly alter the light responses of RGCs in the P23H rat retina. Extracellular recordings were made from RGCs in isolated P23H rat retinas. Responses of RGCs to flashes of light were evaluated before and during bath application of a drug. Both haloperidol and clozapine increased light sensitivity of RGCs on average by ∼0.3 log unit. For those ON-center RGCs that exhibit an abnormally long-latency response to the onset of a small spot of light, both haloperidol and clozapine brought out a short-latency OFF response and markedly reduced the long-latency ON response. The selective serotonin 5-HT2A antagonist MDL 100907 had similar effects on RGCs. The effects of haloperidol on light responses of RGCs can be explained by its D2 receptor antagonism. The effects of clozapine on light responses of RGCs on the other hand may largely be due to its 5-HT2A receptor antagonism. Overall, the results suggest that antipsychotic drugs may be useful in improving vision in patients with retinitis pigmentosa.

Complementary mechanisms create direction selectivity in the fly

PubMed Central

Haag, Juergen; Arenz, Alexander; Serbe, Etienne; Gabbiani, Fabrizio; Borst, Alexander

2016-01-01

How neurons become sensitive to the direction of visual motion represents a classic example of neural computation. Two alternative mechanisms have been discussed in the literature so far: preferred direction enhancement, by which responses are amplified when stimuli move along the preferred direction of the cell, and null direction suppression, where one signal inhibits the response to the subsequent one when stimuli move along the opposite, i.e. null direction. Along the processing chain in the Drosophila optic lobe, directional responses first appear in T4 and T5 cells. Visually stimulating sequences of individual columns in the optic lobe with a telescope while recording from single T4 neurons, we find both mechanisms at work implemented in different sub-regions of the receptive field. This finding explains the high degree of directional selectivity found already in the fly’s primary motion-sensing neurons and marks an important step in our understanding of elementary motion detection. DOI: http://dx.doi.org/10.7554/eLife.17421.001 PMID:27502554

The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity

PubMed Central

Kim, Yeha; Lim, Soyeon; Ha, Taejeong; Song, You-Hyang; Sohn, Young-In; Park, Dae-Jin; Paik, Sun-Sook; Kim-Kaneyama, Joo-ri; Song, Mi-Ryoung; Leung, Amanda; Levine, Edward M; Kim, In-Beom; Goo, Yong Sook; Lee, Seung-Hee; Kang, Kyung Hwa; Kim, Jin Woo

2017-01-01

The visual responses of vertebrates are sensitive to the overall composition of retinal interneurons including amacrine cells, which tune the activity of the retinal circuitry. The expression of Paired-homeobox 6 (PAX6) is regulated by multiple cis-DNA elements including the intronic α-enhancer, which is active in GABAergic amacrine cell subsets. Here, we report that the transforming growth factor ß1-induced transcript 1 protein (Tgfb1i1) interacts with the LIM domain transcription factors Lhx3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina. Tgfb1i1-/- mice show elevated α-enhancer activity leading to overproduction of Pax6ΔPD isoform that supports the GABAergic amacrine cell fate maintenance. Consequently, the Tgfb1i1-/- mouse retinas show a sustained light response, which becomes more transient in mice with the auto-stimulation-defective Pax6ΔPBS/ΔPBS mutation. Together, we show the antagonistic regulation of the α-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation. DOI: http://dx.doi.org/10.7554/eLife.21303.001 PMID:28139974

Direct activation of the Mauthner cell by electric field pulses drives ultrarapid escape responses

PubMed Central

Tabor, Kathryn M.; Bergeron, Sadie A.; Horstick, Eric J.; Jordan, Diana C.; Aho, Vilma; Porkka-Heiskanen, Tarja; Haspel, Gal

2014-01-01

Rapid escape swims in fish are initiated by the Mauthner cells, giant reticulospinal neurons with unique specializations for swift responses. The Mauthner cells directly activate motoneurons and facilitate predator detection by integrating acoustic, mechanosensory, and visual stimuli. In addition, larval fish show well-coordinated escape responses when exposed to electric field pulses (EFPs). Sensitization of the Mauthner cell by genetic overexpression of the voltage-gated sodium channel SCN5 increased EFP responsiveness, whereas Mauthner ablation with an engineered variant of nitroreductase with increased activity (epNTR) eliminated the response. The reaction time to EFPs is extremely short, with many responses initiated within 2 ms of the EFP. Large neurons, such as Mauthner cells, show heightened sensitivity to extracellular voltage gradients. We therefore tested whether the rapid response to EFPs was due to direct activation of the Mauthner cells, bypassing delays imposed by stimulus detection and transmission by sensory cells. Consistent with this, calcium imaging indicated that EFPs robustly activated the Mauthner cell but only rarely fired other reticulospinal neurons. Further supporting this idea, pharmacological blockade of synaptic transmission in zebrafish did not affect Mauthner cell activity in response to EFPs. Moreover, Mauthner cells transgenically expressing a tetrodotoxin (TTX)-resistant voltage-gated sodium channel retained responses to EFPs despite TTX suppression of action potentials in the rest of the brain. We propose that EFPs directly activate Mauthner cells because of their large size, thereby driving ultrarapid escape responses in fish. PMID:24848468

From elements to perception: local and global processing in visual neurons.

PubMed

Spillmann, L

1999-01-01

Gestalt psychologists in the early part of the century challenged psychophysical notions that perceptual phenomena can be understood from a punctate (atomistic) analysis of the elements present in the stimulus. Their ideas slowed later attempts to explain vision in terms of single-cell recordings from individual neurons. A rapprochement between Gestalt phenomenology and neurophysiology seemed unlikely when the first ECVP was held in Marburg, Germany, in 1978. Since that time, response properties of neurons have been discovered that invite an interpretation of visual phenomena (including illusions) in terms of neuronal processing by long-range interactions, as first proposed by Mach and Hering in the last century. This article traces a personal journey into the early days of neurophysiological vision research to illustrate the progress that has taken place from the first attempts to correlate single-cell responses with visual perceptions. Whereas initially the receptive-field properties of individual classes of cells--e.g., contrast, wavelength, orientation, motion, disparity, and spatial-frequency detectors--were used to account for relatively simple visual phenomena, nowadays complex perceptions are interpreted in terms of long-range interactions, involving many neurons. This change in paradigm from local to global processing was made possible by recent findings, in the cortex, on horizontal interactions and backward propagation (feedback loops) in addition to classical feedforward processing. These mechanisms are exemplified by studies of the tilt effect and tilt aftereffect, direction-specific motion adaptation, illusory contours, filling-in and fading, figure--ground segregation by orientation and motion contrast, and pop-out in dynamic visual-noise patterns. Major questions for future research and a discussion of their epistemological implications conclude the article.

Optical clearing of the pancreas for visualization of mature β-cells and vessels in mice.

PubMed

Nishimura, Wataru; Sakaue-Sawano, Asako; Takahashi, Satoru; Miyawaki, Atsushi; Yasuda, Kazuki; Noda, Yasuko

2018-05-04

Glucose metabolism is regulated by insulin, which is produced from β-cells in the pancreas. Because insulin is secreted into vessels in response to blood glucose, vascular structures of the pancreas, especially the relationship between vessels and β-cells, are important for physiological and pathological glucose metabolism. Here, we developed a system to visualize vessels surrounding mature β-cells expressing transcription factor MafA in a three-dimensional manner. Optical clearing of the pancreas prevented light scattering of fluorescence driven by the bacterial artificial chromosome (BAC)-mafA promoter in β-cells. Reconstruction of confocal images demonstrated mature β-cells and the glomerular-like structures of β-cell vasculatures labeled with DyLight 488-conjugated lectin in normal mice as well as in low-dose streptozotocin-injected diabetes model mice with reduced β-cell mass. This technological innovation of organ imaging can be used to investigate morphological changes in vascular structures during transplantation, regeneration and diabetes development.

Neuromorphic VLSI vision system for real-time texture segregation.

PubMed

Shimonomura, Kazuhiro; Yagi, Tetsuya

2008-10-01

The visual system of the brain can perceive an external scene in real-time with extremely low power dissipation, although the response speed of an individual neuron is considerably lower than that of semiconductor devices. The neurons in the visual pathway generate their receptive fields using a parallel and hierarchical architecture. This architecture of the visual cortex is interesting and important for designing a novel perception system from an engineering perspective. The aim of this study is to develop a vision system hardware, which is designed inspired by a hierarchical visual processing in V1, for real time texture segregation. The system consists of a silicon retina, orientation chip, and field programmable gate array (FPGA) circuit. The silicon retina emulates the neural circuits of the vertebrate retina and exhibits a Laplacian-Gaussian-like receptive field. The orientation chip selectively aggregates multiple pixels of the silicon retina in order to produce Gabor-like receptive fields that are tuned to various orientations by mimicking the feed-forward model proposed by Hubel and Wiesel. The FPGA circuit receives the output of the orientation chip and computes the responses of the complex cells. Using this system, the neural images of simple cells were computed in real-time for various orientations and spatial frequencies. Using the orientation-selective outputs obtained from the multi-chip system, a real-time texture segregation was conducted based on a computational model inspired by psychophysics and neurophysiology. The texture image was filtered by the two orthogonally oriented receptive fields of the multi-chip system and the filtered images were combined to segregate the area of different texture orientation with the aid of FPGA. The present system is also useful for the investigation of the functions of the higher-order cells that can be obtained by combining the simple and complex cells.

Emerging feed-forward inhibition allows the robust formation of direction selectivity in the developing ferret visual cortex

PubMed Central

Escobar, Gina M.; Maffei, Arianna; Miller, Paul

2014-01-01

The computation of direction selectivity requires that a cell respond to joint spatial and temporal characteristics of the stimulus that cannot be separated into independent components. Direction selectivity in ferret visual cortex is not present at the time of eye opening but instead develops in the days and weeks following eye opening in a process that requires visual experience with moving stimuli. Classic Hebbian or spike timing-dependent modification of excitatory feed-forward synaptic inputs is unable to produce direction-selective cells from unselective or weakly directionally biased initial conditions because inputs eventually grow so strong that they can independently drive cortical neurons, violating the joint spatial-temporal activation requirement. Furthermore, without some form of synaptic competition, cells cannot develop direction selectivity in response to training with bidirectional stimulation, as cells in ferret visual cortex do. We show that imposing a maximum lateral geniculate nucleus (LGN)-to-cortex synaptic weight allows neurons to develop direction-selective responses that maintain the requirement for joint spatial and temporal activation. We demonstrate that a novel form of inhibitory plasticity, postsynaptic activity-dependent long-term potentiation of inhibition (POSD-LTPi), which operates in the developing cortex at the time of eye opening, can provide synaptic competition and enables robust development of direction-selective receptive fields with unidirectional or bidirectional stimulation. We propose a general model of the development of spatiotemporal receptive fields that consists of two phases: an experience-independent establishment of initial biases, followed by an experience-dependent amplification or modification of these biases via correlation-based plasticity of excitatory inputs that compete against gradually increasing feed-forward inhibition. PMID:24598528

Anatomy and physiology of the afferent visual system.

PubMed

Prasad, Sashank; Galetta, Steven L

2011-01-01

The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

Sequential pictorial presentation of neural interaction in the retina. 2. The depolarizing and hyperpolarizing bipolar cells at rod terminals.

PubMed

Sjöstrand, F S

2002-01-01

Each rod is connected to one depolarizing and one hyperpolarizing bipolar cell. The synaptic connections of cone processes to each bipolar cell and presynaptically to the two rod-bipolar cell synapses establishes conditions for lateral interaction at this level. Thus, the cones raise the threshold for bipolar cell depolarization which is the basis for spatial brightness contrast enhancement and consequently for high visual acuity (Sjöstrand, 2001a). The cones facilitate ganglion cell depolarization by the bipolar cells and cone input prevents horizontal cell blocking of depolarization of the depolarizing bipolar cell, extending rod vision to low illumination. The combination of reduced cone input and transient hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus facilitates ganglion cell depolarization extensively at onset of the stimulus while no corresponding enhancement applies to the ganglion cell response at cessation of the stimulus, possibly establishing conditions for discrimination between on- vs. off-signals in the visual centre. Reduced cone input and hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus accounts for Granit's (1941) 'preexcitatory inhibition'. Presynaptic inhibition maintains transmitter concentration low in the synaptic gap at rod-bipolar cell and bipolar cell-ganglion cell synapses, securing proportional and amplified postsynaptic responses at these synapses. Perfect timing of variations in facilitatory and inhibitory input to the ganglion cell confines the duration of ganglion cell depolarization at onset and at cessation of a light stimulus to that of a single synaptic transmission.

Visual and highly sensitive detection of cancer cells by a colorimetric aptasensor based on cell-triggered cyclic enzymatic signal amplification.

PubMed

Zhang, Xianxia; Xiao, Kunyi; Cheng, Liwei; Chen, Hui; Liu, Baohong; Zhang, Song; Kong, Jilie

2014-06-03

Rapid and efficient detection of cancer cells at their earliest stages is one of the central challenges in cancer diagnostics. We developed a simple, cost-effective, and highly sensitive colorimetric method for visually detecting rare cancer cells based on cell-triggered cyclic enzymatic signal amplification (CTCESA). In the absence of target cells, hairpin aptamer probes (HAPs) and linker DNAs stably coexist in solution, and the linker DNA assembles DNA-AuNPs, producing a purple solution. In the presence of target cells, the specific binding of HAPs to the target cells triggers a conformational switch that results in linker DNA hybridization and cleavage by nicking endonuclease-strand scission cycles. Consequently, the cleaved fragments of linker DNA can no longer assemble into DNA-AuNPs, resulting in a red color. UV-vis spectrometry and photograph analyses demonstrated that this CTCESA-based method exhibited selective and sensitive colorimetric responses to the presence of target CCRF-CEM cells, which could be detected by the naked eye. The linear response for CCRF-CEM cells in a concentration range from 10(2) to 10(4) cells was obtained with a detection limit of 40 cells, which is approximately 20 times lower than the detection limit of normal AuNP-based methods without amplification. Given the high specificity and sensitivity of CTCESA, this colorimetric method provides a sensitive, label-free, and cost-effective approach for early cancer diagnosis and point-to-care applications.

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

PubMed Central

Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei

2017-01-01

Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments. PMID:28111323

Vision-guided ocular growth in a mutant chicken model with diminished visual acuity

PubMed Central

Ritchey, Eric R.; Zelinka, Christopher; Tang, Junhua; Liu, Jun; Code, Kimberly A.; Petersen-Jones, Simon; Fischer, Andy J.

2012-01-01

Visual experience is known to guide ocular growth. We tested the hypothesis that vision-guided ocular growth is disrupted in a model system with diminished visual acuity. We examine whether ocular elongation is influenced by form-deprivation (FD) and lens-imposed defocus in the Retinopathy, Globe Enlarged (RGE) chicken. Young RGE chicks have poor visual acuity, without significant retinal pathology, resulting from a mutation in guanine nucleotide-binding protein β3 (GNB3), also known as transducin β3 or Gβ3. The mutation in GNB3 destabilizes the protein and causes a loss of Gβ3 from photoreceptors and ON-bipolar cells. (Ritchey et al. 2010)FD increased ocular elongation in RGE eyes in a manner similar to that seen in wild-type (WT) eyes. By comparison, the excessive ocular elongation that results from hyperopic defocus was increased, whereas myopic defocus failed to significantly decrease ocular elongation in RGE eyes. Brief daily periods of unrestricted vision interrupting FD prevented ocular elongation in RGE chicks in a manner similar to that seen in WT chicks. Glucagonergic amacrine cells differentially expressed the immediate early gene Egr1 in response to growth-guiding stimuli in RGE retinas, but the defocus-dependent up-regulation of Egr1 was lesser in RGE retinas compared to that of WT retinas. We conclude that high visual acuity, and the retinal signaling mediated by Gβ3, is not required for emmetropization and the excessive ocular elongation caused by FD and hyperopic defocus. However, the loss of acuity and Gβ3 from RGE retinas causes enhanced responses to hyperopic defocus and diminished responses to myopic defocus. PMID:22824538

Firing-rate based network modeling of the dLGN circuit: Effects of cortical feedback on spatiotemporal response properties of relay cells.

PubMed

Mobarhan, Milad Hobbi; Halnes, Geir; Martínez-Cañada, Pablo; Hafting, Torkel; Fyhn, Marianne; Einevoll, Gaute T

2018-05-01

Visually evoked signals in the retina pass through the dorsal geniculate nucleus (dLGN) on the way to the visual cortex. This is however not a simple feedforward flow of information: there is a significant feedback from cortical cells back to both relay cells and interneurons in the dLGN. Despite four decades of experimental and theoretical studies, the functional role of this feedback is still debated. Here we use a firing-rate model, the extended difference-of-Gaussians (eDOG) model, to explore cortical feedback effects on visual responses of dLGN relay cells. For this model the responses are found by direct evaluation of two- or three-dimensional integrals allowing for fast and comprehensive studies of putative effects of different candidate organizations of the cortical feedback. Our analysis identifies a special mixed configuration of excitatory and inhibitory cortical feedback which seems to best account for available experimental data. This configuration consists of (i) a slow (long-delay) and spatially widespread inhibitory feedback, combined with (ii) a fast (short-delayed) and spatially narrow excitatory feedback, where (iii) the excitatory/inhibitory ON-ON connections are accompanied respectively by inhibitory/excitatory OFF-ON connections, i.e. following a phase-reversed arrangement. The recent development of optogenetic and pharmacogenetic methods has provided new tools for more precise manipulation and investigation of the thalamocortical circuit, in particular for mice. Such data will expectedly allow the eDOG model to be better constrained by data from specific animal model systems than has been possible until now for cat. We have therefore made the Python tool pyLGN which allows for easy adaptation of the eDOG model to new situations.

Modulation of microglia in the retina: new insights into diabetic retinopathy.

PubMed

Arroba, Ana I; Valverde, Ángela M

2017-06-01

During last decades, the diagnosis of diabetes has been associated with several chronic complications such as diabetic retinopathy (DR). Recent studies of DR have revealed an inflammatory component, which precedes the detection of alterations in the visual function. During DR, the inflammatory process presents two opposite roles depending on the polarization of resident immune cells of the retina triggering proinflammatory (M1) or antiinflammatory (M2) actions. In an early stage of DR, the M2 response concurs with the M1 and is able to ameliorate inflammation and delay the progression of the disease. However, during the progression of DR, the M1 response is maintained whereas the M2 declines and, in this scenario, the classical proinflammatory signaling pathways are chronically activated leading to retinal neurodegeneration and the loss of visual function. The M1/M2 responses are closely related to the activation and polarization of microglial cells. This review aims to offer an overview of the recent insights into the role of microglial cells during inflammation in DR. We have focused on the possibility of modulating microglia polarization as a new therapeutic strategy in DR treatments.

Development of orientation tuning in simple cells of primary visual cortex

PubMed Central

Moore, Bartlett D.

2012-01-01

Orientation selectivity and its development are basic features of visual cortex. The original model of orientation selectivity proposes that elongated simple cell receptive fields are constructed from convergent input of an array of lateral geniculate nucleus neurons. However, orientation selectivity of simple cells in the visual cortex is generally greater than the linear contributions based on projections from spatial receptive field profiles. This implies that additional selectivity may arise from intracortical mechanisms. The hierarchical processing idea implies mainly linear connections, whereas cortical contributions are generally considered to be nonlinear. We have explored development of orientation selectivity in visual cortex with a focus on linear and nonlinear factors in a population of anesthetized 4-wk postnatal kittens and adult cats. Linear contributions are estimated from receptive field maps by which orientation tuning curves are generated and bandwidth is quantified. Nonlinear components are estimated as the magnitude of the power function relationship between responses measured from drifting sinusoidal gratings and those predicted from the spatial receptive field. Measured bandwidths for kittens are slightly larger than those in adults, whereas predicted bandwidths are substantially broader. These results suggest that relatively strong nonlinearities in early postnatal stages are substantially involved in the development of orientation tuning in visual cortex. PMID:22323631

Visualization of tandem repeat mutagenesis in Bacillus subtilis.

PubMed

Dormeyer, Miriam; Lentes, Sabine; Ballin, Patrick; Wilkens, Markus; Klumpp, Stefan; Kohlheyer, Dietrich; Stannek, Lorena; Grünberger, Alexander; Commichau, Fabian M

2018-03-01

Mutations are crucial for the emergence and evolution of proteins with novel functions, and thus for the diversity of life. Tandem repeats (TRs) are mutational hot spots that are present in the genomes of all organisms. Understanding the molecular mechanism underlying TR mutagenesis at the level of single cells requires the development of mutation reporter systems. Here, we present a mutation reporter system that is suitable to visualize mutagenesis of TRs occurring in single cells of the Gram-positive model bacterium Bacillus subtilis using microfluidic single-cell cultivation. The system allows measuring the elimination of TR units due to growth rate recovery. The cultivation of bacteria carrying the mutation reporter system in microfluidic chambers allowed us for the first time to visualize the emergence of a specific mutation at the level of single cells. The application of the mutation reporter system in combination with microfluidics might be helpful to elucidate the molecular mechanism underlying TR (in)stability in bacteria. Moreover, the mutation reporter system might be useful to assess whether mutations occur in response to nutrient starvation. Copyright © 2018 Elsevier B.V. All rights reserved.

Blood Flow: Multi-scale Modeling and Visualization (July 2011)

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2011-01-01

Multi-scale modeling of arterial blood flow can shed light on the interaction between events happening at micro- and meso-scales (i.e., adhesion of red blood cells to the arterial wall, clot formation) and at macro-scales (i.e., change in flow patterns due to the clot). Coupled numerical simulations of such multi-scale flow require state-of-the-art computers and algorithms, along with techniques for multi-scale visualizations. This animation presents early results of two studies used in the development of a multi-scale visualization methodology. The fisrt illustrates a flow of healthy (red) and diseased (blue) blood cells with a Dissipative Particle Dynamics (DPD) method. Each bloodmore » cell is represented by a mesh, small spheres show a sub-set of particles representing the blood plasma, while instantaneous streamlines and slices represent the ensemble average velocity. In the second we investigate the process of thrombus (blood clot) formation, which may be responsible for the rupture of aneurysms, by concentrating on the platelet blood cells, observing as they aggregate on the wall of an aneruysm. Simulation was performed on Kraken at the National Institute for Computational Sciences. Visualization was produced using resources of the Argonne Leadership Computing Facility at Argonne National Laboratory.« less

Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons.

PubMed

Svirskis, Gytis; Baranauskas, Gytis; Svirskiene, Natasa; Tkatch, Tatiana

2015-01-01

The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum.

Characterizing Responses of Translation Invariant Neurons to Natural Stimuli: Maximally Informative Invariant Dimensions

PubMed Central

Eickenberg, Michael; Rowekamp, Ryan J.; Kouh, Minjoon; Sharpee, Tatyana O.

2012-01-01

Our visual system is capable of recognizing complex objects even when their appearances change drastically under various viewing conditions. Especially in the higher cortical areas, the sensory neurons reflect such functional capacity in their selectivity for complex visual features and invariance to certain object transformations, such as image translation. Due to the strong nonlinearities necessary to achieve both the selectivity and invariance, characterizing and predicting the response patterns of these neurons represents a formidable computational challenge. A related problem is that such neurons are poorly driven by randomized inputs, such as white noise, and respond strongly only to stimuli with complex high-order correlations, such as natural stimuli. Here we describe a novel two-step optimization technique that can characterize both the shape selectivity and the range and coarseness of position invariance from neural responses to natural stimuli. One step in the optimization involves finding the template as the maximally informative dimension given the estimated spatial location where the response could have been triggered within each image. The estimates of the locations that triggered the response are subsequently updated in the next step. Under the assumption of a monotonic relationship between the firing rate and stimulus projections on the template at a given position, the most likely location is the one that has the largest projection on the estimate of the template. The algorithm shows quick convergence during optimization, and the estimation results are reliable even in the regime of small signal-to-noise ratios. When we apply the algorithm to responses of complex cells in the primary visual cortex (V1) to natural movies, we find that responses of the majority of cells were significantly better described by translation invariant models based on one template compared with position-specific models with several relevant features. PMID:22734487

Increased visual gamma power in schizoaffective bipolar disorder.

PubMed

Brealy, J A; Shaw, A; Richardson, H; Singh, K D; Muthukumaraswamy, S D; Keedwell, P A

2015-03-01

Electroencephalography and magnetoencephalography (MEG) studies have identified alterations in gamma-band (30-80 Hz) cortical activity in schizophrenia and mood disorders, consistent with neural models of disturbed glutamate (and GABA) neuron influence over cortical pyramidal cells. Genetic evidence suggests specific deficits in GABA-A receptor function in schizoaffective bipolar disorder (SABP), a clinical syndrome with features of both bipolar disorder and schizophrenia. This study investigated gamma oscillations in this under-researched disorder. MEG was used to measure induced gamma and evoked responses to a visual grating stimulus, known to be a potent inducer of primary visual gamma oscillations, in 15 individuals with remitted SABP, defined using Research Diagnostic Criteria, and 22 age- and sex-matched healthy controls. Individuals with SABP demonstrated increased sustained visual cortical power in the gamma band (t 35 = -2.56, p = 0.015) compared to controls. There were no group differences in baseline gamma power, transient or sustained gamma frequency, alpha band responses or pattern onset visual-evoked responses. Gamma power is increased in remitted SABP, which reflects an abnormality in the cortical inhibitory-excitatory balance. Although an interaction between gamma power and medication can not be ruled out, there were no group differences in evoked responses or baseline measures. Further work is needed in other clinical populations and at-risk relatives. Pharmaco-magnetoencephalography studies will help to elucidate the specific GABA and glutamate pathways affected.

The spatial structure of a nonlinear receptive field.

PubMed

Schwartz, Gregory W; Okawa, Haruhisa; Dunn, Felice A; Morgan, Josh L; Kerschensteiner, Daniel; Wong, Rachel O; Rieke, Fred

2012-11-01

Understanding a sensory system implies the ability to predict responses to a variety of inputs from a common model. In the retina, this includes predicting how the integration of signals across visual space shapes the outputs of retinal ganglion cells. Existing models of this process generalize poorly to predict responses to new stimuli. This failure arises in part from properties of the ganglion cell response that are not well captured by standard receptive-field mapping techniques: nonlinear spatial integration and fine-scale heterogeneities in spatial sampling. Here we characterize a ganglion cell's spatial receptive field using a mechanistic model based on measurements of the physiological properties and connectivity of only the primary excitatory circuitry of the retina. The resulting simplified circuit model successfully predicts ganglion-cell responses to a variety of spatial patterns and thus provides a direct correspondence between circuit connectivity and retinal output.

Are V1 Simple Cells Optimized for Visual Occlusions? A Comparative Study

PubMed Central

Bornschein, Jörg; Henniges, Marc; Lücke, Jörg

2013-01-01

Simple cells in primary visual cortex were famously found to respond to low-level image components such as edges. Sparse coding and independent component analysis (ICA) emerged as the standard computational models for simple cell coding because they linked their receptive fields to the statistics of visual stimuli. However, a salient feature of image statistics, occlusions of image components, is not considered by these models. Here we ask if occlusions have an effect on the predicted shapes of simple cell receptive fields. We use a comparative approach to answer this question and investigate two models for simple cells: a standard linear model and an occlusive model. For both models we simultaneously estimate optimal receptive fields, sparsity and stimulus noise. The two models are identical except for their component superposition assumption. We find the image encoding and receptive fields predicted by the models to differ significantly. While both models predict many Gabor-like fields, the occlusive model predicts a much sparser encoding and high percentages of ‘globular’ receptive fields. This relatively new center-surround type of simple cell response is observed since reverse correlation is used in experimental studies. While high percentages of ‘globular’ fields can be obtained using specific choices of sparsity and overcompleteness in linear sparse coding, no or only low proportions are reported in the vast majority of studies on linear models (including all ICA models). Likewise, for the here investigated linear model and optimal sparsity, only low proportions of ‘globular’ fields are observed. In comparison, the occlusive model robustly infers high proportions and can match the experimentally observed high proportions of ‘globular’ fields well. Our computational study, therefore, suggests that ‘globular’ fields may be evidence for an optimal encoding of visual occlusions in primary visual cortex. PMID:23754938

Neurons Forming Optic Glomeruli Compute Figure–Ground Discriminations in Drosophila

PubMed Central

Aptekar, Jacob W.; Keleş, Mehmet F.; Lu, Patrick M.; Zolotova, Nadezhda M.

2015-01-01

Many animals rely on visual figure–ground discrimination to aid in navigation, and to draw attention to salient features like conspecifics or predators. Even figures that are similar in pattern and luminance to the visual surroundings can be distinguished by the optical disparity generated by their relative motion against the ground, and yet the neural mechanisms underlying these visual discriminations are not well understood. We show in flies that a diverse array of figure–ground stimuli containing a motion-defined edge elicit statistically similar behavioral responses to one another, and statistically distinct behavioral responses from ground motion alone. From studies in larger flies and other insect species, we hypothesized that the circuitry of the lobula—one of the four, primary neuropiles of the fly optic lobe—performs this visual discrimination. Using calcium imaging of input dendrites, we then show that information encoded in cells projecting from the lobula to discrete optic glomeruli in the central brain group these sets of figure–ground stimuli in a homologous manner to the behavior; “figure-like” stimuli are coded similar to one another and “ground-like” stimuli are encoded differently. One cell class responds to the leading edge of a figure and is suppressed by ground motion. Two other classes cluster any figure-like stimuli, including a figure moving opposite the ground, distinctly from ground alone. This evidence demonstrates that lobula outputs provide a diverse basis set encoding visual features necessary for figure detection. PMID:25972183

Neurons forming optic glomeruli compute figure-ground discriminations in Drosophila.

PubMed

Aptekar, Jacob W; Keleş, Mehmet F; Lu, Patrick M; Zolotova, Nadezhda M; Frye, Mark A

2015-05-13

Many animals rely on visual figure-ground discrimination to aid in navigation, and to draw attention to salient features like conspecifics or predators. Even figures that are similar in pattern and luminance to the visual surroundings can be distinguished by the optical disparity generated by their relative motion against the ground, and yet the neural mechanisms underlying these visual discriminations are not well understood. We show in flies that a diverse array of figure-ground stimuli containing a motion-defined edge elicit statistically similar behavioral responses to one another, and statistically distinct behavioral responses from ground motion alone. From studies in larger flies and other insect species, we hypothesized that the circuitry of the lobula--one of the four, primary neuropiles of the fly optic lobe--performs this visual discrimination. Using calcium imaging of input dendrites, we then show that information encoded in cells projecting from the lobula to discrete optic glomeruli in the central brain group these sets of figure-ground stimuli in a homologous manner to the behavior; "figure-like" stimuli are coded similar to one another and "ground-like" stimuli are encoded differently. One cell class responds to the leading edge of a figure and is suppressed by ground motion. Two other classes cluster any figure-like stimuli, including a figure moving opposite the ground, distinctly from ground alone. This evidence demonstrates that lobula outputs provide a diverse basis set encoding visual features necessary for figure detection. Copyright © 2015 the authors 0270-6474/15/357587-13$15.00/0.

The Neural Circuit Mechanisms Underlying the Retinal Response to Motion Reversal

PubMed Central

Chen, Eric Y.; Chou, Janice; Park, Jeongsook; Schwartz, Greg

2014-01-01

To make up for delays in visual processing, retinal circuitry effectively predicts that a moving object will continue moving in a straight line, allowing retinal ganglion cells to anticipate the object's position. However, a sudden reversal of motion triggers a synchronous burst of firing from a large group of ganglion cells, possibly signaling a violation of the retina's motion prediction. To investigate the neural circuitry underlying this response, we used a combination of multielectrode array and whole-cell patch recordings to measure the responses of individual retinal ganglion cells in the tiger salamander to reversing stimuli. We found that different populations of ganglion cells were responsible for responding to the reversal of different kinds of objects, such as bright versus dark objects. Using pharmacology and designed stimuli, we concluded that ON and OFF bipolar cells both contributed to the reversal response, but that amacrine cells had, at best, a minor role. This allowed us to formulate an adaptive cascade model (ACM), similar to the one previously used to describe ganglion cell responses to motion onset. By incorporating the ON pathway into the ACM, we were able to reproduce the time-varying firing rate of fast OFF ganglion cells for all experimentally tested stimuli. Analysis of the ACM demonstrates that bipolar cell gain control is primarily responsible for generating the synchronized retinal response, as individual bipolar cells require a constant time delay before recovering from gain control. PMID:25411485

Regenerating reptile retinas: a comparative approach to restoring retinal ganglion cell function.

PubMed

Williams, D L

2017-02-01

Transection or damage to the mammalian optic nerve generally results in loss of retinal ganglion cells by apoptosis. This cell death is seen less in fish or amphibians where retinal ganglion cell survival and axon regeneration leads to recovery of sight. Reptiles lie somewhere in the middle of this spectrum of nerve regeneration, and different species have been reported to have a significant variation in their retinal ganglion cell regenerative capacity. The ornate dragon lizard Ctenophoris ornatus exhibits a profound capacity for regeneration, whereas the Tenerife wall lizard Gallotia galloti has a more variable response to optic nerve damage. Some individuals regain visual activity such as the pupillomotor responses, whereas in others axons fail to regenerate sufficiently. Even in Ctenophoris, although the retinal ganglion cell axons regenerate adequately enough to synapse in the tectum, they do not make long-term topographic connections allowing recovery of complex visually motivated behaviour. The question then centres on where these intraspecies differences originate. Is it variation in the innate ability of retinal ganglion cells from different species to regenerate with functional validity? Or is it variances between different species in the substrate within which the nerves regenerate, the extracellular environment of the damaged nerve or the supporting cells surrounding the regenerating axons? Investigations of retinal ganglion cell regeneration between different species of lower vertebrates in vivo may shed light on these questions. Or perhaps more interesting are in vitro studies comparing axon regeneration of retinal ganglion cells from various species placed on differing substrates.

Visualization of Cytolytic T Cell Differentiation and Granule Exocytosis with T Cells from Mice Expressing Active Fluorescent Granzyme B

PubMed Central

Mouchacca, Pierre; Schmitt-Verhulst, Anne-Marie; Boyer, Claude

2013-01-01

To evaluate acquisition and activation of cytolytic functions during immune responses we generated knock in (KI) mice expressing Granzyme B (GZMB) as a fusion protein with red fluorescent tdTomato (GZMB-Tom). As for GZMB in wild type (WT) lymphocytes, GZMB-Tom was absent from naïve CD8 and CD4 T cells in GZMB-Tom-KI mice. It was rapidly induced in most CD8 T cells and in a subpopulation of CD4 T cells in response to stimulation with antibodies to CD3/CD28. A fraction of splenic NK cells expressed GZMB-Tom ex vivo with most becoming positive upon culture in IL-2. GZMB-Tom was present in CTL granules and active as a protease when these degranulated into cognate target cells, as shown with target cells expressing a specific FRET reporter construct. Using T cells from mice expressing GZMB-Tom but lacking perforin, we show that the transfer of fluorescent GZMB-Tom into target cells was dependent on perforin, favoring a role for perforin in delivery of GZMB at the target cells’ plasma membranes. Time-lapse video microscopy showed Ca++ signaling in CTL upon interaction with cognate targets, followed by relocalization of GZMB-Tom-containing granules to the synaptic contact zone. A perforin-dependent step was next visualized by the fluorescence signal from the non-permeant dye TO-PRO-3 at the synaptic cleft, minutes before the labeling of the target cell nucleus, characterizing a previously undescribed synaptic event in CTL cytolysis. Transferred OVA-specific GZMB-Tom-expressing CD8 T cells acquired GZMB-Tom expression in Listeria monocytogenes-OVA infected mice as soon as 48h after infection. These GZMB-Tom positive CD8 T cells localized in the splenic T-zone where they interacted with CD11c positive dendritic cells (DC), as shown by GZMB-Tom granule redistribution to the T/DC contact zone. GZMB-Tom-KI mice thus also provide tools to visualize acquisition and activation of cytolytic function in vivo. PMID:23840635

Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits

PubMed Central

Xu, Hong-Ping; Burbridge, Timothy J.; Ye, Meijun; Chen, Minggang; Ge, Xinxin; Zhou, Z. Jimmy

2016-01-01

Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical, in vitro and in vivo electrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of β2 subunits of nicotinic acetylcholine receptors (β2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that β2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the “recurrent network” model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development. SIGNIFICANCE STATEMENT Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic “retinal waves” are initiated in starburst amacrine cells and propagate to retinal ganglion cells and higher-order visual areas, but the mechanism responsible for creating their unique and critical activity pattern is incompletely understood. We demonstrate that cholinergic wave patterns are dictated by recurrent connectivity within starburst amacrine cells, and retinal ganglion cells act as “readouts” of patterned activity. We also show that eye-specific segregation occurs normally without glutamatergic waves, but elimination of both cholinergic and glutamatergic waves completely disrupts visual circuit development. These results suggest that each retinal wave pattern during development is optimized for concurrently refining multiple visual circuits. PMID:27030771

Texture-dependent motion signals in primate middle temporal area

PubMed Central

Gharaei, Saba; Tailby, Chris; Solomon, Selina S; Solomon, Samuel G

2013-01-01

Neurons in the middle temporal (MT) area of primate cortex provide an important stage in the analysis of visual motion. For simple stimuli such as bars and plaids some neurons in area MT – pattern cells – seem to signal motion independent of contour orientation, but many neurons – component cells – do not. Why area MT supports both types of receptive field is unclear. To address this we made extracellular recordings from single units in area MT of anaesthetised marmoset monkeys and examined responses to two-dimensional images with a large range of orientations and spatial frequencies. Component and pattern cell response remained distinct during presentation of these complex spatial textures. Direction tuning curves were sharpest in component cells when a texture contained a narrow range of orientations, but were similar across all neurons for textures containing all orientations. Response magnitude of pattern cells, but not component cells, increased with the spatial bandwidth of the texture. In addition, response variability in all neurons was reduced when the stimulus was rich in spatial texture. Fisher information analysis showed that component cells provide more informative responses than pattern cells when a texture contains a narrow range of orientations, but pattern cells had more informative responses for broadband textures. Component cells and pattern cells may therefore coexist because they provide complementary and parallel motion signals. PMID:24000175

Melanopsin is required for non-image-forming photic responses in blind mice.

PubMed

Panda, Satchidananda; Provencio, Ignacio; Tu, Daniel C; Pires, Susana S; Rollag, Mark D; Castrucci, Ana Maria; Pletcher, Mathew T; Sato, Trey K; Wiltshire, Tim; Andahazy, Mary; Kay, Steve A; Van Gelder, Russell N; Hogenesch, John B

2003-07-25

Although mice lacking rod and cone photoreceptors are blind, they retain many eye-mediated responses to light, possibly through photosensitive retinal ganglion cells. These cells express melanopsin, a photopigment that confers this photosensitivity. Mice lacking melanopsin still retain nonvisual photoreception, suggesting that rods and cones could operate in this capacity. We observed that mice with both outer-retinal degeneration and a deficiency in melanopsin exhibited complete loss of photoentrainment of the circadian oscillator, pupillary light responses, photic suppression of arylalkylamine-N-acetyltransferase transcript, and acute suppression of locomotor activity by light. This indicates the importance of both nonvisual and classical visual photoreceptor systems for nonvisual photic responses in mammals.

Fast Coding of Orientation in Primary Visual Cortex

PubMed Central

Shriki, Oren; Kohn, Adam; Shamir, Maoz

2012-01-01

Understanding how populations of neurons encode sensory information is a major goal of systems neuroscience. Attempts to answer this question have focused on responses measured over several hundred milliseconds, a duration much longer than that frequently used by animals to make decisions about the environment. How reliably sensory information is encoded on briefer time scales, and how best to extract this information, is unknown. Although it has been proposed that neuronal response latency provides a major cue for fast decisions in the visual system, this hypothesis has not been tested systematically and in a quantitative manner. Here we use a simple ‘race to threshold’ readout mechanism to quantify the information content of spike time latency of primary visual (V1) cortical cells to stimulus orientation. We find that many V1 cells show pronounced tuning of their spike latency to stimulus orientation and that almost as much information can be extracted from spike latencies as from firing rates measured over much longer durations. To extract this information, stimulus onset must be estimated accurately. We show that the responses of cells with weak tuning of spike latency can provide a reliable onset detector. We find that spike latency information can be pooled from a large neuronal population, provided that the decision threshold is scaled linearly with the population size, yielding a processing time of the order of a few tens of milliseconds. Our results provide a novel mechanism for extracting information from neuronal populations over the very brief time scales in which behavioral judgments must sometimes be made. PMID:22719237

A neuronal circuit for colour vision based on rod-cone opponency.

PubMed

Joesch, Maximilian; Meister, Markus

2016-04-14

In bright light, cone-photoreceptors are active and colour vision derives from a comparison of signals in cones with different visual pigments. This comparison begins in the retina, where certain retinal ganglion cells have 'colour-opponent' visual responses-excited by light of one colour and suppressed by another colour. In dim light, rod-photoreceptors are active, but colour vision is impossible because they all use the same visual pigment. Instead, the rod signals are thought to splice into retinal circuits at various points, in synergy with the cone signals. Here we report a new circuit for colour vision that challenges these expectations. A genetically identified type of mouse retinal ganglion cell called JAMB (J-RGC), was found to have colour-opponent responses, OFF to ultraviolet (UV) light and ON to green light. Although the mouse retina contains a green-sensitive cone, the ON response instead originates in rods. Rods and cones both contribute to the response over several decades of light intensity. Remarkably, the rod signal in this circuit is antagonistic to that from cones. For rodents, this UV-green channel may play a role in social communication, as suggested by spectral measurements from the environment. In the human retina, all of the components for this circuit exist as well, and its function can explain certain experiences of colour in dim lights, such as a 'blue shift' in twilight. The discovery of this genetically defined pathway will enable new targeted studies of colour processing in the brain.

A Class of Visual Neurons with Wide-Field Properties Is Required for Local Motion Detection.

PubMed

Fisher, Yvette E; Leong, Jonathan C S; Sporar, Katja; Ketkar, Madhura D; Gohl, Daryl M; Clandinin, Thomas R; Silies, Marion

2015-12-21

Visual motion cues are used by many animals to guide navigation across a wide range of environments. Long-standing theoretical models have made predictions about the computations that compare light signals across space and time to detect motion. Using connectomic and physiological approaches, candidate circuits that can implement various algorithmic steps have been proposed in the Drosophila visual system. These pathways connect photoreceptors, via interneurons in the lamina and the medulla, to direction-selective cells in the lobula and lobula plate. However, the functional architecture of these circuits remains incompletely understood. Here, we use a forward genetic approach to identify the medulla neuron Tm9 as critical for motion-evoked behavioral responses. Using in vivo calcium imaging combined with genetic silencing, we place Tm9 within motion-detecting circuitry. Tm9 receives functional inputs from the lamina neurons L3 and, unexpectedly, L1 and passes information onto the direction-selective T5 neuron. Whereas the morphology of Tm9 suggested that this cell would inform circuits about local points in space, we found that the Tm9 spatial receptive field is large. Thus, this circuit informs elementary motion detectors about a wide region of the visual scene. In addition, Tm9 exhibits sustained responses that provide a tonic signal about incoming light patterns. Silencing Tm9 dramatically reduces the response amplitude of T5 neurons under a broad range of different motion conditions. Thus, our data demonstrate that sustained and wide-field signals are essential for elementary motion processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetically Identified Suppressed-by-Contrast Retinal Ganglion Cells Reliably Signal Self-Generated Visual Stimuli

PubMed Central

Tien, Nai-Wen; Pearson, James T.; Heller, Charles R.; Demas, Jay

2015-01-01

Spike trains of retinal ganglion cells (RGCs) are the sole source of visual information to the brain; and understanding how the ∼20 RGC types in mammalian retinae respond to diverse visual features and events is fundamental to understanding vision. Suppressed-by-contrast (SbC) RGCs stand apart from all other RGC types in that they reduce rather than increase firing rates in response to light increments (ON) and decrements (OFF). Here, we genetically identify and morphologically characterize SbC-RGCs in mice, and target them for patch-clamp recordings under two-photon guidance. We find that strong ON inhibition (glycine > GABA) outweighs weak ON excitation, and that inhibition (glycine > GABA) coincides with decreases in excitation at light OFF. These input patterns explain the suppressive spike responses of SbC-RGCs, which are observed in dim and bright light conditions. Inhibition to SbC-RGC is driven by rectified receptive field subunits, leading us to hypothesize that SbC-RGCs could signal pattern-independent changes in the retinal image. Indeed, we find that shifts of random textures matching saccade-like eye movements in mice elicit robust inhibitory inputs and suppress spiking of SbC-RGCs over a wide range of texture contrasts and spatial frequencies. Similarly, stimuli based on kinematic analyses of mouse blinking consistently suppress SbC-RGC spiking. Receiver operating characteristics show that SbC-RGCs are reliable indicators of self-generated visual stimuli that may contribute to central processing of blinks and saccades. SIGNIFICANCE STATEMENT This study genetically identifies and morphologically characterizes suppressed-by-contrast retinal ganglion cells (SbC-RGCs) in mice. Targeted patch-clamp recordings from SbC-RGCs under two-photon guidance elucidate the synaptic mechanisms mediating spike suppression to contrast steps, and reveal that SbC-RGCs respond reliably to stimuli mimicking saccade-like eye movements and blinks. The similarity of responses to saccade-like eye movements and blinks suggests that SbC-RGCs may provide a unified signal for self-generated visual stimuli. PMID:26224863

Contrasting roles for parvalbumin-expressing inhibitory neurons in two forms of adult visual cortical plasticity

PubMed Central

Kaplan, Eitan S; Cooke, Sam F; Komorowski, Robert W; Chubykin, Alexander A; Thomazeau, Aurore; Khibnik, Lena A; Gavornik, Jeffrey P; Bear, Mark F

2016-01-01

The roles played by cortical inhibitory neurons in experience-dependent plasticity are not well understood. Here we evaluate the participation of parvalbumin-expressing (PV+) GABAergic neurons in two forms of experience-dependent modification of primary visual cortex (V1) in adult mice: ocular dominance (OD) plasticity resulting from monocular deprivation and stimulus-selective response potentiation (SRP) resulting from enriched visual experience. These two forms of plasticity are triggered by different events but lead to a similar increase in visual cortical response. Both also require the NMDA class of glutamate receptor (NMDAR). However, we find that PV+ inhibitory neurons in V1 play a critical role in the expression of SRP and its behavioral correlate of familiarity recognition, but not in the expression of OD plasticity. Furthermore, NMDARs expressed within PV+ cells, reversibly inhibited by the psychotomimetic drug ketamine, play a critical role in SRP, but not in the induction or expression of adult OD plasticity. DOI: http://dx.doi.org/10.7554/eLife.11450.001 PMID:26943618

Three Types of Cortical L5 Neurons that Differ in Brain-Wide Connectivity and Function

PubMed Central

Kim, Euiseok J.; Juavinett, Ashley L.; Kyubwa, Espoir M.; Jacobs, Matthew W.; Callaway, Edward M.

2015-01-01

SUMMARY Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. PMID:26671462

Three Types of Cortical Layer 5 Neurons That Differ in Brain-wide Connectivity and Function.

PubMed

Kim, Euiseok J; Juavinett, Ashley L; Kyubwa, Espoir M; Jacobs, Matthew W; Callaway, Edward M

2015-12-16

Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology, and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of neuronal responses during covert search for visual feature conjunctions

PubMed Central

Buracas, Giedrius T.; Albright, Thomas D.

2009-01-01

While searching for an object in a visual scene, an observer's attentional focus and eye movements are often guided by information about object features and spatial locations. Both spatial and feature-specific attention are known to modulate neuronal responses in visual cortex, but little is known of the dynamics and interplay of these mechanisms as visual search progresses. To address this issue, we recorded from directionally selective cells in visual area MT of monkeys trained to covertly search for targets defined by a unique conjunction of color and motion features and to signal target detection with an eye movement to the putative target. Two patterns of response modulation were observed. One pattern consisted of enhanced responses to targets presented in the receptive field (RF). These modulations occurred at the end-stage of search and were more potent during correct target identification than during erroneous saccades to a distractor in RF, thus suggesting that this modulation is not a mere presaccadic enhancement. A second pattern of modulation was observed when RF stimuli were nontargets that shared a feature with the target. The latter effect was observed during early stages of search and is consistent with a global feature-specific mechanism. This effect often terminated before target identification, thus suggesting that it interacts with spatial attention. This modulation was exhibited not only for motion but also for color cue, although MT neurons are known to be insensitive to color. Such cue-invariant attentional effects may contribute to a feature binding mechanism acting across visual dimensions. PMID:19805385

Modulation of neuronal responses during covert search for visual feature conjunctions.

PubMed

Buracas, Giedrius T; Albright, Thomas D

2009-09-29

While searching for an object in a visual scene, an observer's attentional focus and eye movements are often guided by information about object features and spatial locations. Both spatial and feature-specific attention are known to modulate neuronal responses in visual cortex, but little is known of the dynamics and interplay of these mechanisms as visual search progresses. To address this issue, we recorded from directionally selective cells in visual area MT of monkeys trained to covertly search for targets defined by a unique conjunction of color and motion features and to signal target detection with an eye movement to the putative target. Two patterns of response modulation were observed. One pattern consisted of enhanced responses to targets presented in the receptive field (RF). These modulations occurred at the end-stage of search and were more potent during correct target identification than during erroneous saccades to a distractor in RF, thus suggesting that this modulation is not a mere presaccadic enhancement. A second pattern of modulation was observed when RF stimuli were nontargets that shared a feature with the target. The latter effect was observed during early stages of search and is consistent with a global feature-specific mechanism. This effect often terminated before target identification, thus suggesting that it interacts with spatial attention. This modulation was exhibited not only for motion but also for color cue, although MT neurons are known to be insensitive to color. Such cue-invariant attentional effects may contribute to a feature binding mechanism acting across visual dimensions.

