Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping.

PubMed

Beier, Kevin T; Steinberg, Elizabeth E; DeLoach, Katherine E; Xie, Stanley; Miyamichi, Kazunari; Schwarz, Lindsay; Gao, Xiaojing J; Kremer, Eric J; Malenka, Robert C; Luo, Liqun

2015-07-30

Dopamine (DA) neurons in the midbrain ventral tegmental area (VTA) integrate complex inputs to encode multiple signals that influence motivated behaviors via diverse projections. Here, we combine axon-initiated viral transduction with rabies-mediated trans-synaptic tracing and Cre-based cell-type-specific targeting to systematically map input-output relationships of VTA-DA neurons. We found that VTA-DA (and VTA-GABA) neurons receive excitatory, inhibitory, and modulatory input from diverse sources. VTA-DA neurons projecting to different forebrain regions exhibit specific biases in their input selection. VTA-DA neurons projecting to lateral and medial nucleus accumbens innervate largely non-overlapping striatal targets, with the latter also sending extensive extra-striatal axon collaterals. Using electrophysiology and behavior, we validated new circuits identified in our tracing studies, including a previously unappreciated top-down reinforcing circuit from anterior cortex to lateral nucleus accumbens via VTA-DA neurons. This study highlights the utility of our viral-genetic tracing strategies to elucidate the complex neural substrates that underlie motivated behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

How Attention Can Create Synaptic Tags for the Learning of Working Memories in Sequential Tasks

PubMed Central

Rombouts, Jaldert O.; Bohte, Sander M.; Roelfsema, Pieter R.

2015-01-01

Intelligence is our ability to learn appropriate responses to new stimuli and situations. Neurons in association cortex are thought to be essential for this ability. During learning these neurons become tuned to relevant features and start to represent them with persistent activity during memory delays. This learning process is not well understood. Here we develop a biologically plausible learning scheme that explains how trial-and-error learning induces neuronal selectivity and working memory representations for task-relevant information. We propose that the response selection stage sends attentional feedback signals to earlier processing levels, forming synaptic tags at those connections responsible for the stimulus-response mapping. Globally released neuromodulators then interact with tagged synapses to determine their plasticity. The resulting learning rule endows neural networks with the capacity to create new working memory representations of task relevant information as persistent activity. It is remarkably generic: it explains how association neurons learn to store task-relevant information for linear as well as non-linear stimulus-response mappings, how they become tuned to category boundaries or analog variables, depending on the task demands, and how they learn to integrate probabilistic evidence for perceptual decisions. PMID:25742003

A Granular Self-Organizing Map for Clustering and Gene Selection in Microarray Data.

PubMed

Ray, Shubhra Sankar; Ganivada, Avatharam; Pal, Sankar K

2016-09-01

A new granular self-organizing map (GSOM) is developed by integrating the concept of a fuzzy rough set with the SOM. While training the GSOM, the weights of a winning neuron and the neighborhood neurons are updated through a modified learning procedure. The neighborhood is newly defined using the fuzzy rough sets. The clusters (granules) evolved by the GSOM are presented to a decision table as its decision classes. Based on the decision table, a method of gene selection is developed. The effectiveness of the GSOM is shown in both clustering samples and developing an unsupervised fuzzy rough feature selection (UFRFS) method for gene selection in microarray data. While the superior results of the GSOM, as compared with the related clustering methods, are provided in terms of β -index, DB-index, Dunn-index, and fuzzy rough entropy, the genes selected by the UFRFS are not only better in terms of classification accuracy and a feature evaluation index, but also statistically more significant than the related unsupervised methods. The C-codes of the GSOM and UFRFS are available online at http://avatharamg.webs.com/software-code.

Orientation selectivity in inhibition-dominated networks of spiking neurons: effect of single neuron properties and network dynamics.

PubMed

Sadeh, Sadra; Rotter, Stefan

2015-01-01

The neuronal mechanisms underlying the emergence of orientation selectivity in the primary visual cortex of mammals are still elusive. In rodents, visual neurons show highly selective responses to oriented stimuli, but neighboring neurons do not necessarily have similar preferences. Instead of a smooth map, one observes a salt-and-pepper organization of orientation selectivity. Modeling studies have recently confirmed that balanced random networks are indeed capable of amplifying weakly tuned inputs and generating highly selective output responses, even in absence of feature-selective recurrent connectivity. Here we seek to elucidate the neuronal mechanisms underlying this phenomenon by resorting to networks of integrate-and-fire neurons, which are amenable to analytic treatment. Specifically, in networks of perfect integrate-and-fire neurons, we observe that highly selective and contrast invariant output responses emerge, very similar to networks of leaky integrate-and-fire neurons. We then demonstrate that a theory based on mean firing rates and the detailed network topology predicts the output responses, and explains the mechanisms underlying the suppression of the common-mode, amplification of modulation, and contrast invariance. Increasing inhibition dominance in our networks makes the rectifying nonlinearity more prominent, which in turn adds some distortions to the otherwise essentially linear prediction. An extension of the linear theory can account for all the distortions, enabling us to compute the exact shape of every individual tuning curve in our networks. We show that this simple form of nonlinearity adds two important properties to orientation selectivity in the network, namely sharpening of tuning curves and extra suppression of the modulation. The theory can be further extended to account for the nonlinearity of the leaky model by replacing the rectifier by the appropriate smooth input-output transfer function. These results are robust and do not depend on the state of network dynamics, and hold equally well for mean-driven and fluctuation-driven regimes of activity.

Orientation Selectivity in Inhibition-Dominated Networks of Spiking Neurons: Effect of Single Neuron Properties and Network Dynamics

PubMed Central

Sadeh, Sadra; Rotter, Stefan

2015-01-01

The neuronal mechanisms underlying the emergence of orientation selectivity in the primary visual cortex of mammals are still elusive. In rodents, visual neurons show highly selective responses to oriented stimuli, but neighboring neurons do not necessarily have similar preferences. Instead of a smooth map, one observes a salt-and-pepper organization of orientation selectivity. Modeling studies have recently confirmed that balanced random networks are indeed capable of amplifying weakly tuned inputs and generating highly selective output responses, even in absence of feature-selective recurrent connectivity. Here we seek to elucidate the neuronal mechanisms underlying this phenomenon by resorting to networks of integrate-and-fire neurons, which are amenable to analytic treatment. Specifically, in networks of perfect integrate-and-fire neurons, we observe that highly selective and contrast invariant output responses emerge, very similar to networks of leaky integrate-and-fire neurons. We then demonstrate that a theory based on mean firing rates and the detailed network topology predicts the output responses, and explains the mechanisms underlying the suppression of the common-mode, amplification of modulation, and contrast invariance. Increasing inhibition dominance in our networks makes the rectifying nonlinearity more prominent, which in turn adds some distortions to the otherwise essentially linear prediction. An extension of the linear theory can account for all the distortions, enabling us to compute the exact shape of every individual tuning curve in our networks. We show that this simple form of nonlinearity adds two important properties to orientation selectivity in the network, namely sharpening of tuning curves and extra suppression of the modulation. The theory can be further extended to account for the nonlinearity of the leaky model by replacing the rectifier by the appropriate smooth input-output transfer function. These results are robust and do not depend on the state of network dynamics, and hold equally well for mean-driven and fluctuation-driven regimes of activity. PMID:25569445

Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury

PubMed Central

Xie, Cuicui; Ginet, Vanessa; Sun, Yanyan; Koike, Masato; Zhou, Kai; Li, Tao; Li, Hongfu; Li, Qian; Wang, Xiaoyang; Uchiyama, Yasuo; Truttmann, Anita C.; Kroemer, Guido; Puyal, Julien; Blomgren, Klas; Zhu, Changlian

2016-01-01

ABSTRACT Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy. PMID:26727396

Dynamics of Stability of Orientation Maps Recorded with Optical Imaging.

PubMed

Shumikhina, S I; Bondar, I V; Svinov, M M

2018-03-15

Orientation selectivity is an important feature of visual cortical neurons. Optical imaging of the visual cortex allows for the generation of maps of orientation selectivity that reflect the activity of large populations of neurons. To estimate the statistical significance of effects of experimental manipulations, evaluation of the stability of cortical maps over time is required. Here, we performed optical imaging recordings of the visual cortex of anesthetized adult cats. Monocular stimulation with moving clockwise square-wave gratings that continuously changed orientation and direction was used as the mapping stimulus. Recordings were repeated at various time intervals, from 15 min to 16 h. Quantification of map stability was performed on a pixel-by-pixel basis using several techniques. Map reproducibility showed clear dynamics over time. The highest degree of stability was seen in maps recorded 15-45 min apart. Averaging across all time intervals and all stimulus orientations revealed a mean shift of 2.2 ± 0.1°. There was a significant tendency for larger shifts to occur at longer time intervals. Shifts between 2.8° (mean ± 2SD) and 5° were observed more frequently at oblique orientations, while shifts greater than 5° appeared more frequently at cardinal orientations. Shifts greater than 5° occurred rarely overall (5.4% of cases) and never exceeded 11°. Shifts of 10-10.6° (0.7%) were seen occasionally at time intervals of more than 4 h. Our findings should be considered when evaluating the potential effect of experimental manipulations on orientation selectivity mapping studies. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Dual Leucine Zipper Kinase Inhibitors for the Treatment of Neurodegeneration.

PubMed

Siu, Michael; Sengupta Ghosh, Arundhati; Lewcock, Joseph W

2018-06-04

Dual leucine zipper kinase (DLK, MAP3K12) is an essential driver of the neuronal stress response that regulates neurodegeneration in models of acute neuronal injury and chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS. In this review, we provide an overview of DLK signaling mechanisms and describe selected small molecules that have been utilized to inhibit DLK kinase activity in vivo. These compounds represent valuable tools for understanding the role of DLK signaling and evaluating the potential for DLK inhibition as a therapeutic strategy to prevent neuronal degeneration.

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.

Theoretical Limitations on Functional Imaging Resolution in Auditory Cortex

PubMed Central

Chen, Thomas L.; Watkins, Paul V.; Barbour, Dennis L.

2010-01-01

Functional imaging can reveal detailed organizational structure in cerebral cortical areas, but neuronal response features and local neural interconnectivity can influence the resulting images, possibly limiting the inferences that can be drawn about neural function. Discerning the fundamental principles of organizational structure in the auditory cortex of multiple species has been somewhat challenging historically both with functional imaging and with electrophysiology. A possible limitation affecting any methodology using pooled neuronal measures may be the relative distribution of response selectivity throughout the population of auditory cortex neurons. One neuronal response type inherited from the cochlea, for example, exhibits a receptive field that increases in size (i.e., decreases in selectivity) at higher stimulus intensities. Even though these neurons appear to represent a minority of auditory cortex neurons, they are likely to contribute disproportionately to the activity detected in functional images, especially if intense sounds are used for stimulation. To evaluate the potential influence of neuronal subpopulations upon functional images of primary auditory cortex, a model array representing cortical neurons was probed with virtual imaging experiments under various assumptions about the local circuit organization. As expected, different neuronal subpopulations were activated preferentially under different stimulus conditions. In fact, stimulus protocols that can preferentially excite selective neurons, resulting in a relatively sparse activation map, have the potential to improve the effective resolution of functional auditory cortical images. These experimental results also make predictions about auditory cortex organization that can be tested with refined functional imaging experiments. PMID:20079343

Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex

PubMed Central

Xing, Lei; Larsen, Rylan S; Bjorklund, George Reed; Li, Xiaoyan; Wu, Yaohong; Philpot, Benjamin D; Snider, William D; Newbern, Jason M

2016-01-01

Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in developing neocortical excitatory neurons. Our data reveal a critical requirement for ERK/MAPK signaling in the morphological development and survival of large Ctip2+ neurons in layer 5. Loss of Map2k1/2 (Mek1/2) led to deficits in corticospinal tract formation and subsequent corticospinal neuron apoptosis. ERK/MAPK hyperactivation also led to reduced corticospinal axon elongation, but was associated with enhanced arborization. ERK/MAPK signaling was dispensable for axonal outgrowth of layer 2/3 callosal neurons. However, Map2k1/2 deletion led to reduced expression of Arc and enhanced intrinsic excitability in both layers 2/3 and 5, in addition to imbalanced synaptic excitation and inhibition. These data demonstrate selective requirements for ERK/MAPK signaling in layer 5 circuit development and general effects on cortical pyramidal neuron excitability. DOI: http://dx.doi.org/10.7554/eLife.11123.001 PMID:26848828

Persistent poliovirus infection of human fetal brain cells.

PubMed

Pavio, N; Buc-Caron, M H; Colbère-Garapin, F

1996-09-01

It has been suggested that poliovirus (PV), the causative agent of poliomyelitis, could persist in surviving patients. We have previously shown that PV can persistently infect some human cell lines in vitro, particularly neuroblastoma cell lines. We report here an ex vivo model in which PV can persistently infect primary cultures of human fetal brain cells. Two mutations involving capsid residues 142 of VP2 and 95 of VP1 were repeatedly selected during the persistent infections. These residues are located in capsid regions known to be involved in interactions between PV and its receptor. During the first week after infection, viral antigens were found in cells of both the neuronal and glial lineages. In contrast, 2 weeks after infection, viral antigens were detected almost exclusively in cells of the neuronal lineage. They were detected predominantly in cells expressing a marker of early commitment to the neuronal lineage, MAP-5, particularly in neuroblasts. Viral antigens were also found in immature progenitors expressing a neuroepithelium marker, nestin, and in cells expressing a marker of postmitotic neurons, MAP-2. The presence of viral antigens in postmitotic neurons suggests that PV can persist in neurons of patients who have survived poliomyelitis.

Correlation between resting state fMRI total neuronal activity and PET metabolism in healthy controls and patients with disorders of consciousness.

PubMed

Soddu, Andrea; Gómez, Francisco; Heine, Lizette; Di Perri, Carol; Bahri, Mohamed Ali; Voss, Henning U; Bruno, Marie-Aurélie; Vanhaudenhuyse, Audrey; Phillips, Christophe; Demertzi, Athena; Chatelle, Camille; Schrouff, Jessica; Thibaut, Aurore; Charland-Verville, Vanessa; Noirhomme, Quentin; Salmon, Eric; Tshibanda, Jean-Flory Luaba; Schiff, Nicholas D; Laureys, Steven

2016-01-01

The mildly invasive 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established imaging technique to measure 'resting state' cerebral metabolism. This technique made it possible to assess changes in metabolic activity in clinical applications, such as the study of severe brain injury and disorders of consciousness. We assessed the possibility of creating functional MRI activity maps, which could estimate the relative levels of activity in FDG-PET cerebral metabolic maps. If no metabolic absolute measures can be extracted, our approach may still be of clinical use in centers without access to FDG-PET. It also overcomes the problem of recognizing individual networks of independent component selection in functional magnetic resonance imaging (fMRI) resting state analysis. We extracted resting state fMRI functional connectivity maps using independent component analysis and combined only components of neuronal origin. To assess neuronality of components a classification based on support vector machine (SVM) was used. We compared the generated maps with the FDG-PET maps in 16 healthy controls, 11 vegetative state/unresponsive wakefulness syndrome patients and four locked-in patients. The results show a significant similarity with ρ = 0.75 ± 0.05 for healthy controls and ρ = 0.58 ± 0.09 for vegetative state/unresponsive wakefulness syndrome patients between the FDG-PET and the fMRI based maps. FDG-PET, fMRI neuronal maps, and the conjunction analysis show decreases in frontoparietal and medial regions in vegetative patients with respect to controls. Subsequent analysis in locked-in syndrome patients produced also consistent maps with healthy controls. The constructed resting state fMRI functional connectivity map points toward the possibility for fMRI resting state to estimate relative levels of activity in a metabolic map.

Tumor necrosis factor-alpha stimulation of calcitonin gene-related peptide expression and secretion from rat trigeminal ganglion neurons.

PubMed

Bowen, Elizabeth J; Schmidt, Thomas W; Firm, Christina S; Russo, Andrew F; Durham, Paul L

2006-01-01

Expression of the neuropeptide calcitonin gene-related peptide (CGRP) in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders. Elevation of cytokines contributes to the pathology of these diseases. However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factor-alpha (TNF-alpha). TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNF-alpha stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNF-alpha caused a coordinate increase in CGRP promoter activity. TNF-alpha treatment activated the transcription factor NF-kappaB, as well as the Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways. The importance of TNF-alpha induction of MAP kinase pathways was demonstrated by inhibiting MAP kinases with pharmacological reagents and gene transfer with an adenoviral vector encoding MAP kinase phosphatase-1 (MKP-1). We propose that selective and regulated inhibition of MAP kinases in trigeminal neurons may be therapeutically beneficial for inflammatory disorders involving elevated CGRP levels.

Tumor necrosis factor-α stimulation of calcitonin gene-related peptide expression and secretion from rat trigeminal ganglion neurons

PubMed Central

Bowen, Elizabeth J.; Schmidt, Thomas W.; Firm, Christina S.; Russo, Andrew F.; Durham, Paul L.

2006-01-01

Expression of the neuropeptide calcitonin gene-related peptide (CGRP) in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders. Elevation of cytokines contributes to the pathology of these diseases. However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factorα (TNFα). TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNFα stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNFα caused a coordinate increase in CGRP promoter activity. TNFα treatment activated the transcription factor NF-κB, as well as the Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways. The importance of TNFα induction of MAP kinase pathways was demonstrated by inhibiting MAP kinases with pharmacological reagents and gene transfer with an adenoviral vector encoding MAP kinase phosphatase-1 (MKP-1). We propose that selective and regulated inhibition of MAP kinases in trigeminal neurons may be therapeutically beneficial for inflammatory disorders involving elevated CGRP levels. PMID:16277606

Deconstruction of a neural circuit for hunger.

PubMed

Atasoy, Deniz; Betley, J Nicholas; Su, Helen H; Sternson, Scott M

2012-08-09

Hunger is a complex behavioural state that elicits intense food seeking and consumption. These behaviours are rapidly recapitulated by activation of starvation-sensitive AGRP neurons, which present an entry point for reverse-engineering neural circuits for hunger. Here we mapped synaptic interactions of AGRP neurons with multiple cell populations in mice and probed the contribution of these distinct circuits to feeding behaviour using optogenetic and pharmacogenetic techniques. An inhibitory circuit with paraventricular hypothalamus (PVH) neurons substantially accounted for acute AGRP neuron-evoked eating, whereas two other prominent circuits were insufficient. Within the PVH, we found that AGRP neurons target and inhibit oxytocin neurons, a small population that is selectively lost in Prader-Willi syndrome, a condition involving insatiable hunger. By developing strategies for evaluating molecularly defined circuits, we show that AGRP neuron suppression of oxytocin neurons is critical for evoked feeding. These experiments reveal a new neural circuit that regulates hunger state and pathways associated with overeating disorders.

Deconstruction of a neural circuit for hunger

PubMed Central

Atasoy, Deniz; Betley, J. Nicholas; Su, Helen H.; Sternson, Scott M.

2012-01-01

Hunger is a complex behavioural state that elicits intense food seeking and consumption. These behaviours are rapidly recapitulated by activation of starvation-sensitive AGRP neurons, which present an entry point for reverse-engineering neural circuits for hunger. We mapped synaptic interactions of AGRP neurons with multiple cell populations and probed the contribution of these distinct circuits to feeding behaviour using optogenetic and pharmacogenetic techniques. An inhibitory circuit with paraventricular hypothalamus (PVH) neurons substantially accounted for acute AGRP neuron-evoked eating, whereas two other prominent circuits were insufficient. Within the PVH, we found that AGRP neurons target and inhibit oxytocin neurons, a small population that is selectively lost in Prader-Willi syndrome, a condition involving insatiable hunger. By developing strategies for evaluating molecularly-defined circuits, we show that AGRP neuron suppression of oxytocin neurons is critical for evoked feeding. These experiments reveal a new neural circuit that regulates hunger state and pathways associated with overeating disorders. PMID:22801496

Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

PubMed

Amendola, Elena; Zhan, Yang; Mattucci, Camilla; Castroflorio, Enrico; Calcagno, Eleonora; Fuchs, Claudia; Lonetti, Giuseppina; Silingardi, Davide; Vyssotski, Alexei L; Farley, Dominika; Ciani, Elisabetta; Pizzorusso, Tommaso; Giustetto, Maurizio; Gross, Cornelius T

2014-01-01

Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

A second-order orientation-contrast stimulus for population-receptive-field-based retinotopic mapping.

PubMed

Yildirim, Funda; Carvalho, Joana; Cornelissen, Frans W

2018-01-01

Visual field or retinotopic mapping is one of the most frequently used paradigms in fMRI. It uses activity evoked by position-varying high luminance contrast visual patterns presented throughout the visual field for determining the spatial organization of cortical visual areas. While the advantage of using high luminance contrast is that it tends to drive a wide range of neural populations - thus resulting in high signal-to-noise BOLD responses - this may also be a limitation, especially for approaches that attempt to squeeze more information out of the BOLD response, such as population receptive field (pRF) mapping. In that case, more selective stimulation of a subset of neurons - despite reduced signals - could result in better characterization of pRF properties. Here, we used a second-order stimulus based on local differences in orientation texture - to which we refer as orientation contrast - to perform retinotopic mapping. Participants in our experiment viewed arrays of Gabor patches composed of a foreground (a bar) and a background. These could only be distinguished on the basis of a difference in patch orientation. In our analyses, we compare the pRF properties obtained using this new orientation contrast-based retinotopy (OCR) to those obtained using classic luminance contrast-based retinotopy (LCR). Specifically, in higher order cortical visual areas such as LO, our novel approach resulted in non-trivial reductions in estimated population receptive field size of around 30%. A set of control experiments confirms that the most plausible cause for this reduction is that OCR mainly drives neurons sensitive to orientation contrast. We discuss how OCR - by limiting receptive field scatter and reducing BOLD displacement - may result in more accurate pRF localization as well. Estimation of neuronal properties is crucial for interpreting cortical function. Therefore, we conclude that using our approach, it is possible to selectively target particular neuronal populations, opening the way to use pRF modeling to dissect the response properties of more clearly-defined neuronal populations in different visual areas. Copyright © 2017 Elsevier Inc. All rights reserved.

A cellular and regulatory map of the GABAergic nervous system of C. elegans

PubMed Central

Gendrel, Marie; Atlas, Emily G; Hobert, Oliver

2016-01-01

Neurotransmitter maps are important complements to anatomical maps and represent an invaluable resource to understand nervous system function and development. We report here a comprehensive map of neurons in the C. elegans nervous system that contain the neurotransmitter GABA, revealing twice as many GABA-positive neuron classes as previously reported. We define previously unknown glia-like cells that take up GABA, as well as 'GABA uptake neurons' which do not synthesize GABA but take it up from the extracellular environment, and we map the expression of previously uncharacterized ionotropic GABA receptors. We use the map of GABA-positive neurons for a comprehensive analysis of transcriptional regulators that define the GABA phenotype. We synthesize our findings of specification of GABAergic neurons with previous reports on the specification of glutamatergic and cholinergic neurons into a nervous system-wide regulatory map which defines neurotransmitter specification mechanisms for more than half of all neuron classes in C. elegans. DOI: http://dx.doi.org/10.7554/eLife.17686.001 PMID:27740909

Large-scale modeling of the primary visual cortex: influence of cortical architecture upon neuronal response.