Neural network models for spatial data mining, map production, and cortical direction selectivity

NASA Astrophysics Data System (ADS)

Parsons, Olga

A family of ARTMAP neural networks for incremental supervised learning has been developed over the last decade. The Sensor Exploitation Group of MIT Lincoln Laboratory (LL) has incorporated an early version of this network as the recognition engine of a hierarchical system for fusion and data mining of multiple registered geospatial images. The LL system has been successfully fielded, but it is limited to target vs. non-target identifications and does not produce whole maps. This dissertation expands the capabilities of the LL system so that it learns to identify arbitrarily many target classes at once and can thus produce a whole map. This new spatial data mining system is designed particularly to cope with the highly skewed class distributions of typical mapping problems. Specification of a consistent procedure and a benchmark testbed has permitted the evaluation of candidate recognition networks as well as pre- and post-processing and feature extraction options. The resulting default ARTMAP network and mapping methodology set a standard for a variety of related mapping problems and application domains. The second part of the dissertation investigates the development of cortical direction selectivity. The possible role of visual experience and oculomotor behavior in the maturation of cells in the primary visual cortex is studied. The responses of neurons in the thalamus and cortex of the cat are modeled when natural scenes are scanned by several types of eye movements. Inspired by the Hebbian-like synaptic plasticity, which is based upon correlations between cell activations, the second-order statistical structure of thalamo-cortical activity is examined. In the simulations, patterns of neural activity that lead to a correct refinement of cell responses are observed during visual fixation, when small ocular movements occur, but are not observed in the presence of large saccades. Simulations also replicate experiments in which kittens are reared under stroboscopic illumination. The abnormal fixational eye movements of these cats may account for the puzzling finding of a specific loss of cortical direction selectivity but preservation of orientation selectivity. This work indicates that the oculomotor behavior of visual fixation may play an important role in the refinement of cell response selectivity.

Stability of simple/complex classification with contrast and extraclassical receptive field modulation in macaque V1

PubMed Central

Henry, Christopher A.

2013-01-01

A key property of neurons in primary visual cortex (V1) is the distinction between simple and complex cells. Recent reports in cat visual cortex indicate the categorization of simple and complex can change depending on stimulus conditions. We investigated the stability of the simple/complex classification with changes in drive produced by either contrast or modulation by the extraclassical receptive field (eCRF). These two conditions were reported to increase the proportion of simple cells in cat cortex. The ratio of the modulation depth of the response (F1) to the elevation of response (F0) to a drifting grating (F1/F0 ratio) was used as the measure of simple/complex. The majority of V1 complex cells remained classified as complex with decreasing contrast. Near contrast threshold, an equal proportion of simple and complex cells changed their classification. The F1/F0 ratio was stable between optimal and large stimulus areas even for those neurons that showed strong eCRF suppression. There was no discernible overall effect of surrounding spatial context on the F1/F0 ratio. Simple/complex cell classification is relatively stable across a range of stimulus drives, produced by either contrast or eCRF suppression. PMID:23303859

Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury.

PubMed

Weber, Arthur J; Viswanáthan, Suresh; Ramanathan, Chidambaram; Harman, Christine D

2010-01-01

To determine whether application of BDNF to the eye and brain provides a greater level of neuroprotection after optic nerve injury than treatment of the eye alone. Retinal ganglion cell survival and pattern electroretinographic responses were compared in normal cat eyes and in eyes that received (1) a mild nerve crush and no treatment, (2) a single intravitreal injection of BDNF at the time of the nerve injury, or (3) intravitreal treatment combined with 1 to 2 weeks of continuous delivery of BDNF to the visual cortex, bilaterally. Relative to no treatment, administration of BDNF to the eye alone resulted in a significant increase in ganglion cell survival at both 1 and 2 weeks after nerve crush (1 week, 79% vs. 55%; 2 weeks, 60% vs. 31%). Combined treatment of the eye and visual cortex resulted in a modest additional increase (17%) in ganglion cell survival in the 1-week eyes, a further significant increase (55%) in the 2-week eyes, and ganglion cell survival levels for both that were comparable to normal (92%-93% survival). Pattern ERG responses for all the treated eyes were comparable to normal at 1 week after injury; however, at 2 weeks, only the responses of eyes receiving the combined BDNF treatment remained so. Although treatment of the eye alone with BDNF has a significant impact on ganglion cell survival after optic nerve injury, combined treatment of the eye and brain may represent an even more effective approach and should be considered in the development of future optic neuropathy-related neuroprotection strategies.

Expression of inducible heat shock proteins Hsp27 and Hsp70 in the visual pathway of rats subjected to various models of retinal ganglion cell injury.

PubMed

Chidlow, Glyn; Wood, John P M; Casson, Robert J

2014-01-01

Inducible heat shock proteins (Hsps) are upregulated in the central nervous system in response to a wide variety of injuries. Surprisingly, however, no coherent picture has emerged regarding the magnitude, duration and cellular distribution of inducible Hsps in the visual system following injury to retinal ganglion cells (RGCs). The current study sought, therefore, to achieve the following two objectives. The first aim of this study was to systematically characterise the patterns of Hsp27 and -70 expression in the retina and optic nerve in four discrete models of retinal ganglion cell (RGC) degeneration: axonal injury (ON crush), somato-dendritic injury (NMDA-induced excitotoxicity), chronic hypoperfusion (bilateral occlusion of the carotid arteris) and experimental glaucoma. The second aim was to document Hsp27 and -70 expression in the optic tract, the subcortical retinorecipient areas of the brain, and the visual cortex during Wallerian degeneration of RGC axons. Hsp27 was robustly upregulated in the retina in each injury paradigm, with the chronic models, 2VO and experimental glaucoma, displaying a more persistent Hsp27 transcriptional response than the acute models. Hsp27 expression was always associated with astrocytes and with a subset of RGCs in each of the models excluding NMDA. Hsp27 was present within astrocytes of the optic nerve/optic tract in control rats. During Wallerian degeneration, Hsp27 was upregulated in the optic nerve/optic tract and expressed de novo by astrocytes in the lateral geniculate nucleus and the stratum opticum of the superior colliculus. Conversely, the results of our study indicate Hsp70 was minimally induced in any of the models of injury, either in the retina, or in the optic nerve/optic tract, or in the subcortical, retinorecipient areas of the brain. The findings of the present study augment our understanding of the involvement of Hsp27 and Hsp70 in the response of the visual system to RGC degeneration.

Modelling effects on grid cells of sensory input during self‐motion

PubMed Central

Raudies, Florian; Hinman, James R.

2016-01-01

Abstract The neural coding of spatial location for memory function may involve grid cells in the medial entorhinal cortex, but the mechanism of generating the spatial responses of grid cells remains unclear. This review describes some current theories and experimental data concerning the role of sensory input in generating the regular spatial firing patterns of grid cells, and changes in grid cell firing fields with movement of environmental barriers. As described here, the influence of visual features on spatial firing could involve either computations of self‐motion based on optic flow, or computations of absolute position based on the angle and distance of static visual cues. Due to anatomical selectivity of retinotopic processing, the sensory features on the walls of an environment may have a stronger effect on ventral grid cells that have wider spaced firing fields, whereas the sensory features on the ground plane may influence the firing of dorsal grid cells with narrower spacing between firing fields. These sensory influences could contribute to the potential functional role of grid cells in guiding goal‐directed navigation. PMID:27094096

Dorsal raphe nucleus projecting retinal ganglion cells: Why Y cells?

PubMed Central

Pickard, Gary E.; So, Kwok-Fai; Pu, Mingliang

2015-01-01

Retinal ganglion Y (alpha) cells are found in retinas ranging from frogs to mice to primates. The highly conserved nature of the large, fast conducting retinal Y cell is a testament to its fundamental task, although precisely what this task is remained ill-defined. The recent discovery that Y-alpha retinal ganglion cells send axon collaterals to the serotonergic dorsal raphe nucleus (DRN) in addition to the lateral geniculate nucleus (LGN), medial interlaminar nucleus (MIN), pretectum and the superior colliculus (SC) has offered new insights into the important survival tasks performed by these cells with highly branched axons. We propose that in addition to its role in visual perception, the Y-alpha retinal ganglion cell provides concurrent signals via axon collaterals to the DRN, the major source of serotonergic afferents to the forebrain, to dramatically inhibit 5-HT activity during orientation or alerting/escape responses, which dis-facilitates ongoing tonic motor activity while dis-inhibiting sensory information processing throughout the visual system. The new data provide a fresh view of these evolutionarily old retinal ganglion cells. PMID:26363667

Potential roles of cholinergic modulation in the neural coding of location and movement speed

PubMed Central

Dannenberg, Holger; Hinman, James R.; Hasselmo, Michael E.

2016-01-01

Behavioral data suggest that cholinergic modulation may play a role in certain aspects of spatial memory, and neurophysiological data demonstrate neurons that fire in response to spatial dimensions, including grid cells and place cells that respond on the basis of location and running speed. These neurons show firing responses that depend upon the visual configuration of the environment, due to coding in visually-responsive regions of the neocortex. This review focuses on the physiological effects of acetylcholine that may influence the sensory coding of spatial dimensions relevant to behavior. In particular, the local circuit effects of acetylcholine within the cortex regulate the influence of sensory input relative to internal memory representations, via presynaptic inhibition of excitatory and inhibitory synaptic transmission, and the modulation of intrinsic currents in cortical excitatory and inhibitory neurons. In addition, circuit effects of acetylcholine regulate the dynamics of cortical circuits including oscillations at theta and gamma frequencies. These effects of acetylcholine on local circuits and network dynamics could underlie the role of acetylcholine in coding of spatial information for the performance of spatial memory tasks. PMID:27677935

Adaptive Colour Contrast Coding in the Salamander Retina Efficiently Matches Natural Scene Statistics

PubMed Central

Vasserman, Genadiy; Schneidman, Elad; Segev, Ronen

2013-01-01

The visual system continually adjusts its sensitivity to the statistical properties of the environment through an adaptation process that starts in the retina. Colour perception and processing is commonly thought to occur mainly in high visual areas, and indeed most evidence for chromatic colour contrast adaptation comes from cortical studies. We show that colour contrast adaptation starts in the retina where ganglion cells adjust their responses to the spectral properties of the environment. We demonstrate that the ganglion cells match their responses to red-blue stimulus combinations according to the relative contrast of each of the input channels by rotating their functional response properties in colour space. Using measurements of the chromatic statistics of natural environments, we show that the retina balances inputs from the two (red and blue) stimulated colour channels, as would be expected from theoretical optimal behaviour. Our results suggest that colour is encoded in the retina based on the efficient processing of spectral information that matches spectral combinations in natural scenes on the colour processing level. PMID:24205373

Touching force response of the piezoelectric Braille cell.

PubMed

Smithmaitrie, Pruittikorn; Kanjantoe, Jinda; Tandayya, Pichaya

2008-11-01

The objective of this research is to investigate dynamic responses of the piezoelectric Braille cell when it is subjected to both electrical signal and touching force. Physical behavior of the piezoelectric actuator inside the piezoelectric Braille cell is analyzed. The mathematical model of the piezoelectric Braille system is presented. Then, data of visually impaired people using a Braille Note is studied as design information and a reference input for calculation of the piezoelectric Braille response under the touching force. The results show dynamic responses of the piezoelectric Braille cell. The designed piezoelectric bimorph has a settling time of 0.15 second. The relationship between the Braille dot height and applied voltage is linear. The behavior of the piezoelectric Braille dot when it is touched during operation shows that the dot height is decreased as the force increases. The result provides understanding of the piezoelectric Braille cell behavior under both touching force and electrical excitation simultaneously. This is the important issue for the design and development of piezoelectric Braille cells in senses of controlling Braille dot displacement or force-feedback in the future.

Comparing abstract numerical and visual depictions of risk in survey of parental assessment of risk in sickle cell hydroxyurea treatment.

PubMed

Patterson, Chavis A; Barakat, Lamia P; Henderson, Phyllis K; Nall, Faith; Westin, Anna; Dampier, Carlton D; Hsu, Lewis L

2011-01-01

Communicating risk is an important activity in medical decision-making; yet, numeracy is not a universal skill among the American public. We examined the hypothesis that numerical risk information about the use of hydroxyurea for children with sickle cell disease would elicit different risk assessment responses when visual depictions were used instead of abstract numbers and depending on the disease severity. Parents of 81 children with sickle cell disease participated in a survey in which hydroxyurea was first described as carrying a certain chance of risk for both birth defects and cancer. Then, the parents indicated the highest risk at which they would hypothetically consent to the treatment to help their child. Risk presentations were repeated with abstract numerical, pie graph, and 1000 people histogram formats. The χ analyses comparing high-risk to low-risk assessment across presentation formats showed high consistency between visual depictions but low consistency of abstract numerical with visual depictions. The parents of children with SC and other less severe types of SCD were less willing to accept higher risk than those with SS when the data were presented numerically. Given earlier concerns about poor "numeracy" in the US population, visual depictions of risk could be an effective tool for routine communication in health education and medical decision-making.

Spectral and Polarization Sensitivity of the Dipteran Visual System

PubMed Central

McCann, Gilbert D.; Arnett, David W.

1972-01-01

Spectral and polarization sensitivity measurements were made at several levels (retina, first and third optic ganglion, cervical connective, behavior) of the dipteran visual nervous system. At all levels, it was possible to reveal contributions from the retinular cell subsystem cells 1 to 6 or the retinular cell subsystem cells 7 and 8 or both. Only retinular cells 1 to 6 were directly studied, and all possessed the same spectral sensitivity characterized by two approximately equal sensitivity peaks at 350 and 480 nm. All units of both the sustaining and on-off variety in the first optic ganglion exhibited the same spectral sensitivity as that of retinular cells 1 to 6. It was possible to demonstrate for motion detection and optomotor responses two different spectral sensitivities depending upon the spatial wavelength of the stimulus. For long spatial wavelengths, the spectral sensitivity agreed with retinular cells 1 to 6; however, the spectral sensitivity at short spatial wavelengths was characterized by a single peak at 465 nm reflecting contributions from the (7, 8) subsystem. Although the two subsystems exhibited different spectral sensitivities, the difference was small and no indication of color discrimination mechanisms was observed. Although all retinular cells 1 to 6 exhibited a preferred polarization plane, sustaining and on-off units did not. Likewise, motion detection and optomotor responses were insensitive to the polarization plane for long spatial wavelength stimuli; however, sensitivity to select polarization planes was observed for short spatial wavelengths. PMID:5027759

Functional characterization of the extraclassical receptive field in macaque V1: contrast, orientation, and temporal dynamics.

PubMed

Henry, Christopher A; Joshi, Siddhartha; Xing, Dajun; Shapley, Robert M; Hawken, Michael J

2013-04-03

Neurons in primary visual cortex, V1, very often have extraclassical receptive fields (eCRFs). The eCRF is defined as the region of visual space where stimuli cannot elicit a spiking response but can modulate the response of a stimulus in the classical receptive field (CRF). We investigated the dependence of the eCRF on stimulus contrast and orientation in macaque V1 cells for which the laminar location was determined. The eCRF was more sensitive to contrast than the CRF across the whole population of V1 cells with the greatest contrast differential in layer 2/3. We confirmed that many V1 cells experience stronger suppression for collinear than orthogonal stimuli in the eCRF. Laminar analysis revealed that the predominant bias for collinear suppression was found in layers 2/3 and 4b. The laminar pattern of contrast and orientation dependence suggests that eCRF suppression may derive from different neural circuits in different layers, and may be comprised of two distinct components: orientation-tuned and untuned suppression. On average tuned suppression was delayed by ∼25 ms compared with the onset of untuned suppression. Therefore, response modulation by the eCRF develops dynamically and rapidly in time.

Hybrid Antibody-Induced Topographical Redistribution of Surface Immunoglobulins, Alloantigens, and Concanavalin A Receptors on Mouse Lymphoid Cells

PubMed Central

Stackpole, Christopher W.; De Milio, Lawrence T.; Hämmerling, Ulrich; Jacobson, Janet B.; Lardis, Michael P.

1974-01-01

Redistribution of surface immunoglobulins, H-2b, Thy-1.2, and TL.1,2,3 alloantigens, and concanavalin A receptors on mouse lymphoid cells induced by hybrid rabbit F(ab′)2 antibody (anti-mouse immunoglobulin/anti-visual marker or anti-concanavalin A/anti-visual marker) was studied by immunofluorescence. When used directly to label surface immunoglobulin, and indirectly to label alloantigens and concanavalin A receptors, hybrid antibodies induced similar displacement of all surface components from a uniform distribution into “patches” and “caps” at 37°. One hybrid antibody preparation, antimouse immunoglobulin/anti-ferritin, contained negligible amounts of bivalent anti-mouse immunoglobulin antibody, and was therefore “monovalent” for the antimouse immunoglobulin specificity. This observation suggests that factors other than multivalent crosslinking are responsible for hybrid antibody-induced redistribution of cell-surface components. Cap formation induced by hybrid antibody was enhanced markedly by attachment of the visual marker, either ferritin or southern bean mosaic virus, at 37°. At -5°, hybrid antibody does not displace uniformly distributed H-2b alloantigen-alloantibody complexes, but patches of label develop when ferritin attaches to the hybrid antibody. These results explain the patchy distribution of cell-surface components, which is a temperature-independent characteristic of labeling with hybrid antibodies and visual markers for electron microscopy. Images PMID:4595577

CV2/CRMP5-antibody-related Paraneoplastic Optic Neuropathy Associated with Small-cell Lung Cancer.

PubMed

Nakajima, Masanori; Uchibori, Ayumi; Ogawa, Yuki; Miyazaki, Tai; Ichikawa, Yaeko; Kaneko, Kimihiko; Takahashi, Toshiyuki; Nakashima, Ichiro; Shiraishi, Hirokazu; Motomura, Masakatsu; Chiba, Atsuro

2018-06-01

A 61-year-old woman who had smoked for 41 years developed subacute dizziness, ataxic gait, opsoclonus, and right visual impairment. She had right optic disc swelling and optic nerve gadolinium enhancement on magnetic resonance imaging. She had small-cell lung cancer (SCLC), with CV2/collapsin response mediator protein (CRMP) 5 and HuD antibodies in her serum and cerebrospinal fluid. She was diagnosed with paraneoplastic optic neuropathy (PON) accompanied by paraneoplastic opsoclonus-ataxia syndrome. Her symptoms improved after removing the SCLC. Classical PON is rare in Japan. We recommend assaying for CV2/CRMP5 antibodies and searching for cancer in elderly patients with subacute painless visual impairment.

Local thermal injury elicits immediate dynamic behavioural responses by corneal Langerhans cells

PubMed Central

Ward, Brant R; Jester, James V; Nishibu, Akiko; Vishwanath, Mridula; Shalhevet, David; Kumamoto, Tadashi; Petroll, W Matthew; Cavanagh, H Dwight; Takashima, Akira

2007-01-01

Langerhans cells (LCs) represent a special subset of immature dendritic cells (DCs) that reside in epithelial tissues at the environmental interfaces. Although dynamic interactions of mature DCs with T cells have been visualized in lymph nodes, the cellular behaviours linked with the surveillance of tissues for pathogenic signals, an important function of immature DCs, remain unknown. To visualize LCs in situ, bone marrow cells from C57BL/6 mice expressing the enhanced green fluorescent protein (EGFP) transgene were transplanted into syngeneic wild-type recipients. Motile activities of EGFP+ corneal LCs in intact organ cultures were then recorded by time lapse two-photon microscopy. At baseline, corneal LCs exhibited a unique motion, termed dendrite surveillance extension and retraction cycling habitude (dSEARCH), characterized by rhythmic extension and retraction of their dendritic processes through intercellular spaces between epithelial cells. Upon pinpoint injury produced by infrared laser, LCs showed augmented dSEARCH and amoeba-like lateral movement. Interleukin (IL)-1 receptor antagonist completely abrogated both injury-associated changes, suggesting roles for IL-1. In the absence of injury, exogenous IL-1 caused a transient increase in dSEARCH without provoking lateral migration, whereas tumour necrosis factor-α induced both changes. Our results demonstrate rapid cytokine-mediated behavioural responses by LCs to local tissue injury, providing new insights into the biology of LCs. PMID:17250587

Visual Attention in Flies-Dopamine in the Mushroom Bodies Mediates the After-Effect of Cueing.

PubMed

Koenig, Sebastian; Wolf, Reinhard; Heisenberg, Martin

2016-01-01

Visual environments may simultaneously comprise stimuli of different significance. Often such stimuli require incompatible responses. Selective visual attention allows an animal to respond exclusively to the stimuli at a certain location in the visual field. In the process of establishing its focus of attention the animal can be influenced by external cues. Here we characterize the behavioral properties and neural mechanism of cueing in the fly Drosophila melanogaster. A cue can be attractive, repulsive or ineffective depending upon (e.g.) its visual properties and location in the visual field. Dopamine signaling in the brain is required to maintain the effect of cueing once the cue has disappeared. Raising or lowering dopamine at the synapse abolishes this after-effect. Specifically, dopamine is necessary and sufficient in the αβ-lobes of the mushroom bodies. Evidence is provided for an involvement of the αβposterior Kenyon cells.

A comparison of binocular depth mechanisms in areas 17 and 18 of the cat visual cortex

PubMed Central

Ferster, David

1981-01-01

1. The retinal disparity sensitivity of neurones in areas 17 and 18 of the cat visual cortex was examined. The response of each cell to an optimally oriented slit was measured as disparity was varied orthogonally to the receptive field orientation. Eye movements were monitored with a binocular reference cell simultaneously recorded in area 17 (Hubel & Wiesel, 1970). 2. Two types of disparity-sensitive cells were found, similar to those observed in the monkey by Poggio & Fischer (1977). The first type, tuned excitatory cells, were usually binocular and had a sharp peak in their disparity—response curve. They responded maximally at the disparity that brought their receptive fields into superposition on the tangent screen. This disparity closely coincided with the disparity at which the reference cell's receptive fields were also superimposed. By analogy with the monkey this point was taken to be the fixation point, or 0°. The second type, near and far cells, were most often monocular. They gave their weakest response (which was usually no response at all) at 0°. On one side of 0° the response grew linearly for up to 4° and then remained at the maximum. On the other side of zero, it remained at the minimum for up to several degrees before rising towards the maximum. 3. The receptive field organization of several disparity-sensitive cells was examined using the activity profile method of Henry, Bishop & Coombs (1969). The size and strength of the discrete excitatory and inhibitory regions of the receptive fields of a cell could quantitatively account for the shape of its disparity—response curve. 4. The laminar distribution of disparity sensitivity as well as of several other receptive field properties in areas 17 and 18 was studied. The organization of the two areas was remarkably similar in many respects. There was a difference, however, in the proportions of the two types of disparity-sensitive cells in the two areas. Area 17 contained many more tuned excitatory cells than near and far cells, while area 18 had the reverse distribution. In addition, the cells in area 18 were sensitive to a much broader range of disparities. While both areas contain disparity-sensitive neurones, these differences suggest that they play different roles in depth vision. 5. Recent psychophysical and neurophysiological evidence has led to a new model of stereopsis in which depth is signalled by the pooled activity of large groups of cells (Richards, 1971). The current results are consistent with this model. PMID:7264985

Two-photon imaging of formaldehyde in live cells and animals utilizing a lysosome-targetable and acidic pH-activatable fluorescent probe.

PubMed

Xie, Xilei; Tang, Fuyan; Shangguan, Xiaoyan; Che, Shiyi; Niu, Jinye; Xiao, Yongsheng; Wang, Xu; Tang, Bo

2017-06-13

Lyso-TPFP presents lysosomal targetability and an acidic pH-activatable response toward formaldehyde. Thus, it exclusively visualizes lysosomal formaldehyde and is immune against it in neutral cytosol and other organelles. In addition, two-photon fluorescence imaging endows Lyso-TPFP with the capability of in situ tracking formaldehyde in live cells and animals.

Contrast adaptation in cat visual cortex is not mediated by GABA.

PubMed

DeBruyn, E J; Bonds, A B

1986-09-24

The possible involvement of gamma-aminobutyric acid (GABA) in contrast adaptation in single cells in area 17 of the cat was investigated. Iontophoretic application of N-methyl bicuculline increased cell responses, but had no effect on the magnitude of adaptation. These results suggest that contrast adaptation is the result of inhibition through a parallel pathway, but that GABA does not mediate this process.

Direct and Indirect Visualization of Bacterial Effector Delivery into Diverse Plant Cell Types during Infection[OPEN

PubMed Central

Henry, Elizabeth; Jauneau, Alain; Deslandes, Laurent

2017-01-01

To cause disease, diverse pathogens deliver effector proteins into host cells. Pathogen effectors can inhibit defense responses, alter host physiology, and represent important cellular probes to investigate plant biology. However, effector function and localization have primarily been investigated after overexpression in planta. Visualizing effector delivery during infection is challenging due to the plant cell wall, autofluorescence, and low effector abundance. Here, we used a GFP strand system to directly visualize bacterial effectors delivered into plant cells through the type III secretion system. GFP is a beta barrel that can be divided into 11 strands. We generated transgenic Arabidopsis thaliana plants expressing GFP1-10 (strands 1 to 10). Multiple bacterial effectors tagged with the complementary strand 11 epitope retained their biological function in Arabidopsis and tomato (Solanum lycopersicum). Infection of plants expressing GFP1-10 with bacteria delivering GFP11-tagged effectors enabled direct effector detection in planta. We investigated the temporal and spatial delivery of GFP11-tagged effectors during infection with the foliar pathogen Pseudomonas syringae and the vascular pathogen Ralstonia solanacearum. Thus, the GFP strand system can be broadly used to investigate effector biology in planta. PMID:28600390

Localized direction selective responses in the dendrites of visual interneurons of the fly

PubMed Central

2010-01-01

Background The various tasks of visual systems, including course control, collision avoidance and the detection of small objects, require at the neuronal level the dendritic integration and subsequent processing of many spatially distributed visual motion inputs. While much is known about the pooled output in these systems, as in the medial superior temporal cortex of monkeys or in the lobula plate of the insect visual system, the motion tuning of the elements that provide the input has yet received little attention. In order to visualize the motion tuning of these inputs we examined the dendritic activation patterns of neurons that are selective for the characteristic patterns of wide-field motion, the lobula-plate tangential cells (LPTCs) of the blowfly. These neurons are known to sample direction-selective motion information from large parts of the visual field and combine these signals into axonal and dendro-dendritic outputs. Results Fluorescence imaging of intracellular calcium concentration allowed us to take a direct look at the local dendritic activity and the resulting local preferred directions in LPTC dendrites during activation by wide-field motion in different directions. These 'calcium response fields' resembled a retinotopic dendritic map of local preferred directions in the receptive field, the layout of which is a distinguishing feature of different LPTCs. Conclusions Our study reveals how neurons acquire selectivity for distinct visual motion patterns by dendritic integration of the local inputs with different preferred directions. With their spatial layout of directional responses, the dendrites of the LPTCs we investigated thus served as matched filters for wide-field motion patterns. PMID:20384983

Chronic intraventricular administration of lysergic acid diethylamide (LSD) affects the sensitivity of cortical cells to monocular deprivation.

PubMed

McCall, M A; Tieman, D G; Hirsch, H V

1982-11-04

In kittens, but not in adult cats, depriving one eye of pattern vision by suturing the lids shut (monocular deprivation or MD) for one week reduces the proportion of binocular units in the visual cortex. A sensitivity of cortical units in adult cats to MD can be produced by infusing exogenous monoamines into the visual cortex. Since LSD interacts with monoamines, we have examined the effects of chronic administration of LSD on the sensitivity to MD for cortical cells in adult cats. Cats were assigned randomly to one of four conditions: MD/LSD, MD/No-LSD, No-MD/LSD, No-MD/No-LSD. An osmotic minipump delivered either LSD or the vehicle solution alone during a one-week period of MD. The animals showed no obvious anomalies during the administration of the drug. After one week the response properties of single units in area 17 of the visual cortex were studied without knowledge of the contents of the individual minipumps. With the exception of ocular dominance, the response properties of units recorded in all animals did not differ from normal. In the control animals (MD/No-LSD, No-MD/LSD, No-MD/No-LSD) the average proportion of binocular cells was 78%; similar to that observed for normal adult cats. However, in the experimental animals, which received LSD during the period of MD, only 52% of the cells were binocular. Our results suggest that chronic intraventricular administration of LSD affects either directly or indirectly the sensitivity of cortical neurons to MD.

Origin and Function of Tuning Diversity in Macaque Visual Cortex

PubMed Central

Goris, Robbe L.T.; Simoncelli, Eero P.; Movshon, J. Anthony

2016-01-01

SUMMARY Neurons in visual cortex vary in their orientation selectivity. We measured responses of V1 and V2 cells to orientation mixtures and fit them with a model whose stimulus selectivity arises from the combined effects of filtering, suppression, and response nonlinearity. The model explains the diversity of orientation selectivity with neuron-to-neuron variability in all three mechanisms, of which variability in the orientation bandwidth of linear filtering is the most important. The model also accounts for the cells’ diversity of spatial frequency selectivity. Tuning diversity is matched to the needs of visual encoding. The orientation content found in natural scenes is diverse, and neurons with different selectivities are adapted to different stimulus configurations. Single orientations are better encoded by highly selective neurons, while orientation mixtures are better encoded by less selective neurons. A diverse population of neurons therefore provides better overall discrimination capabilities for natural images than any homogeneous population. PMID:26549331

Photochemical restoration of visual responses in blind mice

PubMed Central

Polosukhina, Aleksandra; Litt, Jeffrey; Tochitsky, Ivan; Nemargut, Joseph; Sychev, Yivgeny; De Kouchkovsky, Ivan; Huang, Tracy; Borges, Katharine; Trauner, Dirk; Van Gelder, Russell N.; Kramer, Richard H.

2012-01-01

Summary Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are degenerative blinding diseases caused by the death of rods and cones, leaving the remainder of the visual system intact but largely unable to respond to light. Here we show that, AAQ, a synthetic small molecule photoswitch, can restore light sensitivity to the retina and behavioral responses in vivo in mouse models of RP without exogenous gene delivery. Brief application of AAQ bestows prolonged light sensitivity on multiple types of retinal neurons, resulting in synaptically amplified responses and center-surround antagonism in arrays of retinal ganglion cells (RGCs). Intraocular injection of AAQ restores the pupillary light reflex and locomotory light avoidance responses in mice lacking retinal photoreceptors, indicating reconstitution of light signaling to brain circuits. AAQ and related photoswitch molecules present a new drug strategy for restoring retinal function in degenerative blinding diseases. PMID:22841312

Nanowire arrays restore vision in blind mice.

PubMed

Tang, Jing; Qin, Nan; Chong, Yan; Diao, Yupu; Yiliguma; Wang, Zhexuan; Xue, Tian; Jiang, Min; Zhang, Jiayi; Zheng, Gengfeng

2018-03-06

The restoration of light response with complex spatiotemporal features in retinal degenerative diseases towards retinal prosthesis has proven to be a considerable challenge over the past decades. Herein, inspired by the structure and function of photoreceptors in retinas, we develop artificial photoreceptors based on gold nanoparticle-decorated titania nanowire arrays, for restoration of visual responses in the blind mice with degenerated photoreceptors. Green, blue and near UV light responses in the retinal ganglion cells (RGCs) are restored with a spatial resolution better than 100 µm. ON responses in RGCs are blocked by glutamatergic antagonists, suggesting functional preservation of the remaining retinal circuits. Moreover, neurons in the primary visual cortex respond to light after subretinal implant of nanowire arrays. Improvement in pupillary light reflex suggests the behavioral recovery of light sensitivity. Our study will shed light on the development of a new generation of optoelectronic toolkits for subretinal prosthetic devices.

Population-level coordination of pigment response in individual cyanobacterial cells under altered nitrogen levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murton, Jaclyn; Nagarajan, Aparna; Nguyen, Amelia Y.

Cyanobacterial phycobilisome (PBS) pigment-protein complexes harvest light and transfer the energy to reaction centers. Previous ensemble studies have shown that cyanobacteria respond to changes in nutrient availability by modifying the structure of PBS complexes, but this process has not been visualized for individual pigments at the single-cell level due to spectral overlap. We characterized the response of four key photosynthetic pigments to nitrogen depletion and repletion at the subcellular level in individual, live Synechocystis sp. PCC 6803 cells using hyperspectral confocal fluorescence microscopy and multivariate image analysis. Our results revealed that PBS degradation and re-synthesis comprise a rapid response tomore » nitrogen fluctuations, with coordinated populations of cells undergoing pigment modifications. Chlorophyll fluorescence originating from photosystem I and II decreased during nitrogen starvation, but no alteration in subcellular chlorophyll localization was found. Lastly, we observed differential rod and core pigment responses to nitrogen deprivation, suggesting that PBS complexes undergo a stepwise degradation process.« less

Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy.

PubMed

Melo, Rossana C N; Weller, Peter F

2016-10-01

Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles - EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. Copyright © 2016 Elsevier Inc. All rights reserved.

Population-level coordination of pigment response in individual cyanobacterial cells under altered nitrogen levels

DOE PAGES

Murton, Jaclyn; Nagarajan, Aparna; Nguyen, Amelia Y.; ...

2017-07-21

Cyanobacterial phycobilisome (PBS) pigment-protein complexes harvest light and transfer the energy to reaction centers. Previous ensemble studies have shown that cyanobacteria respond to changes in nutrient availability by modifying the structure of PBS complexes, but this process has not been visualized for individual pigments at the single-cell level due to spectral overlap. We characterized the response of four key photosynthetic pigments to nitrogen depletion and repletion at the subcellular level in individual, live Synechocystis sp. PCC 6803 cells using hyperspectral confocal fluorescence microscopy and multivariate image analysis. Our results revealed that PBS degradation and re-synthesis comprise a rapid response tomore » nitrogen fluctuations, with coordinated populations of cells undergoing pigment modifications. Chlorophyll fluorescence originating from photosystem I and II decreased during nitrogen starvation, but no alteration in subcellular chlorophyll localization was found. Lastly, we observed differential rod and core pigment responses to nitrogen deprivation, suggesting that PBS complexes undergo a stepwise degradation process.« less

The Analysis of Visual Motion: From Computational Theory to Neuronal Mechanisms.

DTIC Science & Technology

1986-12-01

neuronb. Brain Res. 151:599-603. Frost, B . J., Nakayama, K . 1983. Single visual neurons code opposing motion independent JW of direction. Science 220:744...Biol. Cybern. 42:195-204. llolden, A. 1. 1977. Responses of directional ganglion cells in the pigeon retina. J. Physiol., 270:2,53 269. Horn. B . K . P...R. Soc. Iond. B . 223:165-175. 51 % Computations Underlying Motion ttildret ik Koch %V. Longuet-Iliggins, H. C., Prazdny. K . 1981. The interpretation

Objective Methods to Test Visual Dysfunction in the Presence of Cognitive Impairment

DTIC Science & Technology

2011-10-01

retinitis   pigmentosa .    Ophthalmology...response  to  light  stimuli  for  diagnosing   retinal    and  optic  nerve  disorders           We  have... retinal  ganglion  cell  response  using  red  and  blue  stimuli  at  low  and  high   intensities

Modification of response functions of cat visual cortical cells by spatially congruent perturbing stimuli.

PubMed

Kabara, J F; Bonds, A B

2001-12-01

Responses of cat striate cortical cells to a drifting sinusoidal grating were modified by the superimposition of a second, perturbing grating (PG) that did not excite the cell when presented alone. One consequence of the presence of a PG was a shift in the tuning curves. The orientation tuning of all 41 cells exposed to a PG and the spatial frequency tuning of 83% of the 23 cells exposed to a PG showed statistically significant dislocations of both the response function peak and center of mass from their single grating values. As found in earlier reports, the presence of PGs suppressed responsiveness. However, reductions measured at the single grating optimum orientation or spatial frequency were on average 1.3 times greater than the suppression found at the peak of the response function modified by the presence of the PG. Much of the loss in response seen at the single grating optimum is thus a result of a shift in the tuning function rather than outright suppression. On average orientation shifts were repulsive and proportional (approximately 0.10 deg/deg) to the angle between the perturbing stimulus and the optimum single grating orientation. Shifts in the spatial frequency response function were both attractive and repulsive, resulting in an overall average of zero. For both simple and complex cells, PGs generally broadened orientation response function bandwidths. Similarly, complex cell spatial frequency response function bandwidths broadened. Simple cell spatial frequency response functions usually did not change, and those that did broadened only 4% on average. These data support the hypothesis that additional sinusoidal components in compound stimuli retune cells' response functions for orientation and spatial frequency.

Selective representation of task-relevant objects and locations in the monkey prefrontal cortex.

PubMed

Everling, Stefan; Tinsley, Chris J; Gaffan, David; Duncan, John

2006-04-01

In the monkey prefrontal cortex (PFC), task context exerts a strong influence on neural activity. We examined different aspects of task context in a temporal search task. On each trial, the monkey (Macaca mulatta) watched a stream of pictures presented to left or right of fixation. The task was to hold fixation until seeing a particular target, and then to make an immediate saccade to it. Sometimes (unilateral task), the attended pictures appeared alone, with a cue at trial onset indicating whether they would be presented to left or right. Sometimes (bilateral task), the attended picture stream (cued side) was accompanied by an irrelevant stream on the opposite side. In two macaques, we recorded responses from a total of 161 cells in the lateral PFC. Many cells (75/161) showed visual responses. Object-selective responses were strongly shaped by task relevance - with stronger responses to targets than to nontargets, failure to discriminate one nontarget from another, and filtering out of information from an irrelevant stimulus stream. Location selectivity occurred rather independently of object selectivity, and independently in visual responses and delay periods between one stimulus and the next. On error trials, PFC activity followed the correct rules of the task, rather than the incorrect overt behaviour. Together, these results suggest a highly programmable system, with responses strongly determined by the rules and requirements of the task performed.

Cumulative latency advance underlies fast visual processing in desynchronized brain state

PubMed Central

Wang, Xu-dong; Chen, Cheng; Zhang, Dinghong; Yao, Haishan

2014-01-01

Fast sensory processing is vital for the animal to efficiently respond to the changing environment. This is usually achieved when the animal is vigilant, as reflected by cortical desynchronization. However, the neural substrate for such fast processing remains unclear. Here, we report that neurons in rat primary visual cortex (V1) exhibited shorter response latency in the desynchronized state than in the synchronized state. In vivo whole-cell recording from the same V1 neurons undergoing the two states showed that both the resting and visually evoked conductances were higher in the desynchronized state. Such conductance increases of single V1 neurons shorten the response latency by elevating the membrane potential closer to the firing threshold and reducing the membrane time constant, but the effects only account for a small fraction of the observed latency advance. Simultaneous recordings in lateral geniculate nucleus (LGN) and V1 revealed that LGN neurons also exhibited latency advance, with a degree smaller than that of V1 neurons. Furthermore, latency advance in V1 increased across successive cortical layers. Thus, latency advance accumulates along various stages of the visual pathway, likely due to a global increase of membrane conductance in the desynchronized state. This cumulative effect may lead to a dramatic shortening of response latency for neurons in higher visual cortex and play a critical role in fast processing for vigilant animals. PMID:24347634

Adaptation of velocity encoding in synaptically coupled neurons in the fly visual system.

PubMed

Kalb, Julia; Egelhaaf, Martin; Kurtz, Rafael

2008-09-10

Although many adaptation-induced effects on neuronal response properties have been described, it is often unknown at what processing stages in the nervous system they are generated. We focused on fly visual motion-sensitive neurons to identify changes in response characteristics during prolonged visual motion stimulation. By simultaneous recordings of synaptically coupled neurons, we were able to directly compare adaptation-induced effects at two consecutive processing stages in the fly visual motion pathway. This allowed us to narrow the potential sites of adaptation effects within the visual system and to relate them to the properties of signal transfer between neurons. Motion adaptation was accompanied by a response reduction, which was somewhat stronger in postsynaptic than in presynaptic cells. We found that the linear representation of motion velocity degrades during adaptation to a white-noise velocity-modulated stimulus. This effect is caused by an increasingly nonlinear velocity representation rather than by an increase of noise and is similarly strong in presynaptic and postsynaptic neurons. In accordance with this similarity, the dynamics and the reliability of interneuronal signal transfer remained nearly constant. Thus, adaptation is mainly based on processes located in the presynaptic neuron or in more peripheral processing stages. In contrast, changes of transfer properties at the analyzed synapse or in postsynaptic spike generation contribute little to changes in velocity coding during motion adaptation.

Visuocortical Changes During Delay and Trace Aversive Conditioning: Evidence From Steady-State Visual Evoked Potentials

PubMed Central

Miskovic, Vladimir; Keil, Andreas

2015-01-01

The visual system is biased towards sensory cues that have been associated with danger or harm through temporal co-occurrence. An outstanding question about conditioning-induced changes in visuocortical processing is the extent to which they are driven primarily by top-down factors such as expectancy or by low-level factors such as the temporal proximity between conditioned stimuli and aversive outcomes. Here, we examined this question using two different differential aversive conditioning experiments: participants learned to associate a particular grating stimulus with an aversive noise that was presented either in close temporal proximity (delay conditioning experiment) or after a prolonged stimulus-free interval (trace conditioning experiment). In both experiments we probed cue-related cortical responses by recording steady-state visual evoked potentials (ssVEPs). Although behavioral ratings indicated that all participants successfully learned to discriminate between the grating patterns that predicted the presence versus absence of the aversive noise, selective amplification of population-level responses in visual cortex for the conditioned danger signal was observed only when the grating and the noise were temporally contiguous. Our findings are in line with notions purporting that changes in the electrocortical response of visual neurons induced by aversive conditioning are a product of Hebbian associations among sensory cell assemblies rather than being driven entirely by expectancy-based, declarative processes. PMID:23398582

Cumulative latency advance underlies fast visual processing in desynchronized brain state.

PubMed

Wang, Xu-dong; Chen, Cheng; Zhang, Dinghong; Yao, Haishan

2014-01-07

Fast sensory processing is vital for the animal to efficiently respond to the changing environment. This is usually achieved when the animal is vigilant, as reflected by cortical desynchronization. However, the neural substrate for such fast processing remains unclear. Here, we report that neurons in rat primary visual cortex (V1) exhibited shorter response latency in the desynchronized state than in the synchronized state. In vivo whole-cell recording from the same V1 neurons undergoing the two states showed that both the resting and visually evoked conductances were higher in the desynchronized state. Such conductance increases of single V1 neurons shorten the response latency by elevating the membrane potential closer to the firing threshold and reducing the membrane time constant, but the effects only account for a small fraction of the observed latency advance. Simultaneous recordings in lateral geniculate nucleus (LGN) and V1 revealed that LGN neurons also exhibited latency advance, with a degree smaller than that of V1 neurons. Furthermore, latency advance in V1 increased across successive cortical layers. Thus, latency advance accumulates along various stages of the visual pathway, likely due to a global increase of membrane conductance in the desynchronized state. This cumulative effect may lead to a dramatic shortening of response latency for neurons in higher visual cortex and play a critical role in fast processing for vigilant animals.

Peripheral Processing Facilitates Optic Flow-Based Depth Perception

PubMed Central

Li, Jinglin; Lindemann, Jens P.; Egelhaaf, Martin

2016-01-01

Flying insects, such as flies or bees, rely on consistent information regarding the depth structure of the environment when performing their flight maneuvers in cluttered natural environments. These behaviors include avoiding collisions, approaching targets or spatial navigation. Insects are thought to obtain depth information visually from the retinal image displacements (“optic flow”) during translational ego-motion. Optic flow in the insect visual system is processed by a mechanism that can be modeled by correlation-type elementary motion detectors (EMDs). However, it is still an open question how spatial information can be extracted reliably from the responses of the highly contrast- and pattern-dependent EMD responses, especially if the vast range of light intensities encountered in natural environments is taken into account. This question will be addressed here by systematically modeling the peripheral visual system of flies, including various adaptive mechanisms. Different model variants of the peripheral visual system were stimulated with image sequences that mimic the panoramic visual input during translational ego-motion in various natural environments, and the resulting peripheral signals were fed into an array of EMDs. We characterized the influence of each peripheral computational unit on the representation of spatial information in the EMD responses. Our model simulations reveal that information about the overall light level needs to be eliminated from the EMD input as is accomplished under light-adapted conditions in the insect peripheral visual system. The response characteristics of large monopolar cells (LMCs) resemble that of a band-pass filter, which reduces the contrast dependency of EMDs strongly, effectively enhancing the representation of the nearness of objects and, especially, of their contours. We furthermore show that local brightness adaptation of photoreceptors allows for spatial vision under a wide range of dynamic light conditions. PMID:27818631

Alert Response to Motion Onset in the Retina

PubMed Central

Chen, Eric Y.; Marre, Olivier; Fisher, Clark; Schwartz, Greg; Levy, Joshua; da Silveira, Rava Azeredo

2013-01-01

Previous studies have shown that motion onset is very effective at capturing attention and is more salient than smooth motion. Here, we find that this salience ranking is present already in the firing rate of retinal ganglion cells. By stimulating the retina with a bar that appears, stays still, and then starts moving, we demonstrate that a subset of salamander retinal ganglion cells, fast OFF cells, responds significantly more strongly to motion onset than to smooth motion. We refer to this phenomenon as an alert response to motion onset. We develop a computational model that predicts the time-varying firing rate of ganglion cells responding to the appearance, onset, and smooth motion of a bar. This model, termed the adaptive cascade model, consists of a ganglion cell that receives input from a layer of bipolar cells, represented by individual rectified subunits. Additionally, both the bipolar and ganglion cells have separate contrast gain control mechanisms. This model captured the responses to our different motion stimuli over a wide range of contrasts, speeds, and locations. The alert response to motion onset, together with its computational model, introduces a new mechanism of sophisticated motion processing that occurs early in the visual system. PMID:23283327

Multiple vibration modes within the organ of Corti revealed by high-resolution, outer-hair-cell-driven micromechanical motions at acoustic frequencies

NASA Astrophysics Data System (ADS)

Karavitaki, K. Domenica; Guinan, John J.; Mountain, David C.

2018-05-01

Electrically-evoked outer-hair-cell-driven micromechanical motions within the organ of Corti were visualized and quantified using a video stroboscopy system. The resulting radial motions exhibited phase transitions along the radial direction, characteristic of a system that can exhibit multiple modes of vibration. We argue that the interaction of these modes would shape the input to the inner hair cell hair bundles and resulting auditory-nerve response patterns.

Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits.

PubMed

Xu, Hong-Ping; Burbridge, Timothy J; Ye, Meijun; Chen, Minggang; Ge, Xinxin; Zhou, Z Jimmy; Crair, Michael C

2016-03-30

Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical,in vitroandin vivoelectrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of β2 subunits of nicotinic acetylcholine receptors (β2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that β2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the "recurrent network" model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development. Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic "retinal waves" are initiated in starburst amacrine cells and propagate to retinal ganglion cells and higher-order visual areas, but the mechanism responsible for creating their unique and critical activity pattern is incompletely understood. We demonstrate that cholinergic wave patterns are dictated by recurrent connectivity within starburst amacrine cells, and retinal ganglion cells act as "readouts" of patterned activity. We also show that eye-specific segregation occurs normally without glutamatergic waves, but elimination of both cholinergic and glutamatergic waves completely disrupts visual circuit development. These results suggest that each retinal wave pattern during development is optimized for concurrently refining multiple visual circuits. Copyright © 2016 the authors 0270-6474/16/363872-16$15.00/0.

Neural basis of forward flight control and landing in honeybees.

PubMed

Ibbotson, M R; Hung, Y-S; Meffin, H; Boeddeker, N; Srinivasan, M V

2017-11-06

The impressive repertoire of honeybee visually guided behaviors, and their ability to learn has made them an important tool for elucidating the visual basis of behavior. Like other insects, bees perform optomotor course correction to optic flow, a response that is dependent on the spatial structure of the visual environment. However, bees can also distinguish the speed of image motion during forward flight and landing, as well as estimate flight distances (odometry), irrespective of the visual scene. The neural pathways underlying these abilities are unknown. Here we report on a cluster of descending neurons (DNIIIs) that are shown to have the directional tuning properties necessary for detecting image motion during forward flight and landing on vertical surfaces. They have stable firing rates during prolonged periods of stimulation and respond to a wide range of image speeds, making them suitable to detect image flow during flight behaviors. While their responses are not strictly speed tuned, the shape and amplitudes of their speed tuning functions are resistant to large changes in spatial frequency. These cells are prime candidates not only for the control of flight speed and landing, but also the basis of a neural 'front end' of the honeybee's visual odometer.

Human infrared vision is triggered by two-photon chromophore isomerization

PubMed Central

Palczewska, Grazyna; Vinberg, Frans; Stremplewski, Patrycjusz; Bircher, Martin P.; Salom, David; Komar, Katarzyna; Zhang, Jianye; Cascella, Michele; Wojtkowski, Maciej; Kefalov, Vladimir J.; Palczewski, Krzysztof

2014-01-01

Vision relies on photoactivation of visual pigments in rod and cone photoreceptor cells of the retina. The human eye structure and the absorption spectra of pigments limit our visual perception of light. Our visual perception is most responsive to stimulating light in the 400- to 720-nm (visible) range. First, we demonstrate by psychophysical experiments that humans can perceive infrared laser emission as visible light. Moreover, we show that mammalian photoreceptors can be directly activated by near infrared light with a sensitivity that paradoxically increases at wavelengths above 900 nm, and display quadratic dependence on laser power, indicating a nonlinear optical process. Biochemical experiments with rhodopsin, cone visual pigments, and a chromophore model compound 11-cis-retinyl-propylamine Schiff base demonstrate the direct isomerization of visual chromophore by a two-photon chromophore isomerization. Indeed, quantum mechanics modeling indicates the feasibility of this mechanism. Together, these findings clearly show that human visual perception of near infrared light occurs by two-photon isomerization of visual pigments. PMID:25453064

Genome dynamics of the human embryonic kidney 293 lineage in response to cell biology manipulations.

PubMed

Lin, Yao-Cheng; Boone, Morgane; Meuris, Leander; Lemmens, Irma; Van Roy, Nadine; Soete, Arne; Reumers, Joke; Moisse, Matthieu; Plaisance, Stéphane; Drmanac, Radoje; Chen, Jason; Speleman, Frank; Lambrechts, Diether; Van de Peer, Yves; Tavernier, Jan; Callewaert, Nico

2014-09-03

The HEK293 human cell lineage is widely used in cell biology and biotechnology. Here we use whole-genome resequencing of six 293 cell lines to study the dynamics of this aneuploid genome in response to the manipulations used to generate common 293 cell derivatives, such as transformation and stable clone generation (293T); suspension growth adaptation (293S); and cytotoxic lectin selection (293SG). Remarkably, we observe that copy number alteration detection could identify the genomic region that enabled cell survival under selective conditions (i.c. ricin selection). Furthermore, we present methods to detect human/vector genome breakpoints and a user-friendly visualization tool for the 293 genome data. We also establish that the genome structure composition is in steady state for most of these cell lines when standard cell culturing conditions are used. This resource enables novel and more informed studies with 293 cells, and we will distribute the sequenced cell lines to this effect.

The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations.

PubMed

Keenan, Alexandra B; Jenkins, Sherry L; Jagodnik, Kathleen M; Koplev, Simon; He, Edward; Torre, Denis; Wang, Zichen; Dohlman, Anders B; Silverstein, Moshe C; Lachmann, Alexander; Kuleshov, Maxim V; Ma'ayan, Avi; Stathias, Vasileios; Terryn, Raymond; Cooper, Daniel; Forlin, Michele; Koleti, Amar; Vidovic, Dusica; Chung, Caty; Schürer, Stephan C; Vasiliauskas, Jouzas; Pilarczyk, Marcin; Shamsaei, Behrouz; Fazel, Mehdi; Ren, Yan; Niu, Wen; Clark, Nicholas A; White, Shana; Mahi, Naim; Zhang, Lixia; Kouril, Michal; Reichard, John F; Sivaganesan, Siva; Medvedovic, Mario; Meller, Jaroslaw; Koch, Rick J; Birtwistle, Marc R; Iyengar, Ravi; Sobie, Eric A; Azeloglu, Evren U; Kaye, Julia; Osterloh, Jeannette; Haston, Kelly; Kalra, Jaslin; Finkbiener, Steve; Li, Jonathan; Milani, Pamela; Adam, Miriam; Escalante-Chong, Renan; Sachs, Karen; Lenail, Alex; Ramamoorthy, Divya; Fraenkel, Ernest; Daigle, Gavin; Hussain, Uzma; Coye, Alyssa; Rothstein, Jeffrey; Sareen, Dhruv; Ornelas, Loren; Banuelos, Maria; Mandefro, Berhan; Ho, Ritchie; Svendsen, Clive N; Lim, Ryan G; Stocksdale, Jennifer; Casale, Malcolm S; Thompson, Terri G; Wu, Jie; Thompson, Leslie M; Dardov, Victoria; Venkatraman, Vidya; Matlock, Andrea; Van Eyk, Jennifer E; Jaffe, Jacob D; Papanastasiou, Malvina; Subramanian, Aravind; Golub, Todd R; Erickson, Sean D; Fallahi-Sichani, Mohammad; Hafner, Marc; Gray, Nathanael S; Lin, Jia-Ren; Mills, Caitlin E; Muhlich, Jeremy L; Niepel, Mario; Shamu, Caroline E; Williams, Elizabeth H; Wrobel, David; Sorger, Peter K; Heiser, Laura M; Gray, Joe W; Korkola, James E; Mills, Gordon B; LaBarge, Mark; Feiler, Heidi S; Dane, Mark A; Bucher, Elmar; Nederlof, Michel; Sudar, Damir; Gross, Sean; Kilburn, David F; Smith, Rebecca; Devlin, Kaylyn; Margolis, Ron; Derr, Leslie; Lee, Albert; Pillai, Ajay

2018-01-24

The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability. Copyright © 2017 Elsevier Inc. All rights reserved.

Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors

PubMed Central

1977-01-01

Polymorphonuclear leukocyte (PMN) chemotaxis has been examined under conditions which allow phase microscope observations of cells responding to controlled gradients of chemotactic factors. With this visual assay, PMNs can be seen to orient rapidly and reversibly to gradients of N-formylmethionyl peptides. The level of orientation depends upon the mean concentration of peptide present as well as the concentration gradient. The response allows an estimation of the binding constant of the peptide to the cell. In optimal gradients, PMNs can detect a 1% difference in the concentration of peptide. At high cell densities, PMNs incubated with active peptides orient their locomotion away from the center of the cell population. This orientation appears to be due to inactivation of the peptides by the cells. Such inactivation in vivo could help to limit an inflammatory response. PMID:264125

Immunofluorescence Staining Protocols for Major Autophagy Proteins Including LC3, P62, and ULK1 in Mammalian Cells in Response to Normoxia and Hypoxia.

PubMed

Li, Wen; Li, Shupeng; Li, Yifang; Lin, Xiaoying; Hu, Yongquan; Meng, Tian; Wu, Baojin; He, Rongrong; Feng, Du

2018-03-27

Immunofluorescence is an invaluable technique widely used in cell biology. This technique allows visualization of the subcellular distribution of different target proteins or organelles, by specific recognition of the antibody to the endogenous protein itself or to its antigen via the epitope. This technique can be used on tissue sections, cultured cells, or individual cells. Meanwhile, immunofluorescence can also be used in combination with non-antibody fluorescent staining, such as DAPI or fluorescent fusion proteins, e.g., GFP or YFP, etc.Autophagy is a catabolic pathway in which dysfunctional organelles and cellular components are degraded via lysosomes. During this process, cytoplasmic LC3 translocates to autophagosomal membranes. Therefore, cells undergoing autophagy can be identified by visualizing fluorescently labeled LC3 or other autophagy markers. Immunofluorescence is an important part of autophagy detection methods even if observation of the formation of autophagosome by transmission electron microscopy has become a gold standard for characterizing autophagy.By observing the immunofluorescence staining of some key autophagy proteins, we can intuitively evaluate the levels of autophagy in samples. Herein, this protocol describes the predominant method used for the research of autophagy, which mainly focuses on the immunofluorescence staining of cellular LC3, P62, and ULK1 in response to normoxia and hypoxia, by presenting the detailed materials required and methodology.

The stimulus selectivity and connectivity of layer six principal cells reveals cortical microcircuits underlying visual processing.

PubMed

Vélez-Fort, Mateo; Rousseau, Charly V; Niedworok, Christian J; Wickersham, Ian R; Rancz, Ede A; Brown, Alexander P Y; Strom, Molly; Margrie, Troy W

2014-09-17

Sensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway. We show that CC-projecting cells encompass a broad spectrum of selectivity to stimulus orientation and are predominantly innervated by deep layer V1 neurons. In contrast, CT-projecting cells are ultrasparse firing, exquisitely tuned to orientation and direction information, and receive long-range input from higher cortical areas. This segregation in function and connectivity indicates that L6 microcircuits route specific contextual and stimulus-related information within and outside the cortical network. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Profiling antibody responses by multiparametric analysis of primary B cells

PubMed Central

Story, Craig M.; Papa, Eliseo; Hu, Chih-Chi Andrew; Ronan, Jehnna L.; Herlihy, Kara; Ploegh, Hidde L.; Love, J. Christopher

2008-01-01

Determining the efficacy of a vaccine generally relies on measuring neutralizing antibodies in sera. This measure cannot elucidate the mechanisms responsible for the development of immunological memory at the cellular level, however. Quantitative profiles that detail the cellular origin, extent, and diversity of the humoral (antibody-based) immune response would improve both the assessment and development of vaccines. Here, we describe a novel approach to collect multiparametric datasets that describe the specificity, isotype, and apparent affinity of the antibodies secreted from large numbers of individual primary B cells (≈103-104). The antibody/antigen binding curves obtained by this approach can be used to classify closely related populations of cells using algorithms for data clustering, and the relationships among populations can be visualized graphically using affinity heatmaps. The technique described was used to evaluate the diversity of antigen-specific antibody-secreting cells generated during an in vivo humoral response to a series of immunizations designed to mimic a multipart vaccination. Profiles correlating primary antibody-producing cells with the molecular characteristics of their secreted antibodies should facilitate both the evaluation of candidate vaccines and, broadly, studies on the repertoires of antibodies generated in response to infectious or autoimmune diseases. PMID:19004776

Restoration of visual response in aged dystrophic RCS rats using AAV-mediated channelopsin-2 gene transfer.

PubMed

Tomita, Hiroshi; Sugano, Eriko; Yawo, Hiromu; Ishizuka, Toru; Isago, Hitomi; Narikawa, Satoko; Kügler, Sebastian; Tamai, Makoto

2007-08-01

To investigate whether the channelopsin-2 (Chop2) gene would restore visual responses in 10-month-old dystrophic Royal College of Surgeons (aged RCS; rdy/rdy) rats, the authors transferred the Chop2 gene into the retinal cells of aged RCS rats using the adenoassociated virus (AAV) vector. The N-terminal fragment (residues 1-315) of Chop2 was fused to a fluorescent protein, Venus, in frame at the end of the Chop2 coding fragment. The viral vector construct (AAV-Chop2V) for the expression of the Chop2V in the retina was made by subcloning into an adenoassociated virus vector, including the CAG promoter. To evaluate the expression profile of Chop2V in the retina, the rats were killed and the eyes were removed and fixed with 4% paraformaldehyde in 0.1 M phosphate-buffered saline. Retinal wholemount specimens and cryosections were made. Under anesthetized conditions, electrodes for the recording of visually evoked potentials (VEPs) were implanted onto the visual cortex in aged-RCS (rdy/rdy) rats. AAV-Chop2V vectors were then injected into the vitreous cavity of the left eyes. As a control, AAV-Venus vectors were applied to the right eyes. VEPs were evoked by the flash of a blue, white, or red light-emitting diode (LED) and were recorded from the visual cortex of the rats at various time points after the AAV vector injection. Chop2V fluorescence was predominantly observed in retinal ganglion cells (RGCs). Some fluorescence was observed in the inner nuclear layer and the inner plexiform layer neurites. A tendency of recovery was observed in the VEPs of aged RCS (rdy/rdy) rats after the AAV-Chop2V injection but not after the AAV-Venus injection. The visual response of AAV-Chop2V-injected aged RCS (rdy/rdy) rats was less sensitive to the blue LED flash than that of nondystrophic RCS (+/+) rats. The AAV-Chop2V-injected aged RCS (rdy/rdy) rats were insensitive to the red LED flash, which evoked a robust VEP in the RCS (+/+) rats. The visual response of aged RCS (rdy/rdy) rats was partially restored by transduction of the Chop2 gene through AAV into the inner retinal neurons, mainly RGCs. These results suggest that the transduction of Chop2 would provide a new strategy to treat some retinitis pigmentosa (RP) symptoms independent of their etiology.

Cartograms Facilitate Communication of Climate Change Risks and Responsibilities

NASA Astrophysics Data System (ADS)

Döll, Petra

2017-12-01

Communication of climate change (CC) risks is challenging, in particular if global-scale spatially resolved quantitative information is to be conveyed. Typically, visualization of CC risks, which arise from the combination of hazard, exposure and vulnerability, is confined to showing only the hazards in the form of global thematic maps. This paper explores the potential of contiguous value-by-area cartograms, that is, distorted density-equalizing maps, for improving communication of CC risks and the countries' differentiated responsibilities for CC. Two global-scale cartogram sets visualize, as an example, groundwater-related CC risks in 0.5° grid cells, another one the correlation of (cumulative) fossil-fuel carbon dioxide emissions with the countries' population and gross domestic product. Viewers of the latter set visually recognize the lack of global equity and that the countries' wealth has been built on harmful emissions. I recommend that CC risks are communicated by bivariate gridded cartograms showing the hazard in color and population, or a combination of population and a vulnerability indicator, by distortion of grid cells. Gridded cartograms are also appropriate for visualizing the availability of natural resources to humans. For communicating complex information, sets of cartograms should be carefully designed instead of presenting single cartograms. Inclusion of a conventionally distorted map enhances the viewers' capability to take up the information represented by distortion. Empirical studies about the capability of global cartograms to convey complex information and to trigger moral emotions should be conducted, with a special focus on risk communication.

Photovoltaic restoration of sight with high visual acuity

PubMed Central

Lorach, Henri; Goetz, Georges; Smith, Richard; Lei, Xin; Mandel, Yossi; Kamins, Theodore; Mathieson, Keith; Huie, Philip; Harris, James; Sher, Alexander; Palanker, Daniel

2015-01-01

Patients with retinal degeneration lose sight due to gradual demise of photoreceptors. Electrical stimulation of the surviving retinal neurons provides an alternative route for delivery of visual information. We demonstrate that subretinal arrays with 70 μm photovoltaic pixels provide highly localized stimulation, with electrical and visual receptive fields of comparable sizes in rat retinal ganglion cells. Similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies, adaptation to static images and non-linear spatial summation. In rats with retinal degeneration, these photovoltaic arrays provide spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in pigmented rats. Ease of implantation of these wireless and modular arrays, combined with their high resolution opens the door to functional restoration of sight. PMID:25915832

Ultra-high contrast retinal display system for single photoreceptor psychophysics

PubMed Central

Domdei, Niklas; Domdei, Lennart; Reiniger, Jenny L.; Linden, Michael; Holz, Frank G.; Roorda, Austin; Harmening, Wolf M.

2017-01-01

Due to the enormous dynamic range of human photoreceptors in response to light, studying their visual function in the intact retina challenges the stimulation hardware, specifically with regard to the displayable luminance contrast. The adaptive optics scanning laser ophthalmoscope (AOSLO) is an optical platform that focuses light to extremely small retinal extents, approaching the size of single photoreceptor cells. However, the current light modulation techniques produce spurious visible backgrounds which fundamentally limit experimental options. To remove unwanted background light and to improve contrast for high dynamic range visual stimulation in an AOSLO, we cascaded two commercial fiber-coupled acousto-optic modulators (AOMs) and measured their combined optical contrast. By compensating for zero-point differences in the individual AOMs, we demonstrate a multiplicative extinction ratio in the cascade that was in accordance with the extinction ratios of both single AOMs. When latency differences in the AOM response functions were individually corrected, single switch events as short as 50 ns with radiant power contrasts up to 1:1010 were achieved. This is the highest visual contrast reported for any display system so far. We show psychophysically that this contrast ratio is sufficient to stimulate single foveal photoreceptor cells with small and bright enough visible targets that do not contain a detectable background. Background-free stimulation will enable photoreceptor testing with custom adaptation lights. Furthermore, a larger dynamic range in displayable light levels can drive photoreceptor responses in cones as well as in rods. PMID:29359094

Closed-Loop Efficient Searching of Optimal Electrical Stimulation Parameters for Preferential Excitation of Retinal Ganglion Cells

PubMed Central

Guo, Tianruo; Yang, Chih Yu; Tsai, David; Muralidharan, Madhuvanthi; Suaning, Gregg J.; Morley, John W.; Dokos, Socrates; Lovell, Nigel H.

2018-01-01

The ability for visual prostheses to preferentially activate functionally-distinct retinal ganglion cells (RGCs) is important for improving visual perception. This study investigates the use of high frequency stimulation (HFS) to elicit RGC activation, using a closed-loop algorithm to search for optimal stimulation parameters for preferential ON and OFF RGC activation, resembling natural physiological neural encoding in response to visual stimuli. We evaluated the performance of a wide range of electrical stimulation amplitudes and frequencies on RGC responses in vitro using murine retinal preparations. It was possible to preferentially excite either ON or OFF RGCs by adjusting amplitudes and frequencies in HFS. ON RGCs can be preferentially activated at relatively higher stimulation amplitudes (>150 μA) and frequencies (2–6.25 kHz) while OFF RGCs are activated by lower stimulation amplitudes (40–90 μA) across all tested frequencies (1–6.25 kHz). These stimuli also showed great promise in eliciting RGC responses that parallel natural RGC encoding: ON RGCs exhibited an increase in spiking activity during electrical stimulation while OFF RGCs exhibited decreased spiking activity, given the same stimulation amplitude. In conjunction with the in vitro studies, in silico simulations indicated that optimal HFS parameters could be rapidly identified in practice, whilst sampling spiking activity of relevant neuronal subtypes. This closed-loop approach represents a step forward in modulating stimulation parameters to achieve appropriate neural encoding in retinal prostheses, advancing control over RGC subtypes activated by electrical stimulation. PMID:29615857

Dose-Response Calculator for ArcGIS

USGS Publications Warehouse

Hanser, Steven E.; Aldridge, Cameron L.; Leu, Matthias; Nielsen, Scott E.

2011-01-01

The Dose-Response Calculator for ArcGIS is a tool that extends the Environmental Systems Research Institute (ESRI) ArcGIS 10 Desktop application to aid with the visualization of relationships between two raster GIS datasets. A dose-response curve is a line graph commonly used in medical research to examine the effects of different dosage rates of a drug or chemical (for example, carcinogen) on an outcome of interest (for example, cell mutations) (Russell and others, 1982). Dose-response curves have recently been used in ecological studies to examine the influence of an explanatory dose variable (for example, percentage of habitat cover, distance to disturbance) on a predicted response (for example, survival, probability of occurrence, abundance) (Aldridge and others, 2008). These dose curves have been created by calculating the predicted response value from a statistical model at different levels of the explanatory dose variable while holding values of other explanatory variables constant. Curves (plots) developed using the Dose-Response Calculator overcome the need to hold variables constant by using values extracted from the predicted response surface of a spatially explicit statistical model fit in a GIS, which include the variation of all explanatory variables, to visualize the univariate response to the dose variable. Application of the Dose-Response Calculator can be extended beyond the assessment of statistical model predictions and may be used to visualize the relationship between any two raster GIS datasets (see example in tool instructions). This tool generates tabular data for use in further exploration of dose-response relationships and a graph of the dose-response curve.

Loss of calretinin immunoreactive fibers in subcortical visual recipient structures of the RCS dystrophic rat.

PubMed

Vugler, Anthony A; Coffey, Peter J

2003-11-01

The retinae of dystrophic Royal College of Surgeons (RCS) rats exhibit progressive photoreceptor degeneration accompanied by pathology of ganglion cells. To date, little work has examined the consequences of retinal degeneration for central visual structures in dystrophic rats. Here, we use immunohistochemistry for calretinin (CR) to label retinal afferents in the superior colliculus (SC), lateral geniculate nucleus, and olivary pretectal nucleus of RCS rats aged between 2 and 26 months of age. Early indications of fiber loss in the medial dystrophic SC were apparent between 9 and 13 months. Quantitative methods reveal a significant reduction in the level of CR immunoreactivity in visual layers of the medial dystrophic SC at 13 months (P < 0.02). In dystrophic animals aged 19-26 months the loss of CR fibers in SC was dramatic, with well-defined patches of fiber degeneration predominating in medial aspects of the structure. This fiber degeneration in SC was accompanied by increased detection of cells immunoreactive for CR. In several animals, regions of fiber loss were also found to contain strongly parvalbumin-immunoreactive cells. Loss of CR fibers was also observed in the lateral geniculate nucleus and olivary pretectal nucleus. Patterns of fiber loss in the dystrophic SC compliment reports of ganglion cell degeneration in these animals and the response of collicular neurons to degeneration is discussed in terms of plasticity of the dystrophic visual system and properties of calcium binding proteins.

Neural circuits underlying visually evoked escapes in larval zebrafish

PubMed Central

Dunn, Timothy W.; Gebhardt, Christoph; Naumann, Eva A.; Riegler, Clemens; Ahrens, Misha B.; Engert, Florian; Del Bene, Filippo

2015-01-01

SUMMARY Escape behaviors deliver organisms away from imminent catastrophe. Here, we characterize behavioral responses of freely swimming larval zebrafish to looming visual stimuli simulating predators. We report that the visual system alone can recruit lateralized, rapid escape motor programs, similar to those elicited by mechanosensory modalities. Two-photon calcium imaging of retino-recipient midbrain regions isolated the optic tectum as an important center processing looming stimuli, with ensemble activity encoding the critical image size determining escape latency. Furthermore, we describe activity in retinal ganglion cell terminals and superficial inhibitory interneurons in the tectum during looming and propose a model for how temporal dynamics in tectal periventricular neurons might arise from computations between these two fundamental constituents. Finally, laser ablations of hindbrain circuitry confirmed that visual and mechanosensory modalities share the same premotor output network. Together, we establish a circuit for the processing of aversive stimuli in the context of an innate visual behavior. PMID:26804997

Engineering fibrin-based tissue constructs from myofibroblasts and application of constraints and strain to induce cell and collagen reorganization.

PubMed

de Jonge, Nicky; Baaijens, Frank P T; Bouten, Carlijn V C

2013-10-28

Collagen content and organization in developing collagenous tissues can be influenced by local tissue strains and tissue constraint. Tissue engineers aim to use these principles to create tissues with predefined collagen architectures. A full understanding of the exact underlying processes of collagen remodeling to control the final tissue architecture, however, is lacking. In particular, little is known about the (re)orientation of collagen fibers in response to changes in tissue mechanical loading conditions. We developed an in vitro model system, consisting of biaxially-constrained myofibroblast-seeded fibrin constructs, to further elucidate collagen (re)orientation in response to i) reverting biaxial to uniaxial static loading conditions and ii) cyclic uniaxial loading of the biaxially-constrained constructs before and after a change in loading direction, with use of the Flexcell FX4000T loading device. Time-lapse confocal imaging is used to visualize collagen (re)orientation in a nondestructive manner. Cell and collagen organization in the constructs can be visualized in real-time, and an internal reference system allows us to relocate cells and collagen structures for time-lapse analysis. Various aspects of the model system can be adjusted, like cell source or use of healthy and diseased cells. Additives can be used to further elucidate mechanisms underlying collagen remodeling, by for example adding MMPs or blocking integrins. Shape and size of the construct can be easily adapted to specific needs, resulting in a highly tunable model system to study cell and collagen (re)organization.

Separability of stimulus parameter encoding by on-off directionally selective rabbit retinal ganglion cells

PubMed Central

Nowak, Przemyslaw; Dobbins, Allan C.; Gawne, Timothy J.; Grzywacz, Norberto M.

2011-01-01

The ganglion cell output of the retina constitutes a bottleneck in sensory processing in that ganglion cells must encode multiple stimulus parameters in their responses. Here we investigate encoding strategies of On-Off directionally selective retinal ganglion cells (On-Off DS RGCs) in rabbits, a class of cells dedicated to representing motion. The exquisite axial discrimination of these cells to preferred vs. null direction motion is well documented: it is invariant with respect to speed, contrast, spatial configuration, spatial frequency, and motion extent. However, these cells have broad direction tuning curves and their responses also vary as a function of other parameters such as speed and contrast. In this study, we examined whether the variation in responses across multiple stimulus parameters is systematic, that is the same for all cells, and separable, such that the response to a stimulus is a product of the effects of each stimulus parameter alone. We extracellularly recorded single On-Off DS RGCs in a superfused eyecup preparation while stimulating them with moving bars. We found that spike count responses of these cells scaled as independent functions of direction, speed, and luminance. Moreover, the speed and luminance functions were common across the whole sample of cells. Based on these findings, we developed a model that accurately predicted responses of On-Off DS RGCs as products of separable functions of direction, speed, and luminance (r = 0.98; P < 0.0001). Such a multiplicatively separable encoding strategy may simplify the decoding of these cells' outputs by the higher visual centers. PMID:21325684

Distinct retrosplenial cortex cell populations and their spike dynamics during ketamine-induced unconscious state

PubMed Central

Zhao, Fang; Tsien, Joe Z.

2017-01-01

Ketamine is known to induce psychotic-like symptoms, including delirium and visual hallucinations. It also causes neuronal damage and cell death in the retrosplenial cortex (RSC), an area that is thought to be a part of high visual cortical pathways and at least partially responsible for ketamine’s psychotomimetic activities. However, the basic physiological properties of RSC cells as well as their response to ketamine in vivo remained largely unexplored. Here, we combine a computational method, the Inter-Spike Interval Classification Analysis (ISICA), and in vivo recordings to uncover and profile excitatory cell subtypes within layers 2&3 and 5&6 of the RSC in mice within both conscious, sleep, and ketamine-induced unconscious states. We demonstrate two distinct excitatory principal cell sub-populations, namely, high-bursting excitatory principal cells and low-bursting excitatory principal cells, within layers 2&3, and show that this classification is robust over the conscious states, namely quiet awake, and natural unconscious sleep periods. Similarly, we provide evidence of high-bursting and low-bursting excitatory principal cell sub-populations within layers 5&6 that remained distinct during quiet awake and sleep states. We further examined how these subtypes are dynamically altered by ketamine. During ketamine-induced unconscious state, these distinct excitatory principal cell subtypes in both layer 2&3 and layer 5&6 exhibited distinct dynamics. We also uncovered different dynamics of local field potential under various brain states in layer 2&3 and layer 5&6. Interestingly, ketamine administration induced high gamma oscillations in layer 2&3 of the RSC, but not layer 5&6. Our results show that excitatory principal cells within RSC layers 2&3 and 5&6 contain multiple physiologically distinct sub-populations, and they are differentially affected by ketamine. PMID:29073221

Distinct retrosplenial cortex cell populations and their spike dynamics during ketamine-induced unconscious state.

PubMed

Fox, Grace E; Li, Meng; Zhao, Fang; Tsien, Joe Z

2017-01-01

Ketamine is known to induce psychotic-like symptoms, including delirium and visual hallucinations. It also causes neuronal damage and cell death in the retrosplenial cortex (RSC), an area that is thought to be a part of high visual cortical pathways and at least partially responsible for ketamine's psychotomimetic activities. However, the basic physiological properties of RSC cells as well as their response to ketamine in vivo remained largely unexplored. Here, we combine a computational method, the Inter-Spike Interval Classification Analysis (ISICA), and in vivo recordings to uncover and profile excitatory cell subtypes within layers 2&3 and 5&6 of the RSC in mice within both conscious, sleep, and ketamine-induced unconscious states. We demonstrate two distinct excitatory principal cell sub-populations, namely, high-bursting excitatory principal cells and low-bursting excitatory principal cells, within layers 2&3, and show that this classification is robust over the conscious states, namely quiet awake, and natural unconscious sleep periods. Similarly, we provide evidence of high-bursting and low-bursting excitatory principal cell sub-populations within layers 5&6 that remained distinct during quiet awake and sleep states. We further examined how these subtypes are dynamically altered by ketamine. During ketamine-induced unconscious state, these distinct excitatory principal cell subtypes in both layer 2&3 and layer 5&6 exhibited distinct dynamics. We also uncovered different dynamics of local field potential under various brain states in layer 2&3 and layer 5&6. Interestingly, ketamine administration induced high gamma oscillations in layer 2&3 of the RSC, but not layer 5&6. Our results show that excitatory principal cells within RSC layers 2&3 and 5&6 contain multiple physiologically distinct sub-populations, and they are differentially affected by ketamine.

Virtual reality method to analyze visual recognition in mice.

PubMed

Young, Brent Kevin; Brennan, Jayden Nicole; Wang, Ping; Tian, Ning

2018-01-01

Behavioral tests have been extensively used to measure the visual function of mice. To determine how precisely mice perceive certain visual cues, it is necessary to have a quantifiable measurement of their behavioral responses. Recently, virtual reality tests have been utilized for a variety of purposes, from analyzing hippocampal cell functionality to identifying visual acuity. Despite the widespread use of these tests, the training requirement for the recognition of a variety of different visual targets, and the performance of the behavioral tests has not been thoroughly characterized. We have developed a virtual reality behavior testing approach that can essay a variety of different aspects of visual perception, including color/luminance and motion detection. When tested for the ability to detect a color/luminance target or a moving target, mice were able to discern the designated target after 9 days of continuous training. However, the quality of their performance is significantly affected by the complexity of the visual target, and their ability to navigate on a spherical treadmill. Importantly, mice retained memory of their visual recognition for at least three weeks after the end of their behavioral training.

Color opponent receptive fields self-organize in a biophysical model of visual cortex via spike-timing dependent plasticity

PubMed Central

Eguchi, Akihiro; Neymotin, Samuel A.; Stringer, Simon M.

2014-01-01

Although many computational models have been proposed to explain orientation maps in primary visual cortex (V1), it is not yet known how similar clusters of color-selective neurons in macaque V1/V2 are connected and develop. In this work, we address the problem of understanding the cortical processing of color information with a possible mechanism of the development of the patchy distribution of color selectivity via computational modeling. Each color input is decomposed into a red, green, and blue representation and transmitted to the visual cortex via a simulated optic nerve in a luminance channel and red–green and blue–yellow opponent color channels. Our model of the early visual system consists of multiple topographically-arranged layers of excitatory and inhibitory neurons, with sparse intra-layer connectivity and feed-forward connectivity between layers. Layers are arranged based on anatomy of early visual pathways, and include a retina, lateral geniculate nucleus, and layered neocortex. Each neuron in the V1 output layer makes synaptic connections to neighboring neurons and receives the three types of signals in the different channels from the corresponding photoreceptor position. Synaptic weights are randomized and learned using spike-timing-dependent plasticity (STDP). After training with natural images, the neurons display heightened sensitivity to specific colors. Information-theoretic analysis reveals mutual information between particular stimuli and responses, and that the information reaches a maximum with fewer neurons in the higher layers, indicating that estimations of the input colors can be done using the output of fewer cells in the later stages of cortical processing. In addition, cells with similar color receptive fields form clusters. Analysis of spiking activity reveals increased firing synchrony between neurons when particular color inputs are presented or removed (ON-cell/OFF-cell). PMID:24659956

A Role for Mouse Primary Visual Cortex in Motion Perception.

PubMed

Marques, Tiago; Summers, Mathew T; Fioreze, Gabriela; Fridman, Marina; Dias, Rodrigo F; Feller, Marla B; Petreanu, Leopoldo

2018-06-04

Visual motion is an ethologically important stimulus throughout the animal kingdom. In primates, motion perception relies on specific higher-order cortical regions. Although mouse primary visual cortex (V1) and higher-order visual areas show direction-selective (DS) responses, their role in motion perception remains unknown. Here, we tested whether V1 is involved in motion perception in mice. We developed a head-fixed discrimination task in which mice must report their perceived direction of motion from random dot kinematograms (RDKs). After training, mice made around 90% correct choices for stimuli with high coherence and performed significantly above chance for 16% coherent RDKs. Accuracy increased with both stimulus duration and visual field coverage of the stimulus, suggesting that mice in this task integrate motion information in time and space. Retinal recordings showed that thalamically projecting On-Off DS ganglion cells display DS responses when stimulated with RDKs. Two-photon calcium imaging revealed that neurons in layer (L) 2/3 of V1 display strong DS tuning in response to this stimulus. Thus, RDKs engage motion-sensitive retinal circuits as well as downstream visual cortical areas. Contralateral V1 activity played a key role in this motion direction discrimination task because its reversible inactivation with muscimol led to a significant reduction in performance. Neurometric-psychometric comparisons showed that an ideal observer could solve the task with the information encoded in DS L2/3 neurons. Motion discrimination of RDKs presents a powerful behavioral tool for dissecting the role of retino-forebrain circuits in motion processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Supporting High School Student Accomplishment of Biology Content Using Interactive Computer-Based Curricular Case Studies

NASA Astrophysics Data System (ADS)

Oliver, Joseph Steve; Hodges, Georgia W.; Moore, James N.; Cohen, Allan; Jang, Yoonsun; Brown, Scott A.; Kwon, Kyung A.; Jeong, Sophia; Raven, Sara P.; Jurkiewicz, Melissa; Robertson, Tom P.

2017-11-01

Research into the efficacy of modules featuring dynamic visualizations, case studies, and interactive learning environments is reported here. This quasi-experimental 2-year study examined the implementation of three interactive computer-based instructional modules within a curricular unit covering cellular biology concepts in an introductory high school biology course. The modules featured dynamic visualizations and focused on three processes that underlie much of cellular biology: diffusion, osmosis, and filtration. Pre-tests and post-tests were used to assess knowledge growth across the unit. A mixture Rasch model analysis of the post-test data revealed two groups of students. In both years of the study, a large proportion of the students were classified as low-achieving based on their pre-test scores. The use of the modules in the Cell Unit in year 2 was associated with a much larger proportion of the students having transitioned to the high-achieving group than in year 1. In year 2, the same teachers taught the same concepts as year 1 but incorporated the interactive computer-based modules into the cell biology unit of the curriculum. In year 2, 67% of students initially classified as low-achieving were classified as high-achieving at the end of the unit. Examination of responses to assessments embedded within the modules as well as post-test items linked transition to the high-achieving group with correct responses to items that both referenced the visualization and the contextualization of that visualization within the module. This study points to the importance of dynamic visualization within contextualized case studies as a means to support student knowledge acquisition in biology.

Synaptic Basis for Differential Orientation Selectivity between Complex and Simple Cells in Mouse Visual Cortex

PubMed Central

Li, Ya-tang; Liu, Bao-hua; Chou, Xiao-lin; Zhang, Li I.

2015-01-01

In the primary visual cortex (V1), orientation-selective neurons can be categorized into simple and complex cells primarily based on their receptive field (RF) structures. In mouse V1, although previous studies have examined the excitatory/inhibitory interplay underlying orientation selectivity (OS) of simple cells, the synaptic bases for that of complex cells have remained obscure. Here, by combining in vivo loose-patch and whole-cell recordings, we found that complex cells, identified by their overlapping on/off subfields, had significantly weaker OS than simple cells at both spiking and subthreshold membrane potential response levels. Voltage-clamp recordings further revealed that although excitatory inputs to complex and simple cells exhibited a similar degree of OS, inhibition in complex cells was more narrowly tuned than excitation, whereas in simple cells inhibition was more broadly tuned than excitation. The differential inhibitory tuning can primarily account for the difference in OS between complex and simple cells. Interestingly, the differential synaptic tuning correlated well with the spatial organization of synaptic input: the inhibitory visual RF in complex cells was more elongated in shape than its excitatory counterpart and also was more elongated than that in simple cells. Together, our results demonstrate that OS of complex and simple cells is differentially shaped by cortical inhibition based on its orientation tuning profile relative to excitation, which is contributed at least partially by the spatial organization of RFs of presynaptic inhibitory neurons. SIGNIFICANCE STATEMENT Simple and complex cells, two classes of principal neurons in the primary visual cortex (V1), are generally thought to be equally selective for orientation. In mouse V1, we report that complex cells, identified by their overlapping on/off subfields, has significantly weaker orientation selectivity (OS) than simple cells. This can be primarily attributed to the differential tuning selectivity of inhibitory synaptic input: inhibition in complex cells is more narrowly tuned than excitation, whereas in simple cells inhibition is more broadly tuned than excitation. In addition, there is a good correlation between inhibitory tuning selectivity and the spatial organization of inhibitory inputs. These complex and simple cells with differential degree of OS may provide functionally distinct signals to different downstream targets. PMID:26245969

Synaptic Basis for Differential Orientation Selectivity between Complex and Simple Cells in Mouse Visual Cortex.

PubMed

Li, Ya-tang; Liu, Bao-hua; Chou, Xiao-lin; Zhang, Li I; Tao, Huizhong W

2015-08-05

In the primary visual cortex (V1), orientation-selective neurons can be categorized into simple and complex cells primarily based on their receptive field (RF) structures. In mouse V1, although previous studies have examined the excitatory/inhibitory interplay underlying orientation selectivity (OS) of simple cells, the synaptic bases for that of complex cells have remained obscure. Here, by combining in vivo loose-patch and whole-cell recordings, we found that complex cells, identified by their overlapping on/off subfields, had significantly weaker OS than simple cells at both spiking and subthreshold membrane potential response levels. Voltage-clamp recordings further revealed that although excitatory inputs to complex and simple cells exhibited a similar degree of OS, inhibition in complex cells was more narrowly tuned than excitation, whereas in simple cells inhibition was more broadly tuned than excitation. The differential inhibitory tuning can primarily account for the difference in OS between complex and simple cells. Interestingly, the differential synaptic tuning correlated well with the spatial organization of synaptic input: the inhibitory visual RF in complex cells was more elongated in shape than its excitatory counterpart and also was more elongated than that in simple cells. Together, our results demonstrate that OS of complex and simple cells is differentially shaped by cortical inhibition based on its orientation tuning profile relative to excitation, which is contributed at least partially by the spatial organization of RFs of presynaptic inhibitory neurons. Simple and complex cells, two classes of principal neurons in the primary visual cortex (V1), are generally thought to be equally selective for orientation. In mouse V1, we report that complex cells, identified by their overlapping on/off subfields, has significantly weaker orientation selectivity (OS) than simple cells. This can be primarily attributed to the differential tuning selectivity of inhibitory synaptic input: inhibition in complex cells is more narrowly tuned than excitation, whereas in simple cells inhibition is more broadly tuned than excitation. In addition, there is a good correlation between inhibitory tuning selectivity and the spatial organization of inhibitory inputs. These complex and simple cells with differential degree of OS may provide functionally distinct signals to different downstream targets. Copyright © 2015 the authors 0270-6474/15/3511081-13$15.00/0.

Retinal architecture and mfERG: Optic nerve head component response characteristics in MS.

PubMed

Schnurman, Zane S; Frohman, Teresa C; Beh, Shin C; Conger, Darrel; Conger, Amy; Saidha, Shiv; Galetta, Steven; Calabresi, Peter A; Green, Ari J; Balcer, Laura J; Frohman, Elliot M

2014-05-27

To describe a novel neurophysiologic signature of the retinal ganglion cell and to elucidate its relationship to abnormalities in validated structural and functional measures of the visual system. We used multifocal electroretinogram-generated optic nerve head component (ONHC) responses from normal subjects (n = 18), patients with multiple sclerosis (MS) (n = 18), and those with glaucoma (n = 3). We then characterized the relationship between ONHC response abnormalities and performance on low-contrast visual acuity, multifocal visual-evoked potential-induced cortical responses, and average and quadrant retinal nerve fiber layer (RNFL) thicknesses, as measured by spectral-domain optical coherence tomography. Compared with the eyes of normal subjects, the eyes of patients with MS exhibited an increased number of abnormal or absent ONHC responses (p < 0.0001). For every 7-letter reduction in low-contrast letter acuity, there were corresponding 4.6 abnormal ONHC responses at 2.5% contrast (p < 0.0001) and 6.6 abnormalities at the 1.25% contrast level (p < 0.0001). Regarding average RNFL thickness, for each 10-μm thickness reduction, we correspondingly observed 6.8 abnormal ONHC responses (p = 0.0002). The most robust association was between RNFL thinning in the temporal quadrant and ONHC response abnormalities (p < 0.0001). Further characterization of ONHC abnormalities (those that are reversible and irreversible) may contribute to the development of novel neurotherapeutic strategies aimed at achieving neuroprotective, and perhaps even neurorestorative, effects in disorders that target the CNS in general, and MS in particular. © 2014 American Academy of Neurology.

B cell immunopoiesis: visualizing the impact of CD40 engagement on the course of T cell-independent immune responses in an Ig transgenic system.

PubMed

Erickson, L D; Vogel, L A; Cascalho, M; Wong, J; Wabl, M; Durell, B G; Noelle, R J

2000-11-01

This study tracks the fate of antigen-reactive B cells through follicular and extrafollicular responses and addresses the function of CD40 in these processes. The unique feature of this system is the use of transgenic B cells in which the heavy chain locus has been altered by site-directed insertion of a rearranged V(H) DJ(H) exon such that they are able to clonally expand, isotype-switch and follow a normal course of differentiation upon immunization. These Ig transgenic B cells when adoptively transferred into non-transgenic (Tg) mice in measured amounts expanded and differentiated distinctively in response to T cell-independent (TI) or T cell-dependent (TD) antigens. The capacity of these Tg B cells to faithfully recapitulate the humoral immune response to TI and TD antigens provides the means to track clonal B cell behavior in vivo. Challenge with TI antigen in the presence of agonistic anti-CD40 mAb resulted in well-defined alterations of the TI response. In vivo triggering of Tg B cells with TI antigen and CD40 caused an increase in the levels IgG produced and a broadening of the Ig isotype profile, characteristics which partially mimic TD responses. Although some TD characteristics were induced by TI antigen and CD40 triggering, the Tg B cells failed to acquire a germinal center phenotype and failed to generate a memory response. Therefore, TD-like immunity can be only partially reconstituted with CD40 agonists and TI antigens, suggesting that there are additional signals required for germinal center formation and development of memory.

Role of inhibition in the specification of orientation selectivity of cells in the cat striate cortex.

PubMed

Bonds, A B

1989-01-01

Mechanisms supporting orientation selectivity of cat striate cortical cells were studied by stimulation with two superimposed sine-wave gratings of different orientations. One grating (base) generated a discharge of known amplitude which could be modified by the second grating (mask). Masks presented at nonoptimal orientations usually reduced the base-generated response, but the degree of reduction varied widely between cells. Cells with narrow orientation tuning tended to be more susceptible to mask presence than broadly tuned cells; similarly, simple cells generally showed more response reduction than did complex cells. The base and mask stimuli were drifted at different temporal frequencies which, in simple cells, permitted the identification of individual response components from each stimulus. This revealed that the reduction of the base response by the mask usually did not vary regularly with mask orientation, although response facilitation from the mask was orientation selective. In some sharply tuned simple cells, response reduction had clear local maxima near the limits of the cell's orientation-tuning function. Response reduction resulted from a nearly pure rightward shift of the response versus log contrast function. The lowest mask contrast yielding reduction was within 0.1-0.3 log unit of the lowest contrast effective for excitation. The temporal-frequency bandpass of the response-reduction mechanism resembled that of most cortical cells. The spatial-frequency bandpass was much broader than is typical for single cortical cells, spanning essentially the entire visual range of the cat. These findings are compatible with a model in which weak intrinsic orientation-selective excitation is enhanced in two stages: (1) control of threshold by nonorientation-selective inhibition that is continuously dependent on stimulus contrast; and (2) in the more narrowly tuned cells, orientation-selective inhibition that has local maxima serving to increase the slope of the orientation-tuning function.

Fos Expression in Monoaminergic Cell Groups in Response to Sociosexual Interactions in Male and Female Japanese Quail

PubMed Central

Iyilikci, Onur; Baxter, Samantha; Balthazart, Jacques; Ball, Gregory F.

2014-01-01

Monoaminergic neurotransmitters regulate different components of sexual behaviors, but how the different monoaminergic cell groups selectively regulate these behaviors is not well understood. We examined the potential contribution of these different cell groups in the control of different aspects of sexual behaviors in male and female quail. We used double-label immunohistochemistry, labeling the protein product of the immediate early gene, Fos, along with tyrosine hydroxylase (TH) or tryptophan hydroxylase (TPH), markers for catecholaminergic or indolaminergic cells, respectively. Rhythmic Cloacal Sphincter Movements (RCSM) were recorded as a measure of male appetitive sexual behavior. Consummatory sexual behaviors were evaluated based on the species-typical copulation sequence. Enhanced Fos expression in the medial preoptic nucleus and bed nucleus of the stria terminalis was observed in association with both physical and visual contact to the opposite sex for males, but not for females. Fos induction associated with physical contact was observed in the ventral tegmental area and anterior periaqueductal gray in both sexes. In males only, the number of Fos-immunoreactive (ir) cells increased in the visual contact condition in these two dopaminergic cell groups, however no significant effect was observed for double-labeled TH-Fos-ir cells. In addition, consummatory but not appetitive sexual behavior increased Fos expression in TPH-ir cells in the raphe pallidus of males. This increase following physical but not visual contact agrees with the notion that activation of the serotoninergic system is implicated in the development of sexual satiation but not activated by simply viewing a female, in contrast to the dopaminergic system. PMID:24512065

Frequency Responses of Rat Retinal Ganglion Cells

PubMed Central

Cloherty, Shaun L.; Hung, Yu-Shan; Kameneva, Tatiana; Ibbotson, Michael R.

2016-01-01

There are 15–20 different types of retinal ganglion cells (RGC) in the mammalian retina, each encoding different aspects of the visual scene. The mechanism by which post-synaptic signals from the retinal network generate spikes is determined by each cell’s intrinsic electrical properties. Here we investigate the frequency responses of morphologically identified rat RGCs using intracellular injection of sinusoidal current waveforms, to assess their intrinsic capabilities with minimal contributions from the retinal network. Recorded cells were classified according to their morphological characteristics (A, B, C or D-type) and their stratification (inner (i), outer (o) or bistratified) in the inner plexiform layer (IPL). Most cell types had low- or band-pass frequency responses. A2, C1 and C4o cells were band-pass with peaks of 15–30 Hz and low-pass cutoffs above 56 Hz (A2 cells) and ~42 Hz (C1 and C4o cells). A1 and C2i/o cells were low-pass with peaks of 10–15 Hz (cutoffs 19–25 Hz). Bistratified D1 and D2 cells were also low-pass with peaks of 5–10 Hz (cutoffs ~16 Hz). The least responsive cells were the B2 and C3 types (peaks: 2–5 Hz, cutoffs: 8–11 Hz). We found no difference between cells stratifying in the inner and outer IPL (i.e., ON and OFF cells) or between cells with large and small somas or dendritic fields. Intrinsic physiological properties (input resistance, spike width and sag) had little impact on frequency response at low frequencies, but account for 30–40% of response variability at frequencies >30 Hz. PMID:27341669

Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells

PubMed Central

Whang, Katherine A.; LeGall, Camille; Cragnolini, Juan J.; Bierie, Brian; Gostissa, Monica; Grotenbreg, Gijsbert M.; Bhan, Atul; Weinberg, Robert A.

2017-01-01

Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non–small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno–positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used 89Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8+ T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A 89Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies. PMID:28666979

Expression of Inducible Heat Shock Proteins Hsp27 and Hsp70 in the Visual Pathway of Rats Subjected to Various Models of Retinal Ganglion Cell Injury

PubMed Central

Chidlow, Glyn; Wood, John P. M.; Casson, Robert J.

2014-01-01

Inducible heat shock proteins (Hsps) are upregulated in the central nervous system in response to a wide variety of injuries. Surprisingly, however, no coherent picture has emerged regarding the magnitude, duration and cellular distribution of inducible Hsps in the visual system following injury to retinal ganglion cells (RGCs). The current study sought, therefore, to achieve the following two objectives. The first aim of this study was to systematically characterise the patterns of Hsp27 and −70 expression in the retina and optic nerve in four discrete models of retinal ganglion cell (RGC) degeneration: axonal injury (ON crush), somato-dendritic injury (NMDA-induced excitotoxicity), chronic hypoperfusion (bilateral occlusion of the carotid arteris) and experimental glaucoma. The second aim was to document Hsp27 and −70 expression in the optic tract, the subcortical retinorecipient areas of the brain, and the visual cortex during Wallerian degeneration of RGC axons. Hsp27 was robustly upregulated in the retina in each injury paradigm, with the chronic models, 2VO and experimental glaucoma, displaying a more persistent Hsp27 transcriptional response than the acute models. Hsp27 expression was always associated with astrocytes and with a subset of RGCs in each of the models excluding NMDA. Hsp27 was present within astrocytes of the optic nerve/optic tract in control rats. During Wallerian degeneration, Hsp27 was upregulated in the optic nerve/optic tract and expressed de novo by astrocytes in the lateral geniculate nucleus and the stratum opticum of the superior colliculus. Conversely, the results of our study indicate Hsp70 was minimally induced in any of the models of injury, either in the retina, or in the optic nerve/optic tract, or in the subcortical, retinorecipient areas of the brain. The findings of the present study augment our understanding of the involvement of Hsp27 and Hsp70 in the response of the visual system to RGC degeneration. PMID:25535743

Two Visual Pathways in Primates Based on Sampling of Space: Exploitation and Exploration of Visual Information

PubMed Central

Sheth, Bhavin R.; Young, Ryan

2016-01-01

Evidence is strong that the visual pathway is segregated into two distinct streams—ventral and dorsal. Two proposals theorize that the pathways are segregated in function: The ventral stream processes information about object identity, whereas the dorsal stream, according to one model, processes information about either object location, and according to another, is responsible in executing movements under visual control. The models are influential; however recent experimental evidence challenges them, e.g., the ventral stream is not solely responsible for object recognition; conversely, its function is not strictly limited to object vision; the dorsal stream is not responsible by itself for spatial vision or visuomotor control; conversely, its function extends beyond vision or visuomotor control. In their place, we suggest a robust dichotomy consisting of a ventral stream selectively sampling high-resolution/focal spaces, and a dorsal stream sampling nearly all of space with reduced foveal bias. The proposal hews closely to the theme of embodied cognition: Function arises as a consequence of an extant sensory underpinning. A continuous, not sharp, segregation based on function emerges, and carries with it an undercurrent of an exploitation-exploration dichotomy. Under this interpretation, cells of the ventral stream, which individually have more punctate receptive fields that generally include the fovea or parafovea, provide detailed information about object shapes and features and lead to the systematic exploitation of said information; cells of the dorsal stream, which individually have large receptive fields, contribute to visuospatial perception, provide information about the presence/absence of salient objects and their locations for novel exploration and subsequent exploitation by the ventral stream or, under certain conditions, the dorsal stream. We leverage the dichotomy to unify neuropsychological cases under a common umbrella, account for the increased prevalence of multisensory integration in the dorsal stream under a Bayesian framework, predict conditions under which object recognition utilizes the ventral or dorsal stream, and explain why cells of the dorsal stream drive sensorimotor control and motion processing and have poorer feature selectivity. Finally, the model speculates on a dynamic interaction between the two streams that underscores a unified, seamless perception. Existing theories are subsumed under our proposal. PMID:27920670

Two Visual Pathways in Primates Based on Sampling of Space: Exploitation and Exploration of Visual Information.

PubMed

Sheth, Bhavin R; Young, Ryan

2016-01-01

Evidence is strong that the visual pathway is segregated into two distinct streams-ventral and dorsal. Two proposals theorize that the pathways are segregated in function: The ventral stream processes information about object identity, whereas the dorsal stream, according to one model, processes information about either object location, and according to another, is responsible in executing movements under visual control. The models are influential; however recent experimental evidence challenges them, e.g., the ventral stream is not solely responsible for object recognition; conversely, its function is not strictly limited to object vision; the dorsal stream is not responsible by itself for spatial vision or visuomotor control; conversely, its function extends beyond vision or visuomotor control. In their place, we suggest a robust dichotomy consisting of a ventral stream selectively sampling high-resolution/ focal spaces, and a dorsal stream sampling nearly all of space with reduced foveal bias. The proposal hews closely to the theme of embodied cognition: Function arises as a consequence of an extant sensory underpinning. A continuous, not sharp, segregation based on function emerges, and carries with it an undercurrent of an exploitation-exploration dichotomy. Under this interpretation, cells of the ventral stream, which individually have more punctate receptive fields that generally include the fovea or parafovea, provide detailed information about object shapes and features and lead to the systematic exploitation of said information; cells of the dorsal stream, which individually have large receptive fields, contribute to visuospatial perception, provide information about the presence/absence of salient objects and their locations for novel exploration and subsequent exploitation by the ventral stream or, under certain conditions, the dorsal stream. We leverage the dichotomy to unify neuropsychological cases under a common umbrella, account for the increased prevalence of multisensory integration in the dorsal stream under a Bayesian framework, predict conditions under which object recognition utilizes the ventral or dorsal stream, and explain why cells of the dorsal stream drive sensorimotor control and motion processing and have poorer feature selectivity. Finally, the model speculates on a dynamic interaction between the two streams that underscores a unified, seamless perception. Existing theories are subsumed under our proposal.

Tracking the Spatial and Functional Gradient of Monocyte-To-Macrophage Differentiation in Inflamed Lung.