PubMed

McLaughlin, David; Shapley, Robert; Shelley, Michael

2003-01-01

A large-scale computational model of a local patch of input layer 4 [Formula: see text] of the primary visual cortex (V1) of the macaque monkey, together with a coarse-grained reduction of the model, are used to understand potential effects of cortical architecture upon neuronal performance. Both the large-scale point neuron model and its asymptotic reduction are described. The work focuses upon orientation preference and selectivity, and upon the spatial distribution of neuronal responses across the cortical layer. Emphasis is given to the role of cortical architecture (the geometry of synaptic connectivity, of the ordered and disordered structure of input feature maps, and of their interplay) as mechanisms underlying cortical responses within the model. Specifically: (i) Distinct characteristics of model neuronal responses (firing rates and orientation selectivity) as they depend upon the neuron's location within the cortical layer relative to the pinwheel centers of the map of orientation preference; (ii) A time independent (DC) elevation in cortico-cortical conductances within the model, in contrast to a "push-pull" antagonism between excitation and inhibition; (iii) The use of asymptotic analysis to unveil mechanisms which underly these performances of the model; (iv) A discussion of emerging experimental data. The work illustrates that large-scale scientific computation--coupled together with analytical reduction, mathematical analysis, and experimental data, can provide significant understanding and intuition about the possible mechanisms of cortical response. It also illustrates that the idealization which is a necessary part of theoretical modeling can outline in sharp relief the consequences of differing alternative interpretations and mechanisms--with final arbiter being a body of experimental evidence whose measurements address the consequences of these analyses.

Late emergence of the vibrissa direction selectivity map in the rat barrel cortex.

PubMed

Kremer, Yves; Léger, Jean-François; Goodman, Dan; Brette, Romain; Bourdieu, Laurent

2011-07-20

In the neocortex, neuronal selectivities for multiple sensorimotor modalities are often distributed in topographical maps thought to emerge during a restricted period in early postnatal development. Rodent barrel cortex contains a somatotopic map for vibrissa identity, but the existence of maps representing other tactile features has not been clearly demonstrated. We addressed the issue of the existence in the rat cortex of an intrabarrel map for vibrissa movement direction using in vivo two-photon imaging. We discovered that the emergence of a direction map in rat barrel cortex occurs long after all known critical periods in the somatosensory system. This map is remarkably specific, taking a pinwheel-like form centered near the barrel center and aligned to the barrel cortex somatotopy. We suggest that this map may arise from intracortical mechanisms and demonstrate by simulation that the combination of spike-timing-dependent plasticity at synapses between layer 4 and layer 2/3 and realistic pad stimulation is sufficient to produce such a map. Its late emergence long after other classical maps suggests that experience-dependent map formation and refinement continue throughout adult life.

Detecting and Quantifying Topography in Neural Maps

PubMed Central

Yarrow, Stuart; Razak, Khaleel A.; Seitz, Aaron R.; Seriès, Peggy

2014-01-01

Topographic maps are an often-encountered feature in the brains of many species, yet there are no standard, objective procedures for quantifying topography. Topographic maps are typically identified and described subjectively, but in cases where the scale of the map is close to the resolution limit of the measurement technique, identifying the presence of a topographic map can be a challenging subjective task. In such cases, an objective topography detection test would be advantageous. To address these issues, we assessed seven measures (Pearson distance correlation, Spearman distance correlation, Zrehen's measure, topographic product, topological correlation, path length and wiring length) by quantifying topography in three classes of cortical map model: linear, orientation-like, and clusters. We found that all but one of these measures were effective at detecting statistically significant topography even in weakly-ordered maps, based on simulated noisy measurements of neuronal selectivity and sparse sampling of the maps. We demonstrate the practical applicability of these measures by using them to examine the arrangement of spatial cue selectivity in pallid bat A1. This analysis shows that significantly topographic arrangements of interaural intensity difference and azimuth selectivity exist at the scale of individual binaural clusters. PMID:24505279

Behavior Selection of Mobile Robot Based on Integration of Multimodal Information

NASA Astrophysics Data System (ADS)

Chen, Bin; Kaneko, Masahide

Recently, biologically inspired robots have been developed to acquire the capacity for directing visual attention to salient stimulus generated from the audiovisual environment. On purpose to realize this behavior, a general method is to calculate saliency maps to represent how much the external information attracts the robot's visual attention, where the audiovisual information and robot's motion status should be involved. In this paper, we represent a visual attention model where three modalities, that is, audio information, visual information and robot's motor status are considered, while the previous researches have not considered all of them. Firstly, we introduce a 2-D density map, on which the value denotes how much the robot pays attention to each spatial location. Then we model the attention density using a Bayesian network where the robot's motion statuses are involved. Secondly, the information from both of audio and visual modalities is integrated with the attention density map in integrate-fire neurons. The robot can direct its attention to the locations where the integrate-fire neurons are fired. Finally, the visual attention model is applied to make the robot select the visual information from the environment, and react to the content selected. Experimental results show that it is possible for robots to acquire the visual information related to their behaviors by using the attention model considering motion statuses. The robot can select its behaviors to adapt to the dynamic environment as well as to switch to another task according to the recognition results of visual attention.

Neural Correlate of the Thatcher Face Illusion in a Monkey Face-Selective Patch.

PubMed

Taubert, Jessica; Van Belle, Goedele; Vanduffel, Wim; Rossion, Bruno; Vogels, Rufin

2015-07-08

Compelling evidence that our sensitivity to facial structure is conserved across the primate order comes from studies of the "Thatcher face illusion": humans and monkeys notice changes in the orientation of facial features (e.g., the eyes) only when faces are upright, not when faces are upside down. Although it is presumed that face perception in primates depends on face-selective neurons in the inferior temporal (IT) cortex, it is not known whether these neurons respond differentially to upright faces with inverted features. Using microelectrodes guided by functional MRI mapping, we recorded cell responses in three regions of monkey IT cortex. We report an interaction in the middle lateral face patch (ML) between the global orientation of a face and the local orientation of its eyes, a response profile consistent with the perception of the Thatcher illusion. This increased sensitivity to eye orientation in upright faces resisted changes in screen location and was not found among face-selective neurons in other areas of IT cortex, including neurons in another face-selective region, the anterior lateral face patch. We conclude that the Thatcher face illusion is correlated with a pattern of activity in the ML that encodes faces according to a flexible holistic template. Copyright © 2015 the authors 0270-6474/15/359872-07$15.00/0.

The Ste20 Family Kinases MAP4K4, MINK1, and TNIK Converge to Regulate Stress-Induced JNK Signaling in Neurons.

PubMed

Larhammar, Martin; Huntwork-Rodriguez, Sarah; Rudhard, York; Sengupta-Ghosh, Arundhati; Lewcock, Joseph W

2017-11-15

The c-Jun- N -terminal kinase (JNK) signaling pathway regulates nervous system development, axon regeneration, and neuronal degeneration after acute injury or in chronic neurodegenerative disease. Dual leucine zipper kinase (DLK) is required for stress-induced JNK signaling in neurons, yet the factors that initiate DLK/JNK pathway activity remain poorly defined. In the present study, we identify the Ste20 kinases MAP4K4, misshapen-like kinase 1 (MINK1 or MAP4K6) and TNIK Traf2- and Nck-interacting kinase (TNIK or MAP4K7), as upstream regulators of DLK/JNK signaling in neurons. Using a trophic factor withdrawal-based model of neurodegeneration in both male and female embryonic mouse dorsal root ganglion neurons, we show that MAP4K4, MINK1, and TNIK act redundantly to regulate DLK activation and downstream JNK-dependent phosphorylation of c-Jun in response to stress. Targeting MAP4K4, MINK1, and TNIK, but not any of these kinases individually, is sufficient to protect neurons potently from degeneration. Pharmacological inhibition of MAP4Ks blocks stabilization and phosphorylation of DLK within axons and subsequent retrograde translocation of the JNK signaling complex to the nucleus. These results position MAP4Ks as important regulators of the DLK/JNK signaling pathway. SIGNIFICANCE STATEMENT Neuronal degeneration occurs in disparate circumstances: during development to refine neuronal connections, after injury to clear damaged neurons, or pathologically during disease. The dual leucine zipper kinase (DLK)/c-Jun- N -terminal kinase (JNK) pathway represents a conserved regulator of neuronal injury signaling that drives both neurodegeneration and axon regeneration, yet little is known about the factors that initiate DLK activity. Here, we uncover a novel role for a subfamily of MAP4 kinases consisting of MAP4K4, Traf2- and Nck-interacting kinase (TNIK or MAP4K7), and misshapen-like kinase 1 (MINK1 or MAP4K6) in regulating DLK/JNK signaling in neurons. Inhibition of these MAP4Ks blocks stress-induced retrograde JNK signaling and protects from neurodegeneration, suggesting that these kinases may represent attractive therapeutic targets. Copyright © 2017 the authors 0270-6474/17/3711074-11$15.00/0.

MAP kinase-independent signaling in angiotensin II regulation of neuromodulation in SHR neurons.

PubMed

Yang, H; Raizada, M K

1998-09-01

Angiotensin II (Ang II), via its interaction with the angiotensin type 1 (AT1) receptor subtype, causes enhanced stimulation of norepinephrine (NE) neuromodulation. This involves increased transcription of NE transporter, tyrosine hydroxylase, and dopamine ss-hydroxylase genes in Wistar-Kyoto rat (WKY) brain neurons. AT1 receptor-mediated regulation of certain signaling events (such as activation of the Ras-Raf-1-mitogen activated protein (MAP) kinase signaling pathway, nuclear translocation of transcription factors such as Fos and Jun, and the interactions of these factors with AP-1 binding sites) is involved in this NE neuromodulation (Lu et al. J Cell Biol. 1996;135:1609-1617). The aim of this study was to compare the signal transduction mechanism of Ang II regulation of NE neuromodulation in WKY and spontaneously hypertensive rat (SHR) brain neurons, in view of the fact that AT1 receptor expression and Ang II stimulation of NE neuromodulation are higher in SHR neurons compared with WKY neurons. Despite this hyperactivity, Ang II stimulation of Ras, Raf-1, and MAP kinase activities was comparable between the neurons from WKY and SHR. Similarly, central injections of Ang II caused a comparable stimulation of MAP kinase in the hypothalamic and brain stem areas of adult WKY and SHR. Inhibition of MAP kinase by either an MAP kinase kinase inhibitor (PD98059) or an MAP kinase antisense oligonucleotide completely attenuated the stimulatory effects of Ang II on [3H]-NE uptake, NE transporter mRNA, and tyrosine hydroxylase mRNA levels in WKY neurons. These treatments resulted in only 43% to 50% inhibition of [3H]-NE uptake and NE transporter and tyrosine hydroxylase mRNAs in SHR neurons. Thus, Ang II stimulation of NE neuromodulation was completely blocked by MAP kinase inhibition in WKY neurons and only partially blocked in the SHR neurons. These observations suggest the presence of an additional signal transduction pathway involved in NE neuromodulation in SHR neurons that is independent of the MAP kinase pathway.

Specific Contributions of Ventromedial, Anterior Cingulate, and Lateral Prefrontal Cortex for Attentional Selection and Stimulus Valuation

PubMed Central

Kaping, Daniel; Vinck, Martin; Hutchison, R. Matthew; Everling, Stefan; Womelsdorf, Thilo

2011-01-01

Attentional control ensures that neuronal processes prioritize the most relevant stimulus in a given environment. Controlling which stimulus is attended thus originates from neurons encoding the relevance of stimuli, i.e. their expected value, in hand with neurons encoding contextual information about stimulus locations, features, and rules that guide the conditional allocation of attention. Here, we examined how these distinct processes are encoded and integrated in macaque prefrontal cortex (PFC) by mapping their functional topographies at the time of attentional stimulus selection. We find confined clusters of neurons in ventromedial PFC (vmPFC) that predominantly convey stimulus valuation information during attention shifts. These valuation signals were topographically largely separated from neurons predicting the stimulus location to which attention covertly shifted, and which were evident across the complete medial-to-lateral extent of the PFC, encompassing anterior cingulate cortex (ACC), and lateral PFC (LPFC). LPFC responses showed particularly early-onset selectivity and primarily facilitated attention shifts to contralateral targets. Spatial selectivity within ACC was delayed and heterogeneous, with similar proportions of facilitated and suppressed responses during contralateral attention shifts. The integration of spatial and valuation signals about attentional target stimuli was observed in a confined cluster of neurons at the intersection of vmPFC, ACC, and LPFC. These results suggest that valuation processes reflecting stimulus-specific outcome predictions are recruited during covert attentional control. Value predictions and the spatial identification of attentional targets were conveyed by largely separate neuronal populations, but were integrated locally at the intersection of three major prefrontal areas, which may constitute a functional hub within the larger attentional control network. PMID:22215982

Mapping Pathological Phenotypes in a Mouse Model of CDKL5 Disorder

PubMed Central

Amendola, Elena; Zhan, Yang; Mattucci, Camilla; Castroflorio, Enrico; Calcagno, Eleonora; Fuchs, Claudia; Lonetti, Giuseppina; Silingardi, Davide; Vyssotski, Alexei L.; Farley, Dominika; Ciani, Elisabetta; Pizzorusso, Tommaso; Giustetto, Maurizio; Gross, Cornelius T.

2014-01-01

Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder. PMID:24838000

Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1.

PubMed

Dasen, Jeremy S; De Camilli, Alessandro; Wang, Bin; Tucker, Philip W; Jessell, Thomas M

2008-07-25

The precision with which motor neurons innervate target muscles depends on a regulatory network of Hox transcription factors that translates neuronal identity into patterns of connectivity. We show that a single transcription factor, FoxP1, coordinates motor neuron subtype identity and connectivity through its activity as a Hox accessory factor. FoxP1 is expressed in Hox-sensitive motor columns and acts as a dose-dependent determinant of columnar fate. Inactivation of Foxp1 abolishes the output of the motor neuron Hox network, reverting the spinal motor system to an ancestral state. The loss of FoxP1 also changes the pattern of motor neuron connectivity, and in the limb motor axons appear to select their trajectories and muscle targets at random. Our findings show that FoxP1 is a crucial determinant of motor neuron diversification and connectivity, and clarify how this Hox regulatory network controls the formation of a topographic neural map.

Building regional early flood warning systems by AI techniques

NASA Astrophysics Data System (ADS)

Chang, F. J.; Chang, L. C.; Amin, M. Z. B. M.

2017-12-01

Building early flood warning system is essential for the protection of the residents against flood hazards and make actions to mitigate the losses. This study implements AI technology for forecasting multi-step-ahead regional flood inundation maps during storm events. The methodology includes three major schemes: (1) configuring the self-organizing map (SOM) to categorize a large number of regional inundation maps into a meaningful topology; (2) building dynamic neural networks to forecast multi-step-ahead average inundated depths (AID); and (3) adjusting the weights of the selected neuron in the constructed SOM based on the forecasted AID to obtain real-time regional inundation maps. The proposed models are trained, and tested based on a large number of inundation data sets collected in regions with the most frequent and serious flooding in the river basin. The results appear that the SOM topological relationships between individual neurons and their neighbouring neurons are visible and clearly distinguishable, and the hybrid model can continuously provide multistep-ahead visible regional inundation maps with high resolution during storm events, which have relatively small RMSE values and high R2 as compared with numerical simulation data sets. The computing time is only few seconds, and thereby leads to real-time regional flood inundation forecasting and make early flood inundation warning system. We demonstrate that the proposed hybrid ANN-based model has a robust and reliable predictive ability and can be used for early warning to mitigate flood disasters.

Synchrony and the binding problem in macaque visual cortex

PubMed Central

Dong, Yi; Mihalas, Stefan; Qiu, Fangtu; von der Heydt, Rüdiger; Niebur, Ernst

2009-01-01

We tested the binding-by-synchrony hypothesis which proposes that object representations are formed by synchronizing spike activity between neurons that code features of the same object. We studied responses of 32 pairs of neurons recorded with microelectrodes 3 mm apart in the visual cortex of macaques performing a fixation task. Upon mapping the receptive fields of the neurons, a quadrilateral was generated so that two of its sides were centered in the receptive fields at the optimal orientations. This one-figure condition was compared with a two-figure condition in which the neurons were stimulated by two separate figures, keeping the local edges in the receptive fields identical. For each neuron, we also determined its border ownership selectivity (H. Zhou, H. S. Friedman, & R. von der Heydt, 2000). We examined both synchronization and correlation at nonzero time lag. After correcting for effects of the firing rate, we found that synchrony did not depend on the binding condition. However, finding synchrony in a pair of neurons was correlated with finding border-ownership selectivity in both members of the pair. This suggests that the synchrony reflected the connectivity in the network that generates border ownership assignment. Thus, we have not found evidence to support the binding-by-synchrony hypothesis. PMID:19146262

A Hebbian learning rule gives rise to mirror neurons and links them to control theoretic inverse models.

PubMed

Hanuschkin, A; Ganguli, S; Hahnloser, R H R

2013-01-01

Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map-desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop a correlation-based theory of interactions between a sensory and a motor area. We show that a simple eligibility-weighted Hebbian learning rule, operating within a sensorimotor loop during motor explorations and stabilized by heterosynaptic competition, naturally gives rise to mirror neurons as well as control theoretic inverse models encoded in the synaptic weights from sensory to motor neurons. Crucially, we find that the correlational structure or stereotypy of the neural code underlying motor explorations determines the nature of the learned inverse model: random motor codes lead to causal inverses that map sensory activity patterns to their motor causes; such inverses are maximally useful, by allowing the imitation of arbitrary sensory target sequences. By contrast, stereotyped motor codes lead to less useful predictive inverses that map sensory activity to future motor actions. Our theory generalizes previous work on inverse models by showing that such models can be learned in a simple Hebbian framework without the need for error signals or backpropagation, and it makes new conceptual connections between the causal nature of inverse models, the statistical structure of motor variability, and the time-lag between sensory and motor responses of mirror neurons. Applied to bird song learning, our theory can account for puzzling aspects of the song system, including necessity of sensorimotor gating and selectivity of auditory responses to bird's own song (BOS) stimuli.

A Hebbian learning rule gives rise to mirror neurons and links them to control theoretic inverse models

PubMed Central

Hanuschkin, A.; Ganguli, S.; Hahnloser, R. H. R.

2013-01-01

Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map-desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop a correlation-based theory of interactions between a sensory and a motor area. We show that a simple eligibility-weighted Hebbian learning rule, operating within a sensorimotor loop during motor explorations and stabilized by heterosynaptic competition, naturally gives rise to mirror neurons as well as control theoretic inverse models encoded in the synaptic weights from sensory to motor neurons. Crucially, we find that the correlational structure or stereotypy of the neural code underlying motor explorations determines the nature of the learned inverse model: random motor codes lead to causal inverses that map sensory activity patterns to their motor causes; such inverses are maximally useful, by allowing the imitation of arbitrary sensory target sequences. By contrast, stereotyped motor codes lead to less useful predictive inverses that map sensory activity to future motor actions. Our theory generalizes previous work on inverse models by showing that such models can be learned in a simple Hebbian framework without the need for error signals or backpropagation, and it makes new conceptual connections between the causal nature of inverse models, the statistical structure of motor variability, and the time-lag between sensory and motor responses of mirror neurons. Applied to bird song learning, our theory can account for puzzling aspects of the song system, including necessity of sensorimotor gating and selectivity of auditory responses to bird's own song (BOS) stimuli. PMID:23801941

Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons

PubMed Central

Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew CN; Swindale, Nicholas V; Murphy, Timothy H

2017-01-01

Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps. DOI: http://dx.doi.org/10.7554/eLife.19976.001 PMID:28160463

GABAergic Local Interneurons Shape Female Fruit Fly Response to Mating Songs.

PubMed

Yamada, Daichi; Ishimoto, Hiroshi; Li, Xiaodong; Kohashi, Tsunehiko; Ishikawa, Yuki; Kamikouchi, Azusa

2018-05-02

Many animals use acoustic signals to attract a potential mating partner. In fruit flies ( Drosophila melanogaster ), the courtship pulse song has a species-specific interpulse interval (IPI) that activates mating. Although a series of auditory neurons in the fly brain exhibit different tuning patterns to IPIs, it is unclear how the response of each neuron is tuned. Here, we studied the neural circuitry regulating the activity of antennal mechanosensory and motor center (AMMC)-B1 neurons, key secondary auditory neurons in the excitatory neural pathway that relay song information. By performing Ca 2+ imaging in female flies, we found that the IPI selectivity observed in AMMC-B1 neurons differs from that of upstream auditory sensory neurons [Johnston's organ (JO)-B]. Selective knock-down of a GABA A receptor subunit in AMMC-B1 neurons increased their response to short IPIs, suggesting that GABA suppresses AMMC-B1 activity at these IPIs. Connection mapping identified two GABAergic local interneurons that synapse with AMMC-B1 and JO-B. Ca 2+ imaging combined with neuronal silencing revealed that these local interneurons, AMMC-LN and AMMC-B2, shape the response pattern of AMMC-B1 neurons at a 15 ms IPI. Neuronal silencing studies further suggested that both GABAergic local interneurons suppress the behavioral response to artificial pulse songs in flies, particularly those with a 15 ms IPI. Altogether, we identified a circuit containing two GABAergic local interneurons that affects the temporal tuning of AMMC-B1 neurons in the song relay pathway and the behavioral response to the courtship song. Our findings suggest that feedforward inhibitory pathways adjust the behavioral response to courtship pulse songs in female flies. SIGNIFICANCE STATEMENT To understand how the brain detects time intervals between sound elements, we studied the neural pathway that relays species-specific courtship song information in female Drosophila melanogaster We demonstrate that the signal transmission from auditory sensory neurons to key secondary auditory neurons antennal mechanosensory and motor center (AMMC)-B1 is the first-step to generate time interval selectivity of neurons in the song relay pathway. Two GABAergic local interneurons are suggested to shape the interval selectivity of AMMC-B1 neurons by receiving auditory inputs and in turn providing feedforward inhibition onto AMMC-B1 neurons. Furthermore, these GABAergic local interneurons suppress the song response behavior in an interval-dependent manner. Our results provide new insights into the neural circuit basis to adjust neuronal and behavioral responses to a species-specific communication sound. Copyright © 2018 the authors 0270-6474/18/384329-19$15.00/0.

High-yield in vitro recordings from neurons functionally characterized in vivo.

PubMed

Weiler, Simon; Bauer, Joel; Hübener, Mark; Bonhoeffer, Tobias; Rose, Tobias; Scheuss, Volker

2018-06-01

In vivo two-photon calcium imaging provides detailed information about the activity and response properties of individual neurons. However, in vitro methods are often required to study the underlying neuronal connectivity and physiology at the cellular and synaptic levels at high resolution. This protocol provides a fast and reliable workflow for combining the two approaches by characterizing the response properties of individual neurons in mice in vivo using genetically encoded calcium indicators (GECIs), followed by retrieval of the same neurons in brain slices for further analysis in vitro (e.g., circuit mapping). In this approach, a reference frame is provided by fluorescent-bead tracks and sparsely transduced neurons expressing a structural marker in order to re-identify the same neurons. The use of GECIs provides a substantial advancement over previous approaches by allowing for repeated in vivo imaging. This opens the possibility of directly correlating experience-dependent changes in neuronal activity and feature selectivity with changes in neuronal connectivity and physiology. This protocol requires expertise both in in vivo two-photon calcium imaging and in vitro electrophysiology. It takes 3 weeks or more to complete, depending on the time allotted for repeated in vivo imaging of neuronal activity.

Altering spatial priority maps via statistical learning of target selection and distractor filtering.