PubMed

Sen, Debasish; Jones, Stephen M; Oswald, Erin M; Pinkard, Henry; Corbin, Kaitlin; Krummel, Matthew F

2016-01-01

Myeloid-derived cells such as monocytes, dendritic cells (DCs), and macrophages are at the heart of the immune effector function in an inflammatory response. But because of the lack of an efficient imaging system to trace these cells live during their migration and maturation in their native environment at sub-cellular resolution, our knowledge is limited to data available from specific time-points analyzed by flow cytometry, histology, genomics and other immunological methods. Here, we have developed a ratiometric imaging method for measuring monocyte maturation in inflamed mouse lungs in situ using real-time using 2-photon imaging and complementary methods. We visualized that while undifferentiated monocytes were predominantly found only in the vasculature, a semi-differentiated monocyte/macrophage population could enter the tissue and resembled more mature and differentiated populations by morphology and surface phenotype. As these cells entered and differentiated, they were already selectively localized near inflamed airways and their entry was associated with changes in motility and morphology. We were able to visualize these during the act of differentiation, a process that can be demonstrated in this way to be faster on a per-cell basis under inflammatory conditions. Finally, our in situ analyses demonstrated increases, in the differentiating cells, for both antigen uptake and the ability to mediate interactions with T cells. This work, while largely confirming proposed models for in situ differentiation, provides important in situ data on the coordinated site-specific recruitment and differentiation of these cells and helps elaborate the predominance of immune pathology at the airways. Our novel imaging technology to trace immunogenic cell maturation in situ will complement existing information available on in situ differentiation deduced from other immunological methods, and assist better understanding of the spatio-temporal cellular behavior during an inflammatory response.

Non-canonical Phototransduction Mediates Synchronization of the Drosophila melanogaster Circadian Clock and Retinal Light Responses.

PubMed

Ogueta, Maite; Hardie, Roger C; Stanewsky, Ralf

2018-06-04

The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical visual Rhodopsin phototransduction. Here, we show that at least three of the seven Drosophila rhodopsins can utilize an alternative transduction mechanism involving the same α-subunit of the heterotrimeric G protein operating in canonical visual phototransduction (Gq). Surprisingly, in mutants lacking the canonical phospholipase C-β (PLC-β) encoded by the no receptor potential A (norpA) gene, we uncovered a novel transduction pathway using a different PLC-β encoded by the Plc21C gene. This novel pathway is important for behavioral clock resetting to semi-natural light-dark cycles and mediates light-dependent molecular synchronization within the s-LNv clock neurons. The same pathway appears to be responsible for norpA-independent light responses in the compound eye. We show that Rhodopsin 5 (Rh5) and Rh6, present in the R8 subset of retinal photoreceptor cells, drive both the long-term circadian and rapid light responses in the eye. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

In Vivo Visualizing the IFN-β Response Required for Tumor Growth Control in a Therapeutic Model of Polyadenylic-Polyuridylic Acid Administration.

PubMed

Nocera, David Andrés; Roselli, Emiliano; Araya, Paula; Nuñez, Nicolás Gonzalo; Lienenklaus, Stefan; Jablonska, Jadwiga; Weiss, Siegfried; Gatti, Gerardo; Brinkmann, Melanie M; Kröger, Andrea; Morón, Gabriel; Maccioni, Mariana

2016-03-15

The crucial role that endogenously produced IFN-β plays in eliciting an immune response against cancer has recently started to be elucidated. Endogenous IFN-β has an important role in immune surveillance and control of tumor development. Accordingly, the role of TLR agonists as cancer therapeutic agents is being revisited via the strategy of intra/peritumoral injection with the idea of stimulating the production of endogenous type I IFN inside the tumor. Polyadenylic-polyuridylic acid (poly A:U) is a dsRNA mimetic explored empirically in cancer immunotherapy a long time ago with little knowledge regarding its mechanisms of action. In this work, we have in vivo visualized the IFN-β required for the antitumor immune response elicited in a therapeutic model of poly A:U administration. In this study, we have identified the role of host type I IFNs, cell populations that are sources of IFN-β in the tumor microenvironment, and other host requirements for tumor control in this model. One single peritumoral dose of poly A:U was sufficient to induce IFN-β, readily visualized in vivo. IFN-β production relied mainly on the activation of the transcription factor IFN regulatory factor 3 and the molecule UNC93B1, indicating that TLR3 is required for recognizing poly A:U. CD11c(+) cells were an important, but not the only source of IFN-β. Host type I IFN signaling was absolutely required for the reduced tumor growth, prolonged mice survival, and the strong antitumor-specific immune response elicited upon poly A:U administration. These findings add new perspectives to the use of IFN-β-inducing compounds in tumor therapy. Copyright © 2016 by The American Association of Immunologists, Inc.

Population Coding of Visual Space: Comparison of Spatial Representations in Dorsal and Ventral Pathways

PubMed Central

Sereno, Anne B.; Lehky, Sidney R.

2011-01-01

Although the representation of space is as fundamental to visual processing as the representation of shape, it has received relatively little attention from neurophysiological investigations. In this study we characterize representations of space within visual cortex, and examine how they differ in a first direct comparison between dorsal and ventral subdivisions of the visual pathways. Neural activities were recorded in anterior inferotemporal cortex (AIT) and lateral intraparietal cortex (LIP) of awake behaving monkeys, structures associated with the ventral and dorsal visual pathways respectively, as a stimulus was presented at different locations within the visual field. In spatially selective cells, we find greater modulation of cell responses in LIP with changes in stimulus position. Further, using a novel population-based statistical approach (namely, multidimensional scaling), we recover the spatial map implicit within activities of neural populations, allowing us to quantitatively compare the geometry of neural space with physical space. We show that a population of spatially selective LIP neurons, despite having large receptive fields, is able to almost perfectly reconstruct stimulus locations within a low-dimensional representation. In contrast, a population of AIT neurons, despite each cell being spatially selective, provide less accurate low-dimensional reconstructions of stimulus locations. They produce instead only a topologically (categorically) correct rendition of space, which nevertheless might be critical for object and scene recognition. Furthermore, we found that the spatial representation recovered from population activity shows greater translation invariance in LIP than in AIT. We suggest that LIP spatial representations may be dimensionally isomorphic with 3D physical space, while in AIT spatial representations may reflect a more categorical representation of space (e.g., “next to” or “above”). PMID:21344010

Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes

NASA Astrophysics Data System (ADS)

Cho, Alice; Ratliff, Charles; Sampath, Alapakkam; Weiland, James

2016-04-01

Objective. Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. Approach. Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells (RGCs) of both wild type mice and the rd10 mouse model of retinal degeneration. Main results. Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. Significance. During degeneration, physiological changes in RGCs affect the threshold stimulation currents required to evoke action potentials.

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina.

PubMed

White, David T; Sengupta, Sumitra; Saxena, Meera T; Xu, Qingguo; Hanes, Justin; Ding, Ding; Ji, Hongkai; Mumm, Jeff S

2017-05-02

Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral macrophage cells responded to rod cell loss, as evidenced by morphological transitions and increased migration, but did not enter the retina. Retinal microglia displayed multiple hallmarks of immune cell activation: increased migration, translocation to the photoreceptor cell layer, proliferation, and phagocytosis of dying cells. To test function during rod cell regeneration, we coablated microglia and rod cells or applied immune suppression and quantified the kinetics of ( i ) rod cell clearance, ( ii ) MG/progenitor cell proliferation, and ( iii ) rod cell replacement. Coablation and immune suppressants applied before cell loss caused delays in MG/progenitor proliferation rates and slowed the rate of rod cell replacement. Conversely, immune suppressants applied after cell loss had been initiated led to accelerated photoreceptor regeneration kinetics, possibly by promoting rapid resolution of an acute immune response. Our findings suggest that microglia control MG responsiveness to photoreceptor loss and support the development of immune-targeted therapeutic strategies for reversing cell loss associated with degenerative retinal conditions.

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

PubMed Central

White, David T.; Sengupta, Sumitra; Saxena, Meera T.; Xu, Qingguo; Hanes, Justin; Ding, Ding; Ji, Hongkai

2017-01-01

Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration—i.e., selective cell-loss paradigms akin to degenerative disease—are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral macrophage cells responded to rod cell loss, as evidenced by morphological transitions and increased migration, but did not enter the retina. Retinal microglia displayed multiple hallmarks of immune cell activation: increased migration, translocation to the photoreceptor cell layer, proliferation, and phagocytosis of dying cells. To test function during rod cell regeneration, we coablated microglia and rod cells or applied immune suppression and quantified the kinetics of (i) rod cell clearance, (ii) MG/progenitor cell proliferation, and (iii) rod cell replacement. Coablation and immune suppressants applied before cell loss caused delays in MG/progenitor proliferation rates and slowed the rate of rod cell replacement. Conversely, immune suppressants applied after cell loss had been initiated led to accelerated photoreceptor regeneration kinetics, possibly by promoting rapid resolution of an acute immune response. Our findings suggest that microglia control MG responsiveness to photoreceptor loss and support the development of immune-targeted therapeutic strategies for reversing cell loss associated with degenerative retinal conditions. PMID:28416692

Thalamocortical NMDA conductances and intracortical inhibition can explain cortical temporal tuning

NASA Technical Reports Server (NTRS)

Krukowski, A. E.; Miller, K. D.

2001-01-01

Cells in cerebral cortex fail to respond to fast-moving stimuli that evoke strong responses in the thalamic nuclei innervating the cortex. The reason for this behavior has remained a mystery. We study an experimentally motivated model of the thalamic input-recipient layer of cat primary visual cortex that accounts for many aspects of cortical orientation tuning. In this circuit, inhibition dominates over excitation, but temporal modulations of excitation and inhibition occur out of phase with one another, allowing excitation to transiently drive cells. We show that this circuit provides a natural explanation of cortical low-pass temporal frequency tuning, provided N-methyl-D-aspartate (NMDA) receptors are present in thalamocortical synapses in proportions measured experimentally. This suggests a new and unanticipated role for NMDA conductances in shaping the temporal response properties of cortical cells, and suggests that common cortical circuit mechanisms underlie both spatial and temporal response tuning.

Cell Phones, Tablets, and Other Mobile Technology for Users with Visual Impairments

MedlinePlus

... Visual Impairments Cell Phones, Tablets, and Other Mobile Technology for Users with Visual Impairments The Mobile Revolution ... 223 Likes) Cell Phones, Tablets, and Other Mobile Technology Touchscreen Smartphone Accessibility for People with Visual Impairments ...

Smart Plasmonic Glucose Nanosensors as Generic Theranostic Agents for Targeting-Free Cancer Cell Screening and Killing.

PubMed

Chen, Limei; Li, Haijuan; He, Haili; Wu, Haoxi; Jin, Yongdong

2015-07-07

Fast and accurate identification of cancer cells from healthy normal cells in a simple, generic way is very crucial for early cancer detection and treatment. Although functional nanoparticles, like fluorescent quantum dots and plasmonic Au nanoparticles (NPs), have been successfully applied for cancer cell imaging and photothermal therapy, they suffer from the main drawback of needing time-consuming targeting preparation for specific cancer cell detection and selective ablation. The lack of a generic and effective method therefore limits their potential high-throughput cancer cell preliminary screening and theranostic applications. We report herein a generic in vitro method for fast, targeting-free (avoiding time-consuming preparations of targeting moiety for specific cancer cells) visual screening and selective killing of cancer cells from normal cells, by using glucose-responsive/-sensitive glucose oxidase-modified Ag/Au nanoshells (Ag/Au-GOx NSs) as a smart plasmonic theranostic agent. The method is generic to some extent since it is based on the distinct localized surface plasmon resonance (LSPR) responses (and colors) of the smart nanoprobe with cancer cells (typically have a higher glucose uptake level) and normal cells.

Global Sensory Qualities and Aesthetic Experience in Music.

PubMed

Brattico, Pauli; Brattico, Elvira; Vuust, Peter

2017-01-01

A well-known tradition in the study of visual aesthetics holds that the experience of visual beauty is grounded in global computational or statistical properties of the stimulus, for example, scale-invariant Fourier spectrum or self-similarity. Some approaches rely on neural mechanisms, such as efficient computation, processing fluency, or the responsiveness of the cells in the primary visual cortex. These proposals are united by the fact that the contributing factors are hypothesized to be global (i.e., they concern the percept as a whole), formal or non-conceptual (i.e., they concern form instead of content), computational and/or statistical, and based on relatively low-level sensory properties. Here we consider that the study of aesthetic responses to music could benefit from the same approach. Thus, along with local features such as pitch, tuning, consonance/dissonance, harmony, timbre, or beat, also global sonic properties could be viewed as contributing toward creating an aesthetic musical experience. Several such properties are discussed and their neural implementation is reviewed in the light of recent advances in neuroaesthetics.

All-optical recording and stimulation of retinal neurons in vivo in retinal degeneration mice

PubMed Central

Strazzeri, Jennifer M.; Williams, David R.; Merigan, William H.

2018-01-01

Here we demonstrate the application of a method that could accelerate the development of novel therapies by allowing direct and repeatable visualization of cellular function in the living eye, to study loss of vision in animal models of retinal disease, as well as evaluate the time course of retinal function following therapeutic intervention. We use high-resolution adaptive optics scanning light ophthalmoscopy to image fluorescence from the calcium sensor GCaMP6s. In mice with photoreceptor degeneration (rd10), we measured restored visual responses in ganglion cell layer neurons expressing the red-shifted channelrhodopsin ChrimsonR over a six-week period following significant loss of visual responses. Combining a fluorescent calcium sensor, a channelrhodopsin, and adaptive optics enables all-optical stimulation and recording of retinal neurons in the living eye. Because the retina is an accessible portal to the central nervous system, our method also provides a novel non-invasive method of dissecting neuronal processing in the brain. PMID:29596518

Clonal selection versus clonal cooperation: the integrated perception of immune objects

PubMed Central

Nataf, Serge

2016-01-01

Analogies between the immune and nervous systems were first envisioned by the immunologist Niels Jerne who introduced the concepts of antigen "recognition" and immune "memory". However, since then, it appears that only the cognitive immunology paradigm proposed by Irun Cohen, attempted to further theorize the immune system functions through the prism of neurosciences. The present paper is aimed at revisiting this analogy-based reasoning. In particular, a parallel is drawn between the brain pathways of visual perception and the processes allowing the global perception of an "immune object". Thus, in the visual system, distinct features of a visual object (shape, color, motion) are perceived separately by distinct neuronal populations during a primary perception task. The output signals generated during this first step instruct then an integrated perception task performed by other neuronal networks. Such a higher order perception step is by essence a cooperative task that is mandatory for the global perception of visual objects. Based on a re-interpretation of recent experimental data, it is suggested that similar general principles drive the integrated perception of immune objects in secondary lymphoid organs (SLOs). In this scheme, the four main categories of signals characterizing an immune object (antigenic, contextual, temporal and localization signals) are first perceived separately by distinct networks of immunocompetent cells.  Then, in a multitude of SLO niches, the output signals generated during this primary perception step are integrated by TH-cells at the single cell level. This process eventually generates a multitude of T-cell and B-cell clones that perform, at the scale of SLOs, an integrated perception of immune objects. Overall, this new framework proposes that integrated immune perception and, consequently, integrated immune responses, rely essentially on clonal cooperation rather than clonal selection. PMID:27830060

Visualizing Without Vision at the Microscale: Students With Visual Impairments Explore Cells With Touch

NASA Astrophysics Data System (ADS)

Jones, M. Gail; Minogue, James; Oppewal, Tom; Cook, Michelle P.; Broadwell, Bethany

2006-12-01

Science instruction is typically highly dependent on visual representations of scientific concepts that are communicated through textbooks, teacher presentations, and computer-based multimedia materials. Little is known about how students with visual impairments access and interpret these types of visually-dependent instructional materials. This study explored the efficacy of new haptic (simulated tactile feedback and kinesthetics) instructional technology for teaching cell morphology and function to middle and high school students with visual impairments. The study examined students' prior experiences learning about the cell and cell functions in classroom instruction, as well as how haptic feedback technology impacted students' awareness of the 3-D nature of an animal cell, the morphology and function of cell organelles, and students' interest in the haptic technology as an instructional tool. Twenty-one students with visual impairment participated in the study. Students explored a tactile model of the cell with a haptic point probe that allowed them to feel the cell and its organelles. Results showed that students made significant gains in their ability to identify cell organelles and found the technology to be highly interesting as an instructional tool. The need for additional adaptive technology for students with visual impairments is discussed.

Visual detection of glial cell line-derived neurotrophic factor based on a molecular translator and isothermal strand-displacement polymerization reaction.

PubMed

Zhang, Li-Yong; Xing, Tao; Du, Li-Xin; Li, Qing-Min; Liu, Wei-Dong; Wang, Ji-Yue; Cai, Jing

2015-01-01

Glial cell line-derived neurotrophic factor (GDNF) is a small protein that potently promotes the survival of many types of neurons. Detection of GDNF is vital to monitoring the survival of sympathetic and sensory neurons. However, the specific method for GDNF detection is also un-discovered. The purpose of this study is to explore the method for protein detection of GDNF. A novel visual detection method based on a molecular translator and isothermal strand-displacement polymerization reaction (ISDPR) has been proposed for the detection of GDNF. In this study, a molecular translator was employed to convert the input protein to output deoxyribonucleic acid signal, which was further amplified by ISDPR. The product of ISDPR was detected by a lateral flow biosensor within 30 minutes. This novel visual detection method based on a molecular translator and ISDPR has very high sensitivity and selectivity, with a dynamic response ranging from 1 pg/mL to 10 ng/mL, and the detection limit was 1 pg/mL of GDNF. This novel visual detection method exhibits high sensitivity and selectivity, which is very simple and universal for GDNF detection to help disease therapy in clinical practice.

The Touch and Zap method for in vivo whole-cell patch recording of intrinsic and visual responses of cortical neurons and glial cells.

PubMed

Schramm, Adrien E; Marinazzo, Daniele; Gener, Thomas; Graham, Lyle J

2014-01-01

Whole-cell patch recording is an essential tool for quantitatively establishing the biophysics of brain function, particularly in vivo. This method is of particular interest for studying the functional roles of cortical glial cells in the intact brain, which cannot be assessed with extracellular recordings. Nevertheless, a reasonable success rate remains a challenge because of stability, recording duration and electrical quality constraints, particularly for voltage clamp, dynamic clamp or conductance measurements. To address this, we describe "Touch and Zap", an alternative method for whole-cell patch clamp recordings, with the goal of being simpler, quicker and more gentle to brain tissue than previous approaches. Under current clamp mode with a continuous train of hyperpolarizing current pulses, seal formation is initiated immediately upon cell contact, thus the "Touch". By maintaining the current injection, whole-cell access is spontaneously achieved within seconds from the cell-attached configuration by a self-limited membrane electroporation, or "Zap", as seal resistance increases. We present examples of intrinsic and visual responses of neurons and putative glial cells obtained with the revised method from cat and rat cortices in vivo. Recording parameters and biophysical properties obtained with the Touch and Zap method compare favourably with those obtained with the traditional blind patch approach, demonstrating that the revised approach does not compromise the recorded cell. We find that the method is particularly well-suited for whole-cell patch recordings of cortical glial cells in vivo, targeting a wider population of this cell type than the standard method, with better access resistance. Overall, the gentler Touch and Zap method is promising for studying quantitative functional properties in the intact brain with minimal perturbation of the cell's intrinsic properties and local network. Because the Touch and Zap method is performed semi-automatically, this approach is more reproducible and less dependent on experimenter technique.

The Touch and Zap Method for In Vivo Whole-Cell Patch Recording of Intrinsic and Visual Responses of Cortical Neurons and Glial Cells

PubMed Central

Schramm, Adrien E.; Marinazzo, Daniele; Gener, Thomas; Graham, Lyle J.

2014-01-01

Whole-cell patch recording is an essential tool for quantitatively establishing the biophysics of brain function, particularly in vivo. This method is of particular interest for studying the functional roles of cortical glial cells in the intact brain, which cannot be assessed with extracellular recordings. Nevertheless, a reasonable success rate remains a challenge because of stability, recording duration and electrical quality constraints, particularly for voltage clamp, dynamic clamp or conductance measurements. To address this, we describe “Touch and Zap”, an alternative method for whole-cell patch clamp recordings, with the goal of being simpler, quicker and more gentle to brain tissue than previous approaches. Under current clamp mode with a continuous train of hyperpolarizing current pulses, seal formation is initiated immediately upon cell contact, thus the “Touch”. By maintaining the current injection, whole-cell access is spontaneously achieved within seconds from the cell-attached configuration by a self-limited membrane electroporation, or “Zap”, as seal resistance increases. We present examples of intrinsic and visual responses of neurons and putative glial cells obtained with the revised method from cat and rat cortices in vivo. Recording parameters and biophysical properties obtained with the Touch and Zap method compare favourably with those obtained with the traditional blind patch approach, demonstrating that the revised approach does not compromise the recorded cell. We find that the method is particularly well-suited for whole-cell patch recordings of cortical glial cells in vivo, targeting a wider population of this cell type than the standard method, with better access resistance. Overall, the gentler Touch and Zap method is promising for studying quantitative functional properties in the intact brain with minimal perturbation of the cell's intrinsic properties and local network. Because the Touch and Zap method is performed semi-automatically, this approach is more reproducible and less dependent on experimenter technique. PMID:24875855

GABAA receptor-mediated currents in interneurons and pyramidal cells of rat visual cortex

PubMed Central

Xiang, Zixiu; Huguenard, John R; Prince, David A

1998-01-01

We compared γ-aminobutyric acid (GABA)-mediated responses of identified pyramidal cells and fast spiking interneurons in layer V of visual cortical slices from young rats (P11-14). The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was similar in pyramidal cells and interneurons (1.7 vs. 1.9 Hz). For events with 10-90 % rise times less than 0.9 ms, no significant differences were found in mean amplitude (61 vs. 65 pA), mean rise time (0.58 vs. 0.61 ms), or the first time constant of decay (τ1, 6.4 vs. 6.5 ms) between pyramidal cells and interneurons. The second decay time constant (τ2) was significantly longer in interneurons than in pyramidal cells (49 vs. 22 ms). The difference in sIPSC decay kinetics between two cell types also existed in adult rats (P36-42), suggesting the kinetic difference is not due to differential development of GABAA receptors in these cell types. The decay kinetics of monosynaptic evoked IPSCs were also longer in interneurons. As in the case of sIPSCs, the difference was accounted for by the second decay time constant. τ1 and τ2 were, respectively, 13 and 64 ms for interneurons and 12 and 47 ms for pyramidal cells. Cell-attached patch recordings revealed that the mean open time for single Cl− channels in response to 2 μM GABA was significantly longer in interneurons than pyramidal cells (5.0 vs. 2.8 ms). The chord conductance of these channels in interneurons (12 pS) was significantly smaller than in pyramidal cells (15 pS). Single channel currents reversed polarity when the pipette potential was approximately -10 mV for both cell types. These results show that there is a functional diversity of GABAA receptors in electrophysiologically and morphologically identified cortical pyramidal cells and interneurons. This diversity might derive from the different molecular composition of the receptors in these two cell types. PMID:9503333

Absolute Depth Sensitivity in Cat Primary Visual Cortex under Natural Viewing Conditions.

PubMed

Pigarev, Ivan N; Levichkina, Ekaterina V

2016-01-01

Mechanisms of 3D perception, investigated in many laboratories, have defined depth either relative to the fixation plane or to other objects in the visual scene. It is obvious that for efficient perception of the 3D world, additional mechanisms of depth constancy could operate in the visual system to provide information about absolute distance. Neurons with properties reflecting some features of depth constancy have been described in the parietal and extrastriate occipital cortical areas. It has also been shown that, for some neurons in the visual area V1, responses to stimuli of constant angular size differ at close and remote distances. The present study was designed to investigate whether, in natural free gaze viewing conditions, neurons tuned to absolute depths can be found in the primary visual cortex (area V1). Single-unit extracellular activity was recorded from the visual cortex of waking cats sitting on a trolley in front of a large screen. The trolley was slowly approaching the visual scene, which consisted of stationary sinusoidal gratings of optimal orientation rear-projected over the whole surface of the screen. Each neuron was tested with two gratings, with spatial frequency of one grating being twice as high as that of the other. Assuming that a cell is tuned to a spatial frequency, its maximum response to the grating with a spatial frequency twice as high should be shifted to a distance half way closer to the screen in order to attain the same size of retinal projection. For hypothetical neurons selective to absolute depth, location of the maximum response should remain at the same distance irrespective of the type of stimulus. It was found that about 20% of neurons in our experimental paradigm demonstrated sensitivity to particular distances independently of the spatial frequencies of the gratings. We interpret these findings as an indication of the use of absolute depth information in the primary visual cortex.

Visuomotor Transformation in the Fly Gaze Stabilization System

PubMed Central

Huston, Stephen J; Krapp, Holger G

2008-01-01

For sensory signals to control an animal's behavior, they must first be transformed into a format appropriate for use by its motor systems. This fundamental problem is faced by all animals, including humans. Beyond simple reflexes, little is known about how such sensorimotor transformations take place. Here we describe how the outputs of a well-characterized population of fly visual interneurons, lobula plate tangential cells (LPTCs), are used by the animal's gaze-stabilizing neck motor system. The LPTCs respond to visual input arising from both self-rotations and translations of the fly. The neck motor system however is involved in gaze stabilization and thus mainly controls compensatory head rotations. We investigated how the neck motor system is able to selectively extract rotation information from the mixed responses of the LPTCs. We recorded extracellularly from fly neck motor neurons (NMNs) and mapped the directional preferences across their extended visual receptive fields. Our results suggest that—like the tangential cells—NMNs are tuned to panoramic retinal image shifts, or optic flow fields, which occur when the fly rotates about particular body axes. In many cases, tangential cells and motor neurons appear to be tuned to similar axes of rotation, resulting in a correlation between the coordinate systems the two neural populations employ. However, in contrast to the primarily monocular receptive fields of the tangential cells, most NMNs are sensitive to visual motion presented to either eye. This results in the NMNs being more selective for rotation than the LPTCs. Thus, the neck motor system increases its rotation selectivity by a comparatively simple mechanism: the integration of binocular visual motion information. PMID:18651791

Cell Wall Remodeling by a Synthetic Analog Reveals Metabolic Adaptation in Vancomycin Resistant Enterococci.

PubMed

Pidgeon, Sean E; Pires, Marcos M

2017-07-21

Drug-resistant bacterial infections threaten to overburden our healthcare system and disrupt modern medicine. A large class of potent antibiotics, including vancomycin, operate by interfering with bacterial cell wall biosynthesis. Vancomycin-resistant enterococci (VRE) evade the blockage of cell wall biosynthesis by altering cell wall precursors, rendering them drug insensitive. Herein, we reveal the phenotypic plasticity and cell wall remodeling of VRE in response to vancomycin in live bacterial cells via a metabolic probe. A synthetic cell wall analog was designed and constructed to monitor cell wall structural alterations. Our results demonstrate that the biosynthetic pathway for vancomycin-resistant precursors can be hijacked by synthetic analogs to track the kinetics of phenotype induction. In addition, we leveraged this probe to interrogate the response of VRE cells to vancomycin analogs and a series of cell wall-targeted antibiotics. Finally, we describe a proof-of-principle strategy to visually inspect drug resistance induction. Based on our findings, we anticipate that our metabolic probe will play an important role in further elucidating the interplay among the enzymes involved in the VRE biosynthetic rewiring.

A Pooled Analysis on Crizotinib in Treating Chinese Patients with EML4-ALK Positive Non-small-cell Lung Cancer.

PubMed

Li, Yang; Huang, Xin-En

2015-01-01

This analysis was conducted to evaluate the efficacy and safety of crizotinib based regimens in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer. Clinical studies evaluating the efficacy and safety of crizotinib based regimens on response and safety for Chinese patients with EML4-ALK positive non-small-cell lung cancer were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. In crizotinib based regimens, 3 clinical studies which including 128 Chinese patients with EML4-ALK positive non-small-cell lung cancer and treated with crizotinib based regimen were considered eligible for inclusion. Pooled analysis suggested that, in all patients, the pooled RR was 59.3% (76/128) in crizotinib based regimens. ALT/AST mild visual disturbances, nausea, and vomiting were the main side effects. No treatment related death occurred in these crizotinib based treatments. This pooled analysis suggests that crizotinib based regimens are associated with good response rate and accepted toxicities in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.

Visualizing Chemical Interaction Dynamics of Confined DNA Molecules

NASA Astrophysics Data System (ADS)

Henkin, Gilead; Berard, Daniel; Stabile, Frank; Leslie, Sabrina

We present a novel nanofluidic approach to controllably introducing reagent molecules to interact with confined biopolymers and visualizing the reaction dynamics in real time. By dynamically deforming a flow cell using CLiC (Convex Lens-induced Confinement) microscopy, we are able to tune reaction chamber dimensions from micrometer to nanometer scales. We apply this gentle deformation to load and extend DNA polymers within embedded nanotopographies and visualize their interactions with other molecules in solution. Quantifying the change in configuration of polymers within embedded nanotopographies in response to binding/unbinding of reagent molecules provides new insights into their consequent change in physical properties. CLiC technology enables an ultra sensitive, massively parallel biochemical analysis platform which can acces a broader range of interaction parameters than existing devices.

Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration

PubMed Central

Karunarathne, W. K. Ajith; Giri, Lopamudra; Patel, Anilkumar K.; Venkatesh, Kareenhalli V.; Gautam, N.

2013-01-01

There is a dearth of approaches to experimentally direct cell migration by continuously varying signal input to a single cell, evoking all possible migratory responses and quantitatively monitoring the cellular and molecular response dynamics. Here we used a visual blue opsin to recruit the endogenous G-protein network that mediates immune cell migration. Specific optical inputs to this optical trigger of signaling helped steer migration in all possible directions with precision. Spectrally selective imaging was used to monitor cell-wide phosphatidylinositol (3,4,5)-triphosphate (PIP3), cytoskeletal, and cellular dynamics. A switch-like PIP3 increase at the cell front and a decrease at the back were identified, underlying the decisive migratory response. Migration was initiated at the rapidly increasing switch stage of PIP3 dynamics. This result explains how a migratory cell filters background fluctuations in the intensity of an extracellular signal but responds by initiating directionally sensitive migration to a persistent signal gradient across the cell. A two-compartment computational model incorporating a localized activator that is antagonistic to a diffusible inhibitor was able to simulate the switch-like PIP3 response. It was also able simulate the slow dissipation of PIP3 on signal termination. The ability to independently apply similar signaling inputs to single cells detected two cell populations with distinct thresholds for migration initiation. Overall the optical approach here can be applied to understand G-protein–coupled receptor network control of other cell behaviors. PMID:23569254

Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration.

PubMed

Karunarathne, W K Ajith; Giri, Lopamudra; Patel, Anilkumar K; Venkatesh, Kareenhalli V; Gautam, N

2013-04-23

There is a dearth of approaches to experimentally direct cell migration by continuously varying signal input to a single cell, evoking all possible migratory responses and quantitatively monitoring the cellular and molecular response dynamics. Here we used a visual blue opsin to recruit the endogenous G-protein network that mediates immune cell migration. Specific optical inputs to this optical trigger of signaling helped steer migration in all possible directions with precision. Spectrally selective imaging was used to monitor cell-wide phosphatidylinositol (3,4,5)-triphosphate (PIP3), cytoskeletal, and cellular dynamics. A switch-like PIP3 increase at the cell front and a decrease at the back were identified, underlying the decisive migratory response. Migration was initiated at the rapidly increasing switch stage of PIP3 dynamics. This result explains how a migratory cell filters background fluctuations in the intensity of an extracellular signal but responds by initiating directionally sensitive migration to a persistent signal gradient across the cell. A two-compartment computational model incorporating a localized activator that is antagonistic to a diffusible inhibitor was able to simulate the switch-like PIP3 response. It was also able simulate the slow dissipation of PIP3 on signal termination. The ability to independently apply similar signaling inputs to single cells detected two cell populations with distinct thresholds for migration initiation. Overall the optical approach here can be applied to understand G-protein-coupled receptor network control of other cell behaviors.

Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells

PubMed Central

Miraucourt, Loïs S; Tsui, Jennifer; Gobert, Delphine; Desjardins, Jean-François; Schohl, Anne; Sild, Mari; Spratt, Perry; Castonguay, Annie; De Koninck, Yves; Marsh-Armstrong, Nicholas; Wiseman, Paul W; Ruthazer, Edward S

2016-01-01

Type 1 cannabinoid receptors (CB1Rs) are widely expressed in the vertebrate retina, but the role of endocannabinoids in vision is not fully understood. Here, we identified a novel mechanism underlying a CB1R-mediated increase in retinal ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent inhibition of NKCC1 activity. Clomeleon imaging and patch clamp recordings revealed that inhibition of NKCC1 downstream of CB1R activation reduces intracellular Cl− levels in RGCs, hyperpolarizing the resting membrane potential. We confirmed that such hyperpolarization enhances RGC action potential firing in response to subsequent depolarization, consistent with the increased intrinsic excitability of RGCs observed with CB1R activation. Using a dot avoidance assay in freely swimming Xenopus tadpoles, we demonstrate that CB1R activation markedly improves visual contrast sensitivity under low-light conditions. These results highlight a role for endocannabinoids in vision and present a novel mechanism for cannabinoid modulation of neuronal activity through Cl− regulation. DOI: http://dx.doi.org/10.7554/eLife.15932.001 PMID:27501334

Neural dynamics of motion processing and speed discrimination.

PubMed

Chey, J; Grossberg, S; Mingolla, E

1998-09-01

A neural network model of visual motion perception and speed discrimination is presented. The model shows how a distributed population code of speed tuning, that realizes a size-speed correlation, can be derived from the simplest mechanisms whereby activations of multiple spatially short-range filters of different size are transformed into speed-turned cell responses. These mechanisms use transient cell responses to moving stimuli, output thresholds that covary with filter size, and competition. These mechanisms are proposed to occur in the V1-->MT cortical processing stream. The model reproduces empirically derived speed discrimination curves and simulates data showing how visual speed perception and discrimination can be affected by stimulus contrast, duration, dot density and spatial frequency. Model motion mechanisms are analogous to mechanisms that have been used to model 3-D form and figure-ground perception. The model forms the front end of a larger motion processing system that has been used to simulate how global motion capture occurs, and how spatial attention is drawn to moving forms. It provides a computational foundation for an emerging neural theory of 3-D form and motion perception.

Proteomic analysis of secreted proteins by human bronchial epithelial cells in response to cadmium toxicity.

PubMed

Chen, De-Ju; Xu, Yan-Ming; Zheng, Wei; Huang, Dong-Yang; Wong, Wing-Yan; Tai, William Chi-Shing; Cho, Yong-Yeon; Lau, Andy T Y

2015-09-01

For years, many studies have been conducted to investigate the intracellular response of cells challenged with toxic metal(s), yet, the corresponding secretome responses, especially in human lung cells, are largely unexplored. Here, we provide a secretome analysis of human bronchial epithelial cells (BEAS-2B) treated with cadmium chloride (CdCl2 ), with the aim of identifying secreted proteins in response to Cd toxicity. Proteins from control and spent media were separated by two-dimensional electrophoresis and visualized by silver staining. Differentially-secreted proteins were identified by MALDI-TOF-MS analysis and database searching. We characterized, for the first time, the extracellular proteome changes of BEAS-2B dosed with Cd. Our results unveiled that Cd treatment led to the marked upregulation of molecular chaperones, antioxidant enzymes, enzymes associated with glutathione metabolic process, proteins involved in cellular energy metabolism, as well as tumor-suppressors. Pretreatment of cells with the thiol antioxidant glutathione before Cd treatment effectively abrogated the secretion of these proteins and prevented cell death. Taken together, our results demonstrate that Cd causes oxidative stress-induced cytotoxicity; and the differentially-secreted protein signatures could be considered as targets for potential use as extracellular biomarkers upon Cd exposure. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Speed in Information Processing with a Computer Driven Visual Display in a Real-time Digital Simulation. M.S. Thesis - Virginia Polytechnic Inst.

NASA Technical Reports Server (NTRS)

Kyle, R. G.

1972-01-01

Information transfer between the operator and computer-generated display systems is an area where the human factors engineer discovers little useful design data relating human performance to system effectiveness. This study utilized a computer-driven, cathode-ray-tube graphic display to quantify human response speed in a sequential information processing task. The performance criteria was response time to sixteen cell elements of a square matrix display. A stimulus signal instruction specified selected cell locations by both row and column identification. An equal probable number code, from one to four, was assigned at random to the sixteen cells of the matrix and correspondingly required one of four, matched keyed-response alternatives. The display format corresponded to a sequence of diagnostic system maintenance events, that enable the operator to verify prime system status, engage backup redundancy for failed subsystem components, and exercise alternate decision-making judgements. The experimental task bypassed the skilled decision-making element and computer processing time, in order to determine a lower bound on the basic response speed for given stimulus/response hardware arrangement.

Progressive reduction of CMV-specific CD4+ T cells in HIV-1 infected individuals during antiretroviral therapy.

PubMed

Grosse, V; Schulte, A; Weber, K; Mendila, M; Jacobs, R; Schmidt, R E; Heiken, H

2000-08-01

Visualization of antigen-specific T cells has become an important tool in studying immune responses. The aim of this study was to analyze CMV-specific CD4+ T cells in healthy and HIV-infected individuals. Peripheral blood mononuclear cells (PBMC) were examined for antigen-induced intracellular cytokine responses. We found significant numbers of CMV-specific CD4+ T cells detectable in most CMV-IgG+ HIV-1 infected individuals, whereas CMV-specific CD4+ T cells could not be demonstrated in CMV-IgG- patients. Median frequency of CMV-specific CD4+ T cells were lower in HIV-infected subjects who had been treated with highly active antiretroviral therapy (HAART) for more than 1 year than in untreated HIV-infected individuals. In patients under therapy for less than 1 year median CMV-specific CD4+ T cell responder frequency was higher than in subjects treated for more than 1 year but lower than in untreated subjects. HIV suppression with HAART might lead to a progressive reduction of CMV-specific CD4+ T cells indicating an efficient elimination of an opportunistic pathogen.

Neural Mechanisms of Cortical Motion Computation Based on a Neuromorphic Sensory System

PubMed Central

Abdul-Kreem, Luma Issa; Neumann, Heiko

2015-01-01

The visual cortex analyzes motion information along hierarchically arranged visual areas that interact through bidirectional interconnections. This work suggests a bio-inspired visual model focusing on the interactions of the cortical areas in which a new mechanism of feedforward and feedback processing are introduced. The model uses a neuromorphic vision sensor (silicon retina) that simulates the spike-generation functionality of the biological retina. Our model takes into account two main model visual areas, namely V1 and MT, with different feature selectivities. The initial motion is estimated in model area V1 using spatiotemporal filters to locally detect the direction of motion. Here, we adapt the filtering scheme originally suggested by Adelson and Bergen to make it consistent with the spike representation of the DVS. The responses of area V1 are weighted and pooled by area MT cells which are selective to different velocities, i.e. direction and speed. Such feature selectivity is here derived from compositions of activities in the spatio-temporal domain and integrating over larger space-time regions (receptive fields). In order to account for the bidirectional coupling of cortical areas we match properties of the feature selectivity in both areas for feedback processing. For such linkage we integrate the responses over different speeds along a particular preferred direction. Normalization of activities is carried out over the spatial as well as the feature domains to balance the activities of individual neurons in model areas V1 and MT. Our model was tested using different stimuli that moved in different directions. The results reveal that the error margin between the estimated motion and synthetic ground truth is decreased in area MT comparing with the initial estimation of area V1. In addition, the modulated V1 cell activations shows an enhancement of the initial motion estimation that is steered by feedback signals from MT cells. PMID:26554589

The impact of haptic feedback on students' conceptions of the cell

NASA Astrophysics Data System (ADS)

Minogue, James

2005-07-01

The purpose of this study was to investigate the efficacy of adding haptic (sense of touch) feedback to computer generated visualizations for use in middle school science instruction. Current technology allows for the simulation of tactile and kinesthetic sensations via haptic devices and a computer interface. This study, conducted with middle school students (n = 80), explored the cognitive and affective impacts of this innovative technology on students' conceptions of the cell and the process of passive transport. A pretest-posttest control group design was used and participants were randomly assigned to one of two treatment groups (n = 40 for each). Both groups experienced the same core computer-mediated instructional program. This Cell Exploration program engaged students in a 3-D immersive environment that allowed them to actively investigate the form and function of a typical animal cell including its major organelles. The program also engaged students in a study of the structure and function of the cell membrane as it pertains to the process of passive transport and the mechanisms behind the membrane's selective permeability. As they conducted their investigations, students in the experimental group received bi-modal visual and haptic (simulated tactile and kinesthetic) feedback whereas the control group students experienced the program with only visual stimuli. A battery of assessments, including objective and open-ended written response items as well as a haptic performance assessment, were used to gather quantitative and qualitative data regarding changes in students' understandings of the cell concepts prior to and following their completion of the instructional program. Additionally, the impact of haptics on the affective domain of students' learning was assessed using a post-experience semi-structured interview and an attitudinal survey. Results showed that students from both conditions (Visual-Only and Visual + Haptic) found the instructional program interesting and engaging. Additionally, the vast majority of the students reported that they learned a lot about and were more interested in the topic due to their participation. Moreover, students who received the bi-modal (Visual + Haptic) feedback indicated that they experienced lower levels of frustration and spatial disorientation as they conducted their investigations when compared to individuals that relied solely on vision. There were no significant differences measured across the treatment groups on the cognitive assessment items. Despite this finding, the study provided valuable insight into the theoretical and practical considerations involved in the development of multimodal instructional programs.

Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer.

PubMed

Bennicelli, Jeannette; Wright, John Fraser; Komaromy, Andras; Jacobs, Jonathan B; Hauck, Bernd; Zelenaia, Olga; Mingozzi, Federico; Hui, Daniel; Chung, Daniel; Rex, Tonia S; Wei, Zhangyong; Qu, Guang; Zhou, Shangzhen; Zeiss, Caroline; Arruda, Valder R; Acland, Gregory M; Dell'Osso, Lou F; High, Katherine A; Maguire, Albert M; Bennett, Jean

2008-03-01

We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models of the RPE65 form of Leber congenital amaurosis (LCA). Protein expression was optimized by addition of a modified Kozak sequence at the translational start site of hRPE65. Modifications in AAV production and delivery included use of a long stuffer sequence to prevent reverse packaging from the AAV inverted-terminal repeats, and co-injection with a surfactant. The latter allows consistent and predictable delivery of a given dose of vector. We observed improved electroretinograms (ERGs) and visual acuity in Rpe65 mutant mice. This has not been reported previously using AAV2 vectors. Subretinal delivery of 8.25 x 10(10) vector genomes in affected dogs was well tolerated both locally and systemically, and treated animals showed improved visual behavior and pupillary responses, and reduced nystagmus within 2 weeks of injection. ERG responses confirmed the reversal of visual deficit. Immunohistochemistry confirmed transduction of retinal pigment epithelium cells and there was minimal toxicity to the retina as judged by histopathologic analysis. The data demonstrate that AAV2.RPE65 delivers the RPE65 transgene efficiently and quickly to the appropriate target cells in vivo in animal models. This vector holds great promise for treatment of LCA due to RPE65 mutations.

Reversal of Blindness in Animal Models of Leber Congenital Amaurosis Using Optimized AAV2-mediated Gene Transfer

PubMed Central

Bennicelli, Jeannette; Wright, John Fraser; Komaromy, Andras; Jacobs, Jonathan B; Hauck, Bernd; Zelenaia, Olga; Mingozzi, Federico; Hui, Daniel; Chung, Daniel; Rex, Tonia S; Wei, Zhangyong; Qu, Guang; Zhou, Shangzhen; Zeiss, Caroline; Arruda, Valder R; Acland, Gregory M; Dell’Osso, Lou F; High, Katherine A; Maguire, Albert M; Bennett, Jean

2010-01-01

We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models of the RPE65 form of Leber congenital amaurosis (LCA). Protein expression was optimized by addition of a modified Kozak sequence at the translational start site of hRPE65. Modifications in AAV production and delivery included use of a long stuffer sequence to prevent reverse packaging from the AAV inverted-terminal repeats, and co-injection with a surfactant. The latter allows consistent and predictable delivery of a given dose of vector. We observed improved electroretinograms (ERGs) and visual acuity in Rpe65 mutant mice. This has not been reported previously using AAV2 vectors. Subretinal delivery of 8.25 × 1010 vector genomes in affected dogs was well tolerated both locally and systemically, and treated animals showed improved visual behavior and pupillary responses, and reduced nystagmus within 2 weeks of injection. ERG responses confirmed the reversal of visual deficit. Immunohistochemistry confirmed transduction of retinal pigment epithelium cells and there was minimal toxicity to the retina as judged by histopathologic analysis. The data demonstrate that AAV2.RPE65 delivers the RPE65 transgene efficiently and quickly to the appropriate target cells in vivo in animal models. This vector holds great promise for treatment of LCA due to RPE65 mutations. PMID:18209734

Biologically based machine vision: signal analysis of monopolar cells in the visual system of Musca domestica.

PubMed

Newton, Jenny; Barrett, Steven F; Wilcox, Michael J; Popp, Stephanie

2002-01-01

Machine vision for navigational purposes is a rapidly growing field. Many abilities such as object recognition and target tracking rely on vision. Autonomous vehicles must be able to navigate in dynamic enviroments and simultaneously locate a target position. Traditional machine vision often fails to react in real time because of large computational requirements whereas the fly achieves complex orientation and navigation with a relatively small and simple brain. Understanding how the fly extracts visual information and how neurons encode and process information could lead us to a new approach for machine vision applications. Photoreceptors in the Musca domestica eye that share the same spatial information converge into a structure called the cartridge. The cartridge consists of the photoreceptor axon terminals and monopolar cells L1, L2, and L4. It is thought that L1 and L2 cells encode edge related information relative to a single cartridge. These cells are thought to be equivalent to vertebrate bipolar cells, producing contrast enhancement and reduction of information sent to L4. Monopolar cell L4 is thought to perform image segmentation on the information input from L1 and L2 and also enhance edge detection. A mesh of interconnected L4's would correlate the output from L1 and L2 cells of adjacent cartridges and provide a parallel network for segmenting an object's edges. The focus of this research is to excite photoreceptors of the common housefly, Musca domestica, with different visual patterns. The electrical response of monopolar cells L1, L2, and L4 will be recorded using intracellular recording techniques. Signal analysis will determine the neurocircuitry to detect and segment images.

Describing complex cells in primary visual cortex: a comparison of context and multi-filter LN models.

PubMed

Westö, Johan; May, Patrick J C

2018-05-02

Receptive field (RF) models are an important tool for deciphering neural responses to sensory stimuli. The two currently popular RF models are multi-filter linear-nonlinear (LN) models and context models. Models are, however, never correct and they rely on assumptions to keep them simple enough to be interpretable. As a consequence, different models describe different stimulus-response mappings, which may or may not be good approximations of real neural behavior. In the current study, we take up two tasks: First, we introduce new ways to estimate context models with realistic nonlinearities, that is, with logistic and exponential functions. Second, we evaluate context models and multi-filter LN models in terms of how well they describe recorded data from complex cells in cat primary visual cortex. Our results, based on single-spike information and correlation coefficients, indicate that context models outperform corresponding multi-filter LN models of equal complexity (measured in terms of number of parameters), with the best increase in performance being achieved by the novel context models. Consequently, our results suggest that the multi-filter LN-model framework is suboptimal for describing the behavior of complex cells: the context-model framework is clearly superior while still providing interpretable quantizations of neural behavior.

Spatial Tuning Shifts Increase the Discriminability and Fidelity of Population Codes in Visual Cortex

PubMed Central

2017-01-01

Selective visual attention enables organisms to enhance the representation of behaviorally relevant stimuli by altering the encoding properties of single receptive fields (RFs). Yet we know little about how the attentional modulations of single RFs contribute to the encoding of an entire visual scene. Addressing this issue requires (1) measuring a group of RFs that tile a continuous portion of visual space, (2) constructing a population-level measurement of spatial representations based on these RFs, and (3) linking how different types of RF attentional modulations change the population-level representation. To accomplish these aims, we used fMRI to characterize the responses of thousands of voxels in retinotopically organized human cortex. First, we found that the response modulations of voxel RFs (vRFs) depend on the spatial relationship between the RF center and the visual location of the attended target. Second, we used two analyses to assess the spatial encoding quality of a population of voxels. We found that attention increased fine spatial discriminability and representational fidelity near the attended target. Third, we linked these findings by manipulating the observed vRF attentional modulations and recomputing our measures of the fidelity of population codes. Surprisingly, we discovered that attentional enhancements of population-level representations largely depend on position shifts of vRFs, rather than changes in size or gain. Our data suggest that position shifts of single RFs are a principal mechanism by which attention enhances population-level representations in visual cortex. SIGNIFICANCE STATEMENT Although changes in the gain and size of RFs have dominated our view of how attention modulates visual information codes, such hypotheses have largely relied on the extrapolation of single-cell responses to population responses. Here we use fMRI to relate changes in single voxel receptive fields (vRFs) to changes in population-level representations. We find that vRF position shifts contribute more to population-level enhancements of visual information than changes in vRF size or gain. This finding suggests that position shifts are a principal mechanism by which spatial attention enhances population codes for relevant visual information. This poses challenges for labeled line theories of information processing, suggesting that downstream regions likely rely on distributed inputs rather than single neuron-to-neuron mappings. PMID:28242794

Computational model for perception of objects and motions.

PubMed

Yang, WenLu; Zhang, LiQing; Ma, LiBo

2008-06-01

Perception of objects and motions in the visual scene is one of the basic problems in the visual system. There exist 'What' and 'Where' pathways in the superior visual cortex, starting from the simple cells in the primary visual cortex. The former is able to perceive objects such as forms, color, and texture, and the latter perceives 'where', for example, velocity and direction of spatial movement of objects. This paper explores brain-like computational architectures of visual information processing. We propose a visual perceptual model and computational mechanism for training the perceptual model. The computational model is a three-layer network. The first layer is the input layer which is used to receive the stimuli from natural environments. The second layer is designed for representing the internal neural information. The connections between the first layer and the second layer, called the receptive fields of neurons, are self-adaptively learned based on principle of sparse neural representation. To this end, we introduce Kullback-Leibler divergence as the measure of independence between neural responses and derive the learning algorithm based on minimizing the cost function. The proposed algorithm is applied to train the basis functions, namely receptive fields, which are localized, oriented, and bandpassed. The resultant receptive fields of neurons in the second layer have the characteristics resembling that of simple cells in the primary visual cortex. Based on these basis functions, we further construct the third layer for perception of what and where in the superior visual cortex. The proposed model is able to perceive objects and their motions with a high accuracy and strong robustness against additive noise. Computer simulation results in the final section show the feasibility of the proposed perceptual model and high efficiency of the learning algorithm.