PubMed

Ferrante, Oscar; Patacca, Alessia; Di Caro, Valeria; Della Libera, Chiara; Santandrea, Elisa; Chelazzi, Leonardo

2018-05-01

The cognitive system has the capacity to learn and make use of environmental regularities - known as statistical learning (SL), including for the implicit guidance of attention. For instance, it is known that attentional selection is biased according to the spatial probability of targets; similarly, changes in distractor filtering can be triggered by the unequal spatial distribution of distractors. Open questions remain regarding the cognitive/neuronal mechanisms underlying SL of target selection and distractor filtering. Crucially, it is unclear whether the two processes rely on shared neuronal machinery, with unavoidable cross-talk, or they are fully independent, an issue that we directly addressed here. In a series of visual search experiments, participants had to discriminate a target stimulus, while ignoring a task-irrelevant salient distractor (when present). We systematically manipulated spatial probabilities of either one or the other stimulus, or both. We then measured performance to evaluate the direct effects of the applied contingent probability distribution (e.g., effects on target selection of the spatial imbalance in target occurrence across locations) as well as its indirect or "transfer" effects (e.g., effects of the same spatial imbalance on distractor filtering across locations). By this approach, we confirmed that SL of both target and distractor location implicitly bias attention. Most importantly, we described substantial indirect effects, with the unequal spatial probability of the target affecting filtering efficiency and, vice versa, the unequal spatial probability of the distractor affecting target selection efficiency across locations. The observed cross-talk demonstrates that SL of target selection and distractor filtering are instantiated via (at least partly) shared neuronal machinery, as further corroborated by strong correlations between direct and indirect effects at the level of individual participants. Our findings are compatible with the notion that both kinds of SL adjust the priority of specific locations within attentional priority maps of space. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular and cellular organization of taste neurons in adult Drosophila pharynx

PubMed Central

Chen, Yu-Chieh (David); Dahanukar, Anupama

2017-01-01

SUMMARY The Drosophila pharyngeal taste organs are poorly characterized despite their location at important sites for monitoring food quality. Functional analysis of pharyngeal neurons has been hindered by the paucity of molecular tools to manipulate them, as well as their relative inaccessibility for neurophysiological investigations. Here, we generate receptor-to-neuron maps of all three pharyngeal taste organs by performing a comprehensive chemoreceptor-GAL4/LexA expression analysis. The organization of pharyngeal neurons reveals similarities and distinctions in receptor repertoires and neuronal groupings compared to external taste neurons. We validate the mapping results by pinpointing a single pharyngeal neuron required for feeding avoidance of L-canavanine. Inducible activation of pharyngeal taste neurons reveals functional differences between external and internal taste neurons and functional subdivision within pharyngeal sweet neurons. Our results provide road maps of pharyngeal taste organs in an insect model system for probing the role of these understudied neurons in controlling feeding behaviors. PMID:29212040

A tweaking principle for executive control: neuronal circuit mechanism for rule-based task switching and conflict resolution.

PubMed

Ardid, Salva; Wang, Xiao-Jing

2013-12-11

A hallmark of executive control is the brain's agility to shift between different tasks depending on the behavioral rule currently in play. In this work, we propose a "tweaking hypothesis" for task switching: a weak rule signal provides a small bias that is dramatically amplified by reverberating attractor dynamics in neural circuits for stimulus categorization and action selection, leading to an all-or-none reconfiguration of sensory-motor mapping. Based on this principle, we developed a biologically realistic model with multiple modules for task switching. We found that the model quantitatively accounts for complex task switching behavior: switch cost, congruency effect, and task-response interaction; as well as monkey's single-neuron activity associated with task switching. The model yields several testable predictions, in particular, that category-selective neurons play a key role in resolving sensory-motor conflict. This work represents a neural circuit model for task switching and sheds insights in the brain mechanism of a fundamental cognitive capability.

Developmentally induced microencephalopathy in guinea pigs--embryonic glial cell activation marks selective neuronal death.

PubMed

Rossner, S; Brückner, M K; Bigl, V

2001-06-01

We have recently shown that in utero treatment of guinea pigs with the DNA methylating substance methylazoxymethanol acetate (MAM) on gestation day (GD) 24 results in neocortical microencephalopathy, increased protein kinase C activity and altered processing of the amyloid precursor protein in neocortex of the offsprings. In order to identify the primary neuronal lesions produced by MAM-treatment, we mapped the 5-bromo-2'-deoxyuridine (BrdU)-incorporation in dividing neurons on GD 24 and we followed the effects of MAM-treatment on GD 24 on embryonic immediate early gene expression and on glial cell activation. BrdU injected on GD 24 labeled many neurons of the ventricular zone and of the intermediate zone but only scattered neurons of the cortical plate. When time-mated guinea pigs were injected intraperitoneally with MAM on GD 24, we observed the activation of microglial cells in the ventricular/intermediate zone and the appearence of astrocytes between the intermediate zone and the cortical plate, 48 h after intoxification. The activation of glial cells was accompanied by the neuronal expression of c-Fos but not of c-Jun in the ventricular/intermediate zone. Based on our observations on BrdU-incorporation and on the morphological outcome of MAM treatment in the juvenile guinea pig, our data presented here indicate that selective neurodegeneration during development induces the activation of both phagocytotic microglial cells and of astrocytes which might trophically support damaged neurons surviving this lesion procedure.

Genome-Wide Mapping of Collier In Vivo Binding Sites Highlights Its Hierarchical Position in Different Transcription Regulatory Networks

PubMed Central

Dubois, Laurence; Bataillé, Laetitia; Painset, Anaïs; Le Gras, Stéphanie; Jost, Bernard; Crozatier, Michèle; Vincent, Alain

2015-01-01

Collier, the single Drosophila COE (Collier/EBF/Olf-1) transcription factor, is required in several developmental processes, including head patterning and specification of muscle and neuron identity during embryogenesis. To identify direct Collier (Col) targets in different cell types, we used ChIP-seq to map Col binding sites throughout the genome, at mid-embryogenesis. In vivo Col binding peaks were associated to 415 potential direct target genes. Gene Ontology analysis revealed a strong enrichment in proteins with DNA binding and/or transcription-regulatory properties. Characterization of a selection of candidates, using transgenic CRM-reporter assays, identified direct Col targets in dorso-lateral somatic muscles and specific neuron types in the central nervous system. These data brought new evidence that Col direct control of the expression of the transcription regulators apterous and eyes-absent (eya) is critical to specifying neuronal identities. They also showed that cross-regulation between col and eya in muscle progenitor cells is required for specification of muscle identity, revealing a new parallel between the myogenic regulatory networks operating in Drosophila and vertebrates. Col regulation of eya, both in specific muscle and neuronal lineages, may illustrate one mechanism behind the evolutionary diversification of Col biological roles. PMID:26204530

Phosphodiesterase Inhibition Increases CREB Phosphorylation and Restores Orientation Selectivity in a Model of Fetal Alcohol Spectrum Disorders

PubMed Central

Krahe, Thomas E.; Wang, Weili; Medina, Alexandre E.

2009-01-01

Background Fetal alcohol spectrum disorders (FASD) are the leading cause of mental retardation in the western world and children with FASD present altered somatosensory, auditory and visual processing. There is growing evidence that some of these sensory processing problems may be related to altered cortical maps caused by impaired developmental neuronal plasticity. Methodology/Principal Findings Here we show that the primary visual cortex of ferrets exposed to alcohol during the third trimester equivalent of human gestation have decreased CREB phosphorylation and poor orientation selectivity revealed by western blotting, optical imaging of intrinsic signals and single-unit extracellular recording techniques. Treating animals several days after the period of alcohol exposure with a phosphodiesterase type 1 inhibitor (Vinpocetine) increased CREB phosphorylation and restored orientation selectivity columns and neuronal orientation tuning. Conclusions/Significance These findings suggest that CREB function is important for the maturation of orientation selectivity and that plasticity enhancement by vinpocetine may play a role in the treatment of sensory problems in FASD. PMID:19680548

Whole-Brain Mapping of Direct Inputs to and Axonal Projections from GABAergic Neurons in the Parafacial Zone.

PubMed

Su, Yun-Ting; Gu, Meng-Yang; Chu, Xi; Feng, Xiang; Yu, Yan-Qin

2018-06-01

The GABAergic neurons in the parafacial zone (PZ) play an important role in sleep-wake regulation and have been identified as part of a sleep-promoting center in the brainstem, but the long-range connections mediating this function remain poorly characterized. Here, we performed whole-brain mapping of both the inputs and outputs of the GABAergic neurons in the PZ of the mouse brain. We used the modified rabies virus EnvA-ΔG-DsRed combined with a Cre/loxP gene-expression strategy to map the direct monosynaptic inputs to the GABAergic neurons in the PZ, and found that they receive inputs mainly from the hypothalamic area, zona incerta, and parasubthalamic nucleus in the hypothalamus; the substantia nigra, pars reticulata and deep mesencephalic nucleus in the midbrain; and the intermediate reticular nucleus and medial vestibular nucleus (parvocellular part) in the pons and medulla. We also mapped the axonal projections of the PZ GABAergic neurons with adeno-associated virus, and defined the reciprocal connections of the PZ GABAergic neurons with their input and output nuclei. The newly-found inputs and outputs of the PZ were also listed compared with the literature. This cell-type-specific neuronal whole-brain mapping of the PZ GABAergic neurons may reveal the circuits underlying various functions such as sleep-wake regulation.

Neuroarchitecture and neuroanatomy of the Drosophila central complex: A GAL4-based dissection of protocerebral bridge neurons and circuits.

PubMed

Wolff, Tanya; Iyer, Nirmala A; Rubin, Gerald M

2015-05-01

Insects exhibit an elaborate repertoire of behaviors in response to environmental stimuli. The central complex plays a key role in combining various modalities of sensory information with an insect's internal state and past experience to select appropriate responses. Progress has been made in understanding the broad spectrum of outputs from the central complex neuropils and circuits involved in numerous behaviors. Many resident neurons have also been identified. However, the specific roles of these intricate structures and the functional connections between them remain largely obscure. Significant gains rely on obtaining a comprehensive catalog of the neurons and associated GAL4 lines that arborize within these brain regions, and on mapping neuronal pathways connecting these structures. To this end, small populations of neurons in the Drosophila melanogaster central complex were stochastically labeled using the multicolor flip-out technique and a catalog was created of the neurons, their morphologies, trajectories, relative arrangements, and corresponding GAL4 lines. This report focuses on one structure of the central complex, the protocerebral bridge, and identifies just 17 morphologically distinct cell types that arborize in this structure. This work also provides new insights into the anatomical structure of the four components of the central complex and its accessory neuropils. Most strikingly, we found that the protocerebral bridge contains 18 glomeruli, not 16, as previously believed. Revised wiring diagrams that take into account this updated architectural design are presented. This updated map of the Drosophila central complex will facilitate a deeper behavioral and physiological dissection of this sophisticated set of structures. © 2014 Wiley Periodicals, Inc.

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

C5a Increases the Injury to Primary Neurons Elicited by Fibrillar Amyloid Beta.

PubMed

Hernandez, Michael X; Namiranian, Pouya; Nguyen, Eric; Fonseca, Maria I; Tenner, Andrea J

2017-02-01

C5aR1, the proinflammatory receptor for C5a, is expressed in the central nervous system on microglia, endothelial cells, and neurons. Previous work demonstrated that the C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in two Alzheimer's Disease (AD) mouse models. However, the cellular mechanisms of this protection have not been definitively demonstrated. Here, primary cultured mouse neurons treated with exogenous C5a show reproducible loss of MAP-2 staining in a dose-dependent manner within 24 hr of treatment, indicative of injury to neurons. This injury is prevented by the C5aR1 antagonist PMX53, a close analog of PMX205. Furthermore, primary neurons derived from C5aR1 null mice exhibited no MAP-2 loss after exposure to the highest concentration of C5a tested. Primary mouse neurons treated with both 100 nM C5a and 5 µM fibrillar amyloid beta (fAβ), to model what occurs in the AD brain, showed increased MAP-2 loss relative to either C5a or fAβ alone. Blocking C5aR1 with PMX53 (100 nM) blocked the loss of MAP2 in these primary neurons to the level seen with fAβ alone. Similar experiments with primary neurons derived from C5aR1 null mice showed a loss of MAP-2 due to fAβ treatment. However, the addition of C5a to the cultures did not enhance the loss of MAP-2 and the addition of PMX53 to the cultures did not change the MAP-2 loss in response to fAβ. Thus, at least part of the beneficial effects of C5aR1 antagonist in AD mouse models may be due to protection of neurons from the toxic effects of C5a.

Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila.

PubMed

Chihara, Takahiro; Kitabayashi, Aki; Morimoto, Michie; Takeuchi, Ken-ichi; Masuyama, Kaoru; Tonoki, Ayako; Davis, Ronald L; Wang, Jing W; Miura, Masayuki

2014-06-01

Sensory and cognitive performance decline with age. Neural dysfunction caused by nerve death in senile dementia and neurodegenerative disease has been intensively studied; however, functional changes in neural circuits during the normal aging process are not well understood. Caspases are key regulators of cell death, a hallmark of age-related neurodegeneration. Using a genetic probe for caspase-3-like activity (DEVDase activity), we have mapped age-dependent neuronal changes in the adult brain throughout the lifespan of Drosophila. Spatio-temporally restricted caspase activation was observed in the antennal lobe and ellipsoid body, brain structures required for olfaction and visual place memory, respectively. We also found that caspase was activated in an age-dependent manner in specific subsets of Drosophila olfactory receptor neurons (ORNs), Or42b and Or92a neurons. These neurons are essential for mediating innate attraction to food-related odors. Furthermore, age-induced impairments of neural transmission and attraction behavior could be reversed by specific inhibition of caspase in these ORNs, indicating that caspase activation in Or42b and Or92a neurons is responsible for altering animal behavior during normal aging.

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

Nonlinear Maps for Design of Discrete Time Models of Neuronal Network Dynamics

DTIC Science & Technology

2016-02-29

Performance/Technic~ 02-01-2016- 02-29-2016 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Nonlinear Maps for Design of Discrete -Time Models of Neuronal...neuronal model in the form of difference equations that generates neuronal states in discrete moments of time. In this approach, time step can be made...propose to use modern DSP ideas to develop new efficient approaches to the design of such discrete -time models for studies of large-scale neuronal

Locally Contractive Dynamics in Generalized Integrate-and-Fire Neurons*

PubMed Central

Jimenez, Nicolas D.; Mihalas, Stefan; Brown, Richard; Niebur, Ernst; Rubin, Jonathan

2013-01-01

Integrate-and-fire models of biological neurons combine differential equations with discrete spike events. In the simplest case, the reset of the neuronal voltage to its resting value is the only spike event. The response of such a model to constant input injection is limited to tonic spiking. We here study a generalized model in which two simple spike-induced currents are added. We show that this neuron exhibits not only tonic spiking at various frequencies but also the commonly observed neuronal bursting. Using analytical and numerical approaches, we show that this model can be reduced to a one-dimensional map of the adaptation variable and that this map is locally contractive over a broad set of parameter values. We derive a sufficient analytical condition on the parameters for the map to be globally contractive, in which case all orbits tend to a tonic spiking state determined by the fixed point of the return map. We then show that bursting is caused by a discontinuity in the return map, in which case the map is piecewise contractive. We perform a detailed analysis of a class of piecewise contractive maps that we call bursting maps and show that they robustly generate stable bursting behavior. To the best of our knowledge, this work is the first to point out the intimate connection between bursting dynamics and piecewise contractive maps. Finally, we discuss bifurcations in this return map, which cause transitions between spiking patterns. PMID:24489486

Transformation of a Spatial Map across the Hippocampal-Lateral Septal Circuit.

PubMed

Tingley, David; Buzsáki, György

2018-05-15

The hippocampus constructs a map of the environment. How this "cognitive map" is utilized by other brain regions to guide behavior remains unexplored. To examine how neuronal firing patterns in the hippocampus are transmitted and transformed, we recorded neurons in its principal subcortical target, the lateral septum (LS). We observed that LS neurons carry reliable spatial information in the phase of action potentials, relative to hippocampal theta oscillations, while the firing rates of LS neurons remained uninformative. Furthermore, this spatial phase code had an anatomical microstructure within the LS and was bound to the hippocampal spatial code by synchronous gamma frequency cell assemblies. Using a data-driven model, we show that rate-independent spatial tuning arises through the dynamic weighting of CA1 and CA3 cell assemblies. Our findings demonstrate that transformation of the hippocampal spatial map depends on higher-order theta-dependent neuronal sequences. Copyright © 2018 Elsevier Inc. All rights reserved.

How learning might strengthen existing visual object representations in human object-selective cortex.

PubMed

Brants, Marijke; Bulthé, Jessica; Daniels, Nicky; Wagemans, Johan; Op de Beeck, Hans P

2016-02-15

Visual object perception is an important function in primates which can be fine-tuned by experience, even in adults. Which factors determine the regions and the neurons that are modified by learning is still unclear. Recently, it was proposed that the exact cortical focus and distribution of learning effects might depend upon the pre-learning mapping of relevant functional properties and how this mapping determines the informativeness of neural units for the stimuli and the task to be learned. From this hypothesis we would expect that visual experience would strengthen the pre-learning distributed functional map of the relevant distinctive object properties. Here we present a first test of this prediction in twelve human subjects who were trained in object categorization and differentiation, preceded and followed by a functional magnetic resonance imaging session. Specifically, training increased the distributed multi-voxel pattern information for trained object distinctions in object-selective cortex, resulting in a generalization from pre-training multi-voxel activity patterns to after-training activity patterns. Simulations show that the increased selectivity combined with the inter-session generalization is consistent with a training-induced strengthening of a pre-existing selectivity map. No training-related neural changes were detected in other regions. In sum, training to categorize or individuate objects strengthened pre-existing representations in human object-selective cortex, providing a first indication that the neuroanatomical distribution of learning effects depends upon the pre-learning mapping of visual object properties. Copyright © 2015 Elsevier Inc. All rights reserved.

Visual Attention Model Based on Statistical Properties of Neuron Responses

PubMed Central

Duan, Haibin; Wang, Xiaohua

2015-01-01

Visual attention is a mechanism of the visual system that can select relevant objects from a specific scene. Interactions among neurons in multiple cortical areas are considered to be involved in attentional allocation. However, the characteristics of the encoded features and neuron responses in those attention related cortices are indefinite. Therefore, further investigations carried out in this study aim at demonstrating that unusual regions arousing more attention generally cause particular neuron responses. We suppose that visual saliency is obtained on the basis of neuron responses to contexts in natural scenes. A bottom-up visual attention model is proposed based on the self-information of neuron responses to test and verify the hypothesis. Four different color spaces are adopted and a novel entropy-based combination scheme is designed to make full use of color information. Valuable regions are highlighted while redundant backgrounds are suppressed in the saliency maps obtained by the proposed model. Comparative results reveal that the proposed model outperforms several state-of-the-art models. This study provides insights into the neuron responses based saliency detection and may underlie the neural mechanism of early visual cortices for bottom-up visual attention. PMID:25747859

Speed skills: measuring the visual speed analyzing properties of primate MT neurons.

PubMed

Perrone, J A; Thiele, A

2001-05-01

Knowing the direction and speed of moving objects is often critical for survival. However, it is poorly understood how cortical neurons process the speed of image movement. Here we tested MT neurons using moving sine-wave gratings of different spatial and temporal frequencies, and mapped out the neurons' spatiotemporal frequency response profiles. The maps typically had oriented ridges of peak sensitivity as expected for speed-tuned neurons. The preferred speed estimate, derived from the orientation of the maps, corresponded well to the preferred speed when moving bars were presented. Thus, our data demonstrate that MT neurons are truly sensitive to the object speed. These findings indicate that MT is not only a key structure in the analysis of direction of motion and depth perception, but also in the analysis of object speed.

The Stimulus-Dependent Gradient of Cyp26B1+ Olfactory Sensory Neurons Is Necessary for the Functional Integrity of the Olfactory Sensory Map.

PubMed

Login, Hande; Håglin, Sofia; Berghard, Anna; Bohm, Staffan

2015-10-07

Stimulus-dependent expression of the retinoic acid-inactivating enzyme Cyp26B1 in olfactory sensory neurons (OSNs) forms a dorsomedial (DM)-ventrolateral (VL) gradient in the mouse olfactory epithelium. The gradient correlates spatially with different rates of OSN turnover, as well as the functional organization of the olfactory sensory map, into overlapping zones of OSNs that express different odorant receptors (ORs). Here, we analyze transgenic mice that, instead of a stimulus-dependent Cyp26B1 gradient, have constitutive Cyp26B1 levels in all OSNs. Starting postnatally, OSN differentiation is decreased and progenitor proliferation is increased. Initially, these effects are selective to the VL-most zone and correlate with reduced ATF5 expression and accumulation of OSNs that do not express ORs. Transcription factor ATF5 is known to stabilize OR gene choice via onset of the stimulus-transducing enzyme adenylyl cyclase type 3. During further postnatal development of Cyp26B1 mice, an anomalous DM(high)-VL(low) expression gradient of adenylyl cyclase type 3 appears, which coincides with altered OR frequencies and OR zones. All OR zones expand ventrolaterally except for the VL-most zone, which contracts. The expansion results in an increased zonal overlap that is also evident in the innervation pattern of OSN axon terminals in olfactory bulbs. These findings together identify a mechanism by which postnatal sensory-stimulated vitamin A metabolism modifies the generation of spatially specified neurons and their precise topographic connectivity. The distributed patterns of vitamin A-metabolizing enzymes in the nervous system suggest the possibility that the mechanism may also regulate neuroplasticity in circuits other than the olfactory sensory map. The mouse olfactory sensory map is functionally wired according to precise axonal projections of spatially organized classes of olfactory sensory neurons in the nose. The genetically controlled mechanisms that regulate the development of the olfactory sensory map are beginning to be elucidated. Little is known about mechanisms by which sensory stimuli shape the organization of the map after birth. We show that a stimulus-dependent gradient of a retinoic acid-inactivating enzyme Cyp26B1 modifies the composition, localization, and axonal projections of olfactory sensory neuron classes. The mechanism is novel and suggests the interesting possibility that local vitamin A metabolism could also be a mediator of stimulus-dependent modifications of precise spatial connectivity in other parts of the nervous system. Copyright © 2015 the authors 0270-6474/15/3513807-12$15.00/0.

High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA.

PubMed

Kebschull, Justus M; Garcia da Silva, Pedro; Reid, Ashlan P; Peikon, Ian D; Albeanu, Dinu F; Zador, Anthony M

2016-09-07

Neurons transmit information to distant brain regions via long-range axonal projections. In the mouse, area-to-area connections have only been systematically mapped using bulk labeling techniques, which obscure the diverse projections of intermingled single neurons. Here we describe MAPseq (Multiplexed Analysis of Projections by Sequencing), a technique that can map the projections of thousands or even millions of single neurons by labeling large sets of neurons with random RNA sequences ("barcodes"). Axons are filled with barcode mRNA, each putative projection area is dissected, and the barcode mRNA is extracted and sequenced. Applying MAPseq to the locus coeruleus (LC), we find that individual LC neurons have preferred cortical targets. By recasting neuroanatomy, which is traditionally viewed as a problem of microscopy, as a problem of sequencing, MAPseq harnesses advances in sequencing technology to permit high-throughput interrogation of brain circuits. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Featural and temporal attention selectively enhance task-appropriate representations in human V1

PubMed Central

Warren, Scott; Yacoub, Essa; Ghose, Geoffrey

2015-01-01

Our perceptions are often shaped by focusing our attention toward specific features or periods of time irrespective of location. We explore the physiological bases of these non-spatial forms of attention by imaging brain activity while subjects perform a challenging change detection task. The task employs a continuously varying visual stimulus that, for any moment in time, selectively activates functionally distinct subpopulations of primary visual cortex (V1) neurons. When subjects are cued to the timing and nature of the change, the mapping of orientation preference across V1 was systematically shifts toward the cued stimulus just prior to its appearance. A simple linear model can explain this shift: attentional changes are selectively targeted toward neural subpopulations representing the attended feature at the times the feature was anticipated. Our results suggest that featural attention is mediated by a linear change in the responses of task-appropriate neurons across cortex during appropriate periods of time. PMID:25501983

Phase-locking and bistability in neuronal networks with synaptic depression

NASA Astrophysics Data System (ADS)

Akcay, Zeynep; Huang, Xinxian; Nadim, Farzan; Bose, Amitabha

2018-02-01

We consider a recurrent network of two oscillatory neurons that are coupled with inhibitory synapses. We use the phase response curves of the neurons and the properties of short-term synaptic depression to define Poincaré maps for the activity of the network. The fixed points of these maps correspond to phase-locked modes of the network. Using these maps, we analyze the conditions that allow short-term synaptic depression to lead to the existence of bistable phase-locked, periodic solutions. We show that bistability arises when either the phase response curve of the neuron or the short-term depression profile changes steeply enough. The results apply to any Type I oscillator and we illustrate our findings using the Quadratic Integrate-and-Fire and Morris-Lecar neuron models.