Three-Dimensional, Live-Cell Imaging of Chromatin Dynamics in Plant Nuclei Using Chromatin Tagging Systems.

PubMed

Hirakawa, Takeshi; Matsunaga, Sachihiro

2016-01-01

In plants, chromatin dynamics spatiotemporally change in response to various environmental stimuli. However, little is known about chromatin dynamics in the nuclei of plants. Here, we introduce a three-dimensional, live-cell imaging method that can monitor chromatin dynamics in nuclei via a chromatin tagging system that can visualize specific genomic loci in living plant cells. The chromatin tagging system is based on a bacterial operator/repressor system in which the repressor is fused to fluorescent proteins. A recent refinement of promoters for the system solved the problem of gene silencing and abnormal pairing frequencies between operators. Using this system, we can detect the spatiotemporal dynamics of two homologous loci as two fluorescent signals within a nucleus and monitor the distance between homologous loci. These live-cell imaging methods will provide new insights into genome organization, development processes, and subnuclear responses to environmental stimuli in plants.

A cooperation and competition based simple cell receptive field model and study of feed-forward linear and nonlinear contributions to orientation selectivity.

PubMed

Bhaumik, Basabi; Mathur, Mona

2003-01-01

We present a model for development of orientation selectivity in layer IV simple cells. Receptive field (RF) development in the model, is determined by diffusive cooperation and resource limited competition guided axonal growth and retraction in geniculocortical pathway. The simulated cortical RFs resemble experimental RFs. The receptive field model is incorporated in a three-layer visual pathway model consisting of retina, LGN and cortex. We have studied the effect of activity dependent synaptic scaling on orientation tuning of cortical cells. The mean value of hwhh (half width at half the height of maximum response) in simulated cortical cells is 58 degrees when we consider only the linear excitatory contribution from LGN. We observe a mean improvement of 22.8 degrees in tuning response due to the non-linear spiking mechanisms that include effects of threshold voltage and synaptic scaling factor.

3D/4D multiscale imaging in acute lymphoblastic leukemia cells: visualizing dynamics of cell death

NASA Astrophysics Data System (ADS)

Sarangapani, Sreelatha; Mohan, Rosmin Elsa; Patil, Ajeetkumar; Lang, Matthew J.; Asundi, Anand

2017-06-01

Quantitative phase detection is a new methodology that provides quantitative information on cellular morphology to monitor the cell status, drug response and toxicity. In this paper the morphological changes in acute leukemia cells treated with chitosan were detected using d'Bioimager a robust imaging system. Quantitative phase image of the cells was obtained with numerical analysis. Results show that the average area and optical volume of the chitosan treated cells is significantly reduced when compared with the control cells, which reveals the effect of chitosan on the cancer cells. From the results it can be attributed that d'Bioimager can be used as a non-invasive imaging alternative to measure the morphological changes of the living cells in real time.

Attention to Multiple Objects Facilitates Their Integration in Prefrontal and Parietal Cortex.

PubMed

Kim, Yee-Joon; Tsai, Jeffrey J; Ojemann, Jeffrey; Verghese, Preeti

2017-05-10

Selective attention is known to interact with perceptual organization. In visual scenes, individual objects that are distinct and discriminable may occur on their own, or in groups such as a stack of books. The main objective of this study is to probe the neural interaction that occurs between individual objects when attention is directed toward one or more objects. Here we record steady-state visual evoked potentials via electrocorticography to directly assess the responses to individual stimuli and to their interaction. When human participants attend to two adjacent stimuli, prefrontal and parietal cortex shows a selective enhancement of only the neural interaction between stimuli, but not the responses to individual stimuli. When only one stimulus is attended, the neural response to that stimulus is selectively enhanced in prefrontal and parietal cortex. In contrast, early visual areas generally manifest responses to individual stimuli and to their interaction regardless of attentional task, although a subset of the responses is modulated similarly to prefrontal and parietal cortex. Thus, the neural representation of the visual scene as one progresses up the cortical hierarchy becomes more highly task-specific and represents either individual stimuli or their interaction, depending on the behavioral goal. Attention to multiple objects facilitates an integration of objects akin to perceptual grouping. SIGNIFICANCE STATEMENT Individual objects in a visual scene are seen as distinct entities or as parts of a whole. Here we examine how attention to multiple objects affects their neural representation. Previous studies measured single-cell or fMRI responses and obtained only aggregate measures that combined the activity to individual stimuli as well as their potential interaction. Here, we directly measure electrocorticographic steady-state responses corresponding to individual objects and to their interaction using a frequency-tagging technique. Attention to two stimuli increases the interaction component that is a hallmark for perceptual integration of stimuli. Furthermore, this stimulus-specific interaction is represented in prefrontal and parietal cortex in a task-dependent manner. Copyright © 2017 the authors 0270-6474/17/374942-12$15.00/0.

Timing of target discrimination in human frontal eye fields.

PubMed

O'Shea, Jacinta; Muggleton, Neil G; Cowey, Alan; Walsh, Vincent

2004-01-01

Frontal eye field (FEF) neurons discharge in response to behaviorally relevant stimuli that are potential targets for saccades. Distinct visual and motor processes have been dissociated in the FEF of macaque monkeys, but little is known about the visual processing capacity of FEF in humans. We used double-pulse transcranial magnetic stimulation [(d)TMS] to investigate the timing of target discrimination during visual conjunction search. We applied dual TMS pulses separated by 40 msec over the right FEF and vertex. These were applied in five timing conditions to sample separate time windows within the first 200 msec of visual processing. (d)TMS impaired search performance, reflected in reduced d' scores. This effect was limited to a time window between 40 and 80 msec after search array onset. These parameters correspond with single-cell activity in FEF that predicts monkeys' behavioral reports on hit, miss, false alarm, and correct rejection trials. Our findings demonstrate a crucial early role for human FEF in visual target discrimination that is independent of saccade programming.

Adult Visual Cortical Plasticity

PubMed Central

Gilbert, Charles D.; Li, Wu

2012-01-01

The visual cortex has the capacity for experience dependent change, or cortical plasticity, that is retained throughout life. Plasticity is invoked for encoding information during perceptual learning, by internally representing the regularities of the visual environment, which is useful for facilitating intermediate level vision - contour integration and surface segmentation. The same mechanisms have adaptive value for functional recovery after CNS damage, such as that associated with stroke or neurodegenerative disease. A common feature to plasticity in primary visual cortex (V1) is an association field that links contour elements across the visual field. The circuitry underlying the association field includes a plexus of long range horizontal connections formed by cortical pyramidal cells. These connections undergo rapid and exuberant sprouting and pruning in response to removal of sensory input, which can account for the topographic reorganization following retinal lesions. Similar alterations in cortical circuitry may be involved in perceptual learning, and the changes observed in V1 may be representative of how learned information is encoded throughout the cerebral cortex. PMID:22841310

Circumventing photodamage in live-cell microscopy

PubMed Central

Magidson, Valentin; Khodjakov, Alexey

2013-01-01

Fluorescence microscopy has become an essential tool in cell biology. This technique allows researchers to visualize the dynamics of tissue, cells, individual organelles and macromolecular assemblies inside the cell. Unfortunately, fluorescence microscopy is not completely ‘non-invasive’ as the high-intensity excitation light required for excitation of fluorophores is inherently toxic for live cells. Physiological changes induced by excessive illumination can lead to artifacts and abnormal responses. In this chapter we review major factors that contribute to phototoxicity and discuss practical solutions for circumventing photodamage. These solutions include the proper choice of image acquisition parameters, optimization of filter sets, hardware synchronization, and the use of intelligent illumination to avoid unnecessary light exposure. PMID:23931522

Embedding of Cortical Representations by the Superficial Patch System

PubMed Central

Da Costa, Nuno M. A.; Girardin, Cyrille C.; Naaman, Shmuel; Omer, David B.; Ruesch, Elisha; Grinvald, Amiram; Douglas, Rodney J.

2011-01-01

Pyramidal cells in layers 2 and 3 of the neocortex of many species collectively form a clustered system of lateral axonal projections (the superficial patch system—Lund JS, Angelucci A, Bressloff PC. 2003. Anatomical substrates for functional columns in macaque monkey primary visual cortex. Cereb Cortex. 13:15–24. or daisy architecture—Douglas RJ, Martin KAC. 2004. Neuronal circuits of the neocortex. Annu Rev Neurosci. 27:419–451.), but the function performed by this general feature of the cortical architecture remains obscure. By comparing the spatial configuration of labeled patches with the configuration of responses to drifting grating stimuli, we found the spatial organizations both of the patch system and of the cortical response to be highly conserved between cat and monkey primary visual cortex. More importantly, the configuration of the superficial patch system is directly reflected in the arrangement of function across monkey primary visual cortex. Our results indicate a close relationship between the structure of the superficial patch system and cortical responses encoding a single value across the surface of visual cortex (self-consistent states). This relationship is consistent with the spontaneous emergence of orientation response–like activity patterns during ongoing cortical activity (Kenet T, Bibitchkov D, Tsodyks M, Grinvald A, Arieli A. 2003. Spontaneously emerging cortical representations of visual attributes. Nature. 425:954–956.). We conclude that the superficial patch system is the physical encoding of self-consistent cortical states, and that a set of concurrently labeled patches participate in a network of mutually consistent representations of cortical input. PMID:21383233

Visualization of the entire differentiation process of murine M cells: suppression of their maturation in cecal patches.

PubMed

Kimura, S; Yamakami-Kimura, M; Obata, Y; Hase, K; Kitamura, H; Ohno, H; Iwanaga, T

2015-05-01

The microfold (M) cell residing in the follicle-associated epithelium is a specialized epithelial cell that initiates mucosal immune responses by sampling luminal antigens. The differentiation process of M cells remains unclear due to limitations of analytical methods. Here we found that M cells were classified into two functionally different subtypes based on the expression of Glycoprotein 2 (GP2) by newly developed image cytometric analysis. GP2-high M cells actively took up luminal microbeads, whereas GP2-negative or low cells scarcely ingested them, even though both subsets equally expressed the other M-cell signature genes, suggesting that GP2-high M cells represent functionally mature M cells. Further, the GP2-high mature M cells were abundant in Peyer's patch but sparse in the cecal patch: this was most likely due to a decrease in the nuclear translocation of RelB, a downstream transcription factor for the receptor activator of nuclear factor-κB signaling. Given that murine cecum contains a protrusion of beneficial commensals, the restriction of M-cell activity might contribute to preventing the onset of any excessive immune response to the commensals through decelerating the M-cell-dependent uptake of microorganisms.

Making useful gadgets with miniaturized G proteins

PubMed Central

Martemyanov, Kirill A.; Garcia-Marcos, Mikel

2018-01-01

G protein–coupled receptors (GPCRs) relay information from extracellular stimuli to intracellular responses in a wide range of physiological and pathological processes, but understanding their complex effects in live cells is a daunting task. In this issue of JBC, Wan et al. repurpose “mini G proteins”—previously used as affinity tools for structural studies—to develop a suite of probes to visualize GPCR activation in live cells. The approach is expected to revolutionize our understanding of the spatiotemporal control and mechanisms of GPCR signaling. PMID:29752421

Single Unit Recordings of Cells Responsive to Visual, Somatic, Acoustic, and Noxious Stimuli in the Superior Colliculus of the Golden Hamster.

DTIC Science & Technology

1978-08-01

Acoustic, and Noxious Stimuli Thesis in the Superior Colliculus of the Golden 6. PERFORMING OG. REPORT NUMBER Hamster -. _ // 7. AUTHOR( a ) S. CONTRACT...OR GRANT NUMBER(s) James P. Dixon I - "JV 9. PERF 7 MING ORGANIZATION NAME A D10. PROGRAM ELEMENT, PROJECT, TASK AFIT Student at: Virginia...studied in the superior colliculus of the golden hamster. A laminar organiza- tion was observed with cells in the superficial layers responding exclusively

Real-time fluorescence imaging of the DNA damage repair response during mitosis.

PubMed

Miwa, Shinji; Yano, Shuya; Yamamoto, Mako; Matsumoto, Yasunori; Uehara, Fuminari; Hiroshima, Yukihiko; Toneri, Makoto; Murakami, Takashi; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Efimova, Elena V; Tsuchiya, Hiroyuki; Hoffman, Robert M

2015-04-01

The response to DNA damage during mitosis was visualized using real-time fluorescence imaging of focus formation by the DNA-damage repair (DDR) response protein 53BP1 linked to green fluorescent protein (GFP) (53BP1-GFP) in the MiaPaCa-2(Tet-On) pancreatic cancer cell line. To observe 53BP1-GFP foci during mitosis, MiaPaCa-2(Tet-On) 53BP1-GFP cells were imaged every 30 min by confocal microscopy. Time-lapse imaging demonstrated that 11.4 ± 2.1% of the mitotic MiaPaCa-2(Tet-On) 53BP1-GFP cells had increased focus formation over time. Non-mitotic cells did not have an increase in 53BP1-GFP focus formation over time. Some of the mitotic MiaPaCa-2(Tet-On) 53BP1-GFP cells with focus formation became apoptotic. The results of the present report suggest that DNA strand breaks occur during mitosis and undergo repair, which may cause some of the mitotic cells to enter apoptosis in a phenomenon possibly related to mitotic catastrophe. © 2014 Wiley Periodicals, Inc.

Multiple cone pathways are involved in photic regulation of retinal dopamine.

PubMed

Qiao, Sheng-Nan; Zhang, Zhijing; Ribelayga, Christophe P; Zhong, Yong-Mei; Zhang, Dao-Qi

2016-06-30

Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. The sole source of retinal dopamine is dopaminergic amacrine cells (DACs). We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) upon illumination. However, it is still not clear how each class of photosensitive cells generates light responses in DACs. We genetically isolated cone function in mice to specifically examine the cone-mediated responses of DACs and their neural pathways. In addition to the reported excitatory input to DACs from light-increment (ON) bipolar cells, we found that cones alternatively signal to DACs via a retrograde signalling pathway from ipRGCs. Cones also produce ON and light-decrement (OFF) inhibitory responses in DACs, which are mediated by other amacrine cells, likely driven by type 1 and type 2/3a OFF bipolar cells, respectively. Dye injections indicated that DACs had similar morphological profiles with or without ON/OFF inhibition. Our data demonstrate that cones utilize specific parallel excitatory and inhibitory circuits to modulate DAC activity and efficiently regulate dopamine release and the light-adaptive state of the retina.

Brightness and transparency in the early visual cortex.

PubMed

Salmela, Viljami R; Vanni, Simo

2013-06-24

Several psychophysical studies have shown that transparency can have drastic effects on brightness and lightness. However, the neural processes generating these effects have remained unresolved. Several lines of evidence suggest that the early visual cortex is important for brightness perception. While single cell recordings suggest that surface brightness is represented in the primary visual cortex, the results of functional magnetic resonance imaging (fMRI) studies have been discrepant. In addition, the location of the neural representation of transparency is not yet known. We investigated whether the fMRI responses in areas V1, V2, and V3 correlate with brightness and transparency. To dissociate the blood oxygen level-dependent (BOLD) response to brightness from the response to local border contrast and mean luminance, we used variants of White's brightness illusion, both opaque and transparent, in which luminance increments and decrements cancel each other out. The stimuli consisted of a target surface and a surround. The surround luminance was always sinusoidally modulated at 0.5 Hz to induce brightness modulation to the target. The target luminance was constant or modulated in counterphase to null brightness modulation. The mean signal changes were calculated from the voxels in V1, V2, and V3 corresponding to the retinotopic location of the target surface. The BOLD responses were significantly stronger for modulating brightness than for stimuli with constant brightness. In addition, the responses were stronger for transparent than for opaque stimuli, but there was more individual variation. No interaction between brightness and transparency was found. The results show that the early visual areas V1-V3 are sensitive to surface brightness and transparency and suggest that brightness and transparency are represented separately.

Establishment of Genetically Encoded Biosensors for Cytosolic Boric Acid in Plant Cells.

PubMed

Fukuda, Makiha; Wakuta, Shinji; Kamiyo, Jio; Fujiwara, Toru; Takano, Junpei

2018-06-08

Boron (B) is an essential micronutrient for plants. To maintain B concentration in tissues at appropriate levels, plants use boric acid channels belonging to the NIP subfamily of aquaporins and BOR borate exporters. To regulate B transport, these transporters exhibit different cell-type specific expression, polar localization, and B-dependent post-transcriptional regulation. Here, we describe the development of genetically encoded biosensors for cytosolic boric acid to visualize the spatial distribution and temporal dynamics of B in plant tissues. The biosensors were designed based on the function of the NIP5;1 5'-untranslated region (UTR), which promotes mRNA degradation in response to an elevated cytosolic boric acid concentration. The signal intensities of the biosensor coupled with Venus fluorescent protein and a nuclear localization signal (uNIP5;1-Venus) showed a negative correlation with intracellular B concentrations in cultured tobacco BY-2 cells. When expressed in Arabidopsis thaliana, uNIP5;1-Venus enabled quantification of the B distribution in roots at single-cell resolution. In mature roots, cytosolic B levels in stele were maintained under low-B supply, while those in epidermal, cortical, and endodermal cells were influenced by external B concentrations. Another biosensor coupled with a luciferase protein fused to a destabilization PEST sequence (uNIP5;1-Luc) was used to visualize changes in cytosolic boric acid concentrations. Thus, uNIP5;1-Venus/Luc enables visualization of B transport in various plant cells/tissues. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Identification of neuroanatomic circuits from spinal cord to stomach in mouse: retrograde transneuronal viral tracing study.

PubMed

Ye, Da-Wei; Liu, Cheng; Tian, Xue-Bi; Xiang, Hong-Bing

2014-01-01

To determine the spinal innervation and neuronal connections is important for studying gastric carbohydrate metabolism and motor responses. Neurons involved in the efferent control of the stomach were identified following visualization of pseudorabies virus (PRV)-614 retrograde tracing. PRV-614 was injected into the ventral stomach wall in 13 adult C57BL/6J strain male mice. On the fifth day postinjection, animals were humanely sacrificed, and spinal cords were removed and sectioned, and processed for PRV visualization. The virus injected into the ventral stomach wall was specifically transported to the thoracic spinal cord. At 5 d after injection of the PRV-614, stomach enlargement and tissue edema were found, and PRV-614 positive cells were found in the intermediolateral cell column, the intercalates nucleus or the central autonomic nucleus of spinal cord segments T3 to L1, and major PRV-614 labeled cells were focused in the T6-10 segment. Our results revealed neuroanatomical circuits between stomach and the spinal intermediolateral cell column neurons.

Development of Maps of Simple and Complex Cells in the Primary Visual Cortex

PubMed Central

Antolík, Ján; Bednar, James A.

2011-01-01

Hubel and Wiesel (1962) classified primary visual cortex (V1) neurons as either simple, with responses modulated by the spatial phase of a sine grating, or complex, i.e., largely phase invariant. Much progress has been made in understanding how simple-cells develop, and there are now detailed computational models establishing how they can form topographic maps ordered by orientation preference. There are also models of how complex cells can develop using outputs from simple cells with different phase preferences, but no model of how a topographic orientation map of complex cells could be formed based on the actual connectivity patterns found in V1. Addressing this question is important, because the majority of existing developmental models of simple-cell maps group neurons selective to similar spatial phases together, which is contrary to experimental evidence, and makes it difficult to construct complex cells. Overcoming this limitation is not trivial, because mechanisms responsible for map development drive receptive fields (RF) of nearby neurons to be highly correlated, while co-oriented RFs of opposite phases are anti-correlated. In this work, we model V1 as two topographically organized sheets representing cortical layer 4 and 2/3. Only layer 4 receives direct thalamic input. Both sheets are connected with narrow feed-forward and feedback connectivity. Only layer 2/3 contains strong long-range lateral connectivity, in line with current anatomical findings. Initially all weights in the model are random, and each is modified via a Hebbian learning rule. The model develops smooth, matching, orientation preference maps in both sheets. Layer 4 units become simple cells, with phase preference arranged randomly, while those in layer 2/3 are primarily complex cells. To our knowledge this model is the first explaining how simple cells can develop with random phase preference, and how maps of complex cells can develop, using only realistic patterns of connectivity. PMID:21559067

LOW CONDUCTANCE HCN1 ION CHANNELS AUGMENT THE FREQUENCY RESPONSE OF ROD AND CONE PHOTORECEPTORS

PubMed Central

Barrow, Andrew J.; Wu, Samuel M.

2009-01-01

Hyperpolarization-activated cyclic nucleotide gated (HCN) ion channels are expressed in several tissues throughout the body, including the heart, the CNS, and the retina. HCN channels are found in many neurons in the retina, but their most established role is in generating the hyperpolarization-activated current, Ih, in photoreceptors. This current makes the light response of rod and cone photoreceptors more transient, an effect similar to that of a high-pass filter. A unique property of HCN channels is their small single channel current, which is below the thermal noise threshold of measuring electronics. We use nonstationary fluctuation analysis (NSFA) in the intact retina to estimate the conductance of single HCN channels, revealing a conductance of approximately 650 fS in both rod and cone photoreceptors. We also analyze the properties of HCN channels in salamander rods and cones, from the biophysical to the functional level, showing that HCN1 is the predominant isoform in both cells, and demonstrate how HCN1 channels speed up the light response of both rods and cones under distinct adaptational conditions. We show that in rods and cones, HCN channels increase the natural frequency response of single cells by modifying the photocurrent input, which is limited in its frequency response by the speed of a molecular signaling cascade. In doing so, HCN channels form the first of several systems in the retina that augment the speed of the visual response, allowing an animal to perceive visual stimuli that change more quickly than the underlying photocurrent. PMID:19420251

Mapping nonlinear receptive field structure in primate retina at single cone resolution

PubMed Central

Li, Peter H; Greschner, Martin; Gunning, Deborah E; Mathieson, Keith; Sher, Alexander; Litke, Alan M; Paninski, Liam

2015-01-01

The function of a neural circuit is shaped by the computations performed by its interneurons, which in many cases are not easily accessible to experimental investigation. Here, we elucidate the transformation of visual signals flowing from the input to the output of the primate retina, using a combination of large-scale multi-electrode recordings from an identified ganglion cell type, visual stimulation targeted at individual cone photoreceptors, and a hierarchical computational model. The results reveal nonlinear subunits in the circuity of OFF midget ganglion cells, which subserve high-resolution vision. The model explains light responses to a variety of stimuli more accurately than a linear model, including stimuli targeted to cones within and across subunits. The recovered model components are consistent with known anatomical organization of midget bipolar interneurons. These results reveal the spatial structure of linear and nonlinear encoding, at the resolution of single cells and at the scale of complete circuits. DOI: http://dx.doi.org/10.7554/eLife.05241.001 PMID:26517879

Magnetic resonance in studies of glaucoma

PubMed Central

Fiedorowicz, Michał; Dyda, Wojciech; Rejdak, Robert; Grieb, Paweł

2011-01-01

Summary Glaucoma is the second leading cause of blindness. It affects retinal ganglion cells and the optic nerve. However, there is emerging evidence that glaucoma also affects other components of the visual pathway and visual cortex. There is a need to employ new methods of in vivo brain evaluation to characterize these changes. Magnetic resonance (MR) techniques are well suited for this purpose. We review data on the MR evaluation of the visual pathway and the use of MR techniques in the study of glaucoma, both in humans and in animal models. These studies demonstrated decreases in optic nerve diameter, localized white matter loss and decrease in visual cortex density. Studies on rats employing manganese-enhanced MRI showed that axonal transport in the optic nerve is affected. Diffusion tensor MRI revealed signs of degeneration of the optic pathway. Functional MRI showed decreased response of the visual cortex after stimulation of the glaucomatous eye. Magnetic resonance spectroscopy demonstrated changes in metabolite levels in the visual cortex in a rat model of glaucoma, although not in glaucoma patients. Further applications of MR techniques in studies of glaucomatous brains are indicated. PMID:21959626

Exploratory Spatial Analysis of in vitro Respiratory Syncytial Virus Co-infections

PubMed Central

Simeonov, Ivan; Gong, Xiaoyan; Kim, Oekyung; Poss, Mary; Chiaromonte, Francesca; Fricks, John

2010-01-01

The cell response to virus infection and virus perturbation of that response is dynamic and is reflected by changes in cell susceptibility to infection. In this study, we evaluated the response of human epithelial cells to sequential infections with human respiratory syncytial virus strains A2 and B to determine if a primary infection with one strain will impact the ability of cells to be infected with the second as a function of virus strain and time elapsed between the two exposures. Infected cells were visualized with fluorescent markers, and location of all cells in the tissue culture well were identified using imaging software. We employed tools from spatial statistics to investigate the likelihood of a cell being infected given its proximity to a cell infected with either the homologous or heterologous virus. We used point processes, K-functions, and simulation procedures designed to account for specific features of our data when assessing spatial associations. Our results suggest that intrinsic cell properties increase susceptibility of cells to infection, more so for RSV-B than for RSV-A. Further, we provide evidence that the primary infection can decrease susceptibility of cells to the heterologous challenge virus but only at the 16 h time point evaluated in this study. Our research effort highlights the merits of integrating empirical and statistical approaches to gain greater insight on in vitro dynamics of virus-host interactions. PMID:21994640

Ribbon synapses compute temporal contrast and encode luminance in retinal rod bipolar cells

PubMed Central

Oesch, Nicholas W.; Diamond, Jeffrey S.

2011-01-01

Contrast is computed throughout the nervous system to encode changing inputs efficiently. The retina encodes luminance and contrast over a wide range of visual conditions and so must adapt its responses to maintain sensitivity and avoid saturation. Here we show how one type of adaptation allows individual synapses to compute contrast and encode luminance in biphasic responses to step changes in light levels. Light-evoked depletion of the readily releasable vesicle pool (RRP) at rod bipolar cell (RBC) ribbon synapses in rat retina limits the dynamic range available to encode transient but not sustained responses, thereby allowing the transient and sustained components of release to compute temporal contrast and encode mean light levels, respectively. A release/replenishment model shows that a single, homogeneous pool of synaptic vesicles is sufficient to generate this behavior and reveals that the dominant mechanism shaping the biphasic contrast/luminance response is the partial depletion of the RRP. PMID:22019730

Urinary ATP and visualization of intracellular bacteria: a superior diagnostic marker for recurrent UTI in renal transplant recipients?

PubMed

Kelley, Stephen P; Courtneidge, Holly R; Birch, Rebecca E; Contreras-Sanz, Alberto; Kelly, Mark C; Durodie, Jerome; Peppiatt-Wildman, Claire M; Farmer, Christopher K; Delaney, Michael P; Malone-Lee, James; Harber, Mark A; Wildman, Scott S

2014-01-01

Renal transplant recipients (RTR) are highly susceptible to urinary tract infections (UTIs) with over 50% of patients having at least one UTI within the first year. Yet it is generally acknowledged that there is considerable insensitivity and inaccuracy in routine urinalysis when screening for UTIs. Thus a large number of transplant patients with genuine urine infections may go undiagnosed and develop chronic recalcitrant infections, which can be associated with graft loss and morbidity. Given a recent study demonstrating ATP is released by urothelial cells in response to bacteria exposure, possibly acting at metabotropic P2Y receptors mediating a proinflammatory response, we have investigated alternative, and possibly more appropriate, urinalysis techniques in a cohort of RTRs. Mid-stream urine (MSU) samples were collected from 53 outpatient RTRs. Conventional leukocyte esterase and nitrite dipstick tests, and microscopic pyuria counts (in 1 μl), ATP concentration measurements, and identification of intracellular bacteria in shed urothelial cells, were performed on fresh unspun samples and compared to 'gold-standard' bacterial culture results. Of the 53 RTRs, 22% were deemed to have a UTI by 'gold-standard' conventional bacteria culture, whereas 87%, 8% and 4% showed evidence of UTIs according to leukocyte esterase dipstick, nitrite dipstick, and a combination of both dipsticks, respectively. Intracellular bacteria were visualized in shed urothelial cells of 44% of RTRs, however only 1 of the 23 RTRs (44%) was deemed to have a UTI by conventional bacteria culture. A significant association of the 'gold-standard' test with urinary ATP concentration combined with visualization of intracellular bacteria in shed urothelial cells was determined using the Fisher's exact test. It is apparent that standard bedside tests for UTIs give variable results and that seemingly quiescent bacteria in urothelial cells are very common in RTRs and may represent a focus of subclinical infection. Furthermore, our results suggest urinary ATP concentration combined with detection of intracellular bacteria in shed urinary epithelial cells may be a sensitive means by which to detect 'occult' infection in RTRs.

Regulation of spatial selectivity by crossover inhibition.

PubMed

Cafaro, Jon; Rieke, Fred

2013-04-10

Signals throughout the nervous system diverge into parallel excitatory and inhibitory pathways that later converge on downstream neurons to control their spike output. Converging excitatory and inhibitory synaptic inputs can exhibit a variety of temporal relationships. A common motif is feedforward inhibition, in which an increase (decrease) in excitatory input precedes a corresponding increase (decrease) in inhibitory input. The delay of inhibitory input relative to excitatory input originates from an extra synapse in the circuit shaping inhibitory input. Another common motif is push-pull or "crossover" inhibition, in which increases (decreases) in excitatory input occur together with decreases (increases) in inhibitory input. Primate On midget ganglion cells receive primarily feedforward inhibition and On parasol cells receive primarily crossover inhibition; this difference provides an opportunity to study how each motif shapes the light responses of cell types that play a key role in visual perception. For full-field stimuli, feedforward inhibition abbreviated and attenuated responses of On midget cells, while crossover inhibition, though plentiful, had surprisingly little impact on the responses of On parasol cells. Spatially structured stimuli, however, could cause excitatory and inhibitory inputs to On parasol cells to increase together, adopting a temporal relation very much like that for feedforward inhibition. In this case, inhibitory inputs substantially abbreviated a cell's spike output. Thus inhibitory input shapes the temporal stimulus selectivity of both midget and parasol ganglion cells, but its impact on responses of parasol cells depends strongly on the spatial structure of the light inputs.

mRNAs coding for neurotransmitter receptors and voltage-gated sodium channels in the adult rabbit visual cortex after monocular deafferentiation

PubMed Central

Nguyen, Quoc-Thang; Matute, Carlos; Miledi, Ricardo

1998-01-01

It has been postulated that, in the adult visual cortex, visual inputs modulate levels of mRNAs coding for neurotransmitter receptors in an activity-dependent manner. To investigate this possibility, we performed a monocular enucleation in adult rabbits and, 15 days later, collected their left and right visual cortices. Levels of mRNAs coding for voltage-activated sodium channels, and for receptors for kainate/α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), N-methyl-d-aspartate (NMDA), γ-aminobutyric acid (GABA), and glycine were semiquantitatively estimated in the visual cortices ipsilateral and contralateral to the lesion by the Xenopus oocyte/voltage-clamp expression system. This technique also allowed us to study some of the pharmacological and physiological properties of the channels and receptors expressed in the oocytes. In cells injected with mRNA from left or right cortices of monocularly enucleated and control animals, the amplitudes of currents elicited by kainate or AMPA, which reflect the abundance of mRNAs coding for kainate and AMPA receptors, were similar. There was no difference in the sensitivity to kainate and in the voltage dependence of the kainate response. Responses mediated by NMDA, GABA, and glycine were unaffected by monocular enucleation. Sodium channel peak currents, activation, steady-state inactivation, and sensitivity to tetrodotoxin also remained unchanged after the enucleation. Our data show that mRNAs for major neurotransmitter receptors and ion channels in the adult rabbit visual cortex are not obviously modified by monocular deafferentiation. Thus, our results do not support the idea of a widespread dynamic modulation of mRNAs coding for receptors and ion channels by visual activity in the rabbit visual system. PMID:9501250

Restoration of vision in blind individuals using bionic devices: a review with a focus on cortical visual prostheses.

PubMed

Lewis, Philip M; Ackland, Helen M; Lowery, Arthur J; Rosenfeld, Jeffrey V

2015-01-21

The field of neurobionics offers hope to patients with sensory and motor impairment. Blindness is a common cause of major sensory loss, with an estimated 39 million people worldwide suffering from total blindness in 2010. Potential treatment options include bionic devices employing electrical stimulation of the visual pathways. Retinal stimulation can restore limited visual perception to patients with retinitis pigmentosa, however loss of retinal ganglion cells precludes this approach. The optic nerve, lateral geniculate nucleus and visual cortex provide alternative stimulation targets, with several research groups actively pursuing a cortically-based device capable of driving several hundred stimulating electrodes. While great progress has been made since the earliest works of Brindley and Dobelle in the 1960s and 1970s, significant clinical, surgical, psychophysical, neurophysiological, and engineering challenges remain to be overcome before a commercially-available cortical implant will be realized. Selection of candidate implant recipients will require assessment of their general, psychological and mental health, and likely responses to visual cortex stimulation. Implant functionality, longevity and safety may be enhanced by careful electrode insertion, optimization of electrical stimulation parameters and modification of immune responses to minimize or prevent the host response to the implanted electrodes. Psychophysical assessment will include mapping the positions of potentially several hundred phosphenes, which may require repetition if electrode performance deteriorates over time. Therefore, techniques for rapid psychophysical assessment are required, as are methods for objectively assessing the quality of life improvements obtained from the implant. These measures must take into account individual differences in image processing, phosphene distribution and rehabilitation programs that may be required to optimize implant functionality. In this review, we detail these and other challenges facing developers of cortical visual prostheses in addition to briefly outlining the epidemiology of blindness, and the history of cortical electrical stimulation in the context of visual prosthetics. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Layer- and cell-type-specific subthreshold and suprathreshold effects of long-term monocular deprivation in rat visual cortex.

PubMed

Medini, Paolo

2011-11-23

Connectivity and dendritic properties are determinants of plasticity that are layer and cell-type specific in the neocortex. However, the impact of experience-dependent plasticity at the level of synaptic inputs and spike outputs remains unclear along vertical cortical microcircuits. Here I compared subthreshold and suprathreshold sensitivity to prolonged monocular deprivation (MD) in rat binocular visual cortex in layer 4 and layer 2/3 pyramids (4Ps and 2/3Ps) and in thick-tufted and nontufted layer 5 pyramids (5TPs and 5NPs), which innervate different extracortical targets. In normal rats, 5TPs and 2/3Ps are the most binocular in terms of synaptic inputs, and 5NPs are the least. Spike responses of all 5TPs were highly binocular, whereas those of 2/3Ps were dominated by either the contralateral or ipsilateral eye. MD dramatically shifted the ocular preference of 2/3Ps and 4Ps, mostly by depressing deprived-eye inputs. Plasticity was profoundly different in layer 5. The subthreshold ocular preference shift was sevenfold smaller in 5TPs because of smaller depression of deprived inputs combined with a generalized loss of responsiveness, and was undetectable in 5NPs. Despite their modest ocular dominance change, spike responses of 5TPs consistently lost their typically high binocularity during MD. The comparison of MD effects on 2/3Ps and 5TPs, the main affected output cells of vertical microcircuits, indicated that subthreshold plasticity is not uniquely determined by the initial degree of input binocularity. The data raise the question of whether 5TPs are driven solely by 2/3Ps during MD. The different suprathreshold plasticity of the two cell populations could underlie distinct functional deficits in amblyopia.

Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy.

PubMed

Sewald, Xaver

2018-06-20

Viral pathogens have adapted to the host organism to exploit the cellular machinery for virus replication and to modulate the host cells for efficient systemic dissemination and immune evasion. Much of our knowledge of the effects that virus infections have on cells originates from in vitro imaging studies using experimental culture systems consisting of cell lines and primary cells. Recently, intravital microscopy using multi-photon excitation of fluorophores has been applied to observe virus dissemination and pathogenesis in real-time under physiological conditions in living organisms. Critical steps during viral infection and pathogenesis could be studied by direct visualization of fluorescent virus particles, virus-infected cells, and the immune response to viral infection. In this review, I summarize the latest research on in vivo studies of viral infections using multi-photon intravital microscopy (MP-IVM). Initially, the underlying principle of multi-photon microscopy is introduced and experimental challenges during microsurgical animal preparation and fluorescent labeling strategies for intravital imaging are discussed. I will further highlight recent studies that combine MP-IVM with optogenetic tools and transcriptional analysis as a powerful approach to extend the significance of in vivo imaging studies of viral pathogens.

Multiplex bioimaging of piRNA molecular pathway-regulated theragnostic effects in a single breast cancer cell using a piRNA molecular beacon.

PubMed

Lee, Youn Jung; Moon, Sung Ung; Park, Min Geun; Jung, Woon Yong; Park, Yong Keun; Song, Sung Kyu; Ryu, Je Gyu; Lee, Yong Seung; Heo, Hye Jung; Gu, Ha Na; Cho, Su Jeong; Ali, Bahy A; Al-Khedhairy, Abdulaziz A; Lee, Ilkyun; Kim, Soonhag

2016-09-01

Recently, PIWI-interacting small non-coding RNAs (piRNAs) have emerged as novel cancer biomarkers candidate because of their high expression level in various cancer types and role in the control of tumor suppressor genes. In this study, a novel breast cancer theragnostics probe based on a single system targeting the piRNA-36026 (piR-36026) molecular pathway was developed using a piR-36026 molecular beacon (MB). The piR-36026 MB successfully visualized endogenous piR-36026 biogenesis, which is highly expressed in MCF7 cells (a human breast cancer cell line), and simultaneously inhibited piR-36026-mediated cancer progression in vitro and in vivo. We discovered two tumor suppressor proteins, SERPINA1 and LRAT, that were directly regulated as endogenous piR-36026 target genes in MCF7 cells. Furthermore, multiplex bioimaging of a single MCF7 cell following treatment with piR-36026 MB clearly visualized the direct molecular interaction of piRNA-36026 with SERPINA1 or LRAT and subsequent molecular therapeutic responses including caspase-3 and PI in the nucleus. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early detection and visualization of human adenovirus serotype 5-viral vectors carrying foot-and-mouth disease virus or luciferase transgenes in cell lines and bovine tissues

USDA-ARS?s Scientific Manuscript database

Recombinant replication-defective human adenovirus type 5 (Ad5) vaccines containing capsid-coding regions from foot-and-mouth disease virus (FMDV) have been demonstrated to induce effective immune responses and provide homologous protective immunity against FMDV in cattle. However, basic mechanisms ...

Correlation of visual in vitro cytotoxicity ratings of biomaterials with quantitative in vitro cell viability measurements.

PubMed

Bhatia, Sujata K; Yetter, Ann B

2008-08-01

Medical devices and implanted biomaterials are often assessed for biological reactivity using visual scores of cell-material interactions. In such testing, biomaterials are assigned cytotoxicity ratings based on visual evidence of morphological cellular changes, including cell lysis, rounding, spreading, and proliferation. For example, ISO 10993 cytotoxicity testing of medical devices allows the use of a visual grading scale. The present study compared visual in vitro cytotoxicity ratings to quantitative in vitro cytotoxicity measurements for biomaterials to determine the level of correlation between visual scoring and a quantitative cell viability assay. Biomaterials representing a spectrum of biological reactivity levels were evaluated, including organo-tin polyvinylchloride (PVC; a known cytotoxic material), ultra-high molecular weight polyethylene (a known non-cytotoxic material), and implantable tissue adhesives. Each material was incubated in direct contact with mouse 3T3 fibroblast cell cultures for 24 h. Visual scores were assigned to the materials using a 5-point rating scale; the scorer was blinded to the material identities. Quantitative measurements of cell viability were performed using a 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay; again, the assay operator was blinded to material identities. The investigation revealed a high degree of correlation between visual cytotoxicity ratings and quantitative cell viability measurements; a Pearson's correlation gave a correlation coefficient of 0.90 between the visual cytotoxicity score and the percent viable cells. An equation relating the visual cytotoxicity score and the percent viable cells was derived. The results of this study are significant for the design and interpretation of in vitro cytotoxicity studies of novel biomaterials.

An intracellular analysis of the visual responses of neurones in cat visual cortex.

PubMed Central

Douglas, R J; Martin, K A; Whitteridge, D

1991-01-01

1. Extracellular and intracellular recordings were made from neurones in the visual cortex of the cat in order to compare the subthreshold membrane potentials, reflecting the input to the neurone, with the output from the neurone seen as action potentials. 2. Moving bars and edges, generated under computer control, were used to stimulate the neurones. The membrane potential was digitized and averaged for a number of trials after stripping the action potentials. Comparison of extracellular and intracellular discharge patterns indicated that the intracellular impalement did not alter the neurones' properties. Input resistance of the neurone altered little during stable intracellular recordings (30 min-2 h 50 min). 3. Intracellular recordings showed two distinct patterns of membrane potential changes during optimal visual stimulation. The patterns corresponded closely to the division of S-type (simple) and C-type (complex) receptive fields. Simple cells had a complex pattern of membrane potential fluctuations, involving depolarizations alternating with hyperpolarizations. Complex cells had a simple single sustained plateau of depolarization that was often followed but not preceded by a hyperpolarization. In both simple and complex cells the depolarizations led to action potential discharges. The hyperpolarizations were associated with inhibition of action potential discharge. 4. Stimulating simple cells with non-optimal directions of motion produced little or no hyperpolarization of the membrane in most cases, despite a lack of action potential output. Directional complex cells always produced a single plateau of depolarization leading to action potential discharge in both the optimal and non-optimal directions of motion. The directionality could not be predicted on the basis of the position of the hyperpolarizing inhibitory potentials found in the optimal direction. 5. Stimulation of simple cells with non-optimal orientations occasionally produced slight hyperpolarizations and inhibition of action potential discharge. Complex cells, which had broader orientation tuning than simple cells, could show marked hyperpolarization for non-optimal orientations, but this was not generally the case. 6. The data do not support models of directionality and orientation that rely solely on strong inhibitory mechanisms to produce stimulus selectivity. PMID:1804981

The Visual Cycle in the Inner Retina of Chicken and the Involvement of Retinal G-Protein-Coupled Receptor (RGR).

PubMed

Díaz, Nicolás M; Morera, Luis P; Tempesti, Tomas; Guido, Mario E

2017-05-01

The vertebrate retina contains typical photoreceptor (PR) cones and rods responsible for day/night vision, respectively, and intrinsically photosensitive retinal ganglion cells (ipRGCs) involved in the regulation of non-image-forming tasks. Rhodopsin/cone opsin photopigments in visual PRs or melanopsin (Opn4) in ipRGCs utilizes retinaldehyde as a chromophore. The retinoid regeneration process denominated as "visual cycle" involves the retinal pigment epithelium (RPE) or Müller glial cells. Opn4, on the contrary, has been characterized as a bi/tristable photopigment, in which a photon of one wavelength isomerizes 11-cis to all-trans retinal (Ral), with a second photon re-isomerizing it back. However, it is unknown how the chromophore is further metabolized in the inner retina. Nor is it yet clear whether an alternative secondary cycle occurs involving players such as the retinal G-protein-coupled receptor (RGR), a putative photoisomerase of unidentified inner retinal activity. Here, we investigated the role of RGR in retinoid photoisomerization in Opn4x (Xenopus ortholog) (+) RGC primary cultures free of RPE and other cells from chicken embryonic retinas. Opn4x (+) RGCs display significant photic responses by calcium fluorescent imaging and photoisomerize exogenous all-trans to 11-cis Ral and other retinoids. RGR was found to be expressed in developing retina and in primary cultures; when its expression was knocked down, the levels of 11-cis, all-trans Ral, and all-trans retinol in cultures exposed to light were significantly higher and those in all-trans retinyl esters lower than in dark controls. The results support a novel role for RGR in ipRGCs to modulate retinaldehyde levels in light, keeping the balance of inner retinal retinoid pools.

Visual examination apparatus

NASA Technical Reports Server (NTRS)

Haines, R. F.; Fitzgerald, J. W.; Rositano, S. A. (Inventor)

1976-01-01

An automated visual examination apparatus for measuring visual sensitivity and mapping blind spot location including a projection system for displaying to a patient a series of visual stimuli. A response switch enables him to indicate his reaction to the stimuli, and a recording system responsive to both the visual stimuli per se and the patient's response. The recording system thereby provides a correlated permanent record of both stimuli and response from which a substantive and readily apparent visual evaluation can be made.

Neuronal encoding of object and distance information: a model simulation study on naturalistic optic flow processing

PubMed Central

Hennig, Patrick; Egelhaaf, Martin

2011-01-01

We developed a model of the input circuitry of the FD1 cell, an identified motion-sensitive interneuron in the blowfly's visual system. The model circuit successfully reproduces the FD1 cell's most conspicuous property: its larger responses to objects than to spatially extended patterns. The model circuit also mimics the time-dependent responses of FD1 to dynamically complex naturalistic stimuli, shaped by the blowfly's saccadic flight and gaze strategy: the FD1 responses are enhanced when, as a consequence of self-motion, a nearby object crosses the receptive field during intersaccadic intervals. Moreover, the model predicts that these object-induced responses are superimposed by pronounced pattern-dependent fluctuations during movements on virtual test flights in a three-dimensional environment with systematic modifications of the environmental patterns. Hence, the FD1 cell is predicted to detect not unambiguously objects defined by the spatial layout of the environment, but to be also sensitive to objects distinguished by textural features. These ambiguous detection abilities suggest an encoding of information about objects—irrespective of the features by which the objects are defined—by a population of cells, with the FD1 cell presumably playing a prominent role in such an ensemble. PMID:22461769

A Multi-Stage Model for Fundamental Functional Properties in Primary Visual Cortex

PubMed Central

Hesam Shariati, Nastaran; Freeman, Alan W.

2012-01-01

Many neurons in mammalian primary visual cortex have properties such as sharp tuning for contour orientation, strong selectivity for motion direction, and insensitivity to stimulus polarity, that are not shared with their sub-cortical counterparts. Successful models have been developed for a number of these properties but in one case, direction selectivity, there is no consensus about underlying mechanisms. We here define a model that accounts for many of the empirical observations concerning direction selectivity. The model describes a single column of cat primary visual cortex and comprises a series of processing stages. Each neuron in the first cortical stage receives input from a small number of on-centre and off-centre relay cells in the lateral geniculate nucleus. Consistent with recent physiological evidence, the off-centre inputs to cortex precede the on-centre inputs by a small (∼4 ms) interval, and it is this difference that confers direction selectivity on model neurons. We show that the resulting model successfully matches the following empirical data: the proportion of cells that are direction selective; tilted spatiotemporal receptive fields; phase advance in the response to a stationary contrast-reversing grating stepped across the receptive field. The model also accounts for several other fundamental properties. Receptive fields have elongated subregions, orientation selectivity is strong, and the distribution of orientation tuning bandwidth across neurons is similar to that seen in the laboratory. Finally, neurons in the first stage have properties corresponding to simple cells, and more complex-like cells emerge in later stages. The results therefore show that a simple feed-forward model can account for a number of the fundamental properties of primary visual cortex. PMID:22496811

A Simple Network Architecture Accounts for Diverse Reward Time Responses in Primary Visual Cortex

PubMed Central

Hussain Shuler, Marshall G.; Shouval, Harel Z.

2015-01-01

Many actions performed by animals and humans depend on an ability to learn, estimate, and produce temporal intervals of behavioral relevance. Exemplifying such learning of cued expectancies is the observation of reward-timing activity in the primary visual cortex (V1) of rodents, wherein neural responses to visual cues come to predict the time of future reward as behaviorally experienced in the past. These reward-timing responses exhibit significant heterogeneity in at least three qualitatively distinct classes: sustained increase or sustained decrease in firing rate until the time of expected reward, and a class of cells that reach a peak in firing at the expected delay. We elaborate upon our existing model by including inhibitory and excitatory units while imposing simple connectivity rules to demonstrate what role these inhibitory elements and the simple architectures play in sculpting the response dynamics of the network. We find that simply adding inhibition is not sufficient for obtaining the different distinct response classes, and that a broad distribution of inhibitory projections is necessary for obtaining peak-type responses. Furthermore, although changes in connection strength that modulate the effects of inhibition onto excitatory units have a strong impact on the firing rate profile of these peaked responses, the network exhibits robustness in its overall ability to predict the expected time of reward. Finally, we demonstrate how the magnitude of expected reward can be encoded at the expected delay in the network and how peaked responses express this reward expectancy. SIGNIFICANCE STATEMENT Heterogeneity in single-neuron responses is a common feature of neuronal systems, although sometimes, in theoretical approaches, it is treated as a nuisance and seldom considered as conveying a different aspect of a signal. In this study, we focus on the heterogeneous responses in the primary visual cortex of rodents trained with a predictable delayed reward time. We describe under what conditions this heterogeneity can arise by self-organization, and what information it can convey. This study, while focusing on a specific system, provides insight onto how heterogeneity can arise in general while also shedding light onto mechanisms of reinforcement learning using realistic biological assumptions. PMID:26377457

Dynamic differentiation of GABAA-sensitive influences on orientation selectivity of complex cells in the cat striate cortex.

PubMed

Pfleger, B; Bonds, A B

1995-01-01

The influence of GABAA receptors on orientation selectivity of cat complex cells was tested by iontophoresis of the GABAA receptor blockers bicuculline and N-methyl-bicuculline while stimulating with drifting sinusoidal gratings. Reduction of orientation tuning was markedly less than reported in previous studies that used drifting bars as visual stimuli. Only 3/31 cells lost orientation selectivity, with an average increase in bandwidth of 33%, as opposed to half the cells losing selectivity and a bandwidth increase for the remainder of 47% as reported previously. Infusion of GABAA blockers revealed a prominent stimulus onset transient response, lasting about 120 ms, that showed a broadening of orientation selectivity comparable to that found using drifting bars under similar circumstances. We believe that drifting gratings emphasize a steady-state response component that retains, in the presence of GABAA blockers, significant orientation selectivity. Because the onset transient is initially unselective for orientation, we suggest that the steady-state, orientation-selective response component develops from an alternate inhibitory mechanism, possibly mediated by GABAB receptors.

Visual detection of glial cell line-derived neurotrophic factor based on a molecular translator and isothermal strand-displacement polymerization reaction

PubMed Central

Zhang, Li-Yong; Xing, Tao; Du, Li-Xin; Li, Qing-Min; Liu, Wei-Dong; Wang, Ji-Yue; Cai, Jing

2015-01-01

Background Glial cell line-derived neurotrophic factor (GDNF) is a small protein that potently promotes the survival of many types of neurons. Detection of GDNF is vital to monitoring the survival of sympathetic and sensory neurons. However, the specific method for GDNF detection is also un-discovered. The purpose of this study is to explore the method for protein detection of GDNF. Methods A novel visual detection method based on a molecular translator and isothermal strand-displacement polymerization reaction (ISDPR) has been proposed for the detection of GDNF. In this study, a molecular translator was employed to convert the input protein to output deoxyribonucleic acid signal, which was further amplified by ISDPR. The product of ISDPR was detected by a lateral flow biosensor within 30 minutes. Results This novel visual detection method based on a molecular translator and ISDPR has very high sensitivity and selectivity, with a dynamic response ranging from 1 pg/mL to 10 ng/mL, and the detection limit was 1 pg/mL of GDNF. Conclusion This novel visual detection method exhibits high sensitivity and selectivity, which is very simple and universal for GDNF detection to help disease therapy in clinical practice. PMID:25848224

Cross-correlated and oscillatory visual responses of superficial-layer and tecto-reticular neurones in cat superior colliculus.