Neuroarchitecture and neuroanatomy of the Drosophila central complex: A GAL4-based dissection of protocerebral bridge neurons and circuits

PubMed Central

Wolff, Tanya; Iyer, Nirmala A; Rubin, Gerald M

2015-01-01

Insects exhibit an elaborate repertoire of behaviors in response to environmental stimuli. The central complex plays a key role in combining various modalities of sensory information with an insect's internal state and past experience to select appropriate responses. Progress has been made in understanding the broad spectrum of outputs from the central complex neuropils and circuits involved in numerous behaviors. Many resident neurons have also been identified. However, the specific roles of these intricate structures and the functional connections between them remain largely obscure. Significant gains rely on obtaining a comprehensive catalog of the neurons and associated GAL4 lines that arborize within these brain regions, and on mapping neuronal pathways connecting these structures. To this end, small populations of neurons in the Drosophila melanogaster central complex were stochastically labeled using the multicolor flip-out technique and a catalog was created of the neurons, their morphologies, trajectories, relative arrangements, and corresponding GAL4 lines. This report focuses on one structure of the central complex, the protocerebral bridge, and identifies just 17 morphologically distinct cell types that arborize in this structure. This work also provides new insights into the anatomical structure of the four components of the central complex and its accessory neuropils. Most strikingly, we found that the protocerebral bridge contains 18 glomeruli, not 16, as previously believed. Revised wiring diagrams that take into account this updated architectural design are presented. This updated map of the Drosophila central complex will facilitate a deeper behavioral and physiological dissection of this sophisticated set of structures. J. Comp. Neurol. 523:997–1037, 2015. © 2014 Wiley Periodicals, Inc. PMID:25380328

Noninvasive, targeted gene therapy for acute spinal cord injury using LIFU-mediated BDNF-loaded cationic nanobubble destruction.

PubMed

Song, Zhaojun; Ye, Yongjie; Zhang, Zhi; Shen, Jieliang; Hu, Zhenming; Wang, Zhigang; Zheng, Jiazhuang

2018-02-12

Various gene delivery systems have been widely studied for the acute spinal cord injury (SCI) treatment. In the present study, a novel type of brain-derived neurotrophic factor (BDNF)-loaded cationic nanobubbles (CNBs) conjugated with MAP-2 antibody (mAb MAP-2 /BDNF/CNBs) was prepared to provide low-intensity focused ultrasound (LIFU)-targeted gene therapy. In vitro experiments, the ultrasound-targeted tranfection to BDNF overexpressioin in neurons and efficiently inhibition neuronal apoptosis have been demonstrated, and the elaborately designed mAb MAP-2 /BDNF/CNBs can specifically target to the neurons. Furthermore, in a acute SCI rat model, LIFU-mediated mAb MAP-2 /BDNF/CNBs transfection significantly increased BDNF expression, attenuated histological injury, decreased neurons loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in SCI rats. LIFU-mediated mAb MAP-2 /BDNF/CNBs destruction significantly increase transfection efficiency of BDNF gene both in vitro and in vivo, and has a significant neuroprotective effect on the injured spinal cord. Therefore, the combination of LIFU irradiation and gene therapy through mAb MAP-2 /BDNF/CNBs can be considered as a novel non-invasive and targeted treatment for gene therapy of SCI. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Fate-mapping the mammalian hindbrain: segmental origins of vestibular projection neurons assessed using rhombomere-specific Hoxa2 enhancer elements in the mouse embryo.

PubMed

Pasqualetti, Massimo; Díaz, Carmen; Renaud, Jean-Sébastien; Rijli, Filippo M; Glover, Joel C

2007-09-05

As a step toward generating a fate map of identified neuron populations in the mammalian hindbrain, we assessed the contributions of individual rhombomeres to the vestibular nuclear complex, a major sensorimotor area that spans the entire rhombencephalon. Transgenic mice harboring either the lacZ or the enhanced green fluorescent protein reporter genes under the transcriptional control of rhombomere-specific Hoxa2 enhancer elements were used to visualize rhombomere-derived domains. We labeled functionally identifiable vestibular projection neuron groups retrogradely with conjugated dextran-amines at successive embryonic stages and obtained developmental fate maps through direct comparison with the rhombomere-derived domains in the same embryos. The fate maps show that each vestibular neuron group derives from a unique rostrocaudal domain that is relatively stable developmentally, suggesting that anteroposterior migration is not a major contributor to the rostrocaudal patterning of the vestibular system. Most of the groups are multisegmental in origin, and each rhombomere is fated to give rise to two or more vestibular projection neuron types, in a complex pattern that is not segmentally iterated. Comparison with studies in the chicken embryo shows that the rostrocaudal patterning of identified vestibular projection neuron groups is generally well conserved between avians and mammalians but that significant species-specific differences exist in the rostrocaudal limits of particular groups. This mammalian hindbrain fate map can be used as the basis for targeting genetic manipulation to specific subpopulations of vestibular projection neurons.

Associative learning rapidly establishes neuronal representations of upcoming behavioral choices in crows

PubMed Central

Veit, Lena; Pidpruzhnykova, Galyna; Nieder, Andreas

2015-01-01

The ability to form associations between behaviorally relevant sensory stimuli is fundamental for goal-directed behaviors. We investigated neuronal activity in the telencephalic area nidopallium caudolaterale (NCL) while two crows (Corvus corone) performed a delayed association task. Whereas some paired associates were familiar to the crows, novel associations had to be learned and mapped to the same target stimuli within a single session. We found neurons that prospectively encoded the chosen test item during the delay for both familiar and newly learned associations. These neurons increased their selectivity during learning in parallel with the crows' increased behavioral performance. Thus, sustained activity in the NCL actively processes information for the upcoming behavioral choice. These data provide new insights into memory representations of behaviorally meaningful stimuli in birds, and how such representations are formed during learning. The findings suggest that the NCL plays a role in learning arbitrary associations, a cornerstone of corvids’ remarkable behavioral flexibility and adaptability. PMID:26598669

SNAP-25 requirement for dendritic growth of hippocampal neurons.

PubMed

Grosse, G; Grosse, J; Tapp, R; Kuchinke, J; Gorsleben, M; Fetter, I; Höhne-Zell, B; Gratzl, M; Bergmann, M

1999-06-01

Structure and dimension of the dendritic arbor are important determinants of information processing by the nerve cell, but mechanisms and molecules involved in dendritic growth are essentially unknown. We investigated early mechanisms of dendritic growth using mouse fetal hippocampal neurons in primary culture, which form processes during the first week in vitro. We detected a key component of regulated exocytosis, SNAP-25 (synaptosomal associated protein of 25 kDa), in axons and axonal terminals as well as in dendrites identified by the occurrence of the dendritic markers transferrin receptor and MAP2. Selective inactivation of SNAP-25 by botulinum neurotoxin A (BoNTA) resulted in inhibition of axonal growth and of vesicle recycling in axonal terminals. In addition, dendritic growth of hippocampal pyramidal and granule neurons was significantly inhibited by BoNTA. In contrast, cleavage of synaptobrevin by tetanus toxin had an effect on neither axonal nor dendritic growth. Our observations indicate that SNAP-25, but not synaptobrevin, is involved in constitutive axonal growth and dendrite formation by hippocampal neurons.

Response variance in functional maps: neural darwinism revisited.

PubMed

Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

2013-01-01

The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population.

Response Variance in Functional Maps: Neural Darwinism Revisited

PubMed Central

Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

2013-01-01

The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population. PMID:23874733

Early Monocular Defocus Disrupts the Normal Development of Receptive-Field Structure in V2 Neurons of Macaque Monkeys

PubMed Central

Tao, Xiaofeng; Zhang, Bin; Shen, Guofu; Wensveen, Janice; Smith, Earl L.; Nishimoto, Shinji; Ohzawa, Izumi

2014-01-01

Experiencing different quality images in the two eyes soon after birth can cause amblyopia, a developmental vision disorder. Amblyopic humans show the reduced capacity for judging the relative position of a visual target in reference to nearby stimulus elements (position uncertainty) and often experience visual image distortion. Although abnormal pooling of local stimulus information by neurons beyond striate cortex (V1) is often suggested as a neural basis of these deficits, extrastriate neurons in the amblyopic brain have rarely been studied using microelectrode recording methods. The receptive field (RF) of neurons in visual area V2 in normal monkeys is made up of multiple subfields that are thought to reflect V1 inputs and are capable of encoding the spatial relationship between local stimulus features. We created primate models of anisometropic amblyopia and analyzed the RF subfield maps for multiple nearby V2 neurons of anesthetized monkeys by using dynamic two-dimensional noise stimuli and reverse correlation methods. Unlike in normal monkeys, the subfield maps of V2 neurons in amblyopic monkeys were severely disorganized: subfield maps showed higher heterogeneity within each neuron as well as across nearby neurons. Amblyopic V2 neurons exhibited robust binocular suppression and the strength of the suppression was positively correlated with the degree of hereogeneity and the severity of amblyopia in individual monkeys. Our results suggest that the disorganized subfield maps and robust binocular suppression of amblyopic V2 neurons are likely to adversely affect the higher stages of cortical processing resulting in position uncertainty and image distortion. PMID:25297110

Neuronal Polarity: MAP2 Shifts Secretory Vesicles into High Gear for Long-Haul Transport down the Axon.

PubMed

Ribeiro, Luís F; de Wit, Joris

2017-04-19

Accurate control of polarized cargo trafficking is essential for neuronal function. In this issue of Neuron, Gumy et al. (2017) show that MAP2 defines a pre-axonal filtering zone and controls axonal cargo transport by influencing the activities of distinct kinesin motors. Copyright © 2017 Elsevier Inc. All rights reserved.

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

The effect of synaptic plasticity on orientation selectivity in a balanced model of primary visual cortex

PubMed Central

Gonzalo Cogno, Soledad; Mato, Germán

2015-01-01

Orientation selectivity is ubiquitous in the primary visual cortex (V1) of mammals. In cats and monkeys, V1 displays spatially ordered maps of orientation preference. Instead, in mice, squirrels, and rats, orientation selective neurons in V1 are not spatially organized, giving rise to a seemingly random pattern usually referred to as a salt-and-pepper layout. The fact that such different organizations can sharpen orientation tuning leads to question the structural role of the intracortical connections; specifically the influence of plasticity and the generation of functional connectivity. In this work, we analyze the effect of plasticity processes on orientation selectivity for both scenarios. We study a computational model of layer 2/3 and a reduced one-dimensional model of orientation selective neurons, both in the balanced state. We analyze two plasticity mechanisms. The first one involves spike-timing dependent plasticity (STDP), while the second one considers the reconnection of the interactions according to the preferred orientations of the neurons. We find that under certain conditions STDP can indeed improve selectivity but it works in a somehow unexpected way, that is, effectively decreasing the modulated part of the intracortical connectivity as compared to the non-modulated part of it. For the reconnection mechanism we find that increasing functional connectivity leads, in fact, to a decrease in orientation selectivity if the network is in a stable balanced state. Both counterintuitive results are a consequence of the dynamics of the balanced state. We also find that selectivity can increase due to a reconnection process if the resulting connections give rise to an unstable balanced state. We compare these findings with recent experimental results. PMID:26347615

The Topographical Mapping in Drosophila Central Complex Network and Its Signal Routing

PubMed Central

Chang, Po-Yen; Su, Ta-Shun; Shih, Chi-Tin; Lo, Chung-Chuan

2017-01-01

Neural networks regulate brain functions by routing signals. Therefore, investigating the detailed organization of a neural circuit at the cellular levels is a crucial step toward understanding the neural mechanisms of brain functions. To study how a complicated neural circuit is organized, we analyzed recently published data on the neural circuit of the Drosophila central complex, a brain structure associated with a variety of functions including sensory integration and coordination of locomotion. We discovered that, except for a small number of “atypical” neuron types, the network structure formed by the identified 194 neuron types can be described by only a few simple mathematical rules. Specifically, the topological mapping formed by these neurons can be reconstructed by applying a generation matrix on a small set of initial neurons. By analyzing how information flows propagate with or without the atypical neurons, we found that while the general pattern of signal propagation in the central complex follows the simple topological mapping formed by the “typical” neurons, some atypical neurons can substantially re-route the signal pathways, implying specific roles of these neurons in sensory signal integration. The present study provides insights into the organization principle and signal integration in the central complex. PMID:28443014

Single-unit labeling of medial olivocochlear neurons: the cochlear frequency map for efferent axons.

PubMed

Brown, M Christian

2014-06-01

Medial olivocochlear (MOC) neurons are efferent neurons that project axons from the brain to the cochlea. Their action on outer hair cells reduces the gain of the "cochlear amplifier," which shifts the dynamic range of hearing and reduces the effects of noise masking. The MOC effects in one ear can be elicited by sound in that ipsilateral ear or by sound in the contralateral ear. To study how MOC neurons project onto the cochlea to mediate these effects, single-unit labeling in guinea pigs was used to study the mapping of MOC neurons for neurons responsive to ipsilateral sound vs. those responsive to contralateral sound. MOC neurons were sharply tuned to sound frequency with a well-defined characteristic frequency (CF). However, their labeled termination spans in the organ of Corti ranged from narrow to broad, innervating between 14 and 69 outer hair cells per axon in a "patchy" pattern. For units responsive to ipsilateral sound, the midpoint of innervation was mapped according to CF in a relationship generally similar to, but with more variability than, that of auditory-nerve fibers. Thus, based on CF mappings, most of the MOC terminations miss outer hair cells involved in the cochlear amplifier for their CF, which are located more basally. Compared with ipsilaterally responsive neurons, contralaterally responsive neurons had an apical offset in termination and a larger span of innervation (an average of 10.41% cochlear distance), suggesting that when contralateral sound activates the MOC reflex, the actions are different than those for ipsilateral sound. Copyright © 2014 the American Physiological Society.

Single-unit labeling of medial olivocochlear neurons: the cochlear frequency map for efferent axons

PubMed Central

2014-01-01

Medial olivocochlear (MOC) neurons are efferent neurons that project axons from the brain to the cochlea. Their action on outer hair cells reduces the gain of the “cochlear amplifier,” which shifts the dynamic range of hearing and reduces the effects of noise masking. The MOC effects in one ear can be elicited by sound in that ipsilateral ear or by sound in the contralateral ear. To study how MOC neurons project onto the cochlea to mediate these effects, single-unit labeling in guinea pigs was used to study the mapping of MOC neurons for neurons responsive to ipsilateral sound vs. those responsive to contralateral sound. MOC neurons were sharply tuned to sound frequency with a well-defined characteristic frequency (CF). However, their labeled termination spans in the organ of Corti ranged from narrow to broad, innervating between 14 and 69 outer hair cells per axon in a “patchy” pattern. For units responsive to ipsilateral sound, the midpoint of innervation was mapped according to CF in a relationship generally similar to, but with more variability than, that of auditory-nerve fibers. Thus, based on CF mappings, most of the MOC terminations miss outer hair cells involved in the cochlear amplifier for their CF, which are located more basally. Compared with ipsilaterally responsive neurons, contralaterally responsive neurons had an apical offset in termination and a larger span of innervation (an average of 10.41% cochlear distance), suggesting that when contralateral sound activates the MOC reflex, the actions are different than those for ipsilateral sound. PMID:24598524

Early monocular defocus disrupts the normal development of receptive-field structure in V2 neurons of macaque monkeys.

PubMed

Tao, Xiaofeng; Zhang, Bin; Shen, Guofu; Wensveen, Janice; Smith, Earl L; Nishimoto, Shinji; Ohzawa, Izumi; Chino, Yuzo M

2014-10-08

Experiencing different quality images in the two eyes soon after birth can cause amblyopia, a developmental vision disorder. Amblyopic humans show the reduced capacity for judging the relative position of a visual target in reference to nearby stimulus elements (position uncertainty) and often experience visual image distortion. Although abnormal pooling of local stimulus information by neurons beyond striate cortex (V1) is often suggested as a neural basis of these deficits, extrastriate neurons in the amblyopic brain have rarely been studied using microelectrode recording methods. The receptive field (RF) of neurons in visual area V2 in normal monkeys is made up of multiple subfields that are thought to reflect V1 inputs and are capable of encoding the spatial relationship between local stimulus features. We created primate models of anisometropic amblyopia and analyzed the RF subfield maps for multiple nearby V2 neurons of anesthetized monkeys by using dynamic two-dimensional noise stimuli and reverse correlation methods. Unlike in normal monkeys, the subfield maps of V2 neurons in amblyopic monkeys were severely disorganized: subfield maps showed higher heterogeneity within each neuron as well as across nearby neurons. Amblyopic V2 neurons exhibited robust binocular suppression and the strength of the suppression was positively correlated with the degree of hereogeneity and the severity of amblyopia in individual monkeys. Our results suggest that the disorganized subfield maps and robust binocular suppression of amblyopic V2 neurons are likely to adversely affect the higher stages of cortical processing resulting in position uncertainty and image distortion. Copyright © 2014 the authors 0270-6474/14/3413840-15$15.00/0.

Distribution and Intrinsic Membrane Properties of Basal Forebrain GABAergic and Parvalbumin Neurons in the Mouse

PubMed Central

McKenna, James T.; Yang, Chun; Franciosi, Serena; Winston, Stuart; Abarr, Kathleen K.; Rigby, Matthew S.; Yanagawa, Yuchio; McCarley, Robert W.; Brown, Ritchie E.

2013-01-01

The basal forebrain (BF) strongly regulates cortical activation, sleep homeostasis, and attention. Many BF neurons involved in these processes are GABAergic, including a subpopulation of projection neurons containing the calcium-binding protein, parvalbumin (PV). However, technical difficulties in identification have prevented a precise mapping of the distribution of GABAergic and GABA/PV+ neurons in the mouse or a determination of their intrinsic membrane properties. Here we used mice expressing fluorescent proteins in GABAergic (GAD67-GFP knock-in mice) or PV+ neurons (PV-Tomato mice) to study these neurons. Immunohistochemical staining for GABA in GAD67-GFP mice confirmed that GFP selectively labeled BF GABAergic neurons. GFP+ neurons and fibers were distributed throughout the BF, with the highest density in the magnocellular preoptic area (MCPO). Immunohistochemistry for PV indicated that the majority of PV+ neurons in the BF were large (>20 μm) or medium-sized (15–20 μm) GFP+ neurons. Most medium and large-sized BF GFP+ neurons, including those retrogradely labeled from the neocortex, were fast-firing and spontaneously active in vitro. They exhibited prominent hyperpolarization-activated inward currents and subthreshold “spikelets,” suggestive of electrical coupling. PV+ neurons recorded in PV-Tomato mice had similar properties but had significantly narrower action potentials and a higher maximal firing frequency. Another population of smaller GFP+ neurons had properties similar to striatal projection neurons. The fast firing and electrical coupling of BF GABA/PV+ neurons, together with their projections to cortical interneurons and the thalamic reticular nucleus, suggest a strong and synchronous control of the neocortical fast rhythms typical of wakefulness and REM sleep. PMID:23254904

Multimodal Chemosensory Circuits Controlling Male Courtship in Drosophila.

PubMed

Clowney, E Josephine; Iguchi, Shinya; Bussell, Jennifer J; Scheer, Elias; Ruta, Vanessa

2015-09-02

Throughout the animal kingdom, internal states generate long-lasting and self-perpetuating chains of behavior. In Drosophila, males instinctively pursue females with a lengthy and elaborate courtship ritual triggered by activation of sexually dimorphic P1 interneurons. Gustatory pheromones are thought to activate P1 neurons but the circuit mechanisms that dictate their sensory responses to gate entry into courtship remain unknown. Here, we use circuit mapping and in vivo functional imaging techniques to trace gustatory and olfactory pheromone circuits to their point of convergence onto P1 neurons and reveal how their combined input underlies selective tuning to appropriate sexual partners. We identify inhibition, even in response to courtship-promoting pheromones, as a key circuit element that tunes and tempers P1 neuron activity. Our results suggest a circuit mechanism in which balanced excitation and inhibition underlie discrimination of prospective mates and stringently regulate the transition to courtship in Drosophila. Copyright © 2015 Elsevier Inc. All rights reserved.

Multimodal chemosensory circuits controlling male courtship in Drosophila

PubMed Central

Clowney, E. Josephine; Iguchi, Shinya; Bussell, Jennifer J.; Scheer, Elias; Ruta, Vanessa

2015-01-01

Summary Throughout the animal kingdom, internal states generate long-lasting and self-perpetuating chains of behavior. In Drosophila, males instinctively pursue females with a lengthy and elaborate courtship ritual triggered by activation of sexually dimorphic P1 interneurons. Gustatory pheromones are thought to activate P1 neurons but the circuit mechanisms that dictate their sensory responses to gate entry into courtship remain unknown. Here, we use circuit mapping and in vivo functional imaging techniques to trace gustatory and olfactory pheromone circuits to their point of convergence onto P1 neurons and reveal how their combined input underlies selective tuning to appropriate sexual partners. We identify inhibition, even in response to courtship-promoting pheromones, as a key circuit element that tunes and tempers P1 neuron activity. Our results suggest a circuit mechanism in which balanced excitation and inhibition underlie discrimination of prospective mates and stringently regulate the transition to courtship in Drosophila. PMID:26279475

Analysis of connectivity map: Control to glutamate injured and phenobarbital treated neuronal network

NASA Astrophysics Data System (ADS)

Kamal, Hassan; Kanhirodan, Rajan; Srinivas, Kalyan V.; Sikdar, Sujit K.

2010-04-01

We study the responses of a cultured neural network when it is exposed to epileptogenesis glutamate injury causing epilepsy and subsequent treatment with phenobarbital by constructing connectivity map of neurons using correlation matrix. This study is particularly useful in understanding the pharmaceutical drug induced changes in the neuronal network properties with insights into changes at the systems biology level.

Stable long-term chronic brain mapping at the single-neuron level.

PubMed

Fu, Tian-Ming; Hong, Guosong; Zhou, Tao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

2016-10-01

Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

Electromyographic control of functional electrical stimulation in selected patients.

PubMed

Graupe, D; Kohn, K H; Basseas, S; Naccarato, E

1984-07-01

The paper describes initial results of above-lesion electromyographic (EMG) controlled functional electrical stimulation (FES) of paraplegics. Such controlled stimulation is to provide upper-motor-neuron paraplegics (T5 to T12) with self-controlled standing and some walking without braces and with only the help of walkers or crutches. The above-lesion EMG signal employed serves to map the posture of the patient's upper trunk via a computerized mapping of the temporal patterns of that EMG. Such control also has an inherent safety feature in that it prevents the patient from performing a lower-limb movement via FES unless his trunk posture is adequate. Copyright 2013, SLACK Incorporated.

The tonotopic map in the embryonic chicken cochlea.

PubMed

Jones, S M; Jones, T A

1995-02-01

The purpose of the present study was to determine the tonotopic map in the chicken cochlea at 19 days of incubation (E19) by obtaining characteristic frequencies (CFs) for primary afferents, labeling the characterized neurons, and documenting their projections to the papilla. The lowest and highest CFs recorded were 188 and 1623 Hz respectively. The embryonic tonotopic map coincided with maps reported for post-hatch chicks. There were no evidence that neurons selective to low frequencies project inappropriately to more basal locations of the embryonic papilla. Linear regression was used to estimate the frequency gradient (b = 0.037 +/- 0.012 In Hz/% [b +/- SEb]) and intercept (In C, where C = 111 Hz) of the semilog plot of frequency versus cochlear position (in % distance from apex). From these estimates the octave distribution was calculated to be 18.7%/octave or 0.58 mm/octave. These quantities were not significantly different from those found in post hatch chickens. We conclude that the tonotopic map of the avian cochlea for CFs between 100 and 1700 Hz is stable and relatively mature from age E19 to post-hatch day 21 (P21). The most striking sign of immaturity in the E19 embryo is the limited range of high CFs. We offer the hypothesis that, between the ages of E19 and P21, improvements in middle ear admittance alone or in combination with functional maturation of the cochlear base may be the principal factors responsible for the appearance of adult-like high CF limits and not an apically shifting tonotopic map.

The tonotopic map in the embryonic chicken cochlea

NASA Technical Reports Server (NTRS)

Jones, S. M.; Jones, T. A.

1995-01-01

The purpose of the present study was to determine the tonotopic map in the chicken cochlea at 19 days of incubation (E19) by obtaining characteristic frequencies (CFs) for primary afferents, labeling the characterized neurons, and documenting their projections to the papilla. The lowest and highest CFs recorded were 188 and 1623 Hz respectively. The embryonic tonotopic map coincided with maps reported for post-hatch chicks. There were no evidence that neurons selective to low frequencies project inappropriately to more basal locations of the embryonic papilla. Linear regression was used to estimate the frequency gradient (b = 0.037 +/- 0.012 In Hz/% [b +/- SEb]) and intercept (In C, where C = 111 Hz) of the semilog plot of frequency versus cochlear position (in % distance from apex). From these estimates the octave distribution was calculated to be 18.7%/octave or 0.58 mm/octave. These quantities were not significantly different from those found in post hatch chickens. We conclude that the tonotopic map of the avian cochlea for CFs between 100 and 1700 Hz is stable and relatively mature from age E19 to post-hatch day 21 (P21). The most striking sign of immaturity in the E19 embryo is the limited range of high CFs. We offer the hypothesis that, between the ages of E19 and P21, improvements in middle ear admittance alone or in combination with functional maturation of the cochlear base may be the principal factors responsible for the appearance of adult-like high CF limits and not an apically shifting tonotopic map.

Angiotensin II regulation of neuromodulation: downstream signaling mechanism from activation of mitogen-activated protein kinase.

PubMed

Lu, D; Yang, H; Raizada, M K

1996-12-01

Angiotensin II (Ang II) stimulates expression of tyrosine hydroxylase and norepinephrine transporter genes in brain neurons; however, the signal-transduction mechanism is not clearly defined. This study was conducted to determine the involvement of the mitogen-activated protein (MAP) kinase signaling pathway in Ang II stimulation of these genes. MAP kinase was localized in the perinuclear region of the neuronal soma. Ang II caused activation of MAP kinase and its subsequent translocation from the cytoplasmic to nuclear compartment, both effects being mediated by AT1 receptor subtype. Ang II also stimulated SRE- and AP1-binding activities and fos gene expression and its translocation in a MAP kinase-dependent process. These observations are the first demonstration of a downstream signaling pathway involving MAP kinase in Ang II-mediated neuromodulation in noradrenergic neurons.

Different roles of axon guidance cues and patterned spontaneous activity in establishing receptive fields in the mouse superior colliculus.

PubMed

Liu, Mingna; Wang, Lupeng; Cang, Jianhua

2014-01-01

Visual neurons in the superior colliculus (SC) respond to both bright (On) and dark (Off) stimuli in their receptive fields. This receptive field property is due to proper convergence of On- and Off-centered retinal ganglion cells to their target cells in the SC. In this study, we have compared the receptive field structure of individual SC neurons in two lines of mutant mice that are deficient in retinotopic mapping: the ephrin-A knockouts that lack important retinocollicular axonal guidance cues and the nAChR-β2 knockouts that have altered activity-dependent refinement of retinocollicular projections. We find that even though the receptive fields are much larger in the ephrin-A knockouts, their On-Off overlap remains unchanged. These neurons also display normal level of selectivity for stimulus direction and orientation. In contrast, the On-Off overlap is disrupted in the β2 knockouts. Together with the previous finding of disrupted direction and orientation selectivity in the β2 knockout mice, our results indicate that molecular guidance cues and activity-dependent processes play different roles in the development of receptive field properties in the SC.

A comparison of spatial analysis methods for the construction of topographic maps of retinal cell density.

PubMed

Garza-Gisholt, Eduardo; Hemmi, Jan M; Hart, Nathan S; Collin, Shaun P

2014-01-01

Topographic maps that illustrate variations in the density of different neuronal sub-types across the retina are valuable tools for understanding the adaptive significance of retinal specialisations in different species of vertebrates. To date, such maps have been created from raw count data that have been subjected to only limited analysis (linear interpolation) and, in many cases, have been presented as iso-density contour maps with contour lines that have been smoothed 'by eye'. With the use of stereological approach to count neuronal distribution, a more rigorous approach to analysing the count data is warranted and potentially provides a more accurate representation of the neuron distribution pattern. Moreover, a formal spatial analysis of retinal topography permits a more robust comparison of topographic maps within and between species. In this paper, we present a new R-script for analysing the topography of retinal neurons and compare methods of interpolating and smoothing count data for the construction of topographic maps. We compare four methods for spatial analysis of cell count data: Akima interpolation, thin plate spline interpolation, thin plate spline smoothing and Gaussian kernel smoothing. The use of interpolation 'respects' the observed data and simply calculates the intermediate values required to create iso-density contour maps. Interpolation preserves more of the data but, consequently includes outliers, sampling errors and/or other experimental artefacts. In contrast, smoothing the data reduces the 'noise' caused by artefacts and permits a clearer representation of the dominant, 'real' distribution. This is particularly useful where cell density gradients are shallow and small variations in local density may dramatically influence the perceived spatial pattern of neuronal topography. The thin plate spline and the Gaussian kernel methods both produce similar retinal topography maps but the smoothing parameters used may affect the outcome.

Neural Activity during Voluntary Movements in Each Body Representation of the Intracortical Microstimulation-Derived Map in the Macaque Motor Cortex.

PubMed

Higo, Noriyuki; Kunori, Nobuo; Murata, Yumi

2016-01-01

In order to accurately interpret experimental data using the topographic body map identified by conventional intracortical microstimulation (ICMS), it is important to know how neurons in each division of the map respond during voluntary movements. Here we systematically investigated neuronal responses in each body representation of the ICMS map during a reach-grasp-retrieval task that involves the movements of multiple body parts. The topographic body map in the primary motor cortex (M1) generally corresponds to functional divisions of voluntary movements; neurons at the recording sites in each body representation with movement thresholds of 10 μA or less were differentially activated during the task, and the timing of responses was consistent with the movements of the body part represented. Moreover, neurons in the digit representation responded differently for the different types of grasping. In addition, the present study showed that neural activity depends on the ICMS current threshold required to elicit body movements and the location of the recording on the cortical surface. In the ventral premotor cortex (PMv), no correlation was found between the response properties of neurons and the body representation in the ICMS map. Neural responses specific to forelimb movements were often observed in the rostral part of PMv, including the lateral bank of the lower arcuate limb, in which ICMS up to 100 μA evoked no detectable movement. These results indicate that the physiological significance of the ICMS-derived maps is different between, and even within, areas M1 and PMv.

Neural Activity during Voluntary Movements in Each Body Representation of the Intracortical Microstimulation-Derived Map in the Macaque Motor Cortex

PubMed Central

Kunori, Nobuo; Murata, Yumi

2016-01-01

In order to accurately interpret experimental data using the topographic body map identified by conventional intracortical microstimulation (ICMS), it is important to know how neurons in each division of the map respond during voluntary movements. Here we systematically investigated neuronal responses in each body representation of the ICMS map during a reach-grasp-retrieval task that involves the movements of multiple body parts. The topographic body map in the primary motor cortex (M1) generally corresponds to functional divisions of voluntary movements; neurons at the recording sites in each body representation with movement thresholds of 10 μA or less were differentially activated during the task, and the timing of responses was consistent with the movements of the body part represented. Moreover, neurons in the digit representation responded differently for the different types of grasping. In addition, the present study showed that neural activity depends on the ICMS current threshold required to elicit body movements and the location of the recording on the cortical surface. In the ventral premotor cortex (PMv), no correlation was found between the response properties of neurons and the body representation in the ICMS map. Neural responses specific to forelimb movements were often observed in the rostral part of PMv, including the lateral bank of the lower arcuate limb, in which ICMS up to 100 μA evoked no detectable movement. These results indicate that the physiological significance of the ICMS-derived maps is different between, and even within, areas M1 and PMv. PMID:27494282

The time course of saccadic decision making: dynamic field theory.

PubMed

Wilimzig, Claudia; Schneider, Stefan; Schöner, Gregor

2006-10-01

Making a saccadic eye movement involves two decisions, the decision to initiate the saccade and the selection of the visual target of the saccade. Here we provide a theoretical account for the time-courses of these two processes, whose instabilities are the basis of decision making. We show how the cross-over from spatial averaging for fast saccades to selection for slow saccades arises from the balance between excitatory and inhibitory processes. Initiating a saccade involves overcoming fixation, as can be observed in the countermanding paradigm, which we model accounting both for the temporal evolution of the suppression probability and its dependence on fixation activity. The interaction between the two forms of decision making is demonstrated by predicting how the cross-over from averaging to selection depends on the fixation stimulus in gap-step-overlap paradigms. We discuss how the activation dynamics of our model may be mapped onto neuronal structures including the motor map and the fixation cells in superior colliculus.

A map of terminal regulators of neuronal identity in Caenorhabditis elegans

PubMed Central

2016-01-01

Our present day understanding of nervous system development is an amalgam of insights gained from studying different aspects and stages of nervous system development in a variety of invertebrate and vertebrate model systems, with each model system making its own distinctive set of contributions. One aspect of nervous system development that has been among the most extensively studied in the nematode Caenorhabditis elegans is the nature of the gene regulatory programs that specify hardwired, terminal cellular identities. I first summarize a number of maps (anatomical, functional, and molecular) that describe the terminal identity of individual neurons in the C. elegans nervous system. I then provide a comprehensive summary of regulatory factors that specify terminal identities in the nervous system, synthesizing these past studies into a regulatory map of cellular identities in the C. elegans nervous system. This map shows that for three quarters of all neurons in the C. elegans nervous system, regulatory factors that control terminal identity features are known. In‐depth studies of specific neuron types have revealed that regulatory factors rarely act alone, but rather act cooperatively in neuron‐type specific combinations. In most cases examined so far, distinct, biochemically unlinked terminal identity features are coregulated via cooperatively acting transcription factors, termed terminal selectors, but there are also cases in which distinct identity features are controlled in a piecemeal fashion by independent regulatory inputs. The regulatory map also illustrates that identity‐defining transcription factors are reemployed in distinct combinations in different neuron types. However, the same transcription factor can drive terminal differentiation in neurons that are unrelated by lineage, unrelated by function, connectivity and neurotransmitter deployment. Lastly, the regulatory map illustrates the preponderance of homeodomain transcription factors in the control of terminal identities, suggesting that these factors have ancient, phylogenetically conserved roles in controlling terminal neuronal differentiation in the nervous system. WIREs Dev Biol 2016, 5:474–498. doi: 10.1002/wdev.233 For further resources related to this article, please visit the WIREs website. PMID:27136279

Contributions of dopaminergic and non-dopaminergic neurons to VTA-stimulation induced neurovascular responses in brain reward circuits.

PubMed

Brocka, Marta; Helbing, Cornelia; Vincenz, Daniel; Scherf, Thomas; Montag, Dirk; Goldschmidt, Jürgen; Angenstein, Frank; Lippert, Michael

2018-04-30

Mapping the activity of the human mesolimbic dopamine system by BOLD-fMRI is a tempting approach to non-invasively study the action of the brain reward system during different experimental conditions. However, the contribution of dopamine release to the BOLD signal is disputed. To assign the actual contribution of dopaminergic and non-dopaminergic VTA neurons to the formation of BOLD responses in target regions of the mesolimbic system, we used two optogenetic approaches in rats. We either activated VTA dopaminergic neurons selectively, or dopaminergic and mainly glutamatergic projecting neurons together. We further used electrical stimulation to non-selectively activate neurons in the VTA. All three stimulation conditions effectively activated the mesolimbic dopaminergic system and triggered dopamine releases into the NAcc as measured by in vivo fast-scan cyclic voltammetry. Furthermore, both optogenetic stimulation paradigms led to indistinguishable self-stimulation behavior. In contrast to these similarities, however, the BOLD response pattern differed greatly between groups. In general, BOLD responses were weaker and sparser with increasing stimulation specificity for dopaminergic neurons. In addition, repetitive stimulation of the VTA caused a progressive decoupling of dopamine release and BOLD signal strength, and dopamine receptor antagonists were unable to block the BOLD signal elicited by VTA stimulation. To exclude that the sedation during fMRI is the cause of minimal mesolimbic BOLD in response to specific dopaminergic stimulation, we repeated our experiments using CBF SPECT in awake animals. Again, we found activations only for less-specific stimulation. Based on these results we conclude that canonical BOLD responses in the reward system represent mainly the activity of non-dopaminergic neurons. Thus, the minor effects of projecting dopaminergic neurons are concealed by non-dopaminergic activity, a finding which highlights the importance of a careful interpretation of reward-related human fMRI data. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Navigation Patterns and Scent Marking: Underappreciated Contributors to Hippocampal and Entorhinal Spatial Representations?

PubMed

Lebedev, Mikhail A; Pimashkin, Alexey; Ossadtchi, Alexei

2018-01-01

According to the currently prevailing theory, hippocampal formation constructs and maintains cognitive spatial maps. Most of the experimental evidence for this theory comes from the studies on navigation in laboratory rats and mice, typically male animals. While these animals exhibit a rich repertoire of behaviors associated with navigation, including locomotion, head movements, whisking, sniffing, raring and scent marking, the contribution of these behavioral patterns to the hippocampal spatially-selective activity has not been sufficiently studied. Instead, many publications have considered animal position in space as the major variable that affects the firing of hippocampal place cells and entorhinal grid cells. Here we argue that future work should focus on a more detailed examination of different behaviors exhibited during navigation to better understand the mechanism of spatial tuning in hippocampal neurons. As an inquiry in this direction, we have analyzed data from two datasets, shared online, containing recordings from rats navigating in square and round arenas. Our analyses revealed patchy navigation patterns, evident from the spatial maps of animal position, velocity and acceleration. Moreover, grid cells available in the datasets exhibited similar periodicity as the navigation parameters. These findings indicate that activity of grid cells could affect navigation parameters and/or vice versa. Additionally, we speculate that scent marks left by navigating animals could contribute to neuronal responses while rats and mice sniff their environment; the act of sniffing could modulate neuronal discharges even in virtual visual environments. Accordingly, we propose that future experiments should contain additional controls for navigation patterns, whisking, sniffing and maps composed of scent marks.

Selection and parameterization of cortical neurons for neuroprosthetic control.

PubMed

Wahnoun, Remy; He, Jiping; Helms Tillery, Stephen I

2006-06-01

When designing neuroprosthetic interfaces for motor function, it is crucial to have a system that can extract reliable information from available neural signals and produce an output suitable for real life applications. Systems designed to date have relied on establishing a relationship between neural discharge patterns in motor cortical areas and limb movement, an approach not suitable for patients who require such implants but who are unable to provide proper motor behavior to initially tune the system. We describe here a method that allows rapid tuning of a population vector-based system for neural control without arm movements. We trained highly motivated primates to observe a 3D center-out task as the computer played it very slowly. Based on only 10-12 s of neuronal activity observed in M1 and PMd, we generated an initial mapping between neural activity and device motion that the animal could successfully use for neuroprosthetic control. Subsequent tunings of the parameters led to improvements in control, but the initial selection of neurons and estimated preferred direction for those cells remained stable throughout the remainder of the day. Using this system, we have observed that the contribution of individual neurons to the overall control of the system is very heterogeneous. We thus derived a novel measure of unit quality and an indexing scheme that allowed us to rate each neuron's contribution to the overall control. In offline tests, we found that fewer than half of the units made positive contributions to the performance. We tested this experimentally by having the animals control the neuroprosthetic system using only the 20 best neurons. We found that performance in this case was better than when the entire set of available neurons was used. Based on these results, we believe that, with careful task design, it is feasible to parameterize control systems without any overt behaviors and that subsequent control system design will be enhanced with cautious unit selection. These improvements can lead to systems demanding lower bandwidth and computational power, and will pave the way for more feasible clinical systems.

Magnetic Tunnel Junction Mimics Stochastic Cortical Spiking Neurons

NASA Astrophysics Data System (ADS)

Sengupta, Abhronil; Panda, Priyadarshini; Wijesinghe, Parami; Kim, Yusung; Roy, Kaushik

2016-07-01

Brain-inspired computing architectures attempt to mimic the computations performed in the neurons and the synapses in the human brain in order to achieve its efficiency in learning and cognitive tasks. In this work, we demonstrate the mapping of the probabilistic spiking nature of pyramidal neurons in the cortex to the stochastic switching behavior of a Magnetic Tunnel Junction in presence of thermal noise. We present results to illustrate the efficiency of neuromorphic systems based on such probabilistic neurons for pattern recognition tasks in presence of lateral inhibition and homeostasis. Such stochastic MTJ neurons can also potentially provide a direct mapping to the probabilistic computing elements in Belief Networks for performing regenerative tasks.

Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons.

PubMed

Mensi, Skander; Hagens, Olivier; Gerstner, Wulfram; Pozzorini, Christian

2016-02-01

The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics. For that, a new Generalized Integrate-and-Fire model featuring nonlinear firing threshold dynamics and conductance-based adaptation is introduced that outperforms state-of-the-art neuron models in predicting the spiking activity of neurons responding to a variety of in vivo-like fluctuating currents. Our model allows for efficient parameter extraction and can be analytically mapped to a Generalized Linear Model in which both the input filter--describing somatic integration--and the spike-history filter--accounting for spike-frequency adaptation--dynamically adapt to the input statistics, as experimentally observed. Overall, our results provide new insights on the computational role of different biophysical processes known to underlie adaptive coding in single neurons and support previous theoretical findings indicating that the nonlinear dynamics of the firing threshold due to Na+-channel inactivation regulate the sensitivity to rapid input fluctuations.

NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases.

PubMed

Costa, Marta; Manton, James D; Ostrovsky, Aaron D; Prohaska, Steffen; Jefferis, Gregory S X E

2016-07-20

Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish. VIDEO ABSTRACT. Copyright © 2016 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.

Hybrid discrete-time neural networks.

PubMed

Cao, Hongjun; Ibarz, Borja

2010-11-13

Hybrid dynamical systems combine evolution equations with state transitions. When the evolution equations are discrete-time (also called map-based), the result is a hybrid discrete-time system. A class of biological neural network models that has recently received some attention falls within this category: map-based neuron models connected by means of fast threshold modulation (FTM). FTM is a connection scheme that aims to mimic the switching dynamics of a neuron subject to synaptic inputs. The dynamic equations of the neuron adopt different forms according to the state (either firing or not firing) and type (excitatory or inhibitory) of their presynaptic neighbours. Therefore, the mathematical model of one such network is a combination of discrete-time evolution equations with transitions between states, constituting a hybrid discrete-time (map-based) neural network. In this paper, we review previous work within the context of these models, exemplifying useful techniques to analyse them. Typical map-based neuron models are low-dimensional and amenable to phase-plane analysis. In bursting models, fast-slow decomposition can be used to reduce dimensionality further, so that the dynamics of a pair of connected neurons can be easily understood. We also discuss a model that includes electrical synapses in addition to chemical synapses with FTM. Furthermore, we describe how master stability functions can predict the stability of synchronized states in these networks. The main results are extended to larger map-based neural networks.

Nonlinear Maps for Design of Discrete-Time Models of Neuronal Network Dynamics

DTIC Science & Technology

2016-03-31

2016 Performance/Technic~ 03-01-2016- 03-31-2016 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Nonlinear Maps for Design of Discrete -Time Models of...simulations is to design a neuronal model in the form of difference equations that generates neuronal states in discrete moments of time. In this...responsive tiring patterns. We propose to use modern DSP ideas to develop new efficient approaches to the design of such discrete -time models for

Role of phosphatidylinositol 3-kinase in angiotensin II regulation of norepinephrine neuromodulation in brain neurons of the spontaneously hypertensive rat.

PubMed

Yang, H; Raizada, M K

1999-04-01

Chronic stimulation of norepinephrine (NE) neuromodulation by angiotensin II (Ang II) involves activation of the Ras-Raf-MAP kinase signal transduction pathway in Wistar Kyoto (WKY) rat brain neurons. This pathway is only partially responsible for this heightened action of Ang II in the spontaneously hypertensive rat (SHR) brain neurons. In this study, we demonstrate that the MAP kinase-independent signaling pathway in the SHR neuron involves activation of PI3-kinase and protein kinase B (PKB/Akt). Ang II stimulated PI3-kinase activity in both WKY and SHR brain neurons and was accompanied by its translocation from the cytoplasmic to the nuclear compartment. Although the magnitude of stimulation by Ang II was comparable, the stimulation was more persistent in the SHR neuron compared with the WKY rat neuron. Inhibition of PI3-kinase had no significant effect in the WKY rat neuron. However, it caused a 40-50% attenuation of the Ang II-induced increase in norepinephrine transporter (NET) and tyrosine hydroxylase (TH) mRNAs and [3H]-NE uptake in the SHR neuron. In contrast, inhibition of MAP kinase completely attenuated Ang II stimulation of NET and TH mRNA levels in the WKY rat neuron, whereas it caused only a 45% decrease in the SHR neuron. However, an additive attenuation was observed when both kinases of the SHR neurons were inhibited. Ang II also stimulated PKB/Akt activity in both WKY and SHR neurons. This stimulation was 30% higher and lasted longer in the SHR neuron compared with the WKY rat neuron. In conclusion, these observations demonstrate an exclusive involvement of PI3-kinase-PKB-dependent signaling pathway in a heightened NE neuromodulatory action of Ang II in the SHR neuron. Thus, this study offers an excellent potential for the development of new therapies for the treatment of centrally mediated hypertension.

Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons.

PubMed

Goldie, Belinda J; Dun, Matthew D; Lin, Minjie; Smith, Nathan D; Verrills, Nicole M; Dayas, Christopher V; Cairns, Murray J

2014-08-01

Rapid input-restricted change in gene expression is an important aspect of synaptic plasticity requiring complex mechanisms of post-transcriptional mRNA trafficking and regulation. Small non-coding miRNA are uniquely poised to support these functions by providing a nucleic-acid-based specificity component for universal-sequence-dependent RNA binding complexes. We investigated the subcellular distribution of these molecules in resting and potassium chloride depolarized human neuroblasts, and found both selective enrichment and depletion in neurites. Depolarization was associated with a neurite-restricted decrease in miRNA expression; a subset of these molecules was recovered from the depolarization medium in nuclease resistant extracellular exosomes. These vesicles were enriched with primate specific miRNA and the synaptic-plasticity-associated protein MAP1b. These findings further support a role for miRNA as neural plasticity regulators, as they are compartmentalized in neurons and undergo activity-associated redistribution or release into the extracellular matrix. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Recoding a cocaine-place memory engram to a neutral engram in the hippocampus.

PubMed

Trouche, Stéphanie; Perestenko, Pavel V; van de Ven, Gido M; Bratley, Claire T; McNamara, Colin G; Campo-Urriza, Natalia; Black, S Lucas; Reijmers, Leon G; Dupret, David

2016-04-01

The hippocampus provides the brain's memory system with a subset of neurons holding a map-like representation of each environment experienced. We found in mice that optogenetic silencing those neurons active in an environment unmasked a subset of quiet neurons, enabling the emergence of an alternative map. When applied in a cocaine-paired environment, this intervention neutralized an otherwise long-lasting drug-place preference, showing that recoding a spatial memory engram can alleviate associated maladaptive behavior.