PubMed

Chabli, A; Guitton, D; Fortin, S; Molotchnikoff, S

2000-03-01

The present study examined, in the superior colliculus (SC) of anaesthetised cats, the functional connectivity between superficial-layer neurones (SLNs) and tectoreticular neurones (TRNs: collicular output cells). TRNs were antidromically identified by electrical stimulation of the predorsal bundle. The auto- and cross-correlation histograms of visual responses of both types of neurones were recorded and analysed. A delayed, sharp peak in cross-correlograms allowed us to verify whether SLN and TRN cells were coupled; in addition, oscillatory activities were compared to verify if rhythmic responses of SLN sites were transmitted to TRN sites. We found that oscillatory activity was rarely observed in spontaneous activity of superficial (1/74) and TRN sites (1/48). Moving light bars induced oscillation in 31% (23/74) of the superficial-layer and in 23% (11/48) of the TRN sites. The strength of the rhythmic responses was determined by specific ranges of stimulus velocity in 83% (19/23) and 64% (7/11) of oscillating SLN and TRN sites, respectively. Frequencies of oscillations ranged between 5 and 125 Hz and were confined, for 53% of the cells, to the 5-20 Hz band. Thus, the band-width of frequencies of the stimulus-related oscillations in the superior colliculus was broader than the gamma range. Analysis of cross-correlation histograms revealed a significant predominant peak with a mean delay of 2.7+/-0.9 ms in 46% (17/37) of SLN-TRN pairs. Most correlated SLN-TRN pairs (88%: 15/17) had superimposed receptive fields, suggesting they were functionally interconnected. However, individual oscillatory frequencies of correlated and oscillatory SLN and TRN cells were never the same (0/8). Together, these results suggest that the neurones in collicular superficial layer contact TRNs and, consequently, support the idea that the superficial layers contribute to collicular outputs producing eye- and head-orienting movements.

A simple white noise analysis of neuronal light responses.

PubMed

Chichilnisky, E J

2001-05-01

A white noise technique is presented for estimating the response properties of spiking visual system neurons. The technique is simple, robust, efficient and well suited to simultaneous recordings from multiple neurons. It provides a complete and easily interpretable model of light responses even for neurons that display a common form of response nonlinearity that precludes classical linear systems analysis. A theoretical justification of the technique is presented that relies only on elementary linear algebra and statistics. Implementation is described with examples. The technique and the underlying model of neural responses are validated using recordings from retinal ganglion cells, and in principle are applicable to other neurons. Advantages and disadvantages of the technique relative to classical approaches are discussed.

Temporally evolving gain mechanisms of attention in macaque area V4.

PubMed

Sani, Ilaria; Santandrea, Elisa; Morrone, Maria Concetta; Chelazzi, Leonardo

2017-08-01

Cognitive attention and perceptual saliency jointly govern our interaction with the environment. Yet, we still lack a universally accepted account of the interplay between attention and luminance contrast, a fundamental dimension of saliency. We measured the attentional modulation of V4 neurons' contrast response functions (CRFs) in awake, behaving macaque monkeys and applied a new approach that emphasizes the temporal dynamics of cell responses. We found that attention modulates CRFs via different gain mechanisms during subsequent epochs of visually driven activity: an early contrast-gain, strongly dependent on prestimulus activity changes (baseline shift); a time-limited stimulus-dependent multiplicative modulation, reaching its maximal expression around 150 ms after stimulus onset; and a late resurgence of contrast-gain modulation. Attention produced comparable time-dependent attentional gain changes on cells heterogeneously coding contrast, supporting the notion that the same circuits mediate attention mechanisms in V4 regardless of the form of contrast selectivity expressed by the given neuron. Surprisingly, attention was also sometimes capable of inducing radical transformations in the shape of CRFs. These findings offer important insights into the mechanisms that underlie contrast coding and attention in primate visual cortex and a new perspective on their interplay, one in which time becomes a fundamental factor. NEW & NOTEWORTHY We offer an innovative perspective on the interplay between attention and luminance contrast in macaque area V4, one in which time becomes a fundamental factor. We place emphasis on the temporal dynamics of attentional effects, pioneering the notion that attention modulates contrast response functions of V4 neurons via the sequential engagement of distinct gain mechanisms. These findings advance understanding of attentional influences on visual processing and help reconcile divergent results in the literature. Copyright © 2017 the American Physiological Society.

Modulation of Visually Evoked Postural Responses by Contextual Visual, Haptic and Auditory Information: A ‘Virtual Reality Check’

PubMed Central

Meyer, Georg F.; Shao, Fei; White, Mark D.; Hopkins, Carl; Robotham, Antony J.

2013-01-01

Externally generated visual motion signals can cause the illusion of self-motion in space (vection) and corresponding visually evoked postural responses (VEPR). These VEPRs are not simple responses to optokinetic stimulation, but are modulated by the configuration of the environment. The aim of this paper is to explore what factors modulate VEPRs in a high quality virtual reality (VR) environment where real and virtual foreground objects served as static visual, auditory and haptic reference points. Data from four experiments on visually evoked postural responses show that: 1) visually evoked postural sway in the lateral direction is modulated by the presence of static anchor points that can be haptic, visual and auditory reference signals; 2) real objects and their matching virtual reality representations as visual anchors have different effects on postural sway; 3) visual motion in the anterior-posterior plane induces robust postural responses that are not modulated by the presence of reference signals or the reality of objects that can serve as visual anchors in the scene. We conclude that automatic postural responses for laterally moving visual stimuli are strongly influenced by the configuration and interpretation of the environment and draw on multisensory representations. Different postural responses were observed for real and virtual visual reference objects. On the basis that automatic visually evoked postural responses in high fidelity virtual environments should mimic those seen in real situations we propose to use the observed effect as a robust objective test for presence and fidelity in VR. PMID:23840760

Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina

PubMed Central

Mui, Amanda M.; Yang, Victoria; Aung, Moe H.; Fu, Jieming; Adekunle, Adewumi N.; Prall, Brian C.; Sidhu, Curran S.; Park, Han na; Boatright, Jeffrey H.; Iuvone, P. Michael

2018-01-01

Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing. Daily OMR-treated mice were compared to littermate controls that were placed in the OMR chamber without moving gratings. Contrast sensitivity thresholds, electroretinograms (ERGs), visual evoked potentials, and pattern ERGs were acquired at P21. To determine the role of BDNF signaling, a TrkB receptor antagonist (ANA-12) was systemically injected 2 hours prior to OMR testing in another cohort of mice. BDNF immunohistochemistry was performed on retina and brain sections. Retinal DA levels were measured using high-performance liquid chromatography. Daily OMR testing enhanced spatial frequency thresholds and contrast sensitivity compared to controls. OMR-treated mice also had improved rod-driven ERG oscillatory potential response times, greater BDNF immunoreactivity in the retinal ganglion cell layer, and increased retinal DA content compared to controls. VEPs and pattern ERGs were unchanged. Systemic delivery of ANA-12 attenuated OMR-induced visual enhancements. Daily OMR testing during the critical period leads to general visual function improvements accompanied by increased DA and BDNF in the retina, with this process being requisitely mediated by TrkB activation. These results suggest that novel combination therapies involving visual stimulation and using both behavioral and molecular approaches may benefit degenerative retinal diseases or amblyopia. PMID:29408880

Adaptations in rod outer segment disc membranes in response to environmental lighting conditions.

PubMed

Rakshit, Tatini; Senapati, Subhadip; Parmar, Vipul M; Sahu, Bhubanananda; Maeda, Akiko; Park, Paul S-H

2017-10-01

The light-sensing rod photoreceptor cell exhibits several adaptations in response to the lighting environment. While adaptations to short-term changes in lighting conditions have been examined in depth, adaptations to long-term changes in lighting conditions are less understood. Atomic force microscopy was used to characterize the structure of rod outer segment disc membranes, the site of photon absorption by the pigment rhodopsin, to better understand how photoreceptor cells respond to long-term lighting changes. Structural properties of the disc membrane changed in response to housing mice in constant dark or light conditions and these adaptive changes required output from the phototransduction cascade initiated by rhodopsin. Among these were changes in the packing density of rhodopsin in the membrane, which was independent of rhodopsin synthesis and specifically affected scotopic visual function as assessed by electroretinography. Studies here support the concept of photostasis, which maintains optimal photoreceptor cell function with implications in retinal degenerations. Copyright © 2017 Elsevier B.V. All rights reserved.

Dataset of red light induced pupil constriction superimposed on post-illumination pupil response.

PubMed

Lei, Shaobo; Goltz, Herbert C; Sklar, Jaime C; Wong, Agnes M F

2016-09-01

We collected and analyzed pupil diameter data from of 7 visually normal participants to compare the maximum pupil constriction (MPC) induced by "Red Only" vs. "Blue+Red" visual stimulation conditions. The "Red Only" condition consisted of red light (640±10 nm) stimuli of variable intensity and duration presented to dark-adapted eyes with pupils at resting state. This condition stimulates the cone-driven activity of the intrinsically photosensitive retinal ganglion cells (ipRGC). The "Blue+Red" condition consisted of the same red light stimulus presented during ongoing blue (470±17 nm) light-induced post-illumination pupil response (PIPR), representing the cone-driven ipRGC activity superimposed on the melanopsin-driven intrinsic activity of the ipRGCs ("The Absence of Attenuating Effect of Red light Exposure on Pre-existing Melanopsin-Driven Post-illumination Pupil Response" Lei et al. (2016) [1]). MPC induced by the "Red Only" condition was compared with the MPC induced by the "Blue+Red" condition by multiple paired sample t -tests with Bonferroni correction.

Visual examination apparatus

NASA Technical Reports Server (NTRS)

Haines, R. F.; Fitzgerald, J. W.; Rositano, S. A. (Inventor)

1973-01-01

An automated visual examination apparatus for measuring visual sensitivity and mapping blind spot location is described. The apparatus includes a projection system for displaying to a patient a series of visual stimuli, a response switch enabling him to indicate his reaction to the stimuli, and a recording system responsive to both the visual stimuli per se and the patient's response. The recording system provides a correlated permanent record of both stimuli and response from which a substantive and readily apparent visual evaluation can be made.

Global Sensory Qualities and Aesthetic Experience in Music

PubMed Central

Brattico, Pauli; Brattico, Elvira; Vuust, Peter

2017-01-01

A well-known tradition in the study of visual aesthetics holds that the experience of visual beauty is grounded in global computational or statistical properties of the stimulus, for example, scale-invariant Fourier spectrum or self-similarity. Some approaches rely on neural mechanisms, such as efficient computation, processing fluency, or the responsiveness of the cells in the primary visual cortex. These proposals are united by the fact that the contributing factors are hypothesized to be global (i.e., they concern the percept as a whole), formal or non-conceptual (i.e., they concern form instead of content), computational and/or statistical, and based on relatively low-level sensory properties. Here we consider that the study of aesthetic responses to music could benefit from the same approach. Thus, along with local features such as pitch, tuning, consonance/dissonance, harmony, timbre, or beat, also global sonic properties could be viewed as contributing toward creating an aesthetic musical experience. Several such properties are discussed and their neural implementation is reviewed in the light of recent advances in neuroaesthetics. PMID:28424573

Analysis of retinal function using chromatic pupillography in retinitis pigmentosa and the relationship to electrically evoked phosphene thresholds.

PubMed

Kelbsch, Carina; Maeda, Fumiatsu; Lisowska, Jolanta; Lisowski, Lukasz; Strasser, Torsten; Stingl, Krunoslav; Wilhelm, Barbara; Wilhelm, Helmut; Peters, Tobias

2017-06-01

To analyse pupil responses to specific chromatic stimuli in patients with advanced retinitis pigmentosa (RP) to ascertain whether chromatic pupillography can be used as an objective marker for residual retinal function. To examine correlations between parameters of the pupil response and the perception threshold of electrically evoked phosphenes. Chromatic pupillography was performed in 40 patients with advanced RP (visual acuity < 0.02 or visual field ≤5°, non-recordable ERGs) and 40 age-matched healthy subjects. Pupil responses to full-field red (605 nm) and blue (420 nm) stimuli of 28 lx corneal illumination were recorded and analysed for two stimulus durations (1 and 4 seconds). The perception threshold of phosphenes to transcorneal electrostimulation was ascertained and correlated to the pupil responses and visual acuity. Patients with RP showed significantly reduced pupil responses to red and blue stimuli compared with the controls. With red stimuli, pupillary escape could be observed; blue stimuli resulted in a well-preserved postillumination pupil response. Phosphene thresholds were significantly increased in patients with RP and correlated with the parameters of the pupil response if all subjects were considered. Within the RP group alone, this relationship was less pronounced and statistically not significant. Chromatic pupillography demonstrated a significant decrease in outer retinal photoreceptor responses but a persisting and disinhibited intrinsic photosensitive retinal ganglion cell function in advanced RP. These phenomena may be useful as an objective marker for the efficacy of any interventional treatment for hereditary retinal diseases as well as for the selection of suitable patients for an electronic retinal implant. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Visually evoked responses in extrastriate area MT after lesions of striate cortex in early life.

PubMed

Yu, Hsin-Hao; Chaplin, Tristan A; Egan, Gregory W; Reser, David H; Worthy, Katrina H; Rosa, Marcello G P

2013-07-24

Lesions of striate cortex [primary visual cortex (V1)] in adult primates result in blindness. In contrast, V1 lesions in neonates typically allow much greater preservation of vision, including, in many human patients, conscious perception. It is presently unknown how this marked functional difference is related to physiological changes in cortical areas that are spared by the lesions. Here we report a study of the middle temporal area (MT) of adult marmoset monkeys that received unilateral V1 lesions within 6 weeks of birth. In contrast with observations after similar lesions in adult monkeys, we found that virtually all neurons in the region of MT that was deprived of V1 inputs showed robust responses to visual stimulation. These responses were very similar to those recorded in neurons with receptive fields outside the lesion projection zones in terms of firing rate, signal-to-noise ratio, and latency. In addition, the normal retinotopic organization of MT was maintained. Nonetheless, we found evidence of a very specific functional deficit: direction selectivity, a key physiological characteristic of MT that is known to be preserved in many cells after adult V1 lesions, was absent. These results demonstrate that lesion-induced reorganization of afferent pathways is sufficient to develop robust visual function in primate extrastriate cortex, highlighting a likely mechanism for the sparing of vision after neonatal V1 lesions. However, they also suggest that interactions with V1 in early postnatal life are critical for establishing stimulus selectivity in MT.

Temporal Processing in the Visual Cortex of the Awake and Anesthetized Rat.

PubMed

Aasebø, Ida E J; Lepperød, Mikkel E; Stavrinou, Maria; Nøkkevangen, Sandra; Einevoll, Gaute; Hafting, Torkel; Fyhn, Marianne

2017-01-01

The activity pattern and temporal dynamics within and between neuron ensembles are essential features of information processing and believed to be profoundly affected by anesthesia. Much of our general understanding of sensory information processing, including computational models aimed at mathematically simulating sensory information processing, rely on parameters derived from recordings conducted on animals under anesthesia. Due to the high variety of neuronal subtypes in the brain, population-based estimates of the impact of anesthesia may conceal unit- or ensemble-specific effects of the transition between states. Using chronically implanted tetrodes into primary visual cortex (V1) of rats, we conducted extracellular recordings of single units and followed the same cell ensembles in the awake and anesthetized states. We found that the transition from wakefulness to anesthesia involves unpredictable changes in temporal response characteristics. The latency of single-unit responses to visual stimulation was delayed in anesthesia, with large individual variations between units. Pair-wise correlations between units increased under anesthesia, indicating more synchronized activity. Further, the units within an ensemble show reproducible temporal activity patterns in response to visual stimuli that is changed between states, suggesting state-dependent sequences of activity. The current dataset, with recordings from the same neural ensembles across states, is well suited for validating and testing computational network models. This can lead to testable predictions, bring a deeper understanding of the experimental findings and improve models of neural information processing. Here, we exemplify such a workflow using a Brunel network model.

An integrated domain specific language for post-processing and visualizing electrophysiological signals in Java.

PubMed

Strasser, T; Peters, T; Jagle, H; Zrenner, E; Wilke, R

2010-01-01

Electrophysiology of vision - especially the electroretinogram (ERG) - is used as a non-invasive way for functional testing of the visual system. The ERG is a combined electrical response generated by neural and non-neuronal cells in the retina in response to light stimulation. This response can be recorded and used for diagnosis of numerous disorders. For both clinical practice and clinical trials it is important to process those signals in an accurate and fast way and to provide the results as structured, consistent reports. Therefore, we developed a freely available and open-source framework in Java (http://www.eye.uni-tuebingen.de/project/idsI4sigproc). The framework is focused on an easy integration with existing applications. By leveraging well-established software patterns like pipes-and-filters and fluent interfaces as well as by designing the application programming interfaces (API) as an integrated domain specific language (DSL) the overall framework provides a smooth learning curve. Additionally, it already contains several processing methods and visualization features and can be extended easily by implementing the provided interfaces. In this way, not only can new processing methods be added but the framework can also be adopted for other areas of signal processing. This article describes in detail the structure and implementation of the framework and demonstrate its application through the software package used in clinical practice and clinical trials at the University Eye Hospital Tuebingen one of the largest departments in the field of visual electrophysiology in Europe.

Temporal Processing in the Visual Cortex of the Awake and Anesthetized Rat

PubMed Central

Aasebø, Ida E. J.; Stavrinou, Maria; Nøkkevangen, Sandra; Einevoll, Gaute

2017-01-01

Abstract The activity pattern and temporal dynamics within and between neuron ensembles are essential features of information processing and believed to be profoundly affected by anesthesia. Much of our general understanding of sensory information processing, including computational models aimed at mathematically simulating sensory information processing, rely on parameters derived from recordings conducted on animals under anesthesia. Due to the high variety of neuronal subtypes in the brain, population-based estimates of the impact of anesthesia may conceal unit- or ensemble-specific effects of the transition between states. Using chronically implanted tetrodes into primary visual cortex (V1) of rats, we conducted extracellular recordings of single units and followed the same cell ensembles in the awake and anesthetized states. We found that the transition from wakefulness to anesthesia involves unpredictable changes in temporal response characteristics. The latency of single-unit responses to visual stimulation was delayed in anesthesia, with large individual variations between units. Pair-wise correlations between units increased under anesthesia, indicating more synchronized activity. Further, the units within an ensemble show reproducible temporal activity patterns in response to visual stimuli that is changed between states, suggesting state-dependent sequences of activity. The current dataset, with recordings from the same neural ensembles across states, is well suited for validating and testing computational network models. This can lead to testable predictions, bring a deeper understanding of the experimental findings and improve models of neural information processing. Here, we exemplify such a workflow using a Brunel network model. PMID:28791331

In Vivo Biochemistry: Single-Cell Dynamics of Cyclic Di-GMP in Escherichia coli in Response to Zinc Overload.

PubMed

Yeo, Jongchan; Dippel, Andrew B; Wang, Xin C; Hammond, Ming C

2018-01-09

Intracellular signaling enzymes drive critical changes in cellular physiology and gene expression, but their endogenous activities in vivo remain highly challenging to study in real time and for individual cells. Here we show that flow cytometry can be performed in complex media to monitor single-cell population distributions and dynamics of cyclic di-GMP signaling, which controls the bacterial colonization program. These in vivo biochemistry experiments are enabled by our second-generation RNA-based fluorescent (RBF) biosensors, which exhibit high fluorescence turn-on in response to cyclic di-GMP. Specifically, we demonstrate that intracellular levels of cyclic di-GMP in Escherichia coli are repressed with excess zinc, but not with other divalent metals. Furthermore, in both flow cytometry and fluorescence microscopy setups, we monitor the dynamic increase in cellular cyclic di-GMP levels upon zinc depletion and show that this response is due to de-repression of the endogenous diguanylate cyclase DgcZ. In the presence of zinc, cells exhibit enhanced cell motility and increased sensitivity to antibiotics due to inhibited biofilm formation. Taken together, these results showcase the application of RBF biosensors in visualizing single-cell dynamic changes in cyclic di-GMP signaling in direct response to environmental cues such as zinc and highlight our ability to assess whether observed phenotypes are related to specific signaling enzymes and pathways.

Retinoic Acid as a Modulator of T Cell Immunity

PubMed Central

Bono, Maria Rosa; Tejon, Gabriela; Flores-Santibañez, Felipe; Fernandez, Dominique; Rosemblatt, Mario; Sauma, Daniela

2016-01-01

Vitamin A, a generic designation for an array of organic molecules that includes retinal, retinol and retinoic acid, is an essential nutrient needed in a wide array of aspects including the proper functioning of the visual system, maintenance of cell function and differentiation, epithelial surface integrity, erythrocyte production, reproduction, and normal immune function. Vitamin A deficiency is one of the most common micronutrient deficiencies worldwide and is associated with defects in adaptive immunity. Reports from epidemiological studies, clinical trials and experimental studies have clearly demonstrated that vitamin A plays a central role in immunity and that its deficiency is the cause of broad immune alterations including decreased humoral and cellular responses, inadequate immune regulation, weak response to vaccines and poor lymphoid organ development. In this review, we will examine the role of vitamin A in immunity and focus on several aspects of T cell biology such as T helper cell differentiation, function and homing, as well as lymphoid organ development. Further, we will provide an overview of the effects of vitamin A deficiency in the adaptive immune responses and how retinoic acid, through its effect on T cells can fine-tune the balance between tolerance and immunity. PMID:27304965

Intrinsic physiological properties of rat retinal ganglion cells with a comparative analysis.

PubMed

Wong, Raymond C S; Cloherty, Shaun L; Ibbotson, Michael R; O'Brien, Brendan J

2012-10-01

Mammalian retina contains 15-20 different retinal ganglion cell (RGC) types, each of which is responsible for encoding different aspects of the visual scene. The encoding is defined by a combination of RGC synaptic inputs, the neurotransmitter systems used, and their intrinsic physiological properties. Each cell's intrinsic properties are defined by its morphology and membrane characteristics, including the complement and localization of the ion channels expressed. In this study, we examined the hypothesis that the intrinsic properties of individual RGC types are conserved among mammalian species. To do so, we measured the intrinsic properties of 16 morphologically defined rat RGC types and compared these data with cat RGC types. Our data demonstrate that in the rat different morphologically defined RGC types have distinct patterns of intrinsic properties. Variation in these properties across cell types was comparable to that found for cat RGC types. When presumed morphological homologs in rat and cat retina were compared directly, some RGC types had very similar properties. The rat A2 cell exhibited patterns of intrinsic properties nearly identical to the cat alpha cell. In contrast, rat D2 cells (ON-OFF directionally selective) had a very different pattern of intrinsic properties than the cat iota cell. Our data suggest that the intrinsic properties of RGCs with similar morphology and suspected visual function may be subject to variation due to the behavioral needs of the species.

CellMap visualizes protein-protein interactions and subcellular localization

PubMed Central

Dallago, Christian; Goldberg, Tatyana; Andrade-Navarro, Miguel Angel; Alanis-Lobato, Gregorio; Rost, Burkhard

2018-01-01

Many tools visualize protein-protein interaction (PPI) networks. The tool introduced here, CellMap, adds one crucial novelty by visualizing PPI networks in the context of subcellular localization, i.e. the location in the cell or cellular component in which a PPI happens. Users can upload images of cells and define areas of interest against which PPIs for selected proteins are displayed (by default on a cartoon of a cell). Annotations of localization are provided by the user or through our in-house database. The visualizer and server are written in JavaScript, making CellMap easy to customize and to extend by researchers and developers. PMID:29497493

A medaka model of cancer allowing direct observation of transplanted tumor cells in vivo at a cellular-level resolution.

PubMed

Hasegawa, Sumitaka; Maruyama, Kouichi; Takenaka, Hikaru; Furukawa, Takako; Saga, Tsuneo

2009-08-18

The recent success with small fish as an animal model of cancer with the aid of fluorescence technique has attracted cancer modelers' attention because it would be possible to directly visualize tumor cells in vivo in real time. Here, we report a medaka model capable of allowing the observation of various cell behaviors of transplanted tumor cells, such as cell proliferation and metastasis, which were visualized easily in vivo. We established medaka melanoma (MM) cells stably expressing GFP and transplanted them into nonirradiated and irradiated medaka. The tumor cells were grown at the injection sites in medaka, and the spatiotemporal changes were visualized under a fluorescence stereoscopic microscope at a cellular-level resolution, and even at a single-cell level. Tumor dormancy and metastasis were also observed. Interestingly, in irradiated medaka, accelerated tumor growth and metastasis of the transplanted tumor cells were directly visualized. Our medaka model provides an opportunity to visualize in vivo tumor cells "as seen in a culture dish" and would be useful for in vivo tumor cell biology.

Phosphene phenomenon: a new concept.

PubMed

Bókkon, István

2008-05-01

This paper proposes a new biopsychophysical concept of phosphene phenomenon. Namely, visual sensation of phosphenes is due to the intrinsic perception of ultraweak bioluminescent photon emission of cells in the visual system. In other words, phosphenes are bioluminescent biophotons in the visual system induced by various stimuli (mechanical, electrical, magnetic, ionizing radiation, etc.) as well as random bioluminescent biophotons firings of cells in the visual pathway. This biophoton emission can become conscious if induced or spontaneous biophoton emission of cells in the visual system exceeds a distinct threshold. Neuronal biophoton communication can occur by means of non-visual neuronal opsins and natural photosensitive biomolecules. Our interpretation is in direct connection with the functional roles of free radicals and excited biomolecules in living cells.

Retinal ganglion cell responses to voltage and current stimulation in wild-type and rd1 mouse retinas

NASA Astrophysics Data System (ADS)

Goo, Yong Sook; Ye, Jang Hee; Lee, Seokyoung; Nam, Yoonkey; Ryu, Sang Baek; Kim, Kyung Hwan

2011-06-01

Retinal prostheses are being developed to restore vision for those with retinal diseases such as retinitis pigmentosa or age-related macular degeneration. Since neural prostheses depend upon electrical stimulation to control neural activity, optimal stimulation parameters for successful encoding of visual information are one of the most important requirements to enable visual perception. In this paper, we focused on retinal ganglion cell (RGC) responses to different stimulation parameters and compared threshold charge densities in wild-type and rd1 mice. For this purpose, we used in vitro retinal preparations of wild-type and rd1 mice. When the neural network was stimulated with voltage- and current-controlled pulses, RGCs from both wild-type and rd1 mice responded; however the temporal pattern of RGC response is very different. In wild-type RGCs, a single peak within 100 ms appears, while multiple peaks (approximately four peaks) with ~10 Hz rhythm within 400 ms appear in RGCs in the degenerated retina of rd1 mice. We find that an anodic phase-first biphasic voltage-controlled pulse is more efficient for stimulation than a biphasic current-controlled pulse based on lower threshold charge density. The threshold charge densities for activation of RGCs both with voltage- and current-controlled pulses are overall more elevated for the rd1 mouse than the wild-type mouse. Here, we propose the stimulus range for wild-type and rd1 retinas when the optimal modulation of a RGC response is possible.

Objective automated quantification of fluorescence signal in histological sections of rat lens.

PubMed

Talebizadeh, Nooshin; Hagström, Nanna Zhou; Yu, Zhaohua; Kronschläger, Martin; Söderberg, Per; Wählby, Carolina

2017-08-01

Visual quantification and classification of fluorescent signals is the gold standard in microscopy. The purpose of this study was to develop an automated method to delineate cells and to quantify expression of fluorescent signal of biomarkers in each nucleus and cytoplasm of lens epithelial cells in a histological section. A region of interest representing the lens epithelium was manually demarcated in each input image. Thereafter, individual cell nuclei within the region of interest were automatically delineated based on watershed segmentation and thresholding with an algorithm developed in Matlab™. Fluorescence signal was quantified within nuclei, cytoplasms and juxtaposed backgrounds. The classification of cells as labelled or not labelled was based on comparison of the fluorescence signal within cells with local background. The classification rule was thereafter optimized as compared with visual classification of a limited dataset. The performance of the automated classification was evaluated by asking 11 independent blinded observers to classify all cells (n = 395) in one lens image. Time consumed by the automatic algorithm and visual classification of cells was recorded. On an average, 77% of the cells were correctly classified as compared with the majority vote of the visual observers. The average agreement among visual observers was 83%. However, variation among visual observers was high, and agreement between two visual observers was as low as 71% in the worst case. Automated classification was on average 10 times faster than visual scoring. The presented method enables objective and fast detection of lens epithelial cells and quantification of expression of fluorescent signal with an accuracy comparable with the variability among visual observers. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

Autophagy in the eye: Development, degeneration, and aging.

PubMed

Boya, Patricia; Esteban-Martínez, Lorena; Serrano-Puebla, Ana; Gómez-Sintes, Raquel; Villarejo-Zori, Beatriz

2016-11-01

Autophagy is a catabolic pathway that promotes the degradation and recycling of cellular components. Proteins, lipids, and even whole organelles are engulfed in autophagosomes and delivered to the lysosome for elimination. In response to stress, autophagy mediates the degradation of cell components, which are recycled to generate the nutrients and building blocks required to sustain cellular homeostasis. Moreover, it plays an important role in cellular quality control, particularly in neurons, in which the total burden of altered proteins and damaged organelles cannot be reduced by redistribution to daughter cells through cell division. Research has only begun to examine the role of autophagy in the visual system. The retina, a light-sensitive tissue, detects and transmits electrical impulses through the optic nerve to the visual cortex in the brain. Both the retina and the eye are exposed to a variety of environmental insults and stressors, including genetic mutations and age-associated alterations that impair their function. Here, we review the main studies that have sought to explain autophagy's importance in visual function. We describe the role of autophagy in retinal development and cell differentiation, and discuss the implications of autophagy dysregulation both in physiological aging and in important diseases such as age-associated macular degeneration and glaucoma. We also address the putative role of autophagy in promoting photoreceptor survival and discuss how selective autophagy could provide alternative means of protecting retinal cells. The findings reviewed here underscore the important role of autophagy in maintaining proper retinal function and highlight novel therapeutic approaches for blindness and other diseases of the eye. Copyright © 2016 Elsevier Ltd. All rights reserved.

Astrocyte structural reactivity and plasticity in models of retinal detachment.

PubMed

Luna, Gabriel; Keeley, Patrick W; Reese, Benjamin E; Linberg, Kenneth A; Lewis, Geoffrey P; Fisher, Steven K

2016-09-01

Although retinal neurodegenerative conditions such as age-related macular degeneration, glaucoma, diabetic retinopathy, retinitis pigmentosa, and retinal detachment have different etiologies and pathological characteristics, they also have many responses in common at the cellular level, including neural and glial remodeling. Structural changes in Müller cells, the large radial glia of the retina in retinal disease and injury have been well described, that of the retinal astrocytes remains less so. Using modern imaging technology to describe the structural remodeling of retinal astrocytes after retinal detachment is the focus of this paper. We present both a review of critical literature as well as novel work focusing on the responses of astrocytes following rhegmatogenous and serous retinal detachment. The mouse presents a convenient model system in which to study astrocyte reactivity since the Mϋller cell response is muted in comparison to other species thereby allowing better visualization of the astrocytes. We also show data from rat, cat, squirrel, and human retina demonstrating similarities and differences across species. Our data from immunolabeling and dye-filling experiments demonstrate previously undescribed morphological characteristics of normal astrocytes and changes induced by detachment. Astrocytes not only upregulate GFAP, but structurally remodel, becoming increasingly irregular in appearance, and often penetrating deep into neural retina. Understanding these responses, their consequences, and what drives them may prove to be an important component in improving visual outcome in a variety of therapeutic situations. Our data further supports the concept that astrocytes are important players in the retina's overall response to injury and disease. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Live-cell imaging of migrating cells expressing fluorescently-tagged proteins in a three-dimensional matrix.

PubMed

Shih, Wenting; Yamada, Soichiro

2011-12-22

Traditionally, cell migration has been studied on two-dimensional, stiff plastic surfaces. However, during important biological processes such as wound healing, tissue regeneration, and cancer metastasis, cells must navigate through complex, three-dimensional extracellular tissue. To better understand the mechanisms behind these biological processes, it is important to examine the roles of the proteins responsible for driving cell migration. Here, we outline a protocol to study the mechanisms of cell migration using the epithelial cell line (MDCK), and a three-dimensional, fibrous, self-polymerizing matrix as a model system. This optically clear extracellular matrix is easily amenable to live-cell imaging studies and better mimics the physiological, soft tissue environment. This report demonstrates a technique for directly visualizing protein localization and dynamics, and deformation of the surrounding three-dimensional matrix. Examination of protein localization and dynamics during cellular processes provides key insight into protein functions. Genetically encoded fluorescent tags provide a unique method for observing protein localization and dynamics. Using this technique, we can analyze the subcellular accumulation of key, force-generating cytoskeletal components in real-time as the cell maneuvers through the matrix. In addition, using multiple fluorescent tags with different wavelengths, we can examine the localization of multiple proteins simultaneously, thus allowing us to test, for example, whether different proteins have similar or divergent roles. Furthermore, the dynamics of fluorescently tagged proteins can be quantified using Fluorescent Recovery After Photobleaching (FRAP) analysis. This measurement assays the protein mobility and how stably bound the proteins are to the cytoskeletal network. By combining live-cell imaging with the treatment of protein function inhibitors, we can examine in real-time the changes in the distribution of proteins and morphology of migrating cells. Furthermore, we also combine live-cell imaging with the use of fluorescent tracer particles embedded within the matrix to visualize the matrix deformation during cell migration. Thus, we can visualize how a migrating cell distributes force-generating proteins, and where the traction forces are exerted to the surrounding matrix. Through these techniques, we can gain valuable insight into the roles of specific proteins and their contributions to the mechanisms of cell migration.

Transgenerational cell fate profiling

PubMed Central

Jemaà, Mohamed; Galluzzi, Lorenzo; Kepp, Oliver; Castedo, Maria; Rello-Varona, Santiago; Vitale, Ilio; Kroemer, Guido

2013-01-01

The illicit generation of tetraploid cells constitutes a prominent driver of oncogenesis, as it often precedes the development of aneuploidy and genomic instability. In addition, tetraploid (pre-)malignant cells display an elevated resistance against radio- and chemotherapy. Here, we report a strategy to preferentially kill tetraploid tumor cells based on the broad-spectrum kinase inhibitor SP600125. Live videomicroscopy revealed that SP600125 affects the execution of mitosis, impedes proper cell division and/or activates apoptosis in near-to-tetraploid, though less so in parental, cancer cells. We propose a novel graphical model to quantify the differential response of diploid and tetraploid cells to mitotic perturbators, including SP600125, which we baptized “transgenerational cell fate profiling.” We speculate that this representation constitutes a valid alternative to classical “single-cell fate” and “genealogical” profiling and, hence, may facilitate the analysis of cell fate within a heterogeneous population as well as the visual examination of cell cycle alterations. PMID:23255111

Space-time wiring specificity supports direction selectivity in the retina

PubMed Central

Zlateski, Aleksandar; Lee, Kisuk; Richardson, Mark; Turaga, Srinivas C.; Purcaro, Michael; Balkam, Matthew; Robinson, Amy; Behabadi, Bardia F.; Campos, Michael; Denk, Winfried; Seung, H. Sebastian

2014-01-01

How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, we reconstructed Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of “citizen neuroscientists.” Based on quantitative analyses of contact area and branch depth in the retina, we found evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, while another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such “space-time wiring specificity” could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma. PMID:24805243

Space-time wiring specificity supports direction selectivity in the retina.

PubMed

Kim, Jinseop S; Greene, Matthew J; Zlateski, Aleksandar; Lee, Kisuk; Richardson, Mark; Turaga, Srinivas C; Purcaro, Michael; Balkam, Matthew; Robinson, Amy; Behabadi, Bardia F; Campos, Michael; Denk, Winfried; Seung, H Sebastian

2014-05-15

How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, here we reconstruct Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of 'citizen neuroscientists'. On the basis of quantitative analyses of contact area and branch depth in the retina, we find evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, whereas another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such 'space-time wiring specificity' could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma.

Multiscale Simulation of Blood Flow in Brain Arteries with an Aneurysm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leopold Grinberg; Vitali Morozov; Dmitry A. Fedosov

2013-04-24

Multi-scale modeling of arterial blood flow can shed light on the interaction between events happening at micro- and meso-scales (i.e., adhesion of red blood cells to the arterial wall, clot formation) and at macro-scales (i.e., change in flow patterns due to the clot). Coupled numerical simulations of such multi-scale flow require state-of-the-art computers and algorithms, along with techniques for multi-scale visualizations.This animation presents results of studies used in the development of a multi-scale visualization methodology. First we use streamlines to show the path the flow is taking as it moves through the system, including the aneurysm. Next we investigate themore » process of thrombus (blood clot) formation, which may be responsible for the rupture of aneurysms, by concentrating on the platelet blood cells, observing as they aggregate on the wall of the aneurysm.« less

Rapid learning in visual cortical networks.

PubMed

Wang, Ye; Dragoi, Valentin

2015-08-26

Although changes in brain activity during learning have been extensively examined at the single neuron level, the coding strategies employed by cell populations remain mysterious. We examined cell populations in macaque area V4 during a rapid form of perceptual learning that emerges within tens of minutes. Multiple single units and LFP responses were recorded as monkeys improved their performance in an image discrimination task. We show that the increase in behavioral performance during learning is predicted by a tight coordination of spike timing with local population activity. More spike-LFP theta synchronization is correlated with higher learning performance, while high-frequency synchronization is unrelated with changes in performance, but these changes were absent once learning had stabilized and stimuli became familiar, or in the absence of learning. These findings reveal a novel mechanism of plasticity in visual cortex by which elevated low-frequency synchronization between individual neurons and local population activity accompanies the improvement in performance during learning.

Single α-particle irradiation permits real-time visualization of RNF8 accumulation at DNA damaged sites

NASA Astrophysics Data System (ADS)

Muggiolu, Giovanna; Pomorski, Michal; Claverie, Gérard; Berthet, Guillaume; Mer-Calfati, Christine; Saada, Samuel; Devès, Guillaume; Simon, Marina; Seznec, Hervé; Barberet, Philippe

2017-01-01

As well as being a significant source of environmental radiation exposure, α-particles are increasingly considered for use in targeted radiation therapy. A better understanding of α-particle induced damage at the DNA scale can be achieved by following their tracks in real-time in targeted living cells. Focused α-particle microbeams can facilitate this but, due to their low energy (up to a few MeV) and limited range, α-particles detection, delivery, and follow-up observations of radiation-induced damage remain difficult. In this study, we developed a thin Boron-doped Nano-Crystalline Diamond membrane that allows reliable single α-particles detection and single cell irradiation with negligible beam scattering. The radiation-induced responses of single 3 MeV α-particles delivered with focused microbeam are visualized in situ over thirty minutes after irradiation by the accumulation of the GFP-tagged RNF8 protein at DNA damaged sites.

Color tuning in alert macaque V1 assessed with fMRI and single-unit recording shows a bias toward daylight colors.

PubMed

Lafer-Sousa, Rosa; Liu, Yang O; Lafer-Sousa, Luis; Wiest, Michael C; Conway, Bevil R

2012-05-01

Colors defined by the two intermediate directions in color space, "orange-cyan" and "lime-magenta," elicit the same spatiotemporal average response from the two cardinal chromatic channels in the lateral geniculate nucleus (LGN). While we found LGN functional magnetic resonance imaging (fMRI) responses to these pairs of colors were statistically indistinguishable, primary visual cortex (V1) fMRI responses were stronger to orange-cyan. Moreover, linear combinations of single-cell responses to cone-isolating stimuli of V1 cone-opponent cells also yielded stronger predicted responses to orange-cyan over lime-magenta, suggesting these neurons underlie the fMRI result. These observations are consistent with the hypothesis that V1 recombines LGN signals into "higher-order" mechanisms tuned to noncardinal color directions. In light of work showing that natural images and daylight samples are biased toward orange-cyan, our findings further suggest that V1 is adapted to daylight. V1, especially double-opponent cells, may function to extract spatial information from color boundaries correlated with scene-structure cues, such as shadows lit by ambient blue sky juxtaposed with surfaces reflecting sunshine. © 2012 Optical Society of America

Adaptive remodeling of the biliary tree: the essence of liver progenitor cell expansion.

PubMed

Kok, Cindy Yuet-Yin; Miyajima, Atsushi; Itoh, Tohru

2015-07-01

The liver progenitor cell population has long been thought to exist within the liver. However, there are no standardized criteria for defining the liver progenitor cells, and there has been intense debate about the origin of these cells in the adult liver. The characteristics of such cells vary depending on the disease model used and also on the method of analysis. Visualization of three-dimensional biliary structures has revealed that the emergence of liver progenitor cells essentially reflects the adaptive remodeling of the hepatic biliary network in response to liver injury. We propose that the progenitor cell exists as a subpopulation in the biliary tree and show that the appearance of liver progenitor cells in injured parenchyma is reflective of extensive remodeling of the biliary structure. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review.

PubMed

Teh, Seoh Wei; Mok, Pooi Ling; Abd Rashid, Munirah; Bastion, Mae-Lynn Catherine; Ibrahim, Normala; Higuchi, Akon; Murugan, Kadarkarai; Mariappan, Rajan; Subbiah, Suresh Kumar

2018-02-13

Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.

Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review

PubMed Central

Teh, Seoh Wei; Mok, Pooi Ling; Abd Rashid, Munirah; Bastion, Mae-Lynn Catherine; Ibrahim, Normala; Higuchi, Akon; Murugan, Kadarkarai; Mariappan, Rajan

2018-01-01

Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections. PMID:29438279

From perceptive fields to Gestalt.

PubMed

Spillmann, Lothar

2006-01-01

Studies on visual psychophysics and perception conducted in the Freiburg psychophysics laboratory during the last 35 years are reviewed. Many of these were inspired by single-cell neurophysiology in cat and monkey. The aim was to correlate perceptual phenomena and their effects to possible neuronal mechanisms from retina to visual cortex and beyond. Topics discussed include perceptive field organization, figure-ground segregation and grouping, fading and filling-in, and long-range color interaction. While some of these studies succeeded in linking perception to neuronal response patterns, others require further investigation. The task of probing the human brain with perceptual phenomena continues to be a challenge for the future.

Multinomial Bayesian learning for modeling classical and nonclassical receptive field properties.

PubMed

Hosoya, Haruo

2012-08-01

We study the interplay of Bayesian inference and natural image learning in a hierarchical vision system, in relation to the response properties of early visual cortex. We particularly focus on a Bayesian network with multinomial variables that can represent discrete feature spaces similar to hypercolumns combining minicolumns, enforce sparsity of activation to learn efficient representations, and explain divisive normalization. We demonstrate that maximal-likelihood learning using sampling-based Bayesian inference gives rise to classical receptive field properties similar to V1 simple cells and V2 cells, while inference performed on the trained network yields nonclassical context-dependent response properties such as cross-orientation suppression and filling in. Comparison with known physiological properties reveals some qualitative and quantitative similarities.

Can responses to basic non-numerical visual features explain neural numerosity responses?

PubMed

Harvey, Ben M; Dumoulin, Serge O

2017-04-01

Humans and many animals can distinguish between stimuli that differ in numerosity, the number of objects in a set. Human and macaque parietal lobes contain neurons that respond to changes in stimulus numerosity. However, basic non-numerical visual features can affect neural responses to and perception of numerosity, and visual features often co-vary with numerosity. Therefore, it is debated whether numerosity or co-varying low-level visual features underlie neural and behavioral responses to numerosity. To test the hypothesis that non-numerical visual features underlie neural numerosity responses in a human parietal numerosity map, we analyze responses to a group of numerosity stimulus configurations that have the same numerosity progression but vary considerably in their non-numerical visual features. Using ultra-high-field (7T) fMRI, we measure responses to these stimulus configurations in an area of posterior parietal cortex whose responses are believed to reflect numerosity-selective activity. We describe an fMRI analysis method to distinguish between alternative models of neural response functions, following a population receptive field (pRF) modeling approach. For each stimulus configuration, we first quantify the relationships between numerosity and several non-numerical visual features that have been proposed to underlie performance in numerosity discrimination tasks. We then determine how well responses to these non-numerical visual features predict the observed fMRI responses, and compare this to the predictions of responses to numerosity. We demonstrate that a numerosity response model predicts observed responses more accurately than models of responses to simple non-numerical visual features. As such, neural responses in cognitive processing need not reflect simpler properties of early sensory inputs. Copyright © 2017 Elsevier Inc. All rights reserved.

A second visual rhodopsin gene, rh1-2, is expressed in zebrafish photoreceptors and found in other ray-finned fishes.

PubMed

Morrow, James M; Lazic, Savo; Dixon Fox, Monica; Kuo, Claire; Schott, Ryan K; de A Gutierrez, Eduardo; Santini, Francesco; Tropepe, Vincent; Chang, Belinda S W

2017-01-15

Rhodopsin (rh1) is the visual pigment expressed in rod photoreceptors of vertebrates that is responsible for initiating the critical first step of dim-light vision. Rhodopsin is usually a single copy gene; however, we previously discovered a novel rhodopsin-like gene expressed in the zebrafish retina, rh1-2, which we identified as a functional photosensitive pigment that binds 11-cis retinal and activates in response to light. Here, we localized expression of rh1-2 in the zebrafish retina to a subset of peripheral photoreceptor cells, which indicates a partially overlapping expression pattern with rh1 We also expressed, purified and characterized Rh1-2, including investigation of the stability of the biologically active intermediate. Using fluorescence spectroscopy, we found the half-life of the rate of retinal release of Rh1-2 following photoactivation to be more similar to that of the visual pigment rhodopsin than to the non-visual pigment exo-rhodopsin (exorh), which releases retinal around 5 times faster. Phylogenetic and molecular evolutionary analyses show that rh1-2 has ancient origins within teleost fishes, is under similar selective pressure to rh1, and likely experienced a burst of positive selection following its duplication and divergence from rh1 These findings indicate that rh1-2 is another functional visual rhodopsin gene, which contradicts the prevailing notion that visual rhodopsin is primarily found as a single copy gene within ray-finned fishes. The reasons for retention of this duplicate gene, as well as possible functional consequences for the visual system, are discussed. © 2017. Published by The Company of Biologists Ltd.

Emergence of order in visual system development.

PubMed Central

Shatz, C J

1996-01-01

Neural connections in the adult central nervous system are highly precise. In the visual system, retinal ganglion cells send their axons to target neurons in the lateral geniculate nucleus (LGN) in such a way that axons originating from the two eyes terminate in adjacent but nonoverlapping eye-specific layers. During development, however, inputs from the two eyes are intermixed, and the adult pattern emerges gradually as axons from the two eyes sort out to form the layers. Experiments indicate that the sorting-out process, even though it occurs in utero in higher mammals and always before vision, requires retinal ganglion cell signaling; blocking retinal ganglion cell action potentials with tetrodotoxin prevents the formation of the layers. These action potentials are endogenously generated by the ganglion cells, which fire spontaneously and synchronously with each other, generating "waves" of activity that travel across the retina. Calcium imaging of the retina shows that the ganglion cells undergo correlated calcium bursting to generate the waves and that amacrine cells also participate in the correlated activity patterns. Physiological recordings from LGN neurons in vitro indicate that the quasiperiodic activity generated by the retinal ganglion cells is transmitted across the synapse between ganglion cells to drive target LGN neurons. These observations suggest that (i) a neural circuit within the immature retina is responsible for generating specific spatiotemporal patterns of neural activity; (ii) spontaneous activity generated in the retina is propagated across central synapses; and (iii) even before the photoreceptors are present, nerve cell function is essential for correct wiring of the visual system during early development. Since spontaneously generated activity is known to be present elsewhere in the developing CNS, this process of activity-dependent wiring could be used throughout the nervous system to help refine early sets of neural connections into their highly precise adult patterns. Images Fig. 1 Fig. 4 PMID:8570602

Enduring critical period plasticity visualized by transcranial flavoprotein imaging in mouse primary visual cortex.

PubMed

Tohmi, Manavu; Kitaura, Hiroki; Komagata, Seiji; Kudoh, Masaharu; Shibuki, Katsuei

2006-11-08

Experience-dependent plasticity in the visual cortex was investigated using transcranial flavoprotein fluorescence imaging in mice anesthetized with urethane. On- and off-responses in the primary visual cortex were elicited by visual stimuli. Fluorescence responses and field potentials elicited by grating patterns decreased similarly as contrasts of visual stimuli were reduced. Fluorescence responses also decreased as spatial frequency of grating stimuli increased. Compared with intrinsic signal imaging in the same mice, fluorescence imaging showed faster responses with approximately 10 times larger signal changes. Retinotopic maps in the primary visual cortex and area LM were constructed using fluorescence imaging. After monocular deprivation (MD) of 4 d starting from postnatal day 28 (P28), deprived eye responses were suppressed compared with nondeprived eye responses in the binocular zone but not in the monocular zone. Imaging faithfully recapitulated a critical period for plasticity with maximal effects of MD observed around P28 and not in adulthood even under urethane anesthesia. Visual responses were compared before and after MD in the same mice, in which the skull was covered with clear acrylic dental resin. Deprived eye responses decreased after MD, whereas nondeprived eye responses increased. Effects of MD during a critical period were tested 2 weeks after reopening of the deprived eye. Significant ocular dominance plasticity was observed in responses elicited by moving grating patterns, but no long-lasting effect was found in visual responses elicited by light-emitting diode light stimuli. The present results indicate that transcranial flavoprotein fluorescence imaging is a powerful tool for investigating experience-dependent plasticity in the mouse visual cortex.

Hypergravity Stimulates the Extracellular Matrix/Integrin-Signaling Axis and Proliferation in Primary Osteoblasts

NASA Technical Reports Server (NTRS)

Parra, M.; Vercoutere, W.; Roden, C.; Banerjee, I.; Krauser, W.; Holton, E.; Searby, N.; Globus, R.; Almeida, E.