Reducing contralateral SI activity reveals hindlimb receptive fields in the SI forelimb-stump representation of neonatally amputated rats.

PubMed

Pluto, Charles P; Chiaia, Nicolas L; Rhoades, Robert W; Lane, Richard D

2005-09-01

In adult rats that sustained forelimb amputation on the day of birth, >30% of multiunit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) also respond to cutaneous hindlimb stimulation when cortical GABA(A+B) receptors are blocked (GRB). This study examined whether hindlimb receptive fields could also be revealed in forelimb-stump sites by reducing one known source of excitatory input to SI GABAergic neurons, the contralateral SI cortex. Corpus callosum projection neurons connect homotopic SI regions, making excitatory contacts onto pyramidal cells and interneurons. Thus in addition to providing monosynaptic excitation in SI, callosal fibers can produce disynaptic inhibition through excitatory synapses with inhibitory interneurons. Based on the latter of these connections, we hypothesized that inactivating the contralateral (intact) SI forelimb region would "unmask" normally suppressed hindlimb responses by reducing the activity of SI GABAergic neurons. The SI forelimb-stump representation was first mapped under normal conditions and then during GRB to identify stump/hindlimb responsive sites. After GRB had dissipated, the contralateral (intact) SI forelimb region was mapped and reversibly inactivated with injections of 4% lidocaine, and selected forelimb-stump sites were retested. Contralateral SI inactivation revealed hindlimb responses in approximately 60% of sites that were stump/hindlimb responsive during GRB. These findings indicate that activity in the contralateral SI contributes to the suppression of reorganized hindlimb receptive fields in neonatally amputated rats.

Spatial selectivity and binaural responses in the inferior colliculus of the great horned owl.

PubMed

Volman, S F; Konishi, M

1989-09-01

In this study we have investigated the processing of auditory cues for sound localization in the great horned owl (Bubo virginianus). Previous studies have shown that the barn owl, whose ears are asymmetrically oriented in the vertical plane, has a 2-dimensional, topographic representation of auditory space in the external division of the inferior colliculus (ICx). As in the barn owl, the great horned owl's ICx is anatomically distinct and projects to the optic tectum. Neurons in ICx respond over only a small range of azimuths (mean = 32 degrees), and azimuth is topographically mapped. In contrast to the barn owl, the great horned owl has bilaterally symmetrical ears and its receptive fields are not restricted in elevation. The binaural cues available for sound localization were measured both with cochlear microphonic recordings and with a microphone attached to a probe tube in the auditory canal. Interaural time disparity (ITD) varied monotonically with azimuth. Interaural intensity differences (IID) also changed with azimuth, but the largest IIDs were less than 15 dB, and the variation was not monotonic. Neither ITD nor IID varied systematically with changes in the vertical position of a sound source. We used dichotic stimulation to determine the sensitivity of ICx neurons to these binaural cues. Best ITD of ICx units was topographically mapped and strongly correlated with receptive-field azimuth. The width of ITD tuning curves, measured at 50% of the maximum response, averaged 72 microseconds. All ICx neurons responded only to binaural stimulation and had nonmonotonic IID tuning curves. Best IID was weakly, but significantly, correlated with best ITD (r = 0.39, p less than 0.05). The IID tuning curves, however, were broad (mean 50% width = 24 dB), and 67% of the units had best IIDs within 5 dB of 0 dB IID. ITD tuning was sensitive to variations in IID in the direction opposite to that expected for time-intensity trading, but the magnitude of this effect was only 1.5 microseconds/dB IID. We conclude that, in the great horned owl, the spatial selectivity of ICx neurons arises primarily from their ITD tuning. Except for the absence of elevation selectivity and the narrow range of best IIDs, ICx in the great horned owl appears to be organized much the same as in the barn owl.

A Comparison of Spatial Analysis Methods for the Construction of Topographic Maps of Retinal Cell Density

PubMed Central

Garza-Gisholt, Eduardo; Hemmi, Jan M.; Hart, Nathan S.; Collin, Shaun P.

2014-01-01

Topographic maps that illustrate variations in the density of different neuronal sub-types across the retina are valuable tools for understanding the adaptive significance of retinal specialisations in different species of vertebrates. To date, such maps have been created from raw count data that have been subjected to only limited analysis (linear interpolation) and, in many cases, have been presented as iso-density contour maps with contour lines that have been smoothed ‘by eye’. With the use of stereological approach to count neuronal distribution, a more rigorous approach to analysing the count data is warranted and potentially provides a more accurate representation of the neuron distribution pattern. Moreover, a formal spatial analysis of retinal topography permits a more robust comparison of topographic maps within and between species. In this paper, we present a new R-script for analysing the topography of retinal neurons and compare methods of interpolating and smoothing count data for the construction of topographic maps. We compare four methods for spatial analysis of cell count data: Akima interpolation, thin plate spline interpolation, thin plate spline smoothing and Gaussian kernel smoothing. The use of interpolation ‘respects’ the observed data and simply calculates the intermediate values required to create iso-density contour maps. Interpolation preserves more of the data but, consequently includes outliers, sampling errors and/or other experimental artefacts. In contrast, smoothing the data reduces the ‘noise’ caused by artefacts and permits a clearer representation of the dominant, ‘real’ distribution. This is particularly useful where cell density gradients are shallow and small variations in local density may dramatically influence the perceived spatial pattern of neuronal topography. The thin plate spline and the Gaussian kernel methods both produce similar retinal topography maps but the smoothing parameters used may affect the outcome. PMID:24747568

Investigating the role of the superior colliculus in active vision with the visual search paradigm.

PubMed

Shen, Kelly; Valero, Jerome; Day, Gregory S; Paré, Martin

2011-06-01

We review here both the evidence that the functional visuomotor organization of the optic tectum is conserved in the primate superior colliculus (SC) and the evidence for the linking proposition that SC discriminating activity instantiates saccade target selection. We also present new data in response to questions that arose from recent SC visual search studies. First, we observed that SC discriminating activity predicts saccade initiation when monkeys perform an unconstrained search for a target defined by either a single visual feature or a conjunction of two features. Quantitative differences between the results in these two search tasks suggest, however, that SC discriminating activity does not only reflect saccade programming. This finding concurs with visual search studies conducted in posterior parietal cortex and the idea that, during natural active vision, visual attention is shifted concomitantly with saccade programming. Second, the analysis of a large neuronal sample recorded during feature search revealed that visual neurons in the superficial layers do possess discriminating activity. In addition, the hypotheses that there are distinct types of SC neurons in the deeper layers and that they are differently involved in saccade target selection were not substantiated. Third, we found that the discriminating quality of single-neuron activity substantially surpasses the ability of the monkeys to discriminate the target from distracters, raising the possibility that saccade target selection is a noisy process. We discuss these new findings in light of the visual search literature and the view that the SC is a visual salience map for orienting eye movements. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Neural coding of image structure and contrast polarity of Cartesian, hyperbolic, and polar gratings in the primary and secondary visual cortex of the tree shrew.

PubMed

Poirot, Jordan; De Luna, Paolo; Rainer, Gregor

2016-04-01

We comprehensively characterize spiking and visual evoked potential (VEP) activity in tree shrew V1 and V2 using Cartesian, hyperbolic, and polar gratings. Neural selectivity to structure of Cartesian gratings was higher than other grating classes in both visual areas. From V1 to V2, structure selectivity of spiking activity increased, whereas corresponding VEP values tended to decrease, suggesting that single-neuron coding of Cartesian grating attributes improved while the cortical columnar organization of these neurons became less precise from V1 to V2. We observed that neurons in V2 generally exhibited similar selectivity for polar and Cartesian gratings, suggesting that structure of polar-like stimuli might be encoded as early as in V2. This hypothesis is supported by the preference shift from V1 to V2 toward polar gratings of higher spatial frequency, consistent with the notion that V2 neurons encode visual scene borders and contours. Neural sensitivity to modulations of polarity of hyperbolic gratings was highest among all grating classes and closely related to the visual receptive field (RF) organization of ON- and OFF-dominated subregions. We show that spatial RF reconstructions depend strongly on grating class, suggesting that intracortical contributions to RF structure are strongest for Cartesian and polar gratings. Hyperbolic gratings tend to recruit least cortical elaboration such that the RF maps are similar to those generated by sparse noise, which most closely approximate feedforward inputs. Our findings complement previous literature in primates, rodents, and carnivores and highlight novel aspects of shape representation and coding occurring in mammalian early visual cortex. Copyright © 2016 the American Physiological Society.

Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights From Simultaneous Cardioneural Mapping.

PubMed

Hamon, David; Rajendran, Pradeep S; Chui, Ray W; Ajijola, Olujimi A; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S; Armour, J Andrew; Ardell, Jeffrey L; Shivkumar, Kalyanam

2017-04-01

Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system, a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on intrinsic cardiac nervous system function in generating cardiac neuronal and electric instability using a novel cardioneural mapping approach. In a porcine model (n=8), neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli ( P <0.001). Compared with fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response ( P <0.05 versus short CI), particularly on convergent neurons ( P <0.05), as well as neurons receiving sympathetic ( P <0.05) and parasympathetic input ( P <0.05). The greatest cardiac electric instability was also observed after variable (short) CI PVCs. Variable CI PVCs affect critical populations of intrinsic cardiac nervous system neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling, leading to cardiomyopathy. © 2017 American Heart Association, Inc.

Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights from Simultaneous Cardio-Neural Mapping

PubMed Central

Hamon, David; Rajendran, Pradeep S.; Chui, Ray W.; Ajijola, Olujimi A.; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S.; Armour, J. Andrew; Ardell, Jeffrey L.; Shivkumar, Kalyanam

2017-01-01

Background Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system (ICNS), a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on ICNS function in generating cardiac neuronal and electrical instability using a novel cardio-neural mapping approach. Methods and Results In a porcine model (n=8) neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli (P<0.001). Compared to fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response (P<0.05 versus short CI), particularly on convergent neurons (P<0.05), as well as neurons receiving sympathetic (P<0.05) and parasympathetic input (P<0.05). The greatest cardiac electrical instability was also observed following variable (short) CI PVCs. Conclusions Variable CI PVCs affect critical populations of ICNS neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling leading to cardiomyopathy. PMID:28408652

The wiring diagram of a glomerular olfactory system

PubMed Central

Berck, Matthew E; Khandelwal, Avinash; Claus, Lindsey; Hernandez-Nunez, Luis; Si, Guangwei; Tabone, Christopher J; Li, Feng; Truman, James W; Fetter, Rick D; Louis, Matthieu; Samuel, Aravinthan DT; Cardona, Albert

2016-01-01

The sense of smell enables animals to react to long-distance cues according to learned and innate valences. Here, we have mapped with electron microscopy the complete wiring diagram of the Drosophila larval antennal lobe, an olfactory neuropil similar to the vertebrate olfactory bulb. We found a canonical circuit with uniglomerular projection neurons (uPNs) relaying gain-controlled ORN activity to the mushroom body and the lateral horn. A second, parallel circuit with multiglomerular projection neurons (mPNs) and hierarchically connected local neurons (LNs) selectively integrates multiple ORN signals already at the first synapse. LN-LN synaptic connections putatively implement a bistable gain control mechanism that either computes odor saliency through panglomerular inhibition, or allows some glomeruli to respond to faint aversive odors in the presence of strong appetitive odors. This complete wiring diagram will support experimental and theoretical studies towards bridging the gap between circuits and behavior. DOI: http://dx.doi.org/10.7554/eLife.14859.001 PMID:27177418

Semaphorin-1a prevents Drosophila olfactory projection neuron dendrites from mis-targeting into select antennal lobe regions.

PubMed

Shen, Hung-Chang; Chu, Sao-Yu; Hsu, Tsai-Chi; Wang, Chun-Han; Lin, I-Ya; Yu, Hung-Hsiang

2017-04-01

Elucidating how appropriate neurite patterns are generated in neurons of the olfactory system is crucial for comprehending the construction of the olfactory map. In the Drosophila olfactory system, projection neurons (PNs), primarily derived from four neural stem cells (called neuroblasts), populate their cell bodies surrounding to and distribute their dendrites in distinct but overlapping patterns within the primary olfactory center of the brain, the antennal lobe (AL). However, it remains unclear whether the same molecular mechanisms are employed to generate the appropriate dendritic patterns in discrete AL glomeruli among PNs produced from different neuroblasts. Here, by examining a previously explored transmembrane protein Semaphorin-1a (Sema-1a) which was proposed to globally control initial PN dendritic targeting along the dorsolateral-to-ventromedial axis of the AL, we discover a new role for Sema-1a in preventing dendrites of both uni-glomerular and poly-glomerular PNs from aberrant invasion into select AL regions and, intriguingly, this Sema-1a-deficient dendritic mis-targeting phenotype seems to associate with the origins of PNs from which they are derived. Further, ectopic expression of Sema-1a resulted in PN dendritic mis-projection from a select AL region into adjacent glomeruli, strengthening the idea that Sema-1a plays an essential role in preventing abnormal dendritic accumulation in select AL regions. Taken together, these results demonstrate that Sema-1a repulsion keeps dendrites of different types of PNs away from each other, enabling the same types of PN dendrites to be sorted into destined AL glomeruli and permitting for functional assembly of olfactory circuitry.

Neural correlates of target selection for reaching movements in superior colliculus

PubMed Central

McPeek, Robert M.

2014-01-01

We recently demonstrated that inactivation of the primate superior colliculus (SC) causes a deficit in target selection for arm-reaching movements when the reach target is located in the inactivated field (Song JH, Rafal RD, McPeek RM. Proc Natl Acad Sci USA 108: E1433–E1440, 2011). This is consistent with the notion that the SC is part of a general-purpose target selection network beyond eye movements. To understand better the role of SC activity in reach target selection, we examined how individual SC neurons in the intermediate layers discriminate a reach target from distractors. Monkeys reached to touch a color oddball target among distractors while maintaining fixation. We found that many SC neurons robustly discriminate the goal of the reaching movement before the onset of the reach even though no saccade is made. To identify these cells in the context of conventional SC cell classification schemes, we also recorded visual, delay-period, and saccade-related responses in a delayed saccade task. On average, SC cells that discriminated the reach target from distractors showed significantly higher visual and delay-period activity than nondiscriminating cells, but there was no significant difference in saccade-related activity. Whereas a majority of SC neurons that discriminated the reach target showed significant delay-period activity, all nondiscriminating cells lacked such activity. We also found that some cells without delay-period activity did discriminate the reach target from distractors. We conclude that the majority of intermediate-layer SC cells discriminate a reach target from distractors, consistent with the idea that the SC contains a priority map used for effector-independent target selection. PMID:25505107

Spatial structure of cone inputs to receptive fields in primate lateral geniculate nucleus

NASA Astrophysics Data System (ADS)

Reid, R. Clay; Shapley, Robert M.

1992-04-01

HUMAN colour vision depends on three classes of cone photoreceptors, those sensitive to short (S), medium (M) or long (L) wavelengths, and on how signals from these cones are combined by neurons in the retina and brain. Macaque monkey colour vision is similar to human, and the receptive fields of macaque visual neurons have been used as an animal model of human colour processing1. P retinal ganglion cells and parvocellular neurons are colour-selective neurons in macaque retina and lateral geniculate nucleus. Interactions between cone signals feeding into these neurons are still unclear. On the basis of experimental results with chromatic adaptation, excitatory and inhibitory inputs from L and M cones onto P cells (and parvocellular neurons) were thought to be quite specific2,3 (Fig. la). But these experiments with spatially diffuse adaptation did not rule out the 'mixed-surround' hypothesis: that there might be one cone-specific mechanism, the receptive field centre, and a surround mechanism connected to all cone types indiscriminately (Fig. le). Recent work has tended to support the mixed-surround hypothesis4-8. We report here the development of new stimuli to measure spatial maps of the linear L-, M- and S-cone inputs to test the hypothesis definitively. Our measurements contradict the mixed-surround hypothesis and imply cone specificity in both centre and surround.

Classic cadherin expressions balance postnatal neuronal positioning and dendrite dynamics to elaborate the specific cytoarchitecture of the mouse cortical area.

PubMed

Egusa, Saki F; Inoue, Yukiko U; Asami, Junko; Terakawa, Youhei W; Hoshino, Mikio; Inoue, Takayoshi

2016-04-01

A unique feature of the mammalian cerebral cortex is in its tangential parcellation via anatomical and functional differences. However, the cellular and/or molecular machinery involved in cortical arealization remain largely unknown. Here we map expression profiles of classic cadherins in the postnatal mouse barrel field of the primary somatosensory area (S1BF) and generate a novel bacterial artificial chromosome transgenic (BAC-Tg) mouse line selectively illuminating nuclei of cadherin-6 (Cdh6)-expressing layer IV barrel neurons to confirm that tangential cellular assemblage of S1BF is established by postnatal day 5 (P5). When we electroporate the cadherins expressed in both barrel neurons and thalamo-cortical axon (TCA) terminals limited to the postnatal layer IV neurons, S1BF cytoarchitecture is disorganized with excess elongation of dendrites at P7. Upon delivery of dominant negative molecules for all classic cadherins, tangential cellular positioning and biased dendritic arborization of barrel neurons are significantly altered. These results underscore the value of classic cadherin-mediated sorting among neuronal cell bodies, dendrites and TCA terminals in postnatally elaborating the S1BF-specific tangential cytoarchitecture. Additionally, how the "protocortex" machinery affects classic cadherin expression profiles in the process of cortical arealization is examined and discussed. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons

PubMed Central

Mensi, Skander; Hagens, Olivier; Gerstner, Wulfram; Pozzorini, Christian

2016-01-01

The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics. For that, a new Generalized Integrate-and-Fire model featuring nonlinear firing threshold dynamics and conductance-based adaptation is introduced that outperforms state-of-the-art neuron models in predicting the spiking activity of neurons responding to a variety of in vivo-like fluctuating currents. Our model allows for efficient parameter extraction and can be analytically mapped to a Generalized Linear Model in which both the input filter—describing somatic integration—and the spike-history filter—accounting for spike-frequency adaptation—dynamically adapt to the input statistics, as experimentally observed. Overall, our results provide new insights on the computational role of different biophysical processes known to underlie adaptive coding in single neurons and support previous theoretical findings indicating that the nonlinear dynamics of the firing threshold due to Na+-channel inactivation regulate the sensitivity to rapid input fluctuations. PMID:26907675

A Discrete Population of Neurons in the Lateral Amygdala Is Specifically Activated by Contextual Fear Conditioning

ERIC Educational Resources Information Center

Wilson, Yvette M.; Murphy, Mark

2009-01-01

There is no clear identification of the neurons involved in fear conditioning in the amygdala. To search for these neurons, we have used a genetic approach, the "fos-tau-lacZ" (FTL) mouse, to map functionally activated expression in neurons following contextual fear conditioning. We have identified a discrete population of neurons in the lateral…

Optogenetic mapping of brain circuitry

NASA Astrophysics Data System (ADS)

Augustine, George J.; Berglund, Ken; Gill, Harin; Hoffmann, Carolin; Katarya, Malvika; Kim, Jinsook; Kudolo, John; Lee, Li M.; Lee, Molly; Lo, Daniel; Nakajima, Ryuichi; Park, Min Yoon; Tan, Gregory; Tang, Yanxia; Teo, Peggy; Tsuda, Sachiko; Wen, Lei; Yoon, Su-In

2012-10-01

Studies of the brain promise to be revolutionized by new experimental strategies that harness the combined power of optical techniques and genetics. We have mapped the circuitry of the mouse brain by using both optogenetic actuators that control neuronal activity and optogenetic sensors that detect neuronal activity. Using the light-activated cation channel, channelrhodopsin-2, to locally photostimulate neurons allows high-speed mapping of local and long-range circuitry. For example, with this approach we have mapped local circuits in the cerebral cortex, cerebellum and many other brain regions. Using the fluorescent sensor for chloride ions, Clomeleon, allows imaging of the spatial and temporal dimensions of inhibitory circuits in the brain. This approach allows imaging of both conventional "phasic" synaptic inhibition as well as unconventional "tonic" inhibition. The combined use of light to both control and monitor neural activity creates unprecedented opportunities to explore brain function, screen pharmaceutical agents, and potentially to use light to ameliorate psychiatric and neurological disorders.

The Representation of Orientation in Macaque V2: Four Stripes Not Three

PubMed Central

Felleman, Daniel J.; Lim, Heejin; Xiao, Youping; Wang, Yi; Eriksson, Anastasia; Parajuli, Arun

2015-01-01

Area V2 of macaque monkeys is traditionally thought to consist of 3 distinct functional compartments with characteristic cortical connections and functional properties. Orientation selectivity is one property that has frequently been used to distinguish V2 stripes, however, this receptive field property has been found in a high percentage of neurons across V2 compartments. Using quantitative intrinsic cortical imaging, we derived maps of preferred orientation, orientation selectivity, and orientation gradient in thin stripes, thick stripes, and interstripes in area V2. Orientation-selective responses were found in each V2 stripe, but the magnitude and organization of orientation selectivity differed significantly from stripe to stripe. Remarkably, the 2 pale stripes flanking each cytochrome oxidase dense stripe differed significantly in their representation of orientation resulting in their distinction as type-I and type-II interstripes. V2 orientation maps are characterized by clockwise and anticlockwise “orientation pinwheels”, but unlike V1, they are not homogeneously distributed across V2. Furthermore, V2 stripes contain large-scale sequences of preferred orientation. These analyses demonstrate that V2 consists of 4 distinct functional compartments; thick stripes and type-II interstripes, which are strongly orientation selective and thin stripes and type-I interstripes, which are significantly less selective for orientation and exhibit larger orientation gradient magnitudes. PMID:24614951

Transsynaptic Mapping of Second-Order Taste Neurons in Flies by trans-Tango.

PubMed

Talay, Mustafa; Richman, Ethan B; Snell, Nathaniel J; Hartmann, Griffin G; Fisher, John D; Sorkaç, Altar; Santoyo, Juan F; Chou-Freed, Cambria; Nair, Nived; Johnson, Mark; Szymanski, John R; Barnea, Gilad

2017-11-15

Mapping neural circuits across defined synapses is essential for understanding brain function. Here we describe trans-Tango, a technique for anterograde transsynaptic circuit tracing and manipulation. At the core of trans-Tango is a synthetic signaling pathway that is introduced into all neurons in the animal. This pathway converts receptor activation at the cell surface into reporter expression through site-specific proteolysis. Specific labeling is achieved by presenting a tethered ligand at the synapses of genetically defined neurons, thereby activating the pathway in their postsynaptic partners and providing genetic access to these neurons. We first validated trans-Tango in the Drosophila olfactory system and then implemented it in the gustatory system, where projections beyond the first-order receptor neurons are not fully characterized. We identified putative second-order neurons within the sweet circuit that include projection neurons targeting known neuromodulation centers in the brain. These experiments establish trans-Tango as a flexible platform for transsynaptic circuit analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

NeuroLines: A Subway Map Metaphor for Visualizing Nanoscale Neuronal Connectivity.

PubMed

Al-Awami, Ali K; Beyer, Johanna; Strobelt, Hendrik; Kasthuri, Narayanan; Lichtman, Jeff W; Pfister, Hanspeter; Hadwiger, Markus

2014-12-01

We present NeuroLines, a novel visualization technique designed for scalable detailed analysis of neuronal connectivity at the nanoscale level. The topology of 3D brain tissue data is abstracted into a multi-scale, relative distance-preserving subway map visualization that allows domain scientists to conduct an interactive analysis of neurons and their connectivity. Nanoscale connectomics aims at reverse-engineering the wiring of the brain. Reconstructing and analyzing the detailed connectivity of neurons and neurites (axons, dendrites) will be crucial for understanding the brain and its development and diseases. However, the enormous scale and complexity of nanoscale neuronal connectivity pose big challenges to existing visualization techniques in terms of scalability. NeuroLines offers a scalable visualization framework that can interactively render thousands of neurites, and that supports the detailed analysis of neuronal structures and their connectivity. We describe and analyze the design of NeuroLines based on two real-world use-cases of our collaborators in developmental neuroscience, and investigate its scalability to large-scale neuronal connectivity data.

Descending projections from the basal forebrain to the orexin neurons in mice.

PubMed

Agostinelli, Lindsay J; Ferrari, Loris L; Mahoney, Carrie E; Mochizuki, Takatoshi; Lowell, Bradford B; Arrigoni, Elda; Scammell, Thomas E

2017-05-01

The orexin (hypocretin) neurons play an essential role in promoting arousal, and loss of the orexin neurons results in narcolepsy, a condition characterized by chronic sleepiness and cataplexy. The orexin neurons excite wake-promoting neurons in the basal forebrain (BF), and a reciprocal projection from the BF back to the orexin neurons may help promote arousal and motivation. The BF contains at least three different cell types (cholinergic, glutamatergic, and γ-aminobutyric acid (GABA)ergic neurons) across its different regions (medial septum, diagonal band, magnocellular preoptic area, and substantia innominata). Given the neurochemical and anatomical heterogeneity of the BF, we mapped the pattern of BF projections to the orexin neurons across multiple BF regions and neuronal types. We performed conditional anterograde tracing using mice that express Cre recombinase only in neurons producing acetylcholine, glutamate, or GABA. We found that the orexin neurons are heavily apposed by axon terminals of glutamatergic and GABAergic neurons of the substantia innominata (SI) and magnocellular preoptic area, but there was no innervation by the cholinergic neurons. Channelrhodopsin-assisted circuit mapping (CRACM) demonstrated that glutamatergic SI neurons frequently form functional synapses with the orexin neurons, but, surprisingly, functional synapses from SI GABAergic neurons were rare. Considering their strong reciprocal connections, BF and orexin neurons likely work in concert to promote arousal, motivation, and other behaviors. J. Comp. Neurol. 525:1668-1684, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Paeoniflorin, a Monoterpene Glycoside, Protects the Brain from Cerebral Ischemic Injury via Inhibition of Apoptosis.

PubMed

Zhang, Yuqin; Li, Huang; Huang, Mingqing; Huang, Mei; Chu, Kedan; Xu, Wei; Zhang, Shengnan; Que, Jinhua; Chen, Lidian

2015-01-01

Paeoniflorin (PF) is a principal bioactive component, which exhibits many pharmacological effects, including protection against ischemic injury. This paper aimed to investigate the protective effect of PF both in vivo and in vitro. Middle cerebral artery occlusion (MCAO) was performed on male Sprague-Dawley (SD) rat for 2 h, and different doses of PF or vehicle were administered 2 h after reperfusion. Rats were sacrificed after 7 days treatment of PF/vehicle. PF treatment for 7 days ameliorated MCAO-induced neurological deficit and decreased the infarct area. Further study demonstrated that PF inhibited the over-activation of astrocytes and apoptosis of neurons, and PF promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, NMDA-induced neuron apoptosis was employed. The in vitro study revealed that PF treatment protected against NMDA-induced cell apoptosis and neuronal loss via up-regulation of neuronal specific marker NeuN, MAP-2 and Bcl-2 and the down-regulation Bax. Taken together, the present study demonstrates that PF produces its protective effect by inhibiting the over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN, MAP-2, and B-cell lymphoma-2 (Bcl-2), and down-regulation Bax. Our study reveals that PF may be a potential neuroprotective agent for stroke and can provide basic data for clinical use.

Receptive-field subfields of V2 neurons in macaque monkeys are adult-like near birth.

PubMed

Zhang, Bin; Tao, Xiaofeng; Shen, Guofu; Smith, Earl L; Ohzawa, Izumi; Chino, Yuzo M

2013-02-06

Infant primates can discriminate texture-defined form despite their relatively low visual acuity. The neuronal mechanisms underlying this remarkable visual capacity of infants have not been studied in nonhuman primates. Since many V2 neurons in adult monkeys can extract the local features in complex stimuli that are required for form vision, we used two-dimensional dynamic noise stimuli and local spectral reverse correlation to measure whether the spatial map of receptive-field subfields in individual V2 neurons is sufficiently mature near birth to capture local features. As in adults, most V2 neurons in 4-week-old monkeys showed a relatively high degree of homogeneity in the spatial matrix of facilitatory subfields. However, ∼25% of V2 neurons had the subfield map where the neighboring facilitatory subfields substantially differed in their preferred orientations and spatial frequencies. Over 80% of V2 neurons in both infants and adults had "tuned" suppressive profiles in their subfield maps that could alter the tuning properties of facilitatory profiles. The differences in the preferred orientations between facilitatory and suppressive profiles were relatively large but extended over a broad range. Response immaturities in infants were mild; the overall strength of facilitatory subfield responses was lower than that in adults, and the optimal correlation delay ("latency") was longer in 4-week-old infants. These results suggest that as early as 4 weeks of age, the spatial receptive-field structure of V2 neurons is as complex as in adults and the ability of V2 neurons to compare local features of neighboring stimulus elements is nearly adult like.

The neural representation of the gender of faces in the primate visual system: A computer modeling study.

PubMed

Minot, Thomas; Dury, Hannah L; Eguchi, Akihiro; Humphreys, Glyn W; Stringer, Simon M

2017-03-01

We use an established neural network model of the primate visual system to show how neurons might learn to encode the gender of faces. The model consists of a hierarchy of 4 competitive neuronal layers with associatively modifiable feedforward synaptic connections between successive layers. During training, the network was presented with many realistic images of male and female faces, during which the synaptic connections are modified using biologically plausible local associative learning rules. After training, we found that different subsets of output neurons have learned to respond exclusively to either male or female faces. With the inclusion of short range excitation within each neuronal layer to implement a self-organizing map architecture, neurons representing either male or female faces were clustered together in the output layer. This learning process is entirely unsupervised, as the gender of the face images is not explicitly labeled and provided to the network as a supervisory training signal. These simulations are extended to training the network on rotating faces. It is found that by using a trace learning rule incorporating a temporal memory trace of recent neuronal activity, neurons responding selectively to either male or female faces were also able to learn to respond invariantly over different views of the faces. This kind of trace learning has been previously shown to operate within the primate visual system by neurophysiological and psychophysical studies. The computer simulations described here predict that similar neurons encoding the gender of faces will be present within the primate visual system. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Modeling the Development of Goal-Specificity in Mirror Neurons.

PubMed

Thill, Serge; Svensson, Henrik; Ziemke, Tom

2011-12-01

Neurophysiological studies have shown that parietal mirror neurons encode not only actions but also the goal of these actions. Although some mirror neurons will fire whenever a certain action is perceived (goal-independently), most will only fire if the motion is perceived as part of an action with a specific goal. This result is important for the action-understanding hypothesis as it provides a potential neurological basis for such a cognitive ability. It is also relevant for the design of artificial cognitive systems, in particular robotic systems that rely on computational models of the mirror system in their interaction with other agents. Yet, to date, no computational model has explicitly addressed the mechanisms that give rise to both goal-specific and goal-independent parietal mirror neurons. In the present paper, we present a computational model based on a self-organizing map, which receives artificial inputs representing information about both the observed or executed actions and the context in which they were executed. We show that the map develops a biologically plausible organization in which goal-specific mirror neurons emerge. We further show that the fundamental cause for both the appearance and the number of goal-specific neurons can be found in geometric relationships between the different inputs to the map. The results are important to the action-understanding hypothesis as they provide a mechanism for the emergence of goal-specific parietal mirror neurons and lead to a number of predictions: (1) Learning of new goals may mostly reassign existing goal-specific neurons rather than recruit new ones; (2) input differences between executed and observed actions can explain observed corresponding differences in the number of goal-specific neurons; and (3) the percentage of goal-specific neurons may differ between motion primitives.

A systematic approach to selecting task relevant neurons.

PubMed

Kahn, Kevin; Saxena, Shreya; Eskandar, Emad; Thakor, Nitish; Schieber, Marc; Gale, John T; Averbeck, Bruno; Eden, Uri; Sarma, Sridevi V

2015-04-30

Since task related neurons cannot be specifically targeted during surgery, a critical decision to make is to select which neurons are task-related when performing data analysis. Including neurons unrelated to the task degrade decoding accuracy and confound neurophysiological results. Traditionally, task-related neurons are selected as those with significant changes in firing rate when a stimulus is applied. However, this assumes that neurons' encoding of stimuli are dominated by their firing rate with little regard to temporal dynamics. This paper proposes a systematic approach for neuron selection, which uses a likelihood ratio test to capture the contribution of stimulus to spiking activity while taking into account task-irrelevant intrinsic dynamics that affect firing rates. This approach is denoted as the model deterioration excluding stimulus (MDES) test. MDES is compared to firing rate selection in four case studies: a simulation, a decoding example, and two neurophysiology examples. The MDES rankings in the simulation match closely with ideal rankings, while firing rate rankings are skewed by task-irrelevant parameters. For decoding, 95% accuracy is achieved using the top 8 MDES-ranked neurons, while the top 12 firing-rate ranked neurons are needed. In the neurophysiological examples, MDES matches published results when firing rates do encode salient stimulus information, and uncovers oscillatory modulations in task-related neurons that are not captured when neurons are selected using firing rates. These case studies illustrate the importance of accounting for intrinsic dynamics when selecting task-related neurons and following the MDES approach accomplishes that. MDES selects neurons that encode task-related information irrespective of these intrinsic dynamics which can bias firing rate based selection. Copyright © 2015 Elsevier B.V. All rights reserved.

Song tutoring in presinging zebra finch juveniles biases a small population of higher-order song-selective neurons toward the tutor song.

PubMed

Adret, Patrice; Meliza, C Daniel; Margoliash, Daniel

2012-10-01

We explored physiological changes correlated with song tutoring by recording the responses of caudal nidopallium neurons of zebra finches aged P21-P24 (days post hatching) to a broad spectrum of natural and synthetic stimuli. Those birds raised with their fathers tended to show behavioral evidence of song memorization but not of singing; thus auditory responses were not confounded by the birds' own vocalizations. In study 1, 37 of 158 neurons (23%) in 17 of 22 tutored and untutored birds were selective for only 1 of 10 stimuli comprising broadband signals, early juvenile songs and calls, female calls, and adult songs. Approximately 30% of the selective neurons (12/37 neurons in 9 birds) were selective for adult conspecific songs. All these were found in the song system nuclei HVC and paraHVC. Of 122 neurons (17 birds) in tutored birds, all of the conspecific song-selective neurons (8 neurons in 6 birds) were selective for the adult tutor song; none was selective for unfamiliar song. In study 2 with a different sampling strategy, we found that 11 of 12 song-selective neurons in 6 of 7 birds preferred the tutor song; none preferred unfamiliar or familiar conspecific songs. Most of these neurons were found in caudal lateral nidopallium (NCL) below HVC. Thus by the time a bird begins to sing, there are small numbers of tutor song-selective neurons distributed in several forebrain regions. We hypothesize that a small population of higher-order auditory neurons is innately selective for complex features of behaviorally relevant stimuli and these responses are modified by specific perceptual/social experience during development.

Song tutoring in presinging zebra finch juveniles biases a small population of higher-order song-selective neurons toward the tutor song

PubMed Central

Adret, Patrice; Meliza, C. Daniel

2012-01-01

We explored physiological changes correlated with song tutoring by recording the responses of caudal nidopallium neurons of zebra finches aged P21–P24 (days post hatching) to a broad spectrum of natural and synthetic stimuli. Those birds raised with their fathers tended to show behavioral evidence of song memorization but not of singing; thus auditory responses were not confounded by the birds' own vocalizations. In study 1, 37 of 158 neurons (23%) in 17 of 22 tutored and untutored birds were selective for only 1 of 10 stimuli comprising broadband signals, early juvenile songs and calls, female calls, and adult songs. Approximately 30% of the selective neurons (12/37 neurons in 9 birds) were selective for adult conspecific songs. All these were found in the song system nuclei HVC and paraHVC. Of 122 neurons (17 birds) in tutored birds, all of the conspecific song-selective neurons (8 neurons in 6 birds) were selective for the adult tutor song; none was selective for unfamiliar song. In study 2 with a different sampling strategy, we found that 11 of 12 song-selective neurons in 6 of 7 birds preferred the tutor song; none preferred unfamiliar or familiar conspecific songs. Most of these neurons were found in caudal lateral nidopallium (NCL) below HVC. Thus by the time a bird begins to sing, there are small numbers of tutor song-selective neurons distributed in several forebrain regions. We hypothesize that a small population of higher-order auditory neurons is innately selective for complex features of behaviorally relevant stimuli and these responses are modified by specific perceptual/social experience during development. PMID:22786956

Methyllycaconitine: a non-radiolabeled ligand for mapping α7 neuronal nicotinic acetylcholine receptors - in vivo target localization and biodistribution in rat brain.

PubMed

Nirogi, Ramakrishna; Kandikere, Vishwottam; Bhyrapuneni, Gopinadh; Saralaya, Ramanatha; Muddana, Nageswararao; Komarneni, Prashanth

2012-07-01

Reduction of cerebral cortical and hippocampal α7 neuronal nicotinic acetylcholine receptor (nAChR) density was observed in the Alzheimer's disease (AD) and other neurodegenerative diseases. Mapping the subtypes of nAChRs with selective ligand by viable, quick and consistent method in preclinical drug discovery may lead to rapid development of more effective therapeutic agents. The objective of this study was to evaluate the use of methyllycaconitine (MLA) in non-radiolabeled form for mapping α7 nAChRs in rat brain. MLA pharmacokinetic and brain penetration properties were assessed in male Wistar rats. The tracer properties of MLA were evaluated in rat brain by dose and time dependent differential regional distribution studies. Target specificity was validated after blocking with potent α7 nAChR agonists ABBF, PNU282987 and nicotine. High performance liquid chromatography combined with triple quad mass spectral detector (LC-MS/MS) was used to measure the plasma and brain tissue concentrations of MLA. MLA has shown rapid brain uptake followed by a 3-5 fold higher specific binding in regions containing the α7 nAChRs (hypothalamus - 1.60 ng/g), when compared to non-specific regions (striatum - 0.53 ng/g, hippocampus - 0.46 ng/g, midbrain - 0.37 ng/g, frontal cortex - 0.35 ng/g and cerebellum - 0.30 ng/g). Pretreatment with potent α7 nAChR agonists significantly blocked the MLA uptake in hypothalamus. The non-radiolabeled MLA binding to brain region was comparable with the α7 mRNA localization and receptor distribution reported for [(3)H] MLA in rat brain. The rat pharmacokinetic, brain penetration and differential brain regional distribution features favor that MLA is suitable to use in preclinical stage for mapping α7 nAChRs. Hence, this approach can be employed as an essential tool for quicker development of novel selective ligand to map variation in the α7 receptor densities, as well as to evaluate potential new chemical entities targeting neurodegenerative diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Fast assembling of neuron fragments in serial 3D sections.

PubMed

Chen, Hanbo; Iascone, Daniel Maxim; da Costa, Nuno Maçarico; Lein, Ed S; Liu, Tianming; Peng, Hanchuan

2017-09-01

Reconstructing neurons from 3D image-stacks of serial sections of thick brain tissue is very time-consuming and often becomes a bottleneck in high-throughput brain mapping projects. We developed NeuronStitcher, a software suite for stitching non-overlapping neuron fragments reconstructed in serial 3D image sections. With its efficient algorithm and user-friendly interface, NeuronStitcher has been used successfully to reconstruct very large and complex human and mouse neurons.

Calpastatin inhibits motor neuron death and increases survival of hSOD1(G93A) mice.

PubMed

Rao, Mala V; Campbell, Jabbar; Palaniappan, Arti; Kumar, Asok; Nixon, Ralph A

2016-04-01

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with a poorly understood cause and no effective treatment. Given that calpains mediate neurodegeneration in other pathological states and are abnormally activated in ALS, we investigated the possible ameliorative effects of inhibiting calpain over-activation in hSOD1(G93A) transgenic (Tg) mice in vivo by neuron-specific over-expression of calpastatin (CAST), the highly selective endogenous inhibitor of calpains. Our data indicate that over-expression of CAST in hSOD1(G93A) mice, which lowered calpain activation to levels comparable to wild-type mice, inhibited the abnormal breakdown of cytoskeletal proteins (spectrin, MAP2 and neurofilaments), and ameliorated motor axon loss. Disease onset in hSOD1(G93A) /CAST mice compared to littermate hSOD1(G93A) mice is delayed, which accounts for their longer time of survival. We also find that neuronal over-expression of CAST in hSOD1(G93A) transgenic mice inhibited production of putative neurotoxic caspase-cleaved tau and activation of Cdk5, which have been implicated in neurodegeneration in ALS models, and also reduced the formation of SOD1 oligomers. Our data indicate that inhibition of calpain with CAST is neuroprotective in an ALS mouse model. CAST (encoding calpastatin) inhibits hyperactivated calpain to prevent motor neuron disease operating through a cascade of events as indicated in the schematic, with relevance to amyotrophic lateral sclerosis (ALS). We propose that over-expression of CAST in motor neurons of hSOD1(G93A) mice inhibits activation of CDK5, breakdown of cytoskeletal proteins (NFs, MAP2 and Tau) and regulatory molecules (Cam Kinase IV, Calcineurin A), and disease-causing proteins (TDP-43, α-Synuclein and Huntingtin) to prevent neuronal loss and delay neurological deficits. In our experiments, CAST could also inhibit cleavage of Bid, Bax, AIF to prevent mitochondrial, ER and lysosome-mediated cell death mechanisms. Similarly, CAST over-expression in neurons attenuated pathological effects of TDP-43, α-synuclein and Huntingtin. These results suggest a potential value of specific small molecule inhibitors of calpains in delaying the development of ALS. Read the Editorial Highlight for this article on page 140. © 2016 International Society for Neurochemistry.

Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons.

PubMed

do Carmo, Jussara M; da Silva, Alexandre A; Cai, Zhengwei; Lin, Shuying; Dubinion, John H; Hall, John E

2011-05-01

Although the central nervous system melanocortin system is an important regulator of energy balance, the role of proopiomelanocortin (POMC) neurons in mediating the chronic effects of leptin on appetite, blood pressure, and glucose regulation is unknown. Using Cre/loxP technology we tested whether leptin receptor deletion in POMC neurons (LepR(flox/flox)/POMC-Cre mice) attenuates the chronic effects of leptin to increase mean arterial pressure (MAP), enhance glucose use and oxygen consumption, and reduce appetite. LepR(flox/flox)/POMC-Cre, wild-type, LepR(flox/flox), and POMC-Cre mice were instrumented for MAP and heart rate measurement by telemetry and venous catheters for infusions. LepR(flox/flox)/POMC-Cre mice were heavier, hyperglycemic, hyperinsulinemic, and hyperleptinemic compared with wild-type, LepR(flox/flox), and POMC-Cre mice. Despite exhibiting features of metabolic syndrome, LepR(flox/flox)/POMC-Cre mice had normal MAP and heart rate compared with LepR(flox/flox) but lower MAP and heart rate compared with wild-type mice. After a 5-day control period, leptin was infused (2 μg/kg per minute, IV) for 7 days. In control mice, leptin increased MAP by ≈5 mm Hg despite decreasing food intake by ≈35%. In contrast, leptin infusion in LepR(flox/flox)/POMC-Cre mice reduced MAP by ≈3 mm Hg and food intake by ≈28%. Leptin significantly decreased insulin and glucose levels in control mice but not in LepR(flox/flox)/POMC-Cre mice. Leptin increased oxygen consumption in LepR(flox/flox)/POMC-Cre and wild-type mice. Activation of POMC neurons is necessary for the chronic effects of leptin to raise MAP and reduce insulin and glucose levels, whereas leptin receptors in other areas of the brain other than POMC neurons appear to play a key role in mediating the chronic effects of leptin on appetite and oxygen consumption.

A Topological Paradigm for Hippocampal Spatial Map Formation Using Persistent Homology

PubMed Central

Dabaghian, Y.; Mémoli, F.; Frank, L.; Carlsson, G.

2012-01-01

An animal's ability to navigate through space rests on its ability to create a mental map of its environment. The hippocampus is the brain region centrally responsible for such maps, and it has been assumed to encode geometric information (distances, angles). Given, however, that hippocampal output consists of patterns of spiking across many neurons, and downstream regions must be able to translate those patterns into accurate information about an animal's spatial environment, we hypothesized that 1) the temporal pattern of neuronal firing, particularly co-firing, is key to decoding spatial information, and 2) since co-firing implies spatial overlap of place fields, a map encoded by co-firing will be based on connectivity and adjacency, i.e., it will be a topological map. Here we test this topological hypothesis with a simple model of hippocampal activity, varying three parameters (firing rate, place field size, and number of neurons) in computer simulations of rat trajectories in three topologically and geometrically distinct test environments. Using a computational algorithm based on recently developed tools from Persistent Homology theory in the field of algebraic topology, we find that the patterns of neuronal co-firing can, in fact, convey topological information about the environment in a biologically realistic length of time. Furthermore, our simulations reveal a “learning region” that highlights the interplay between the parameters in combining to produce hippocampal states that are more or less adept at map formation. For example, within the learning region a lower number of neurons firing can be compensated by adjustments in firing rate or place field size, but beyond a certain point map formation begins to fail. We propose that this learning region provides a coherent theoretical lens through which to view conditions that impair spatial learning by altering place cell firing rates or spatial specificity. PMID:22912564

Organization of dopamine and serotonin system: Anatomical and functional mapping of monosynaptic inputs using rabies virus.

PubMed

Ogawa, Sachie K; Watabe-Uchida, Mitsuko

2017-05-02

Dopamine and serotonin play critical roles in flexible behaviors and are related to various psychiatric and motor disorders. This paper reviews the global organization of dopamine and serotonin systems through recent findings using a modified rabies virus. We first introduce methods for comprehensive mapping of monosynaptic inputs. We then describe quantitative comparisons across the data regarding monosynaptic inputs to dopamine neurons versus serotonin neurons. There is surprising similarity between the input to dopamine neurons in the ventral tegmental area (VTA) and the input to serotonin neurons in the dorsal raphe (DR), suggesting functional interactions between these systems. We next introduce studies of mapping monosynaptic inputs to subpopulations of dopamine neurons specified by their projection targets. It was found that the population of dopamine neurons that project to the tail of the striatum (TS) forms an anatomically distinct outlier, suggesting a unique function. From these series of anatomical studies, we propose that there are three information flows that regulate these neuromodulatory systems: the midline stream to serotonin neurons in median raphe (MR) and B6, the central stream to value-coding dopamine neurons and serotonin neurons in rostral DR, and the lateral stream to TS-projecting dopamine neurons. Finally we introduce a new approach to investigate firing patterns of monosynaptic inputs to dopamine neurons in behaving animals. Combining anatomical and physiological findings, we propose that within the central stream, dopamine neurons broadcast a central teaching signal rather than personal teaching signals to multiple brain areas, which are computed in a redundant way in multi-layered neural circuits. Examination of global organization of the dopamine and serotonin circuits not only revealed the complexity of the systems but also revealed some principles of their organization. We will also discuss limitations, practical issues and the possibility of future improvements of the rabies virus-mediated tracing system. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuronal networks and self-organizing maps: new computer techniques in the acoustic evaluation of the infant cry.