2003-01-01

We set out to determine the molecular mechanisms involved in the proliferative response of primary rat osteoblasts to mechanical stimulation using cell culture centrifugation as a model for hypergravity. We hypothesized that this proliferative response is mediated by specific integrin/Extracellular Matrix (ECM) interactions. To investigate this question we developed a cell culture centrifuge and an automated system that performs cell fixation during hypergravity loading. We generated expression vectors for various focal adhesion and cytoskeletal proteins fused to GFP or dsRed and visualized these structures in transfected (or infected) osteoblasts. The actin cytoskeleton was also visualized using rhodamine-phalloidin staining and Focal Adhesion Kinase (FAK) levels were assessed biochemically. We observed that a 24 hour exposure to 50-g stimulated proliferation compared to the 1-g control when cells were plated on fibronectin, collagen Type I , and collagen Type IV, but not on uncoated tissue culture plastic surfaces. This proliferative response was greatest for osteoblasts grown on fibronectin (2-fold increase over 1-g control) and collagen Type I (1.4 fold increase over 1-g control), suggesting that specific matrices and integrins are involved in the signaling pathways required for proliferation. Exposing osteoblasts grown on different matrices to 10-g or 25-g showed that effects on proliferation depended on both matrix type and loading level. We found that osteoblasts exposed to a short pulse of hypergravity during adhesion spread further and had more GFP-FAK containing focal adhesions compared to their 1-g controls. While overall levels of FAK did not change, more FAK was in the active (phosphorylated) form under hypergravity than in the 1-g controls. Cytoskeletal F-actin organization into filaments was also more prominent after brief exposures to hypergravity during the first five minutes of adhesion. These results suggest that specific integrins sense hypergravity and activate distinct matrix-dependent FAK signaling pathways that can enhance proliferation. Our results also imply that brief exposures to hypergravity accelerate cell adhesion and spreading processes via the focal adhesion-signaling axis. These results support the role of the ECM/integrin-signaling axis in osteoblast response to hypergravity loading.

Modeling a space-variant cortical representation for apparent motion.

PubMed

Wurbs, Jeremy; Mingolla, Ennio; Yazdanbakhsh, Arash

2013-08-06

Receptive field sizes of neurons in early primate visual areas increase with eccentricity, as does temporal processing speed. The fovea is evidently specialized for slow, fine movements while the periphery is suited for fast, coarse movements. In either the fovea or periphery discrete flashes can produce motion percepts. Grossberg and Rudd (1989) used traveling Gaussian activity profiles to model long-range apparent motion percepts. We propose a neural model constrained by physiological data to explain how signals from retinal ganglion cells to V1 affect the perception of motion as a function of eccentricity. Our model incorporates cortical magnification, receptive field overlap and scatter, and spatial and temporal response characteristics of retinal ganglion cells for cortical processing of motion. Consistent with the finding of Baker and Braddick (1985), in our model the maximum flash distance that is perceived as an apparent motion (Dmax) increases linearly as a function of eccentricity. Baker and Braddick (1985) made qualitative predictions about the functional significance of both stimulus and visual system parameters that constrain motion perception, such as an increase in the range of detectable motions as a function of eccentricity and the likely role of higher visual processes in determining Dmax. We generate corresponding quantitative predictions for those functional dependencies for individual aspects of motion processing. Simulation results indicate that the early visual pathway can explain the qualitative linear increase of Dmax data without reliance on extrastriate areas, but that those higher visual areas may serve as a modulatory influence on the exact Dmax increase.

Sensory convergence in the parieto-insular vestibular cortex

PubMed Central

Shinder, Michael E.

2014-01-01

Vestibular signals are pervasive throughout the central nervous system, including the cortex, where they likely play different roles than they do in the better studied brainstem. Little is known about the parieto-insular vestibular cortex (PIVC), an area of the cortex with prominent vestibular inputs. Neural activity was recorded in the PIVC of rhesus macaques during combinations of head, body, and visual target rotations. Activity of many PIVC neurons was correlated with the motion of the head in space (vestibular), the twist of the neck (proprioceptive), and the motion of a visual target, but was not associated with eye movement. PIVC neurons responded most commonly to more than one stimulus, and responses to combined movements could often be approximated by a combination of the individual sensitivities to head, neck, and target motion. The pattern of visual, vestibular, and somatic sensitivities on PIVC neurons displayed a continuous range, with some cells strongly responding to one or two of the stimulus modalities while other cells responded to any type of motion equivalently. The PIVC contains multisensory convergence of self-motion cues with external visual object motion information, such that neurons do not represent a specific transformation of any one sensory input. Instead, the PIVC neuron population may define the movement of head, body, and external visual objects in space and relative to one another. This comparison of self and external movement is consistent with insular cortex functions related to monitoring and explains many disparate findings of previous studies. PMID:24671533

Effects of visual attention on chromatic and achromatic detection sensitivities.

PubMed

Uchikawa, Keiji; Sato, Masayuki; Kuwamura, Keiko

2014-05-01

Visual attention has a significant effect on various visual functions, such as response time, detection and discrimination sensitivity, and color appearance. It has been suggested that visual attention may affect visual functions in the early visual pathways. In this study we examined selective effects of visual attention on sensitivities of the chromatic and achromatic pathways to clarify whether visual attention modifies responses in the early visual system. We used a dual task paradigm in which the observer detected a peripheral test stimulus presented at 4 deg eccentricities while the observer concurrently carried out an attention task in the central visual field. In experiment 1, it was confirmed that peripheral spectral sensitivities were reduced more for short and long wavelengths than for middle wavelengths with the central attention task so that the spectral sensitivity function changed its shape by visual attention. This indicated that visual attention affected the chromatic response more strongly than the achromatic response. In experiment 2 it was obtained that the detection thresholds increased in greater degrees in the red-green and yellow-blue chromatic directions than in the white-black achromatic direction in the dual task condition. In experiment 3 we showed that the peripheral threshold elevations depended on the combination of color-directions of the central and peripheral stimuli. Since the chromatic and achromatic responses were separately processed in the early visual pathways, the present results provided additional evidence that visual attention affects responses in the early visual pathways.

Attentional modulation of cell-class specific gamma-band synchronization in awake monkey area V4

PubMed Central

Vinck, Martin; Womelsdorf, Thilo; Buffalo, Elizabeth A.; Desimone, Robert; Fries, Pascal

2013-01-01

Summary Selective visual attention is subserved by selective neuronal synchronization, entailing precise orchestration among excitatory and inhibitory cells. We tentatively identified these as broad (BS) and narrow spiking (NS) cells and analyzed their synchronization to the local field potential in two macaque monkeys performing a selective visual attention task. Across cells, gamma phases scattered widely but were unaffected by stimulation or attention. During stimulation, NS cells lagged BS cells on average by ~60° and gamma synchronized twice as strongly. Attention enhanced and reduced the gamma locking of strongly and weakly activated cells, respectively. During a pre-stimulus attentional cue period, BS cells showed weak gamma synchronization, while NS cells gamma synchronized as strongly as with visual stimulation. These analyses reveal the cell-type specific dynamics of the gamma cycle in macaque visual cortex and suggest that attention affects neurons differentially depending on cell type and activation level. PMID:24267656

Examination of silicon solar cells by means of the Scanning Laser Acoustic Microscope (SLAM)

NASA Technical Reports Server (NTRS)

Vorres, C.; Yuhas, D. E.

1981-01-01

The Scanning Laser Acoustic Microscope produces images of internal structure in materials. The acoustic microscope is an imaging system based upon acoustic rather than electromagnetic waves. Variations in the elastic propertis are primarily responsible for structure visualized in acoustic micrographs. The instrument used in these investigations is the SONOMICROSCOPE 100 which can be operated at ultrasonic frequencies of from 30 MHz to 500 MHz. The examination of the silicon solar cells was made at 100 MHz. Data are presented in the form of photomicrographs.

The use of the color Doppler ultrasonography in the diagnosis and monitoring of an atypical case of giant-cell arteritis.

PubMed

Martins, N; Polido-Pereira, J; Rodrigues, A M; Soares, F; Batista, P; Pereira da Silva, J A

2016-01-01

Giant Cell Arteritis (GCA) is a large vessels vasculitis that is typically characterised by headache, scalp tenderness, jaw claudication and visual disturbances. Temporal arteries color Doppler ultrasonography (CDUS) is a sensitive and non-invasive image technique used in the diagnosis of this disease. This work highlights the importance of CDUS in the diagnostic workup of GCA and also demonstrates it´s usefullness in the evaluation and documentation of the response to corticosteroids therapy in an atypical case of ACG.

Peak firing rates of rat anterodorsal thalamic head direction cells are higher during faster passive rotations.

PubMed

Zugaro, Michaël B; Berthoz, Alain; Wiener, Sidney I

2002-01-01

Head direction cells discharge selectively when the head of the animal is oriented in a specific direction. The goal of this study was to determine how sensory signals arising from passive rotations (e.g., triggered by vestibular stimulation and dynamic visual inputs) influence the responses of anterodorsal thalamic head direction cells in the absence of voluntary movement cues (e.g., motor command, efference copy, and associated kinesthetic signals). Three unrestrained rats consumed water from a reservoir at the center of a circular platform while passively subjected to sinusoidal rotatory oscillations at fast (153 +/- 27 degrees/s, sd) and slow (38 +/- 15 degrees/s) peak velocities. In 14 anterodorsal thalamic head direction cells, the preferred directions, angular response ranges and baseline firing rates remained stable, but the peak firing rates were, on average, 36% higher during the fast rotations (Wilcoxon matched-pairs test, p < 0.001; variation range: +11% to approximately +100%). No cell changed its peak firing rate by less than 10%, while three cells (21%) increased their peak firing rates by more than 50%. The velocity-dependent increase in peak firing rates was similar for left and right rotations, and the skewness of the directional response curves were not significantly different between left and right turns (Wilcoxon matched-pairs tests, n = 14, ns). These results show that sensory signals concerning self-movements modulate the responses of the head direction cells in the absence of active locomotion.

Sensitivity of complex cells in cat striate cortex to relative motion.

PubMed

Hammond, P; Smith, A T

1984-06-03

Sensitivity of 95 complex cells to relative motion between oriented bars and textured backgrounds was investigated monocularly in the striate cortex of lightly anesthetized, paralyzed cats. Cells were classified conventionally. Those in deep layers were either direction-selective, or strongly preferred one direction of motion, and responded well to background texture motion alone: backgrounds potentiated the response to the bar in the cell's preferred direction when moved in phase, or in the opposite direction when moved in antiphase; other combinations depressed the level of response compared with that for the bar alone. The majority of direction-selective or strongly direction-biased cells in superficial layers behaved similarly. The most interesting superficial-layer cells were bidirectional or weakly direction-biased, and recorded closer to the cortical surface than the direction-selective neurons. A majority showed preference for relative motion, some for antiphase, others for in-phase motion, regardless of the absolute direction of motion across the receptive field, which could not be accounted for on the basis of separate responses to bars and backgrounds alone. Three of the superficial-layer direction-selective cells also showed preference for antiphase relative motion. In a few complex cells from superficial laminae, backgrounds were either without influence on responses to oriented stimuli, or purely suppressive. Visual backgrounds against which objects are perceived are usually neither featureless nor motionless: the results suggest that most complex cells in striate cortex are sensitive to the context in which objects are seen and susceptible to relationships between objects and their backgrounds in relative motion.

Axonal Conduction Delays, Brain State, and Corticogeniculate Communication

PubMed Central

2017-01-01

Thalamocortical conduction times are short, but layer 6 corticothalamic axons display an enormous range of conduction times, some exceeding 40–50 ms. Here, we investigate (1) how axonal conduction times of corticogeniculate (CG) neurons are related to the visual information conveyed to the thalamus, and (2) how alert versus nonalert awake brain states affect visual processing across the spectrum of CG conduction times. In awake female Dutch-Belted rabbits, we found 58% of CG neurons to be visually responsive, and 42% to be unresponsive. All responsive CG neurons had simple, orientation-selective receptive fields, and generated sustained responses to stationary stimuli. CG axonal conduction times were strongly related to modulated firing rates (F1 values) generated by drifting grating stimuli, and their associated interspike interval distributions, suggesting a continuum of visual responsiveness spanning the spectrum of axonal conduction times. CG conduction times were also significantly related to visual response latency, contrast sensitivity (C-50 values), directional selectivity, and optimal stimulus velocity. Increasing alertness did not cause visually unresponsive CG neurons to become responsive and did not change the response linearity (F1/F0 ratios) of visually responsive CG neurons. However, for visually responsive CG neurons, increased alertness nearly doubled the modulated response amplitude to optimal visual stimulation (F1 values), significantly shortened response latency, and dramatically increased response reliability. These effects of alertness were uniform across the broad spectrum of CG axonal conduction times. SIGNIFICANCE STATEMENT Corticothalamic neurons of layer 6 send a dense feedback projection to thalamic nuclei that provide input to sensory neocortex. While sensory information reaches the cortex after brief thalamocortical axonal delays, corticothalamic axons can exhibit conduction delays of <2 ms to 40–50 ms. Here, in the corticogeniculate visual system of awake rabbits, we investigate the functional significance of this axonal diversity, and the effects of shifting alert/nonalert brain states on corticogeniculate processing. We show that axonal conduction times are strongly related to multiple visual response properties, suggesting a continuum of visual responsiveness spanning the spectrum of corticogeniculate axonal conduction times. We also show that transitions between awake brain states powerfully affect corticogeniculate processing, in some ways more strongly than in layer 4. PMID:28559382

Precision Cut Mouse Lung Slices to Visualize Live Pulmonary Dendritic Cells

PubMed Central

Lyons-Cohen, Miranda R.; Thomas, Seddon Y.; Cook, Donald N.; Nakano, Hideki

2017-01-01

SHORT ABSTRACT We describe a method for generating precision-cut lung slices (PCLS) and immunostaining them to visualize the localization of various immune cell types in the lung. Our protocol can be extended to visualize the location and function of many different cell types under a variety of conditions. LONG ABSTRACT Inhalation of allergens and pathogens elicits multiple changes in a variety of immune cell types in the lung. Flow cytometry is a powerful technique for quantitative analysis of cell surface proteins on immune cells, but it provides no information on the localization and migration patterns of these cells within the lung. Similarly, in vitro chemotaxis assays can be performed to study the potential of cells to respond to chemotactic factors in vitro, but these assays do not reproduce the complex environment of the intact lung. In contrast to these aforementioned techniques, the location of individual cell types within the lung can be readily visualized by generating precision-cut lung slices (PCLS), staining them with commercially available, fluorescently tagged antibodies, and visualizing the sections by confocal microscopy. PCLS can be used for both live and fixed lung tissue, and the slices can encompass areas as large as a cross section of an entire lobe. We have used this protocol to successfully visualize the location of a wide variety of cell types in the lung, including distinct types of dendritic cells, macrophages, neutrophils, T cells and B cells, as well as structural cells such as lymphatic, endothelial, and epithelial cells. The ability to visualize cellular interactions, such as those between dendritic cells and T cells, in live, three-dimensional lung tissue, can reveal how cells move within the lung and interact with one another at steady state and during inflammation. Thus, when used in combination with other procedures, such as flow cytometry and quantitative PCR, PCLS can contribute to a comprehensive understanding of cellular events that underlie allergic and inflammatory diseases of the lung. PMID:28448013

Visual processing during recovery from vegetative state to consciousness: comparing behavioral indices to brain responses.

PubMed

Wijnen, V J M; Eilander, H J; de Gelder, B; van Boxtel, G J M

2014-11-01

Auditory stimulation is often used to evoke responses in unresponsive patients who have suffered severe brain injury. In order to investigate visual responses, we examined visual evoked potentials (VEPs) and behavioral responses to visual stimuli in vegetative patients during recovery to consciousness. Behavioral responses to visual stimuli (visual localization, comprehension of written commands, and object manipulation) and flash VEPs were repeatedly examined in eleven vegetative patients every two weeks for an average period of 2.6months, and patients' VEPs were compared to a healthy control group. Long-term outcome of the patients was assessed 2-3years later. Visual response scores increased during recovery to consciousness for all scales: visual localization, comprehension of written commands, and object manipulation. VEP amplitudes were smaller, and latencies were longer in the patient group relative to the controls. VEPs characteristics at first measurement were related to long-term outcome up to three years after injury. Our findings show the improvement of visual responding with recovery from the vegetative state to consciousness. Elementary visual processing is present, yet according to VEP responses, poorer in vegetative and minimally conscious state than in healthy controls, and remains poorer when patients recovered to consciousness. However, initial VEPs are related to long-term outcome. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Macroglia-derived thrombospondin 2 regulates alterations of presynaptic proteins of retinal neurons following elevated hydrostatic pressure.

PubMed

Wang, Shuchao; Hu, Tu; Wang, Zhen; Li, Na; Zhou, Lihong; Liao, Lvshuang; Wang, Mi; Liao, Libin; Wang, Hui; Zeng, Leping; Fan, Chunling; Zhou, Hongkang; Xiong, Kun; Huang, Jufang; Chen, Dan

2017-01-01

Many studies on retinal injury and repair following elevated intraocular pressure suggest that the survival ratio of retinal neurons has been improved by various measures. However, the visual function recovery is far lower than expected. The homeostasis of retinal synapses in the visual signal pathway is the key structural basis for the delivery of visual signals. Our previous studies found that complicated changes in the synaptic structure between retinal neurons occurred much earlier than obvious degeneration of retinal ganglion cells in rat retinae. The lack of consideration of these earlier retinal synaptic changes in the rescue strategy may be partly responsible for the limited visual function recovery with the types of protective methods for retinal neurons used following elevated intraocular pressure. Thus, research on the modulatory mechanisms of the synaptic changes after elevated intraocular pressure injury may give new light to visual function rescue. In this study, we found that thrombospondin 2, an important regulator of synaptogenesis in central nervous system development, was distributed in retinal macroglia cells, and its receptor α2δ-1 was in retinal neurons. Cell cultures including mixed retinal macroglia cells/neuron cultures and retinal neuron cultures were exposed to elevated hydrostatic pressure for 2 h. The expression levels of glial fibrillary acidic protein (the marker of activated macroglia cells), thrombospondin 2, α2δ-1 and presynaptic proteins were increased following elevated hydrostatic pressure in mixed cultures, but the expression levels of postsynaptic proteins were not changed. SiRNA targeting thrombospondin 2 could decrease the upregulation of presynaptic proteins induced by the elevated hydrostatic pressure. However, in retinal neuron cultures, elevated hydrostatic pressure did not affect the expression of presynaptic or postsynaptic proteins. Rather, the retinal neuron cultures with added recombinant thrombospondin 2 protein upregulated the level of presynaptic proteins. Finally, gabapentin decreased the expression of presynaptic proteins in mixed cultures by blocking the interaction of thrombospondin 2 and α2δ-1. Taken together, these results indicate that activated macroglia cells may participate in alterations of presynaptic proteins of retinal neurons following elevated hydrostatic pressure, and macroglia-derived thrombospondin 2 may modulate these changes via binding to its neuronal receptor α2δ-1.

Acetylcholine contributes to the integration of self-movement cues in head direction cells.

PubMed

Yoder, Ryan M; Chan, Jeremy H M; Taube, Jeffrey S

2017-08-01

Acetylcholine contributes to accurate performance on some navigational tasks, but details of its contribution to the underlying brain signals are not fully understood. The medial septal area provides widespread cholinergic input to various brain regions, but selective damage to medial septal cholinergic neurons generally has little effect on landmark-based navigation, or the underlying neural representations of location and directional heading in visual environments. In contrast, the loss of medial septal cholinergic neurons disrupts navigation based on path integration, but no studies have tested whether these path integration deficits are associated with disrupted head direction (HD) cell activity. Therefore, we evaluated HD cell responses to visual cue rotations in a familiar arena, and during navigation between familiar and novel arenas, after muscarinic receptor blockade with systemic atropine. Atropine treatment reduced the peak firing rate of HD cells, but failed to significantly affect other HD cell firing properties. Atropine also failed to significantly disrupt the dominant landmark control of the HD signal, even though we used a procedure that challenged this landmark control. In contrast, atropine disrupted HD cell stability during navigation between familiar and novel arenas, where path integration normally maintains a consistent HD cell signal across arenas. These results suggest that acetylcholine contributes to path integration, in part, by facilitating the use of idiothetic cues to maintain a consistent representation of directional heading. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A rhodamine-based fluorescent probe for colorimetric and fluorescence lighting-up determination of toxic thiophenols in environmental water and living cells.

PubMed

Wu, Juanjuan; Ye, Zhuo; Wu, Feng; Wang, Hongying; Zeng, Lintao; Bao, Guang-Ming

2018-05-01

Thiophenols are a class of highly toxic environmental pollutant, hence it is very necessary to monitor thiophenols in environment and living cells with an efficient and reliable method. Herein, a novel fluorescent probe for thiophenols has been developed, which exhibited a colorimetric and fluorescence turn-on dual response towards thiophenols with good selectivity and fast response. The sensing mechanism for thiophenols was attributed to nucleophilic substitution reaction, which was confirmed by HPLC. The probe exhibited good recovery (from 90% to 107%) and low limit of detection for thiophenols (37nM) in industrial wastewater. Moreover, the probe has been successfully employed to visualize thiophenol in living cells. Therefore, the fluorescent probe has good capability for monitoring thiophenols in environmental samples and biological systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Re-examining overlap between tactile and visual motion responses within hMT+ and STS

PubMed Central

Jiang, Fang; Beauchamp, Michael S.; Fine, Ione

2015-01-01

Here we examine overlap between tactile and visual motion BOLD responses within the human MT+ complex. Although several studies have reported tactile responses overlapping with hMT+, many used group average analyses, leaving it unclear whether these responses were restricted to sub-regions of hMT+. Moreover, previous studies either employed a tactile task or passive stimulation, leaving it unclear whether or not tactile responses in hMT+ are simply the consequence of visual imagery. Here we carried out a replication of one of the classic papers finding tactile responses in hMT+ (Hagen et al. 2002). We mapped MT and MST in individual subjects using visual field localizers. We then examined responses to tactile motion on the arm, either presented passively or in the presence of a visual task performed at fixation designed to minimize visualization of the concurrent tactile stimulation. To our surprise, without a visual task, we found only weak tactile motion responses in MT (6% of voxels showing tactile responses) and MST (2% of voxels). With an unrelated visual task designed to withdraw attention from the tactile modality, responses in MST reduced to almost nothing (<1% regions). Consistent with previous results, we did observe tactile responses in STS regions superior and anterior to hMT+. Despite the lack of individual overlap, group averaged responses produced strong spurious overlap between tactile and visual motion responses within hMT+ that resembled those observed in previous studies. The weak nature of tactile responses in hMT+ (and their abolition by withdrawal of attention) suggests that hMT+ may not serve as a supramodal motion processing module. PMID:26123373

Visual Working Memory Enhances the Neural Response to Matching Visual Input.

PubMed

Gayet, Surya; Guggenmos, Matthias; Christophel, Thomas B; Haynes, John-Dylan; Paffen, Chris L E; Van der Stigchel, Stefan; Sterzer, Philipp

2017-07-12

Visual working memory (VWM) is used to maintain visual information available for subsequent goal-directed behavior. The content of VWM has been shown to affect the behavioral response to concurrent visual input, suggesting that visual representations originating from VWM and from sensory input draw upon a shared neural substrate (i.e., a sensory recruitment stance on VWM storage). Here, we hypothesized that visual information maintained in VWM would enhance the neural response to concurrent visual input that matches the content of VWM. To test this hypothesis, we measured fMRI BOLD responses to task-irrelevant stimuli acquired from 15 human participants (three males) performing a concurrent delayed match-to-sample task. In this task, observers were sequentially presented with two shape stimuli and a retro-cue indicating which of the two shapes should be memorized for subsequent recognition. During the retention interval, a task-irrelevant shape (the probe) was briefly presented in the peripheral visual field, which could either match or mismatch the shape category of the memorized stimulus. We show that this probe stimulus elicited a stronger BOLD response, and allowed for increased shape-classification performance, when it matched rather than mismatched the concurrently memorized content, despite identical visual stimulation. Our results demonstrate that VWM enhances the neural response to concurrent visual input in a content-specific way. This finding is consistent with the view that neural populations involved in sensory processing are recruited for VWM storage, and it provides a common explanation for a plethora of behavioral studies in which VWM-matching visual input elicits a stronger behavioral and perceptual response. SIGNIFICANCE STATEMENT Humans heavily rely on visual information to interact with their environment and frequently must memorize such information for later use. Visual working memory allows for maintaining such visual information in the mind's eye after termination of its retinal input. It is hypothesized that information maintained in visual working memory relies on the same neural populations that process visual input. Accordingly, the content of visual working memory is known to affect our conscious perception of concurrent visual input. Here, we demonstrate for the first time that visual input elicits an enhanced neural response when it matches the content of visual working memory, both in terms of signal strength and information content. Copyright © 2017 the authors 0270-6474/17/376638-10$15.00/0.

Peptide-MHC-based nanomedicines for autoimmunity function as T-cell receptor microclustering devices

NASA Astrophysics Data System (ADS)

Singha, Santiswarup; Shao, Kun; Yang, Yang; Clemente-Casares, Xavier; Solé, Patricia; Clemente, Antonio; Blanco, Jesús; Dai, Qin; Song, Fayi; Liu, Shang Wan; Yamanouchi, Jun; Umeshappa, Channakeshava Sokke; Nanjundappa, Roopa Hebbandi; Detampel, Pascal; Amrein, Matthias; Fandos, César; Tanguay, Robert; Newbigging, Susan; Serra, Pau; Khadra, Anmar; Chan, Warren C. W.; Santamaria, Pere

2017-07-01

We have shown that nanoparticles (NPs) can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo. Nanoparticles coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHC) blunted autoimmune responses by triggering the differentiation and expansion of antigen-specific regulatory T cells in vivo. Here, we define the engineering principles impacting biological activity, detail a synthesis process yielding safe and stable compounds, and visualize how these nanomedicines interact with cognate T cells. We find that the triggering properties of pMHC-NPs are a function of pMHC intermolecular distance and involve the sustained assembly of large antigen receptor microclusters on murine and human cognate T cells. These compounds show no off-target toxicity in zebrafish embryos, do not cause haematological, biochemical or histological abnormalities, and are rapidly captured by phagocytes or processed by the hepatobiliary system. This work lays the groundwork for the design of ligand-based NP formulations to re-program in vivo cellular responses using nanotechnology.

Visualizing High-Efficiency HIV Transfer | Center for Cancer Research

Cancer.gov

The Human Immunodeficiency Virus (HIV), the causative agent of Acquired Immunodeficiency Syndrome (AIDS), infects and eventually kills CD4 receptor-expressing T cells, which are critical for proper immune system function. The gp120 protein on the surface of HIV particles is known to bind CD4 and a co-receptor, either CCR5 or CXCR4, leading to fusion of the virus and T cell membranes and infection of the cell. The most efficient means of viral infection occurs when an uninfected T cell interacts with a dendritic cell (DC) that has previously come in contact with HIV. Antigen presenting cells, such as DCs, normally circulate throughout the body binding or engulfing foreign material and presenting it to T cells to initiate an immune response. HIV takes advantage of this close cell-cell association to propagate, so knowing the cells’ spatial arrangement during viral transmission could elucidate novel modes of treatment.

Cellular profile of the peritumoral inflammatory infiltrate in squamous cells carcinoma of oral mucosa: Correlation with the expression of Ki67 and histologic grading

PubMed Central

Vieira, Fabricio LD; Vieira, Beatriz J; Guimaraes, Marco AM; Aarestrup, Fernando M

2008-01-01

Background Squamous cells carcinoma is the most important malignant tumor with primary site in the oral cavity and, given the great exposure of mucosa and lips to the etiologic factors of this neoplasm, its incidence is high. Investigation of the prognostic determinants is significant for the expectations of treatment proposal and cure of the patient. The local immune response represented by peritumoral inflammatory infiltrate is a possible prognostic factor. Methods In this study, oral mucosa samples of squamous cells carcinoma were analyzed, separated according to their histological classification as well as the phenotypical profile of the cells comprising the peritumoral inflammatory infiltrate was investigated by immunohistochemical method, in addiction, the cell proliferation index via protein Ki67 expression was determinated. Results The T lymphocytes made up most of this inflammatory infiltrate, and among these cells, there was a predominance of T CD8 lymphocytes relative to the T CD4 lymphocytes. The B lymhocytes were the second most visualized leucocyte cell type followed by macrophages and neutrophils. The immunohistochemical assessment of Ki-67 positive cells revealed a greater expression of this protein in samples of undifferentiated squamous cells carcinoma. Conclusion The results suggest that the cellular immune response is the main defense mechanism in squamous cells carcinoma of oral mucosa, expressed by the large number of T lymphocytes and macrophages, and that the greatest intensity of local response may be associated with the best prognosis. PMID:18764952

Simulator of human visual perception

NASA Astrophysics Data System (ADS)

Bezzubik, Vitalii V.; Belashenkov, Nickolai R.

2016-04-01

Difference of Circs (DoC) model allowing to simulate the response of neurons - ganglion cells as a reaction to stimuli is represented and studied in relation with representation of receptive fields of human retina. According to this model the response of neurons is reduced to execution of simple arithmetic operations and the results of these calculations well correlate with experimental data in wide range of stimuli parameters. The simplicity of the model and reliability of reproducing of responses allow to propose the conception of a device which can simulate the signals generated by ganglion cells as a reaction to presented stimuli. The signals produced according to DoC model are considered as a result of primary processing of information received from receptors independently of their type and may be sent to higher levels of nervous system of living creatures for subsequent processing. Such device may be used as a prosthesis for disabled organ.

Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging

PubMed Central

2011-01-01

Background Stem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate in vivo. Non-invasive cell tracking can provide knowledge about mechanisms responsible for functional improvement of host tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label and visualize various cell types with magnetic resonance imaging (MRI). In this study we performed experiments designed to investigate the biological properties, including proliferation, viability and differentiation capacity of mesenchymal cells (MSCs) labeled with clinically approved SPIONs. Results Rat and mouse MSCs were isolated, cultured, and incubated with dextran-covered SPIONs (ferumoxide) alone or with poly-L-lysine (PLL) or protamine chlorhydrate for 4 or 24 hrs. Labeling efficiency was evaluated by dextran immunocytochemistry and MRI. Cell proliferation and viability were evaluated in vitro with Ki67 immunocytochemistry and live/dead assays. Ferumoxide-labeled MSCs could be induced to differentiate to adipocytes, osteocytes and chondrocytes. We analyzed ferumoxide retention in MSCs with or without mitomycin C pretreatment. Approximately 95% MSCs were labeled when incubated with ferumoxide for 4 or 24 hrs in the presence of PLL or protamine, whereas labeling of MSCs incubated with ferumoxide alone was poor. Proliferative capacity was maintained in MSCs incubated with ferumoxide and PLL for 4 hrs, however, after 24 hrs it was reduced. MSCs incubated with ferumoxide and protamine were efficiently visualized by MRI; they maintained proliferation and viability for up to 7 days and remained competent to differentiate. After 21 days MSCs pretreated with mitomycin C still showed a large number of ferumoxide-labeled cells. Conclusions The efficient and long lasting uptake and retention of SPIONs by MSCs using a protocol employing ferumoxide and protamine may be applicable to patients, since both ferumoxides and protamine are approved for human use. PMID:21542946

Long adaptation reveals mostly attractive shifts of orientation tuning in cat primary visual cortex.

PubMed

Ghisovan, N; Nemri, A; Shumikhina, S; Molotchnikoff, S

2009-12-15

In the adult brain, sensory cortical neurons undergo transient changes of their response properties following prolonged exposure to an appropriate stimulus (adaptation). In cat V1, orientation-selective cells shift their preferred orientation after being adapted to a non-preferred orientation. There are conflicting reports as to the direction of those shifts, towards (attractive) or away (repulsive) from the adapter. Moreover, the mechanisms underlying attractive shifts remain unexplained. In the present investigation we show that attractive shifts are the most frequent outcome of a 12 min adaptation. Overall, cells displaying selectivity for oblique orientations exhibit significantly larger shifts than cells tuned to cardinal orientations. In addition, cells selective to cardinal orientations had larger shift amplitudes when the absolute difference between the original preferred orientation and the adapting orientation increased. Conversely, cells tuned to oblique orientations exhibited larger shift amplitudes when this absolute orientation difference was narrower. Hence, neurons tuned to oblique contours appear to show more plasticity in response to small perturbations. Two different mechanisms appear to produce attractive and repulsive orientation shifts. Attractive shifts result from concurrent response depression on the non-adapted flank and selective response facilitation on the adapted flank of the orientation tuning curve. In contrast, repulsive shifts are caused solely by response depression on the adapted flank. We suggest that an early mechanism leads to repulsive shifts while attractive shifts engage a subsequent late facilitation. A potential role for attractive shifts may be improved stimulus discrimination around the adapting orientation.

Magnetic Labeling of Activated Microglia in Experimental Gliomas1

PubMed Central

Fleige, Gerrit; Nolte, Christiane; Synowitz, Michael; Seeberger, Florian; Kettenmann, Helmut; Zimmer, Claus

2001-01-01

Abstract Microglia, as intrinsic immunoeffector cells of the central nervous system (CNS), play a very sensitive, crucial role in the response to almost any brain pathology where they are activated to a phagocytic state. Based on the characteristic features of activated microglia, we investigated whether these cells can be visualized with magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxides (USPIOs). The hypothesis of this study was that MR microglia visualization could not only reveal the extent of the tumor, but also allow for assessing the status of immunologic defense. Using USPIOs in cell culture experiments and in a rat glioma model, we showed that microglia can be labeled magnetically. Labeled microglia are detected by confocal microscopy within and around tumors in a typical border-like pattern. Quantitative in vitro studies revealed that microglia internalize amounts of USPIOs that are significantly higher than those incorporated by tumor cells and astrocytes. Labeled microglia can be detected and quantified with MRI in cell phantoms, and the extent of the tumor can be seen in glioma-bearing rats in vivo. We conclude that magnetic labeling of microglia provides a potential tool for MRI of gliomas, which reflects tumor morphology precisely. Furthermore, the results suggest that MRI may yield functional data on the immunologic reaction of the CNS. PMID:11774031

Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melo, Rossana C.N., E-mail: rossana.melo@ufjf.edu.br; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215; Weller, Peter F.

Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombreromore » Vesicles – EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. - Highlights: • Application of EM to understand the complex secretory pathway in human eosinophils. • EM techniques reveal an active vesicular system associated with secretory granules. • Tubular vesicles are involved in the transport of granule-derived immune mediators.« less

Subcortical orientation biases explain orientation selectivity of visual cortical cells.

PubMed

Vidyasagar, Trichur R; Jayakumar, Jaikishan; Lloyd, Errol; Levichkina, Ekaterina V

2015-04-01

The primary visual cortex of carnivores and primates shows an orderly progression of domains of neurons that are selective to a particular orientation of visual stimuli such as bars and gratings. We recorded from single-thalamic afferent fibers that terminate in these domains to address the issue whether the orientation sensitivity of these fibers could form the basis of the remarkable orientation selectivity exhibited by most cortical cells. We first performed optical imaging of intrinsic signals to obtain a map of orientation domains on the dorsal aspect of the anaesthetized cat's area 17. After confirming using electrophysiological recordings the orientation preferences of single neurons within one or two domains in each animal, we pharmacologically silenced the cortex to leave only the afferent terminals active. The inactivation of cortical neurons was achieved by the superfusion of either kainic acid or muscimol. Responses of single geniculate afferents were then recorded by the use of high impedance electrodes. We found that the orientation preferences of the afferents matched closely with those of the cells in the orientation domains that they terminated in (Pearson's r = 0.633, n = 22, P = 0.002). This suggests a possible subcortical origin for cortical orientation selectivity. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

PubMed

Schur, Rebecca M; Gao, Songqi; Yu, Guanping; Chen, Yu; Maeda, Akiko; Palczewski, Krzysztof; Lu, Zheng-Rong

2018-01-24

No clinically approved therapies are currently available that prevent the onset of photoreceptor death in retinal degeneration. Signaling between retinal neurons is regulated by the release and uptake of neurotransmitters, wherein GABA is the main inhibitory neurotransmitter. In this work, novel 3-chloropropiophenone derivatives and the clinical anticonvulsants tiagabine and vigabatrin were tested to modulate GABA signaling and protect against light-induced retinal degeneration. Abca4 -/- Rdh8 -/- mice, an accelerated model of retinal degeneration, were exposed to intense light after prophylactic injections of one of these compounds. Imaging and functional assessments of the retina indicated that these compounds successfully protected photoreceptor cells from degeneration to maintain a full-visual-field response. Furthermore, these compounds demonstrated a strong safety profile in wild-type mice and did not compromise visual function or damage the retina, despite repeated administration. These results indicate that modulating inhibitory GABA signaling can offer prophylactic protection against light-induced retinal degeneration.-Schur, R. M., Gao, S., Yu, G., Chen, Y., Maeda, A., Palczewski, K., Lu, Z.-R. New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

Assessment of the reliability of standard automated perimetry in regions of glaucomatous damage.

PubMed

Gardiner, Stuart K; Swanson, William H; Goren, Deborah; Mansberger, Steven L; Demirel, Shaban

2014-07-01

Visual field testing uses high-contrast stimuli in areas of severe visual field loss. However, retinal ganglion cells saturate with high-contrast stimuli, suggesting that the probability of detecting perimetric stimuli may not increase indefinitely as contrast increases. Driven by this concept, this study examines the lower limit of perimetric sensitivity for reliable testing by standard automated perimetry. Evaluation of a diagnostic test. A total of 34 participants with moderate to severe glaucoma; mean deviation at their last clinic visit averaged -10.90 dB (range, -20.94 to -3.38 dB). A total of 75 of the 136 locations tested had a perimetric sensitivity of ≤ 19 dB. Frequency-of-seeing curves were constructed at 4 nonadjacent visual field locations by the Method of Constant Stimuli (MOCS), using 35 stimulus presentations at each of 7 contrasts. Locations were chosen a priori and included at least 2 with glaucomatous damage but a sensitivity of ≥ 6 dB. Cumulative Gaussian curves were fit to the data, first assuming a 5% false-negative rate and subsequently allowing the asymptotic maximum response probability to be a free parameter. The strength of the relation (R(2)) between perimetric sensitivity (mean of last 2 clinic visits) and MOCS sensitivity (from the experiment) for all locations with perimetric sensitivity within ± 4 dB of each selected value, at 0.5 dB intervals. Bins centered at sensitivities ≥ 19 dB always had R(2) >0.1. All bins centered at sensitivities ≤ 15 dB had R(2) <0.1, an indication that sensitivities are unreliable. No consistent conclusions could be drawn between 15 and 19 dB. At 57 of the 81 locations with perimetric sensitivity <19 dB, including 49 of the 63 locations ≤ 15 dB, the fitted asymptotic maximum response probability was <80%, consistent with the hypothesis of response saturation. At 29 of these locations the asymptotic maximum was <50%, and so contrast sensitivity (50% response rate) is undefined. Clinical visual field testing may be unreliable when visual field locations have sensitivity below approximately 15 to 19 dB because of a reduction in the asymptotic maximum response probability. Researchers and clinicians may have difficulty detecting worsening sensitivity in these visual field locations, and this difficulty may occur commonly in patients with glaucoma with moderate to severe glaucomatous visual field loss. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Arterial spin labeling fMRI measurements of decreased blood flow in primary visual cortex correlates with decreased visual function in human glaucoma.

PubMed

Duncan, Robert O; Sample, Pamela A; Bowd, Christopher; Weinreb, Robert N; Zangwill, Linda M

2012-05-01

Altered metabolic activity has been identified as a potential contributing factor to the neurodegeneration associated with primary open angle glaucoma (POAG). Consequently, we sought to determine whether there is a relationship between the loss of visual function in human glaucoma and resting blood perfusion within primary visual cortex (V1). Arterial spin labeling (ASL) functional magnetic resonance imaging (fMRI) was conducted in 10 participants with POAG. Resting cerebral blood flow (CBF) was measured from dorsal and ventral V1. Behavioral measurements of visual function were obtained using standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology perimetry (FDT). Measurements of CBF were compared to differences in visual function for the superior and inferior hemifield. Differences in CBF between ventral and dorsal V1 were correlated with differences in visual function for the superior versus inferior visual field. A statistical bootstrapping analysis indicated that the observed correlations between fMRI responses and measurements of visual function for SAP (r=0.49), SWAP (r=0.63), and FDT (r=0.43) were statistically significant (all p<0.05). Resting blood perfusion in human V1 is correlated with the loss of visual function in POAG. Altered CBF may be a contributing factor to glaucomatous optic neuropathy, or it may be an indication of post-retinal glaucomatous neurodegeneration caused by damage to the retinal ganglion cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Melanopsin and the Non-visual Photochemistry in the Inner Retina of Vertebrates.

PubMed

Díaz, Nicolás M; Morera, Luis P; Guido, Mario E

2016-01-01

Melanopsin (Opn4), a member of the G-protein-coupled receptor family, is a vitamin A-based opsin in the vertebrate retina that has been shown to be involved in the synchronization of circadian rhythms, pupillary light reflexes, melatonin suppression and other light-regulated tasks. In nonmammalian vertebrates there are two Opn4 genes, Opn4m and Opn4x, the mammalian and Xenopus orthologs respectively. Opn4x is only expressed in nonmammalian vertebrates including reptiles, fish and birds, while Opn4m is found in a subset of retinal ganglion cells (RGCs), the intrinsically photosensitive (ip) RGCs of the inner retina of both mammals and nonmammalian vertebrates. All opsins described utilize retinaldehyde as chromophore, photoisomerized from 11-cis- to all-trans-retinal upon light exposure. Visual retinal photoreceptor cones and rods, responsible for day and night vision respectively, recycle retinoids through a process called the visual cycle that involves the retinal pigment epithelium or glial Müller cells. Although Opn4 has been characterized as a bistable photopigment, little is known about the mechanism/s involved in its chromophore regeneration. In this review, we will attempt to shed light on the visual cycle taking place in the inner retina and discuss the state of the art in the nonvisual photochemistry of vertebrates. © 2015 The American Society of Photobiology.

Transplantation of reprogrammed embryonic stem cells improves visual function in a mouse model for retinitis pigmentosa.

PubMed

Wang, Nan-Kai; Tosi, Joaquin; Kasanuki, Jennifer Mie; Chou, Chai Lin; Kong, Jian; Parmalee, Nancy; Wert, Katherine J; Allikmets, Rando; Lai, Chi-Chun; Chien, Chung-Liang; Nagasaki, Takayuki; Lin, Chyuan-Sheng; Tsang, Stephen H

2010-04-27

To study whether C57BL/6J-Tyr/J (C2J) mouse embryonic stem (ES) cells can differentiate into retinal pigment epithelial (RPE) cells in vitro and then restore retinal function in a model for retinitis pigmentosa: Rpe65/Rpe65 C57BL6 mice. Yellow fluorescent protein (YFP)-labeled C2J ES cells were induced to differentiate into RPE-like structures on PA6 feeders. RPE-specific markers are expressed from differentiated cells in vitro. After differentiation, ES cell-derived RPE-like cells were transplanted into the subretinal space of postnatal day 5 Rpe65/Rpe65 mice. Live imaging of YFP-labeled C2J ES cells demonstrated survival of the graft. Electroretinograms (ERGs) were performed on transplanted mice to evaluate the functional outcome of transplantation. RPE-like cells derived from ES cells sequentially express multiple RPE-specific markers. After transplantation, YFP-labeled cells can be tracked with live imaging for as long as 7 months. Although more than half of the mice were complicated with retinal detachments or tumor development, one fourth of the mice showed increased electroretinogram responses in the transplanted eyes. Rpe65/Rpe65 mice transplanted with RPE-like cells showed significant visual recovery during a 7-month period, whereas those injected with saline, PA6 feeders, or undifferentiated ES cells showed no rescue. ES cells can differentiate, morphologically, and functionally, into RPE-like cells. Based on these findings, differentiated ES cells have the potential for the development of new therapeutic approaches for RPE-specific diseases such as certain forms of retinitis pigmentosa and macular degeneration. Nevertheless, stringent control of retinal detachment and teratoma development will be necessary before initiation of treatment trials.

Cooperative synchronized assemblies enhance orientation discrimination.

PubMed

Samonds, Jason M; Allison, John D; Brown, Heather A; Bonds, A B

2004-04-27

There is no clear link between the broad tuning of single neurons and the fine behavioral capabilities of orientation discrimination. We recorded from populations of cells in the cat visual cortex (area 17) to examine whether the joint activity of cells can support finer discrimination than found in individual responses. Analysis of joint firing yields a substantial advantage (i.e., cooperation) in fine-angle discrimination. This cooperation increases to more considerable levels as the population of an assembly is increased. The cooperation in a population of six cells provides encoding of orientation with an information advantage that is at least 2-fold in terms of requiring either fewer cells or less time than independent coding. This cooperation suggests that correlated or synchronized activity can increase information.

Audio-Visual Integration in a Redundant Target Paradigm: A Comparison between Rhesus Macaque and Man

PubMed Central

Bremen, Peter; Massoudi, Rooholla; Van Wanrooij, Marc M.; Van Opstal, A. J.

2017-01-01

The mechanisms underlying multi-sensory interactions are still poorly understood despite considerable progress made since the first neurophysiological recordings of multi-sensory neurons. While the majority of single-cell neurophysiology has been performed in anesthetized or passive-awake laboratory animals, the vast majority of behavioral data stems from studies with human subjects. Interpretation of neurophysiological data implicitly assumes that laboratory animals exhibit perceptual phenomena comparable or identical to those observed in human subjects. To explicitly test this underlying assumption, we here characterized how two rhesus macaques and four humans detect changes in intensity of auditory, visual, and audio-visual stimuli. These intensity changes consisted of a gradual envelope modulation for the sound, and a luminance step for the LED. Subjects had to detect any perceived intensity change as fast as possible. By comparing the monkeys' results with those obtained from the human subjects we found that (1) unimodal reaction times differed across modality, acoustic modulation frequency, and species, (2) the largest facilitation of reaction times with the audio-visual stimuli was observed when stimulus onset asynchronies were such that the unimodal reactions would occur at the same time (response, rather than physical synchrony), and (3) the largest audio-visual reaction-time facilitation was observed when unimodal auditory stimuli were difficult to detect, i.e., at slow unimodal reaction times. We conclude that despite marked unimodal heterogeneity, similar multisensory rules applied to both species. Single-cell neurophysiology in the rhesus macaque may therefore yield valuable insights into the mechanisms governing audio-visual integration that may be informative of the processes taking place in the human brain. PMID:29238295

Audio-Visual Integration in a Redundant Target Paradigm: A Comparison between Rhesus Macaque and Man.

PubMed

Bremen, Peter; Massoudi, Rooholla; Van Wanrooij, Marc M; Van Opstal, A J

2017-01-01

The mechanisms underlying multi-sensory interactions are still poorly understood despite considerable progress made since the first neurophysiological recordings of multi-sensory neurons. While the majority of single-cell neurophysiology has been performed in anesthetized or passive-awake laboratory animals, the vast majority of behavioral data stems from studies with human subjects. Interpretation of neurophysiological data implicitly assumes that laboratory animals exhibit perceptual phenomena comparable or identical to those observed in human subjects. To explicitly test this underlying assumption, we here characterized how two rhesus macaques and four humans detect changes in intensity of auditory, visual, and audio-visual stimuli. These intensity changes consisted of a gradual envelope modulation for the sound, and a luminance step for the LED. Subjects had to detect any perceived intensity change as fast as possible. By comparing the monkeys' results with those obtained from the human subjects we found that (1) unimodal reaction times differed across modality, acoustic modulation frequency, and species, (2) the largest facilitation of reaction times with the audio-visual stimuli was observed when stimulus onset asynchronies were such that the unimodal reactions would occur at the same time (response, rather than physical synchrony), and (3) the largest audio-visual reaction-time facilitation was observed when unimodal auditory stimuli were difficult to detect, i.e., at slow unimodal reaction times. We conclude that despite marked unimodal heterogeneity, similar multisensory rules applied to both species. Single-cell neurophysiology in the rhesus macaque may therefore yield valuable insights into the mechanisms governing audio-visual integration that may be informative of the processes taking place in the human brain.

Bioplausible multiscale filtering in retino-cortical processing as a mechanism in perceptual grouping.

PubMed

Nematzadeh, Nasim; Powers, David M W; Lewis, Trent W

2017-12-01

Why does our visual system fail to reconstruct reality, when we look at certain patterns? Where do Geometrical illusions start to emerge in the visual pathway? How far should we take computational models of vision with the same visual ability to detect illusions as we do? This study addresses these questions, by focusing on a specific underlying neural mechanism involved in our visual experiences that affects our final perception. Among many types of visual illusion, 'Geometrical' and, in particular, 'Tilt Illusions' are rather important, being characterized by misperception of geometric patterns involving lines and tiles in combination with contrasting orientation, size or position. Over the last decade, many new neurophysiological experiments have led to new insights as to how, when and where retinal processing takes place, and the encoding nature of the retinal representation that is sent to the cortex for further processing. Based on these neurobiological discoveries, we provide computer simulation evidence from modelling retinal ganglion cells responses to some complex Tilt Illusions, suggesting that the emergence of tilt in these illusions is partially related to the interaction of multiscale visual processing performed in the retina. The output of our low-level filtering model is presented for several types of Tilt Illusion, predicting that the final tilt percept arises from multiple-scale processing of the Differences of Gaussians and the perceptual interaction of foreground and background elements. The model is a variation of classical receptive field implementation for simple cells in early stages of vision with the scales tuned to the object/texture sizes in the pattern. Our results suggest that this model has a high potential in revealing the underlying mechanism connecting low-level filtering approaches to mid- and high-level explanations such as 'Anchoring theory' and 'Perceptual grouping'.

Axonal Conduction Delays, Brain State, and Corticogeniculate Communication.

PubMed

Stoelzel, Carl R; Bereshpolova, Yulia; Alonso, Jose-Manuel; Swadlow, Harvey A

2017-06-28

Thalamocortical conduction times are short, but layer 6 corticothalamic axons display an enormous range of conduction times, some exceeding 40-50 ms. Here, we investigate (1) how axonal conduction times of corticogeniculate (CG) neurons are related to the visual information conveyed to the thalamus, and (2) how alert versus nonalert awake brain states affect visual processing across the spectrum of CG conduction times. In awake female Dutch-Belted rabbits, we found 58% of CG neurons to be visually responsive, and 42% to be unresponsive. All responsive CG neurons had simple, orientation-selective receptive fields, and generated sustained responses to stationary stimuli. CG axonal conduction times were strongly related to modulated firing rates (F1 values) generated by drifting grating stimuli, and their associated interspike interval distributions, suggesting a continuum of visual responsiveness spanning the spectrum of axonal conduction times. CG conduction times were also significantly related to visual response latency, contrast sensitivity (C-50 values), directional selectivity, and optimal stimulus velocity. Increasing alertness did not cause visually unresponsive CG neurons to become responsive and did not change the response linearity (F1/F0 ratios) of visually responsive CG neurons. However, for visually responsive CG neurons, increased alertness nearly doubled the modulated response amplitude to optimal visual stimulation (F1 values), significantly shortened response latency, and dramatically increased response reliability. These effects of alertness were uniform across the broad spectrum of CG axonal conduction times. SIGNIFICANCE STATEMENT Corticothalamic neurons of layer 6 send a dense feedback projection to thalamic nuclei that provide input to sensory neocortex. While sensory information reaches the cortex after brief thalamocortical axonal delays, corticothalamic axons can exhibit conduction delays of <2 ms to 40-50 ms. Here, in the corticogeniculate visual system of awake rabbits, we investigate the functional significance of this axonal diversity, and the effects of shifting alert/nonalert brain states on corticogeniculate processing. We show that axonal conduction times are strongly related to multiple visual response properties, suggesting a continuum of visual responsiveness spanning the spectrum of corticogeniculate axonal conduction times. We also show that transitions between awake brain states powerfully affect corticogeniculate processing, in some ways more strongly than in layer 4. Copyright © 2017 the authors 0270-6474/17/376342-17$15.00/0.

Visual responses of ganglion cells of a New-World primate, the capuchin monkey, Cebus apella.

PubMed

Lee, B B; Silveira, L C; Yamada, E S; Hunt, D M; Kremers, J; Martin, P R; Troy, J B; da Silva-Filho, M

2000-11-01

1. The genetic basis of colour vision in New-World primates differs from that in humans and other Old-World primates. Most New-World primate species show a polymorphism; all males are dichromats and most females trichromats. 2. In the retina of Old-World primates such as the macaque, the physiological correlates of trichromacy are well established. Comparison of the retinae in New- and Old-World species may help constrain hypotheses as to the evolution of colour vision and the pathways associated with it. 3. Ganglion cell behaviour was recorded from trichromatic and dichromatic members of a New-World species (the capuchin monkey, Cebus apella) and compared with macaque data. Despite some differences in quantitative detail (such as a temporal response extended to higher frequencies), results from trichromatic animals strongly resembled those from the macaque. 4. In particular, cells of the parvocellular (PC) pathway showed characteristic frequency-dependent changes in responsivity to luminance and chromatic modulation, cells of the magnocellular (MC) pathway showed frequency-doubled responses to chromatic modulation, and the surround of MC cells received a chromatic input revealed on changing the phase of heterochromatically modulated lights. 5. Ganglion cells of dichromats were colour-blind versions of those of trichromats. 6. This strong physiological homology is consistent with a common origin of trichromacy in New- and Old-World monkeys; in the New-World primate the presence of two pigments in the middle-to-long wavelength range permits full expression of the retinal mechanisms of trichromatic vision.

Subadditive responses to extremely short blue and green pulsed light on visual evoked potentials, pupillary constriction and electroretinograms.

PubMed

Lee, Soomin; Uchiyama, Yuria; Shimomura, Yoshihiro; Katsuura, Tetsuo

2017-11-17

The simultaneous exposure to blue and green light was reported to result in less melatonin suppression than monochromatic exposure to blue or green light. Here, we conducted an experiment using extremely short blue- and green-pulsed light to examine their visual and nonvisual effects on visual evoked potentials (VEPs), pupillary constriction, electroretinograms (ERGs), and subjective evaluations. Twelve adult male subjects were exposed to three light conditions: blue-pulsed light (2.5-ms pulse width), green-pulsed light (2.5-ms pulse width), and simultaneous blue- and green-pulsed light with white background light. We measured the subject's pupil diameter three times in each condition. Then, after 10 min of rest, the subject was exposed to the same three light conditions. We measured the averaged ERG and VEP during 210 pulsed-light exposures in each condition. We also determined subjective evaluations using a visual analog scale (VAS) method. The pupillary constriction during the simultaneous exposure to blue- and green-pulsed light was significantly lower than that during the blue-pulsed light exposure despite the double irradiance intensity of the combination. We also found that the b/|a| wave of the ERGs during the simultaneous exposure to blue- and green-pulsed light was lower than that during the blue-pulsed light exposure. We confirmed the subadditive response to pulsed light on pupillary constriction and ERG. However, the P100 of the VEPs during the blue-pulsed light were smaller than those during the simultaneous blue- and green-pulsed light and green-pulsed light, indicating that the P100 amplitude might depend on the luminance of light. Our findings demonstrated the effect of the subadditive response to extremely short pulsed light on pupillary constriction and ERG responses. The effects on ipRGCs by the blue-pulsed light exposure are apparently reduced by the simultaneous irradiation of green light. The blue versus yellow (b/y) bipolar cells in the retina might be responsible for this phenomenon.

Mouse strain and injection site are crucial for detecting linked suppression in transplant recipients by trans-vivo DTH assay.

PubMed

Burlingham, W J; Jankowska-Gan, E

2007-02-01

Chemokine-driven accumulation of lymphocytes, mononuclear and polymorphonuclear proinflammatory cells in antigenic tissue sites is a key feature of several types of T-cell-dependent autoimmunity and transplant rejection pathology. It is now clear that the immune system expends considerable energy to control this process, exemplified by the sequential layers of regulatory cell input, both innate and adaptive, designed to prevent a classical Type IV or 'delayed-type' hypersensitivity (DTH) reaction from occurring in the visual field of the eye. Yet, despite an abundance of in vitro assays currently available to the human T-cell immunologist, none of them adequately models the human DTH response and its various control features. The theme of this article is that it is relatively easy to model the effector side of the human DTH response with xenogeneic adoptive transfer models. However, we show that in order to detect inhibition of a recall DTH in response to colocalized donor antigen (linked suppression)--a characteristic feature of peripheral tolerance to an organ transplant--both the challenge site and the immunocompetence of the mouse adoptive host are critical factors limiting the sensitivity of the trans-vivo DTH test.

Revealing the cell-material interface with nanometer resolution by FIB-SEM

PubMed Central

Santoro, Francesca; Zhao, Wenting; Joubert, Lydia-Marie; Duan, Liting; Schnitker, Jan; van de Burgt, Yoeri; Lou, Hsin-Ya; Liu, Bofei; Salleo, Alberto; Cui, Lifeng; Cui, Yi; Cui, Bianxiao

2018-01-01

The interface between cells and non-biological surfaces regulates cell attachment, chronic tissue responses, and ultimately the success of medical implants or biosensors. Clinical and laboratory studies show that topological features of the surface profoundly influences cellular responses, e.g. titanium surfaces with nano- and microtopographical structures enhance osteoblast attachment and host-implant integration as compare to smooth surface. To understand how cells and tissues respond to different topographical features, it is of critical importance to directly visualize the cell-materials interface at the relevant nanometer length scale. Here, we present a new method for in situ examination of the cell-to-material interface at any desired location, based on focused-ion beam milling and scanning electron microscopy imaging (FIB-SEM) to resolve the cell membrane-to-material interface with 10 nm resolution. By examining how cell membranes interact with topographical features such as nanoscale protrusions or invaginations, we discovered that the cell membrane readily deforms inward and wraps around protruding structures, but hardly deforms outward to contour invaginating structures. This asymmetric membrane response (inward vs. outward deformation) causes the cleft width between the cell membrane and the nanostructure surface to vary for more than an order of magnitude. Our results suggest that surface topology is a crucial consideration for the development of medical implants or biosensors whose performances are strongly influenced by the cell-to-material interface. We anticipate that the method can be used to explore the direct interaction of cells/tissue with medical devices such as metal implants in the future. PMID:28682058

Müller Glial Cell-Provided Cellular Light Guidance through the Vital Guinea-Pig Retina

PubMed Central

Agte, Silke; Junek, Stephan; Matthias, Sabrina; Ulbricht, Elke; Erdmann, Ines; Wurm, Antje; Schild, Detlev; Käs, Josef A.; Reichenbach, Andreas

2011-01-01

In vertebrate eyes, images are projected onto an inverted retina where light passes all retinal layers on its way to the photoreceptor cells. Light scattering within this tissue should impair vision. We show that radial glial (Müller) cells in the living retina minimize intraretinal light scatter and conserve the diameter of a beam that hits a single Müller cell endfoot. Thus, light arrives at individual photoreceptors with high intensity. This leads to an optimized signal/noise ratio, which increases visual sensitivity and contrast. Moreover, we show that the ratio between Müller cells and cones—responsible for acute vision—is roughly 1. This suggests that high spatiotemporal resolution may be achieved by each cone receiving its part of the image via its individual Müller cell-light guide. PMID:22261048

A Neural Theory of Visual Attention: Bridging Cognition and Neurophysiology

ERIC Educational Resources Information Center

Bundesen, Claus; Habekost, Thomas; Kyllingsbaek, Soren

2005-01-01

A neural theory of visual attention (NTVA) is presented. NTVA is a neural interpretation of C. Bundesen's (1990) theory of visual attention (TVA). In NTVA, visual processing capacity is distributed across stimuli by dynamic remapping of receptive fields of cortical cells such that more processing resources (cells) are devoted to behaviorally…

Single-cell-based system to monitor carrier driven cellular auxin homeostasis

PubMed Central

2013-01-01

Background Abundance and distribution of the plant hormone auxin play important roles in plant development. Besides other metabolic processes, various auxin carriers control the cellular level of active auxin and, hence, are major regulators of cellular auxin homeostasis. Despite the developmental importance of auxin transporters, a simple medium-to-high throughput approach to assess carrier activities is still missing. Here we show that carrier driven depletion of cellular auxin correlates with reduced nuclear auxin signaling in tobacco Bright Yellow-2 (BY-2) cell cultures. Results We developed an easy to use transient single-cell-based system to detect carrier activity. We use the relative changes in signaling output of the auxin responsive promoter element DR5 to indirectly visualize auxin carrier activity. The feasibility of the transient approach was demonstrated by pharmacological and genetic interference with auxin signaling and transport. As a proof of concept, we provide visual evidence that the prominent auxin transport proteins PIN-FORMED (PIN)2 and PIN5 regulate cellular auxin homeostasis at the plasma membrane and endoplasmic reticulum (ER), respectively. Our data suggest that PIN2 and PIN5 have different sensitivities to the auxin transport inhibitor 1-naphthylphthalamic acid (NPA). Also the putative PIN-LIKES (PILS) auxin carrier activity at the ER is insensitive to NPA in our system, indicating that NPA blocks intercellular, but not intracellular auxin transport. Conclusions This single-cell-based system is a useful tool by which the activity of putative auxin carriers, such as PINs, PILS and WALLS ARE THIN1 (WAT1), can be indirectly visualized in a medium-to-high throughput manner. Moreover, our single cell system might be useful to investigate also other hormonal signaling pathways, such as cytokinin. PMID:23379388

Adaptive Acceleration of Visually Evoked Smooth Eye Movements in Mice

PubMed Central

2016-01-01

The optokinetic response (OKR) consists of smooth eye movements following global motion of the visual surround, which suppress image slip on the retina for visual acuity. The effective performance of the OKR is limited to rather slow and low-frequency visual stimuli, although it can be adaptably improved by cerebellum-dependent mechanisms. To better understand circuit mechanisms constraining OKR performance, we monitored how distinct kinematic features of the OKR change over the course of OKR adaptation, and found that eye acceleration at stimulus onset primarily limited OKR performance but could be dramatically potentiated by visual experience. Eye acceleration in the temporal-to-nasal direction depended more on the ipsilateral floccular complex of the cerebellum than did that in the nasal-to-temporal direction. Gaze-holding following the OKR was also modified in parallel with eye-acceleration potentiation. Optogenetic manipulation revealed that synchronous excitation and inhibition of floccular complex Purkinje cells could effectively accelerate eye movements in the nasotemporal and temporonasal directions, respectively. These results collectively delineate multiple motor pathways subserving distinct aspects of the OKR in mice and constrain hypotheses regarding cellular mechanisms of the cerebellum-dependent tuning of movement acceleration. SIGNIFICANCE STATEMENT Although visually evoked smooth eye movements, known as the optokinetic response (OKR), have been studied in various species for decades, circuit mechanisms of oculomotor control and adaptation remain elusive. In the present study, we assessed kinematics of the mouse OKR through the course of adaptation training. Our analyses revealed that eye acceleration at visual-stimulus onset primarily limited working velocity and frequency range of the OKR, yet could be dramatically potentiated during OKR adaptation. Potentiation of eye acceleration exhibited different properties between the nasotemporal and temporonasal OKRs, indicating distinct visuomotor circuits underlying the two. Lesions and optogenetic manipulation of the cerebellum provide constraints on neural circuits mediating visually driven eye acceleration and its adaptation. PMID:27335412

A Simple Network Architecture Accounts for Diverse Reward Time Responses in Primary Visual Cortex.

PubMed

Huertas, Marco A; Hussain Shuler, Marshall G; Shouval, Harel Z

2015-09-16

Many actions performed by animals and humans depend on an ability to learn, estimate, and produce temporal intervals of behavioral relevance. Exemplifying such learning of cued expectancies is the observation of reward-timing activity in the primary visual cortex (V1) of rodents, wherein neural responses to visual cues come to predict the time of future reward as behaviorally experienced in the past. These reward-timing responses exhibit significant heterogeneity in at least three qualitatively distinct classes: sustained increase or sustained decrease in firing rate until the time of expected reward, and a class of cells that reach a peak in firing at the expected delay. We elaborate upon our existing model by including inhibitory and excitatory units while imposing simple connectivity rules to demonstrate what role these inhibitory elements and the simple architectures play in sculpting the response dynamics of the network. We find that simply adding inhibition is not sufficient for obtaining the different distinct response classes, and that a broad distribution of inhibitory projections is necessary for obtaining peak-type responses. Furthermore, although changes in connection strength that modulate the effects of inhibition onto excitatory units have a strong impact on the firing rate profile of these peaked responses, the network exhibits robustness in its overall ability to predict the expected time of reward. Finally, we demonstrate how the magnitude of expected reward can be encoded at the expected delay in the network and how peaked responses express this reward expectancy. Heterogeneity in single-neuron responses is a common feature of neuronal systems, although sometimes, in theoretical approaches, it is treated as a nuisance and seldom considered as conveying a different aspect of a signal. In this study, we focus on the heterogeneous responses in the primary visual cortex of rodents trained with a predictable delayed reward time. We describe under what conditions this heterogeneity can arise by self-organization, and what information it can convey. This study, while focusing on a specific system, provides insight onto how heterogeneity can arise in general while also shedding light onto mechanisms of reinforcement learning using realistic biological assumptions. Copyright © 2015 the authors 0270-6474/15/3512659-14$15.00/0.

Novel integrative genomic tool for interrogating lithium response in bipolar disorder

PubMed Central

Hunsberger, J G; Chibane, F L; Elkahloun, A G; Henderson, R; Singh, R; Lawson, J; Cruceanu, C; Nagarajan, V; Turecki, G; Squassina, A; Medeiros, C D; Del Zompo, M; Rouleau, G A; Alda, M; Chuang, D-M

2015-01-01

We developed a novel integrative genomic tool called GRANITE (Genetic Regulatory Analysis of Networks Investigational Tool Environment) that can effectively analyze large complex data sets to generate interactive networks. GRANITE is an open-source tool and invaluable resource for a variety of genomic fields. Although our analysis is confined to static expression data, GRANITE has the capability of evaluating time-course data and generating interactive networks that may shed light on acute versus chronic treatment, as well as evaluating dose response and providing insight into mechanisms that underlie therapeutic versus sub-therapeutic doses or toxic doses. As a proof-of-concept study, we investigated lithium (Li) response in bipolar disorder (BD). BD is a severe mood disorder marked by cycles of mania and depression. Li is one of the most commonly prescribed and decidedly effective treatments for many patients (responders), although its mode of action is not yet fully understood, nor is it effective in every patient (non-responders). In an in vitro study, we compared vehicle versus chronic Li treatment in patient-derived lymphoblastoid cells (LCLs) (derived from either responders or non-responders) using both microRNA (miRNA) and messenger RNA gene expression profiling. We present both Li responder and non-responder network visualizations created by our GRANITE analysis in BD. We identified by network visualization that the Let-7 family is consistently downregulated by Li in both groups where this miRNA family has been implicated in neurodegeneration, cell survival and synaptic development. We discuss the potential of this analysis for investigating treatment response and even providing clinicians with a tool for predicting treatment response in their patients, as well as for providing the industry with a tool for identifying network nodes as targets for novel drug discovery. PMID:25646593

Novel integrative genomic tool for interrogating lithium response in bipolar disorder.

PubMed

Hunsberger, J G; Chibane, F L; Elkahloun, A G; Henderson, R; Singh, R; Lawson, J; Cruceanu, C; Nagarajan, V; Turecki, G; Squassina, A; Medeiros, C D; Del Zompo, M; Rouleau, G A; Alda, M; Chuang, D-M

2015-02-03

We developed a novel integrative genomic tool called GRANITE (Genetic Regulatory Analysis of Networks Investigational Tool Environment) that can effectively analyze large complex data sets to generate interactive networks. GRANITE is an open-source tool and invaluable resource for a variety of genomic fields. Although our analysis is confined to static expression data, GRANITE has the capability of evaluating time-course data and generating interactive networks that may shed light on acute versus chronic treatment, as well as evaluating dose response and providing insight into mechanisms that underlie therapeutic versus sub-therapeutic doses or toxic doses. As a proof-of-concept study, we investigated lithium (Li) response in bipolar disorder (BD). BD is a severe mood disorder marked by cycles of mania and depression. Li is one of the most commonly prescribed and decidedly effective treatments for many patients (responders), although its mode of action is not yet fully understood, nor is it effective in every patient (non-responders). In an in vitro study, we compared vehicle versus chronic Li treatment in patient-derived lymphoblastoid cells (LCLs) (derived from either responders or non-responders) using both microRNA (miRNA) and messenger RNA gene expression profiling. We present both Li responder and non-responder network visualizations created by our GRANITE analysis in BD. We identified by network visualization that the Let-7 family is consistently downregulated by Li in both groups where this miRNA family has been implicated in neurodegeneration, cell survival and synaptic development. We discuss the potential of this analysis for investigating treatment response and even providing clinicians with a tool for predicting treatment response in their patients, as well as for providing the industry with a tool for identifying network nodes as targets for novel drug discovery.

Visual spatial attention enhances the amplitude of positive and negative fMRI responses to visual stimulation in an eccentricity-dependent manner

PubMed Central

Bressler, David W.; Fortenbaugh, Francesca C.; Robertson, Lynn C.; Silver, Michael A.

2013-01-01

Endogenous visual spatial attention improves perception and enhances neural responses to visual stimuli at attended locations. Although many aspects of visual processing differ significantly between central and peripheral vision, little is known regarding the neural substrates of the eccentricity dependence of spatial attention effects. We measured amplitudes of positive and negative fMRI responses to visual stimuli as a function of eccentricity in a large number of topographically-organized cortical areas. Responses to each stimulus were obtained when the stimulus was attended and when spatial attention was directed to a stimulus in the opposite visual hemifield. Attending to the stimulus increased both positive and negative response amplitudes in all cortical areas we studied: V1, V2, V3, hV4, VO1, LO1, LO2, V3A/B, IPS0, TO1, and TO2. However, the eccentricity dependence of these effects differed considerably across cortical areas. In early visual, ventral, and lateral occipital cortex, attentional enhancement of positive responses was greater for central compared to peripheral eccentricities. The opposite pattern was observed in dorsal stream areas IPS0 and putative MT homolog TO1, where attentional enhancement of positive responses was greater in the periphery. Both the magnitude and the eccentricity dependence of attentional modulation of negative fMRI responses closely mirrored that of positive responses across cortical areas. PMID:23562388

Tracking the evolution of crossmodal plasticity and visual functions before and after sight restoration

PubMed Central

Dormal, Giulia; Lepore, Franco; Harissi-Dagher, Mona; Albouy, Geneviève; Bertone, Armando; Rossion, Bruno

2014-01-01

Visual deprivation leads to massive reorganization in both the structure and function of the occipital cortex, raising crucial challenges for sight restoration. We tracked the behavioral, structural, and neurofunctional changes occurring in an early and severely visually impaired patient before and 1.5 and 7 mo after sight restoration with magnetic resonance imaging. Robust presurgical auditory responses were found in occipital cortex despite residual preoperative vision. In primary visual cortex, crossmodal auditory responses overlapped with visual responses and remained elevated even 7 mo after surgery. However, these crossmodal responses decreased in extrastriate occipital regions after surgery, together with improved behavioral vision and with increases in both gray matter density and neural activation in low-level visual regions. Selective responses in high-level visual regions involved in motion and face processing were observable even before surgery and did not evolve after surgery. Taken together, these findings demonstrate that structural and functional reorganization of occipital regions are present in an individual with a long-standing history of severe visual impairment and that such reorganizations can be partially reversed by visual restoration in adulthood. PMID:25520432

Real-time visualization of immune cell clearance of Aspergillus fumigatus spores and hyphae.

PubMed

Knox, Benjamin P; Huttenlocher, Anna; Keller, Nancy P

2017-08-01

Invasive aspergillosis (IA) is a disease of the immunocompromised host and generally caused by the opportunistic fungal pathogen Aspergillus fumigatus. While both host and fungal factors contribute to disease severity and outcome, there are fundamental features of IA development including fungal morphological transition from infectious conidia to tissue-penetrating hyphae as well as host defenses rooted in mechanisms of innate phagocyte function. Here we address recent advances in the field and use real-time in vivo imaging in the larval zebrafish to visually highlight conserved vertebrate innate immune behaviors including macrophage phagocytosis of conidia and neutrophil responses post-germination. Copyright © 2017 Elsevier Inc. All rights reserved.

Applications of multiphoton microscopy in the field of colorectal cancer

NASA Astrophysics Data System (ADS)

Wang, Shu; Li, Lianhuang; Zhu, Xiaoqin; Zheng, Liqin; Zhuo, Shuangmu; Chen, Jianxin

2018-06-01

Multiphoton microscopy (MPM) is a powerful tool for visualizing cellular and subcellular details within living tissue by its unique advantages of being label-free, its intrinsic optical sectioning ability, near-infrared excitation for deep penetration depth into tissue, reduced photobleaching and phototoxicity in the out-of-focus regions, and being capable of providing quantitative information. In this review, we focus on applications of MPM in the field of colorectal cancer, including monitoring cancer progression, detecting tumor metastasis and microenvironment, evaluating the cancer therapy response, and visualizing and ablating pre-invasive cancer cells. We also present one of the major challenges and the future research direction to exploit a colorectal multiphoton endoscope.

Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.

PubMed

Kondo, Yuki; Nurani, Alif Meem; Saito, Chieko; Ichihashi, Yasunori; Saito, Masato; Yamazaki, Kyoko; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Fukuda, Hiroo

2016-06-01

Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. © 2016 American Society of Plant Biologists. All rights reserved.

Representation of the visual field in the primary visual area of the marmoset monkey: magnification factors, point-image size, and proportionality to retinal ganglion cell density.

PubMed

Chaplin, Tristan A; Yu, Hsin-Hao; Rosa, Marcello G P

2013-04-01

The primary visual area (V1) forms a systematic map of the visual field, in which adjacent cell clusters represent adjacent points of visual space. A precise quantification of this map is key to understanding the anatomical relationships between neurons located in different stations of the visual pathway, as well as the neural bases of visual performance in different regions of the visual field. We used computational methods to quantify the visual topography of V1 in the marmoset (Callithrix jacchus), a small diurnal monkey. The receptive fields of neurons throughout V1 were mapped in two anesthetized animals using electrophysiological recordings. Following histological reconstruction, precise 3D reconstructions of the V1 surface and recording sites were generated. We found that the areal magnification factor (M(A) ) decreases with eccentricity following a function that has the same slope as that observed in larger diurnal primates, including macaque, squirrel, and capuchin monkeys, and humans. However, there was no systematic relationship between M(A) and polar angle. Despite individual variation in the shape of V1, the relationship between M(A) and eccentricity was preserved across cases. Comparison between V1 and the retinal ganglion cell density demonstrated preferential magnification of central space in the cortex. The size of the cortical compartment activated by a punctiform stimulus decreased from the foveal representation towards the peripheral representation. Nonetheless, the relationship between the receptive field sizes of V1 cells and the density of ganglion cells suggested that each V1 cell receives information from a similar number of retinal neurons, throughout the visual field. Copyright © 2012 Wiley Periodicals, Inc.

OVEREXPRESSION OF SERUM RESPONSE FACTOR IN ASTROCYTES IMPROVES NEURONAL PLASTICITY IN A MODEL OF EARLY ALCOHOL EXPOSURE

PubMed Central

PAUL, ARCO P.; MEDINA, ALEXANDRE E.

2012-01-01

Neuronal plasticity deficits underlie many of the cognitive problems seen in Fetal Alcohol Spectrum Disorders (FASD). We have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. Recently, we showed that this deficit could be reversed by overexpression of serum response factor (SRF) in the primary visual cortex during the period of monocular deprivation (MD). Surprisingly, this restoration was observed throughout the extent of visual cortex and most of the cells transfected by the virus were positive for the astrocytic marker GFAP rather than the neuronal marker NeuN. Here we test whether overexpression of SRF exclusively in astrocytes is sufficient to restore OD plasticity in alcohol-exposed ferrets. To accomplish that, first we exposed cultured astrocytes to Sindbis viruses carrying either a constitutively active form of SRF (SRF+), a dominant negative (SRF−) or control GFP. After 24h, these astrocytes were implanted in the visual cortex of alcohol-exposed animals or saline controls one day before MD. Optical imaging of intrinsic signals showed that alcohol-exposed animals that were implanted with astrocytes expressing SRF, but not SRF− or GFP, showed robust restoration of OD plasticity in all visual cortex. These findings suggest that overexpression of SRF exclusively in astrocytes can improve neuronal plasticity in FASD. PMID:22742904

Gamma Oscillations and Visual Binding

NASA Astrophysics Data System (ADS)

Robinson, Peter A.; Kim, Jong Won

2006-03-01

At the root of visual perception is the mechanism the brain uses to analyze features in a scene and bind related ones together. Experiments show this process is linked to oscillations of brain activity in the 30-100 Hz gamma band. Oscillations at different sites have correlation functions (CFs) that often peak at zero lag, implying simultaneous firing, even when conduction delays are large. CFs are strongest between cells stimulated by related features. Gamma oscillations are studied here by modeling mm-scale patchy interconnections in the visual cortex. Resulting predictions for gamma responses to stimuli account for numerous experimental findings, including why oscillations and zero-lag synchrony are associated, observed connections with feature preferences, the shape of the zero-lag peak, and variations of CFs with attention. Gamma waves are found to obey the Schroedinger equation, opening the possibility of cortical analogs of quantum phenomena. Gamma instabilities are tied to observations of gamma activity linked to seizures and hallucinations.

What are the Shapes of Response Time Distributions in Visual Search?

PubMed Central

Palmer, Evan M.; Horowitz, Todd S.; Torralba, Antonio; Wolfe, Jeremy M.

2011-01-01

Many visual search experiments measure reaction time (RT) as their primary dependent variable. Analyses typically focus on mean (or median) RT. However, given enough data, the RT distribution can be a rich source of information. For this paper, we collected about 500 trials per cell per observer for both target-present and target-absent displays in each of three classic search tasks: feature search, with the target defined by color; conjunction search, with the target defined by both color and orientation; and spatial configuration search for a 2 among distractor 5s. This large data set allows us to characterize the RT distributions in detail. We present the raw RT distributions and fit several psychologically motivated functions (ex-Gaussian, ex-Wald, Gamma, and Weibull) to the data. We analyze and interpret parameter trends from these four functions within the context of theories of visual search. PMID:21090905

A simple approach to ignoring irrelevant variables by population decoding based on multisensory neurons

PubMed Central

Kim, HyungGoo R.; Pitkow, Xaq; Angelaki, Dora E.

2016-01-01

Sensory input reflects events that occur in the environment, but multiple events may be confounded in sensory signals. For example, under many natural viewing conditions, retinal image motion reflects some combination of self-motion and movement of objects in the world. To estimate one stimulus event and ignore others, the brain can perform marginalization operations, but the neural bases of these operations are poorly understood. Using computational modeling, we examine how multisensory signals may be processed to estimate the direction of self-motion (i.e., heading) and to marginalize out effects of object motion. Multisensory neurons represent heading based on both visual and vestibular inputs and come in two basic types: “congruent” and “opposite” cells. Congruent cells have matched heading tuning for visual and vestibular cues and have been linked to perceptual benefits of cue integration during heading discrimination. Opposite cells have mismatched visual and vestibular heading preferences and are ill-suited for cue integration. We show that decoding a mixed population of congruent and opposite cells substantially reduces errors in heading estimation caused by object motion. In addition, we present a general formulation of an optimal linear decoding scheme that approximates marginalization and can be implemented biologically by simple reinforcement learning mechanisms. We also show that neural response correlations induced by task-irrelevant variables may greatly exceed intrinsic noise correlations. Overall, our findings suggest a general computational strategy by which neurons with mismatched tuning for two different sensory cues may be decoded to perform marginalization operations that dissociate possible causes of sensory inputs. PMID:27334948

Cellular and laminar expression of Dab-1 during the postnatal critical period in cat visual cortex and the effects of dark rearing.

PubMed

Kiser, Paul J; Liu, Zijing; Wilt, Steven D; Mower, George D

2011-04-06

This study describes postnatal critical period changes in cellular and laminar expression of Dab-1, a gene shown to play a role in controlling neuronal positioning during embryonic brain development, in cat visual cortex and the effects of dark rearing (DR). At 1week, there is dense cellular staining which is uniform across cortical layers and very light neuropil staining. At the peak of the critical period (5weeks), dense cell staining is largely restricted to large pyramidal cells of deep layer III and layer V, there is faint cell body staining throughout all cortical layers, neuropil staining is markedly increased and uniform in layers III to VI. This dramatic change in laminar and cellular labeling is independent of visual input, since immunostaining is similar in 5-week DR cats. By 10weeks, the mature laminar and cellular staining pattern is established and the major subsequent change is a further reduction in the density of cellular staining in all cortical layers. Neuropil staining is pronounced and uniform across cortical layers. These developmental changes are altered by DR. Quantification by cell counts indicated that age and DR interact such that differences in cellular expression are opposite in direction between 5- and 20-week-old cats. This bidirectional regulation of cellular expression is the same in all cortical laminae. The bidirectional regulation of cellular expression matches the effects of age and DR on physiological plasticity during the critical period as assessed by ocular dominance shifts in response to monocular deprivation. Copyright © 2011 Elsevier B.V. All rights reserved.

Positive visual phenomena in space: A scientific case and a safety issue in space travel.

PubMed

Sannita, Walter G; Narici, Livio; Picozza, Piergiorgio

2006-07-01

Most astronauts on Apollo, Skylab, and MIR reported 'flashes of light' occurring in different shapes and apparently moving across the visual field, in the absence of auditory, somatosensory, or olfactory abnormal percepts. A temporal correlation with heavy nuclei or protons has been documented in space and comparable phosphenes were observed by volunteers whose eyes were exposed to accelerated heavy ions at intensities below the threshold for Cerenkov visible radiation. An interaction between heavy ions and the retina was suggested. However, the biophysics of heavy ions or protons action remains undefined, the effects on photoreceptors and neuroretina have not been differentiated, and some direct action on the visual cortex never ruled out. Phosphenes are common in migraine and are known to occur also in response to the electrical stimulation of ganglion cells (in retinas without photoreceptors), optic pathways or visual cortex, with mechanisms that bypass the chemically gated channels. Intrinsic photosensitive ganglion cells exist in the retina of teleost fish and mammals. In the hypothesis of a peculiar sensitivity to subatomic particles of the visual system, phosphenes due to the activation of processes by-passing the photoreceptors would raise questions about human safety in space. The issue is particularly relevant with experiments of increasing duration being now operative in the International Space Station (ISS) and with plans of space travel outside the geomagnetic shield. Research is in progress both in the ISS and on animal models, in the framework of the NASA/ESA actions to improve the astronauts' health in space.

Face-selective neurons maintain consistent visual responses across months

PubMed Central

McMahon, David B. T.; Jones, Adam P.; Bondar, Igor V.; Leopold, David A.

2014-01-01

Face perception in both humans and monkeys is thought to depend on neurons clustered in discrete, specialized brain regions. Because primates are frequently called upon to recognize and remember new individuals, the neuronal representation of faces in the brain might be expected to change over time. The functional properties of neurons in behaving animals are typically assessed over time periods ranging from minutes to hours, which amounts to a snapshot compared to a lifespan of a neuron. It therefore remains unclear how neuronal properties observed on a given day predict that same neuron's activity months or years later. Here we show that the macaque inferotemporal cortex contains face-selective cells that show virtually no change in their patterns of visual responses over time periods as long as one year. Using chronically implanted microwire electrodes guided by functional MRI targeting, we obtained distinct profiles of selectivity for face and nonface stimuli that served as fingerprints for individual neurons in the anterior fundus (AF) face patch within the superior temporal sulcus. Longitudinal tracking over a series of daily recording sessions revealed that face-selective neurons maintain consistent visual response profiles across months-long time spans despite the influence of ongoing daily experience. We propose that neurons in the AF face patch are specialized for aspects of face perception that demand stability as opposed to plasticity. PMID:24799679

Face-selective neurons maintain consistent visual responses across months.

PubMed

McMahon, David B T; Jones, Adam P; Bondar, Igor V; Leopold, David A

2014-06-03

Face perception in both humans and monkeys is thought to depend on neurons clustered in discrete, specialized brain regions. Because primates are frequently called upon to recognize and remember new individuals, the neuronal representation of faces in the brain might be expected to change over time. The functional properties of neurons in behaving animals are typically assessed over time periods ranging from minutes to hours, which amounts to a snapshot compared to a lifespan of a neuron. It therefore remains unclear how neuronal properties observed on a given day predict that same neuron's activity months or years later. Here we show that the macaque inferotemporal cortex contains face-selective cells that show virtually no change in their patterns of visual responses over time periods as long as one year. Using chronically implanted microwire electrodes guided by functional MRI targeting, we obtained distinct profiles of selectivity for face and nonface stimuli that served as fingerprints for individual neurons in the anterior fundus (AF) face patch within the superior temporal sulcus. Longitudinal tracking over a series of daily recording sessions revealed that face-selective neurons maintain consistent visual response profiles across months-long time spans despite the influence of ongoing daily experience. We propose that neurons in the AF face patch are specialized for aspects of face perception that demand stability as opposed to plasticity.

Mechanisms creating transient and sustained photoresponses in mammalian retinal ganglion cells

PubMed Central

Zhao, Xiwu; Jaeckel, Elizabeth R.; Chervenak, Andrew P.

2017-01-01

Retinal neurons use sustained and transient light responses to encode visual stimuli of different frequency ranges, but the underlying mechanisms remain poorly understood. In particular, although earlier studies in retinal ganglion cells (RGCs) proposed seven potential mechanisms, all seven have since been disputed, and it remains unknown whether different RGC types use different mechanisms or how many mechanisms are used by each type. Here, we conduct a comprehensive survey in mice and rats of 12 candidate mechanisms that could conceivably produce tonic rod/cone-driven ON responses in intrinsically photosensitive RGCs (ipRGCs) and transient ON responses in three types of direction-selective RGCs (TRHR+, Hoxd10+ ON, and Hoxd10+ ON-OFF cells). We find that the tonic kinetics of ipRGCs arises from their substantially above-threshold resting potentials, input from sustained ON bipolar cells, absence of amacrine cell inhibition of presynaptic ON bipolar cells, and mGluR7-mediated maintenance of light-evoked glutamatergic input. All three types of direction-selective RGCs receive input from transient ON bipolar cells, and each type uses additional strategies to promote photoresponse transience: presynaptic inhibition and dopaminergic modulation for TRHR+ cells, center/surround antagonism and relatively negative resting potentials for Hoxd10+ ON cells, and presynaptic inhibition for Hoxd10+ ON-OFF cells. We find that the sustained nature of ipRGCs’ rod/cone-driven responses depends neither on melanopsin nor on N-methyl-d-aspartate (NMDA) receptors, whereas the transience of the direction-selective cells’ responses is influenced neither by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor desensitization nor by glutamate uptake. For all cells, we further rule out spike frequency adaptation and intracellular Ca2+ as determinants of photoresponse kinetics. In conclusion, different RGC types use diverse mechanisms to produce sustained or transient light responses. Parenthetically, we find evidence in both mice and rats that the kinetics of light-induced mGluR6 deactivation determines whether an ON bipolar cell responds tonically or transiently to light. PMID:28153865

Quantitative analysis of random migration of cells using time-lapse video microscopy.

PubMed

Jain, Prachi; Worthylake, Rebecca A; Alahari, Suresh K

2012-05-13

Cell migration is a dynamic process, which is important for embryonic development, tissue repair, immune system function, and tumor invasion (1, 2). During directional migration, cells move rapidly in response to an extracellular chemotactic signal, or in response to intrinsic cues (3) provided by the basic motility machinery. Random migration occurs when a cell possesses low intrinsic directionality, allowing the cells to explore their local environment. Cell migration is a complex process, in the initial response cell undergoes polarization and extends protrusions in the direction of migration (2). Traditional methods to measure migration such as the Boyden chamber migration assay is an easy method to measure chemotaxis in vitro, which allows measuring migration as an end point result. However, this approach neither allows measurement of individual migration parameters, nor does it allow to visualization of morphological changes that cell undergoes during migration. Here, we present a method that allows us to monitor migrating cells in real time using video - time lapse microscopy. Since cell migration and invasion are hallmarks of cancer, this method will be applicable in studying cancer cell migration and invasion in vitro. Random migration of platelets has been considered as one of the parameters of platelet function (4), hence this method could also be helpful in studying platelet functions. This assay has the advantage of being rapid, reliable, reproducible, and does not require optimization of cell numbers. In order to maintain physiologically suitable conditions for cells, the microscope is equipped with CO(2) supply and temperature thermostat. Cell movement is monitored by taking pictures using a camera fitted to the microscope at regular intervals. Cell migration can be calculated by measuring average speed and average displacement, which is calculated by Slidebook software.

Locomotion Enhances Neural Encoding of Visual Stimuli in Mouse V1

PubMed Central

2017-01-01

Neurons in mouse primary visual cortex (V1) are selective for particular properties of visual stimuli. Locomotion causes a change in cortical state that leaves their selectivity unchanged but strengthens their responses. Both locomotion and the change in cortical state are thought to be initiated by projections from the mesencephalic locomotor region, the latter through a disinhibitory circuit in V1. By recording simultaneously from a large number of single neurons in alert mice viewing moving gratings, we investigated the relationship between locomotion and the information contained within the neural population. We found that locomotion improved encoding of visual stimuli in V1 by two mechanisms. First, locomotion-induced increases in firing rates enhanced the mutual information between visual stimuli and single neuron responses over a fixed window of time. Second, stimulus discriminability was improved, even for fixed population firing rates, because of a decrease in noise correlations across the population. These two mechanisms contributed differently to improvements in discriminability across cortical layers, with changes in firing rates most important in the upper layers and changes in noise correlations most important in layer V. Together, these changes resulted in a threefold to fivefold reduction in the time needed to precisely encode grating direction and orientation. These results support the hypothesis that cortical state shifts during locomotion to accommodate an increased load on the visual system when mice are moving. SIGNIFICANCE STATEMENT This paper contains three novel findings about the representation of information in neurons within the primary visual cortex of the mouse. First, we show that locomotion reduces by at least a factor of 3 the time needed for information to accumulate in the visual cortex that allows the distinction of different visual stimuli. Second, we show that the effect of locomotion is to increase information in cells of all layers of the visual cortex. Third, we show that the means by which information is enhanced by locomotion differs between the upper layers, where the major effect is the increasing of firing rates, and in layer V, where the major effect is the reduction in noise correlations. PMID:28264980

FRET-based reporters for the direct visualization of abscisic acid concentration changes and distribution in Arabidopsis

PubMed Central

Waadt, Rainer; Hitomi, Kenichi; Nishimura, Noriyuki; Hitomi, Chiharu; Adams, Stephen R; Getzoff, Elizabeth D; Schroeder, Julian I

2014-01-01

Abscisic acid (ABA) is a plant hormone that regulates plant growth and development and mediates abiotic stress responses. Direct cellular monitoring of dynamic ABA concentration changes in response to environmental cues is essential for understanding ABA action. We have developed ABAleons: ABA-specific optogenetic reporters that instantaneously convert the phytohormone-triggered interaction of ABA receptors with PP2C-type phosphatases to send a fluorescence resonance energy transfer (FRET) signal in response to ABA. We report the design, engineering and use of ABAleons with ABA affinities in the range of 100–600 nM to map ABA concentration changes in plant tissues with spatial and temporal resolution. High ABAleon expression can partially repress Arabidopsis ABA responses. ABAleons report ABA concentration differences in distinct cell types, ABA concentration increases in response to low humidity and NaCl in guard cells and to NaCl and osmotic stress in roots and ABA transport from the hypocotyl to the shoot and root. DOI: http://dx.doi.org/10.7554/eLife.01739.001 PMID:24737861

[Aging affects early stage direction selectivity of MT cells in rhesus monkeys].

PubMed

Liang, Zhen; Chen, Yue-Ming; Meng, Xue; Wang, Yi; Zhou, Bao-Zhuo; Xie, Ying-Ying; He, Wen-Sheng

2012-10-01

The middle temporal area (MT/V5) plays an important role in motion processing. Neurons in this area have a strongly selective response to the moving direction of objects and as such, the selectivity of MT neurons was proposed to be a neural mechanism for the perception of motion. Our previous studies have found degradation in direction selectivity of MT neurons in old monkeys, but this direction selectivity was calculated during the whole response time and the results were not able to uncover the mechanism of motion perception over a time course. Furthermore, experiments have found that direction selectivity was enhanced by attention at a later stage. Therefore, the response should be excluded in experiments with anesthesia. To further characterize the neural mechanism over a time course, we investigated the age-related changes of direction selectivity in the early stage by comparing the proportions of direction selective MT cells in old and young macaque monkeys using in vivo single-cell recording techniques. Our results show that the proportion of early-stage-direction-selective cells is lower in old monkeys than in young monkeys, and that the early stage direction bias (esDB) of old MT cells decreased relative to young MT cells. Furthermore, the proportion of MT cells having strong early stage direction selectivity in old monkeys was decreased. Accordingly, the functional degradation in the early stage of MT cells may mediate perceptual declines of old primates in visual motion tasks.

Linking express saccade occurance to stimulus properties and sensorimotor integration in the superior colliculus.

PubMed

Marino, Robert A; Levy, Ron; Munoz, Douglas P

2015-08-01

Express saccades represent the fastest possible eye movements to visual targets with reaction times that approach minimum sensory-motor conduction delays. Previous work in monkeys has identified two specific neural signals in the superior colliculus (SC: a midbrain sensorimotor integration structure involved in gaze control) that are required to execute express saccades: 1) previsual activity consisting of a low-frequency increase in action potentials in sensory-motor neurons immediately before the arrival of a visual response; and 2) a transient visual-sensory response consisting of a high-frequency burst of action potentials in visually responsive neurons resulting from the appearance of a visual target stimulus. To better understand how these two neural signals interact to produce express saccades, we manipulated the arrival time and magnitude of visual responses in the SC by altering target luminance and we examined the corresponding influences on SC activity and express saccade generation. We recorded from saccade neurons with visual-, motor-, and previsual-related activity in the SC of monkeys performing the gap saccade task while target luminance was systematically varied between 0.001 and 42.5 cd/m(2) against a black background (∼0.0001 cd/m(2)). Our results demonstrated that 1) express saccade latencies were linked directly to the arrival time in the SC of visual responses produced by abruptly appearing visual stimuli; 2) express saccades were generated toward both dim and bright targets whenever sufficient previsual activity was present; and 3) target luminance altered the likelihood of producing an express saccade. When an express saccade was generated, visuomotor neurons increased their activity immediately before the arrival of the visual response in the SC and saccade initiation. Furthermore, the visual and motor responses of visuomotor neurons merged into a single burst of action potentials, while the visual response of visual-only neurons was unaffected. A linear combination model was used to test which SC signals best predicted the likelihood of producing an express saccade. In addition to visual response magnitude and previsual activity of saccade neurons, the model identified presaccadic activity (activity occurring during the 30-ms epoch immediately before saccade initiation) as a third important signal for predicting express saccades. We conclude that express saccades can be predicted by visual, previsual, and presaccadic signals recorded from visuomotor neurons in the intermediate layers of the SC. Copyright © 2015 the American Physiological Society.

Linking express saccade occurance to stimulus properties and sensorimotor integration in the superior colliculus

PubMed Central

Levy, Ron; Munoz, Douglas P.

2015-01-01

Express saccades represent the fastest possible eye movements to visual targets with reaction times that approach minimum sensory-motor conduction delays. Previous work in monkeys has identified two specific neural signals in the superior colliculus (SC: a midbrain sensorimotor integration structure involved in gaze control) that are required to execute express saccades: 1) previsual activity consisting of a low-frequency increase in action potentials in sensory-motor neurons immediately before the arrival of a visual response; and 2) a transient visual-sensory response consisting of a high-frequency burst of action potentials in visually responsive neurons resulting from the appearance of a visual target stimulus. To better understand how these two neural signals interact to produce express saccades, we manipulated the arrival time and magnitude of visual responses in the SC by altering target luminance and we examined the corresponding influences on SC activity and express saccade generation. We recorded from saccade neurons with visual-, motor-, and previsual-related activity in the SC of monkeys performing the gap saccade task while target luminance was systematically varied between 0.001 and 42.5 cd/m2 against a black background (∼0.0001 cd/m2). Our results demonstrated that 1) express saccade latencies were linked directly to the arrival time in the SC of visual responses produced by abruptly appearing visual stimuli; 2) express saccades were generated toward both dim and bright targets whenever sufficient previsual activity was present; and 3) target luminance altered the likelihood of producing an express saccade. When an express saccade was generated, visuomotor neurons increased their activity immediately before the arrival of the visual response in the SC and saccade initiation. Furthermore, the visual and motor responses of visuomotor neurons merged into a single burst of action potentials, while the visual response of visual-only neurons was unaffected. A linear combination model was used to test which SC signals best predicted the likelihood of producing an express saccade. In addition to visual response magnitude and previsual activity of saccade neurons, the model identified presaccadic activity (activity occurring during the 30-ms epoch immediately before saccade initiation) as a third important signal for predicting express saccades. We conclude that express saccades can be predicted by visual, previsual, and presaccadic signals recorded from visuomotor neurons in the intermediate layers of the SC. PMID:26063770

ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal.

PubMed

Quazi, Faraz; Molday, Robert S

2014-04-01

The visual cycle is a series of enzyme-catalyzed reactions which converts all-trans-retinal to 11-cis-retinal for the regeneration of visual pigments in rod and cone photoreceptor cells. Although essential for vision, 11-cis-retinal like all-trans-retinal is highly toxic due to its highly reactive aldehyde group and has to be detoxified by either reduction to retinol or sequestration within retinal-binding proteins. Previous studies have focused on the role of the ATP-binding cassette transporter ABCA4 associated with Stargardt macular degeneration and retinol dehydrogenases (RDH) in the clearance of all-trans-retinal from photoreceptors following photoexcitation. How rod and cone cells prevent the accumulation of 11-cis-retinal in photoreceptor disk membranes in excess of what is required for visual pigment regeneration is not known. Here we show that ABCA4 can transport N-11-cis-retinylidene-phosphatidylethanolamine (PE), the Schiff-base conjugate of 11-cis-retinal and PE, from the lumen to the cytoplasmic leaflet of disk membranes. This transport function together with chemical isomerization to its all-trans isomer and reduction to all-trans-retinol by RDH can prevent the accumulation of excess 11-cis-retinal and its Schiff-base conjugate and the formation of toxic bisretinoid compounds as found in ABCA4-deficient mice and individuals with Stargardt macular degeneration. This segment of the visual cycle in which excess 11-cis-retinal is converted to all-trans-retinol provides a rationale for the unusually high content of PE and its long-chain unsaturated docosahexaenoyl group in photoreceptor membranes and adds insight into the molecular mechanisms responsible for Stargardt macular degeneration.

Visual Field Defects and Retinal Ganglion Cell Losses in Human Glaucoma Patients

PubMed Central

Harwerth, Ronald S.; Quigley, Harry A.

2007-01-01

Objective The depth of visual field defects are correlated with retinal ganglion cell densities in experimental glaucoma. This study was to determine whether a similar structure-function relationship holds for human glaucoma. Methods The study was based on retinal ganglion cell densities and visual thresholds of patients with documented glaucoma (Kerrigan-Baumrind, et al.) The data were analyzed by a model that predicted ganglion cell densities from standard clinical perimetry, which were then compared to histologic cell counts. Results The model, without free parameters, produced accurate and relatively precise quantification of ganglion cell densities associated with visual field defects. For 437 sets of data, the unity correlation for predicted vs. measured cell densities had a coefficient of determination of 0.39. The mean absolute deviation of the predicted vs. measured values was 2.59 dB, the mean and SD of the distribution of residual errors of prediction was -0.26 ± 3.22 dB. Conclusions Visual field defects by standard clinical perimetry are proportional to neural losses caused by glaucoma. Clinical Relevance The evidence for quantitative structure-function relationships provides a scientific basis of interpreting glaucomatous neuropathy from visual thresholds and supports the application of standard perimetry to establish the stage of the disease. PMID:16769839

Visual receptive field properties of cells in the optic tectum of the archer fish.

PubMed

Ben-Tov, Mor; Kopilevich, Ivgeny; Donchin, Opher; Ben-Shahar, Ohad; Giladi, Chen; Segev, Ronen

2013-08-01

The archer fish is well known for its extreme visual behavior in shooting water jets at prey hanging on vegetation above water. This fish is a promising model in the study of visual system function because it can be trained to respond to artificial targets and thus to provide valuable psychophysical data. Although much behavioral data have indeed been collected over the past two decades, little is known about the functional organization of the main visual area supporting this visual behavior, namely, the fish optic tectum. In this article we focus on a fundamental aspect of this functional organization and provide a detailed analysis of receptive field properties of cells in the archer fish optic tectum. Using extracellular measurements to record activities of single cells, we first measure their retinotectal mapping. We then determine their receptive field properties such as size, selectivity for stimulus direction and orientation, tuning for spatial frequency, and tuning for temporal frequency. Finally, on the basis of all these measurements, we demonstrate that optic tectum cells can be classified into three categories: orientation-tuned cells, direction-tuned cells, and direction-agnostic cells. Our results provide an essential basis for future investigations of information processing in the archer fish visual system.