PubMed

Schönweiler, R; Kaese, S; Möller, S; Rinscheid, A; Ptok, M

1996-12-05

Neuronal networks are computer-based techniques for the evaluation and control of complex information systems and processes. So far, they have been used in engineering, telecommunications, artificial speech and speech recognition. A new approach in neuronal network is the self-organizing map (Kohonen map). In the phase of 'learning', the map adapts to the patterns of the primary signals. If, the phase of 'using the map', the input signal hits the field of the primary signals, it resembles them and is called a 'winner'. In our study, we recorded the cries of newborns and young infants using digital audio tape (DAT) and a high quality microphone. The cries were elicited by tactile stimuli wearing headphones. In 27 cases, delayed auditory feedback was presented to the children using a headphone and an additional three-head tape-recorder. Spectrographic characteristics of the cries were classified by 20-step bark spectra and then applied to the neuronal networks. It was possible to recognize similarities of different cries of the same children as well as interindividual differences, which are also audible to experienced listeners. Differences were obvious in profound hearing loss. We know much about the cries of both healthy and sick infants, but a reliable investigation regimen, which can be used for clinical routine purposes, has yet not been developed. If, in the future, it becomes possible to classify spectrographic characteristics automatically, even if they are not audible, neuronal networks may be helpful in the early diagnosis of infant diseases.

Relationships between selective neuronal loss and microglial activation after ischaemic stroke in man.

PubMed

Morris, Rhiannon S; Simon Jones, P; Alawneh, Josef A; Hong, Young T; Fryer, Tim D; Aigbirhio, Franklin I; Warburton, Elizabeth A; Baron, Jean-Claude

2018-05-09

Modern ischaemic stroke management involves intravenous thrombolysis followed by mechanical thrombectomy, which allows markedly higher rates of recanalization and penumbral salvage than thrombolysis alone. However, <50% of treated patients eventually enjoy independent life. It is therefore important to identify complementary therapeutic targets. In rodent models, the salvaged penumbra is consistently affected by selective neuronal loss, which may hinder recovery by interfering with plastic processes, as well as by microglial activation, which may exacerbate neuronal death. However, whether the salvaged penumbra in man is similarly affected is still unclear. Here we determined whether these two processes affect the non-infarcted penumbra in man and, if so, whether they are inter-related. We prospectively recruited patients with (i) acute middle-cerebral artery stroke; (ii) penumbra present on CT perfusion obtained <4.5 h of stroke onset; and (iii) early neurological recovery as a marker of penumbral salvage. PET with 11C-flumazenil and 11C-PK11195, as well as MRI to map the final infarct, were obtained at predefined follow-up times. The presence of selective neuronal loss and microglial activation was determined voxel-wise within the MRI normal-appearing ipsilateral non-infarcted zone and surviving penumbra masks, and their inter-relationship was assessed both across and within patients. Dilated infarct contours were consistently excluded to control for partial volume effects. Across the 16 recruited patients, there was reduced 11C-flumazenil and increased 11C-PK11195 binding in the whole ipsilateral non-infarcted zone (P = 0.04 and 0.02, respectively). Within the non-infarcted penumbra, 11C-flumazenil was also reduced (P = 0.001), but without clear increase in 11C-PK11195 (P = 0.18). There was no significant correlation between 11C-flumazenil and 11C-PK11195 in either compartment. This mechanistic study provides direct evidence for the presence of both neuronal loss and microglial activation in the ipsilateral non-infarcted zone. Further, we demonstrate the presence of neuronal loss affecting the surviving penumbra, with no or only mild microglial activation, and no significant relationship between these two processes. Thus, microglial activation may not contribute to penumbral neuronal loss in man, and its presence in the ipsilateral hemisphere may merely reflect secondary remote degeneration. Selective neuronal loss in the surviving penumbra may represent a novel therapeutic target as an adjunct to penumbral salvage to further improve functional outcome. However, microglial activation may not stand as the primary therapeutic approach. Protecting the penumbra by acutely improving perfusion and oxygenation in conjunction with thrombectomy for example, may be a better approach. 11C-flumazenil PET would be useful to monitor the effects of such therapies.

Functional topography of single cortical cells: an intracellular approach combined with optical imaging.

PubMed

Buzás, P; Eysel, U T; Kisvárday, Z F

1998-11-01

Pyramidal cells mediating long-range corticocortical connections have been assumed to play an important role in visual perceptual mechanisms [C.D. Gilbert, Horizontal integration and cortical dynamics, Neuron 9 (1992) 1-13]. However, no information is available as yet on the specificity of individual pyramidal cells with respect to functional maps, e.g., orientation map. Here, we show a combination of techniques with which the functional topography of single pyramidal neurons can be explored in utmost detail. To this end, we used optical imaging of intrinsic signals followed by intracellular recording and staining with biocytin in vivo. The axonal and dendritic trees of the labelled neurons were reconstructed in three dimensions and aligned with corresponding functional orientation maps. The results indicate that, contrary to the sharp orientation tuning of neurons shown by the recorded spike activity, the efferent connections (axon terminal distribution) of the same pyramidal cells were found to terminate at a much broader range of orientations. Copyright 1998 Elsevier Science B.V.

Cell Type-Specific Circuit Mapping Reveals the Presynaptic Connectivity of Developing Cortical Circuits

PubMed Central

Cocas, Laura A.; Fernandez, Gloria; Barch, Mariya; Doll, Jason; Zamora Diaz, Ivan

2016-01-01

The mammalian cerebral cortex is a dense network composed of local, subcortical, and intercortical synaptic connections. As a result, mapping cell type-specific neuronal connectivity in the cerebral cortex in vivo has long been a challenge for neurobiologists. In particular, the development of excitatory and inhibitory interneuron presynaptic input has been hard to capture. We set out to analyze the development of this connectivity in the first postnatal month using a murine model. First, we surveyed the connectivity of one of the earliest populations of neurons in the brain, the Cajal-Retzius (CR) cells in the neocortex, which are known to be critical for cortical layer formation and are hypothesized to be important in the establishment of early cortical networks. We found that CR cells receive inputs from deeper-layer excitatory neurons and inhibitory interneurons in the first postnatal week. We also found that both excitatory pyramidal neurons and inhibitory interneurons received broad inputs in the first postnatal week, including inputs from CR cells. Expanding our analysis into the more mature brain, we assessed the inputs onto inhibitory interneurons and excitatory projection neurons, labeling neuronal progenitors with Cre drivers to study discrete populations of neurons in older cortex, and found that excitatory cortical and subcortical inputs are refined by the fourth week of development, whereas local inhibitory inputs increase during this postnatal period. Cell type-specific circuit mapping is specific, reliable, and effective, and can be used on molecularly defined subtypes to determine connectivity in the cortex. SIGNIFICANCE STATEMENT Mapping cortical connectivity in the developing mammalian brain has been an intractable problem, in part because it has not been possible to analyze connectivity with cell subtype precision. Our study systematically targets the presynaptic connections of discrete neuronal subtypes in both the mature and developing cerebral cortex. We analyzed the connections that Cajal-Retzius cells make and receive, and found that these cells receive inputs from deeper-layer excitatory neurons and inhibitory interneurons in the first postnatal week. We assessed the inputs onto inhibitory interneurons and excitatory projection neurons, the major two types of neurons in the cortex, and found that excitatory inputs are refined by the fourth week of development, whereas local inhibitory inputs increase during this postnatal period. PMID:26985044

[The detector, the command neuron and plastic convergence].

PubMed

Sokolov, E N

1977-01-01

The paper deals with the structure of detectors, the function of commanding neurones and the problem of relationship between detectors and commanding neurons. An example of hierarchial organization of detectors is provided by the colour analyser in which a layer of receptors, a layer of opponent neurones and a layer of colour-selective detectors are singled out. The colour detector is selectively sensitive to a certain combination of excitations at the input. If the detector is selectively activated by a certain combination of excitations at the input, the selective activation of the commanding neurone through a pool of motoneurones brings about a reaction at the output, specific in its organization. The reflexogenic zone of the reaction is determined by the detectors which converge on the commanding neurone controlling the given reaction. The plasticity of the reaction results from a plastic convergence of the detectors on the commanding neurone which controls the reaction. This comprises selective switching off the detectors from the commanding neurone (habituation) and connecting the detectors to the commanding neurone (facilitation).

Self-organized criticality in single-neuron excitability

NASA Astrophysics Data System (ADS)

Gal, Asaf; Marom, Shimon

2013-12-01

We present experimental and theoretical arguments, at the single-neuron level, suggesting that neuronal response fluctuations reflect a process that positions the neuron near a transition point that separates excitable and unexcitable phases. This view is supported by the dynamical properties of the system as observed in experiments on isolated cultured cortical neurons, as well as by a theoretical mapping between the constructs of self-organized criticality and membrane excitability biophysics.

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.

Functional transformations of odor inputs in the mouse olfactory bulb.

PubMed

Adam, Yoav; Livneh, Yoav; Miyamichi, Kazunari; Groysman, Maya; Luo, Liqun; Mizrahi, Adi

2014-01-01

Sensory inputs from the nasal epithelium to the olfactory bulb (OB) are organized as a discrete map in the glomerular layer (GL). This map is then modulated by distinct types of local neurons and transmitted to higher brain areas via mitral and tufted cells. Little is known about the functional organization of the circuits downstream of glomeruli. We used in vivo two-photon calcium imaging for large scale functional mapping of distinct neuronal populations in the mouse OB, at single cell resolution. Specifically, we imaged odor responses of mitral cells (MCs), tufted cells (TCs) and glomerular interneurons (GL-INs). Mitral cells population activity was heterogeneous and only mildly correlated with the olfactory receptor neuron (ORN) inputs, supporting the view that discrete input maps undergo significant transformations at the output level of the OB. In contrast, population activity profiles of TCs were dense, and highly correlated with the odor inputs in both space and time. Glomerular interneurons were also highly correlated with the ORN inputs, but showed higher activation thresholds suggesting that these neurons are driven by strongly activated glomeruli. Temporally, upon persistent odor exposure, TCs quickly adapted. In contrast, both MCs and GL-INs showed diverse temporal response patterns, suggesting that GL-INs could contribute to the transformations MCs undergo at slow time scales. Our data suggest that sensory odor maps are transformed by TCs and MCs in different ways forming two distinct and parallel information streams.

Orientation-Cue Invariant Population Responses to Contrast-Modulated and Phase-Reversed Contour Stimuli in Macaque V1 and V2

PubMed Central

An, Xu; Gong, Hongliang; Yin, Jiapeng; Wang, Xiaochun; Pan, Yanxia; Zhang, Xian; Lu, Yiliang; Yang, Yupeng; Toth, Zoltan; Schiessl, Ingo; McLoughlin, Niall; Wang, Wei

2014-01-01

Visual scenes can be readily decomposed into a variety of oriented components, the processing of which is vital for object segregation and recognition. In primate V1 and V2, most neurons have small spatio-temporal receptive fields responding selectively to oriented luminance contours (first order), while only a subgroup of neurons signal non-luminance defined contours (second order). So how is the orientation of second-order contours represented at the population level in macaque V1 and V2? Here we compared the population responses in macaque V1 and V2 to two types of second-order contour stimuli generated either by modulation of contrast or phase reversal with those to first-order contour stimuli. Using intrinsic signal optical imaging, we found that the orientation of second-order contour stimuli was represented invariantly in the orientation columns of both macaque V1 and V2. A physiologically constrained spatio-temporal energy model of V1 and V2 neuronal populations could reproduce all the recorded population responses. These findings suggest that, at the population level, the primate early visual system processes the orientation of second-order contours initially through a linear spatio-temporal filter mechanism. Our results of population responses to different second-order contour stimuli support the idea that the orientation maps in primate V1 and V2 can be described as a spatial-temporal energy map. PMID:25188576

Semaphorin-1a prevents Drosophila olfactory projection neuron dendrites from mis-targeting into select antennal lobe regions

PubMed Central

Chu, Sao-Yu; Wang, Chun-Han; Lin, I-Ya

2017-01-01

Elucidating how appropriate neurite patterns are generated in neurons of the olfactory system is crucial for comprehending the construction of the olfactory map. In the Drosophila olfactory system, projection neurons (PNs), primarily derived from four neural stem cells (called neuroblasts), populate their cell bodies surrounding to and distribute their dendrites in distinct but overlapping patterns within the primary olfactory center of the brain, the antennal lobe (AL). However, it remains unclear whether the same molecular mechanisms are employed to generate the appropriate dendritic patterns in discrete AL glomeruli among PNs produced from different neuroblasts. Here, by examining a previously explored transmembrane protein Semaphorin-1a (Sema-1a) which was proposed to globally control initial PN dendritic targeting along the dorsolateral-to-ventromedial axis of the AL, we discover a new role for Sema-1a in preventing dendrites of both uni-glomerular and poly-glomerular PNs from aberrant invasion into select AL regions and, intriguingly, this Sema-1a-deficient dendritic mis-targeting phenotype seems to associate with the origins of PNs from which they are derived. Further, ectopic expression of Sema-1a resulted in PN dendritic mis-projection from a select AL region into adjacent glomeruli, strengthening the idea that Sema-1a plays an essential role in preventing abnormal dendritic accumulation in select AL regions. Taken together, these results demonstrate that Sema-1a repulsion keeps dendrites of different types of PNs away from each other, enabling the same types of PN dendrites to be sorted into destined AL glomeruli and permitting for functional assembly of olfactory circuitry. PMID:28448523

Stability and chaos of Rulkov map-based neuron network with electrical synapse

NASA Astrophysics Data System (ADS)

Wang, Caixia; Cao, Hongjun

2015-02-01

In this paper, stability and chaos of a simple system consisting of two identical Rulkov map-based neurons with the bidirectional electrical synapse are investigated in detail. On the one hand, as a function of control parameters and electrical coupling strengthes, the conditions for stability of fixed points of this system are obtained by using the qualitative analysis. On the other hand, chaos in the sense of Marotto is proved by a strict mathematical way. These results could be useful for building-up large-scale neurons networks with specific dynamics and rich biophysical phenomena.

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.

Texture coarseness responsive neurons and their mapping in layer 2–3 of the rat barrel cortex in vivo

PubMed Central

Garion, Liora; Dubin, Uri; Rubin, Yoav; Khateb, Mohamed; Schiller, Yitzhak; Azouz, Rony; Schiller, Jackie

2014-01-01

Texture discrimination is a fundamental function of somatosensory systems, yet the manner by which texture is coded and spatially represented in the barrel cortex are largely unknown. Using in vivo two-photon calcium imaging in the rat barrel cortex during artificial whisking against different surface coarseness or controlled passive whisker vibrations simulating different coarseness, we show that layer 2–3 neurons within barrel boundaries differentially respond to specific texture coarsenesses, while only a minority of neurons responded monotonically with increased or decreased surface coarseness. Neurons with similar preferred texture coarseness were spatially clustered. Multi-contact single unit recordings showed a vertical columnar organization of texture coarseness preference in layer 2–3. These findings indicate that layer 2–3 neurons perform high hierarchical processing of tactile information, with surface coarseness embodied by distinct neuronal subpopulations that are spatially mapped onto the barrel cortex. DOI: http://dx.doi.org/10.7554/eLife.03405.001 PMID:25233151

Fine-scale topography in sensory systems: insights from Drosophila and vertebrates

PubMed Central

Kaneko, Takuya; Ye, Bing

2015-01-01

To encode the positions of sensory stimuli, sensory circuits form topographic maps in the central nervous system through specific point-to-point connections between pre- and post-synaptic neurons. In vertebrate visual systems, the establishment of topographic maps involves the formation of a coarse topography followed by that of fine-scale topography that distinguishes the axon terminals of neighboring neurons. It is known that intrinsic differences in the form of broad gradients of guidance molecules instruct coarse topography while neuronal activity is required for fine-scale topography. On the other hand, studies in the Drosophila visual system have shown that intrinsic differences in cell adhesion among the axon terminals of neighboring neurons instruct the fine-scale topography. Recent studies on activity-dependent topography in the Drosophila somatosensory system have revealed a role of neuronal activity in creating molecular differences among sensory neurons for establishing fine-scale topography, implicating a conserved principle. Here we review the findings in both Drosophila and vertebrates and propose an integrated model for fine-scale topography. PMID:26091779

Fine-scale topography in sensory systems: insights from Drosophila and vertebrates.

PubMed

Kaneko, Takuya; Ye, Bing

2015-09-01

To encode the positions of sensory stimuli, sensory circuits form topographic maps in the central nervous system through specific point-to-point connections between pre- and postsynaptic neurons. In vertebrate visual systems, the establishment of topographic maps involves the formation of a coarse topography followed by that of fine-scale topography that distinguishes the axon terminals of neighboring neurons. It is known that intrinsic differences in the form of broad gradients of guidance molecules instruct coarse topography while neuronal activity is required for fine-scale topography. On the other hand, studies in the Drosophila visual system have shown that intrinsic differences in cell adhesion among the axon terminals of neighboring neurons instruct the fine-scale topography. Recent studies on activity-dependent topography in the Drosophila somatosensory system have revealed a role of neuronal activity in creating molecular differences among sensory neurons for establishing fine-scale topography, implicating a conserved principle. Here we review the findings in both Drosophila and vertebrates and propose an integrated model for fine-scale topography.

Encoding of head direction by hippocampal place cells in bats.

PubMed

Rubin, Alon; Yartsev, Michael M; Ulanovsky, Nachum

2014-01-15

Most theories of navigation rely on the concept of a mental map and compass. Hippocampal place cells are neurons thought to be important for representing the mental map; these neurons become active when the animal traverses a specific location in the environment (the "place field"). Head-direction cells are found outside the hippocampus, and encode the animal's head orientation, thus implementing a neural compass. The prevailing view is that the activity of head-direction cells is not tuned to a single place, while place cells do not encode head direction. However, little work has been done to investigate in detail the possible head-directional tuning of hippocampal place cells across species. Here we addressed this by recording the activity of single neurons in the hippocampus of two evolutionarily distant bat species, Egyptian fruit bat and big brown bat, which crawled randomly in three different open-field arenas. We found that a large fraction of hippocampal neurons, in both bat species, showed conjunctive sensitivity to the animal's spatial position (place field) and to its head direction. We introduced analytical methods to demonstrate that the head-direction tuning was significant even after controlling for the behavioral coupling between position and head direction. Surprisingly, some hippocampal neurons preserved their head direction tuning even outside the neuron's place field, suggesting that "spontaneous" extra-field spikes are not noise, but in fact carry head-direction information. Overall, these findings suggest that bat hippocampal neurons can convey both map information and compass information.

Age-dependent increase of blood-brain barrier permeability and neuron-binding autoantibodies in S100B knockout mice.

PubMed

Wu, Hao; Brown, Eric V; Acharya, Nimish K; Appelt, Denah M; Marks, Alexander; Nagele, Robert G; Venkataraman, Venkat

2016-04-15

S100B is a calcium-sensor protein that impacts multiple signal transduction pathways. It is widely considered to be an important biomarker for several neuronal diseases as well as blood-brain barrier (BBB) breakdown. In this report, we demonstrate a BBB deficiency in mice that lack S100B through detection of leaked Immunoglobulin G (IgG) in the brain parenchyma. IgG leaks and IgG-binding to selected neurons were observed in S100B knockout (S100BKO) mice at 6 months of age but not at 3 months. By 9 months, IgG leaks persisted and the density of IgG-bound neurons increased significantly. These results reveal a chronic increase in BBB permeability upon aging in S100BKO mice for the first time. Moreover, coincident with the increase in IgG-bound neurons, autoantibodies targeting brain proteins were detected in the serum via western blots. These events were concurrent with compromise of neurons, increase of activated microglia and lack of astrocytic activation as evidenced by decreased expression of microtubule-associated protein type 2 (MAP2), elevated number of CD68 positive cells and unaltered expression of glial fibrillary acidic protein (GFAP) respectively. Results suggest a key role for S100B in maintaining BBB functional integrity and, further, propose the S100BKO mouse as a valuable model system to explore the link between chronic functional compromise of the BBB, generation of brain-reactive autoantibodies and neuronal dysfunctions. Copyright © 2016. Published by Elsevier B.V.

An NV-Diamond Magnetic Imager for Neuroscience

NASA Astrophysics Data System (ADS)

Turner, Matthew; Schloss, Jennifer; Bauch, Erik; Hart, Connor; Walsworth, Ronald

2017-04-01

We present recent progress towards imaging time-varying magnetic fields from neurons using nitrogen-vacancy centers in diamond. The diamond neuron imager is noninvasive, label-free, and achieves single-cell resolution and state-of-the-art broadband sensitivity. By imaging magnetic fields from injected currents in mammalian neurons, we will map functional neuronal network connections and illuminate biophysical properties of neurons invisible to traditional electrophysiology. Furthermore, through enhancing magnetometer sensitivity, we aim to demonstrate real-time imaging of action potentials from networks of mammalian neurons.

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.

Identification of polypeptides with selective affinity to intact mouse cerebellar granule neurons from a random peptide-presenting phage library.

PubMed

Hou, Sheng T; Dove, Mike; Anderson, Erica; Zhang, Jiangbing; MacKenzie, C Roger

2004-09-30

Targeting of postmitotic neurons selectively for gene delivery poses a challenge. One way to achieve such a selective targeting is to link the gene delivery vector with small ligand-binding polypeptides which have selective affinity to intact neurons. In order to identify such novel neuron selective polypeptides, we screened a phage-display library displaying random 12-mer polypeptides and subtractively bio-panned for clones having selectivity towards cultured mouse cerebellar granule neurons. The selected phage clones were amplified and sequenced. Affinities of these clones to neurons were determined by the visible presence or absence of fluorescence of phage particles as detected by immunocytochemistry using an antibody to M-13 phage. This affinity was further qualified by how much phage was bound, and where in or on the cell it tended to accumulate. The selectivity of binding to neurons was determined by the negative binding of these clones to several cultured non-neuronal cells, including, primary glial cells, NT2 cells, human embryonic kidney 293 cells, neuroblastoma cells, and mouse 3T3 cells. Among the 46 clones that we have sequenced and characterized, four clones appeared to have excellent selectivity in binding to neurons. Homology comparison of these polypeptides revealed that three of them contained a consensus D(E)-W(F)-I(N)-D-W motif. This motif was also present in the Bdm1 gene product which was predominantly expressed in postnatal brains. Further characterizations of these polypeptides are required to reveal the utilities of these peptides to function as an effective linker to facilitate gene transfer selectively to neurons.

Role of proopiomelanocortin neuron Stat3 in regulating arterial pressure and mediating the chronic effects of leptin.

PubMed

Dubinion, John H; do Carmo, Jussara M; Adi, Ahmad; Hamza, Shereen; da Silva, Alexandre A; Hall, John E

2013-05-01

Although signal transducer and activator of transcription 3 (Stat3) is a key second messenger by which leptin regulates appetite and body weight, its role in specific neuronal populations in metabolic regulation and in mediating the chronic effects of leptin on blood pressure is unknown. The current study tested the hypothesis that Stat3 signaling in proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on mean arterial pressure (MAP), as well as on glucose regulation, energy expenditure, and food intake. Stat3(flox/flox) mice were crossed with POMC-Cre mice to generate mice with Stat3 deletion specifically in POMC neurons (Stat3(flox/flox)/POMC-Cre). Oxygen consumption (Vo2), carbon dioxide respiration (Vco2), motor activity, heat production, food intake, and MAP were measured 24 hours/d. After baseline measurements, leptin was infused (4 μg/kg per min, IP) for 7 days. Stat3(flox/flox)/POMC-Cre mice were hyperphagic, heavier, and had increased respiratory quotients compared with control Stat3(flox/flox) mice. Baseline MAP was not different between the groups, and chronic leptin infusion reduced food intake similarly in both groups (27 versus 29%). Vo2, Vco2, and heat production responses to leptin were not significantly different in control and Stat3(flox/flox)/POMC-Cre mice. However, leptin-mediated increases in MAP were completely abolished, and blood pressure responses to acute air-jet stress were attenuated in male Stat3(flox/flox)/POMC-Cre mice. These results indicate that Stat3 signaling in POMC neurons is essential for leptin-mediated increases in MAP, but not for anorexic or thermogenic effects of leptin.

Weak orientation and direction selectivity in lateral geniculate nucleus representing central vision in the gray squirrel Sciurus carolinensis

PubMed Central

Zaltsman, Julia B.; Heimel, J. Alexander

2015-01-01

Classic studies of lateral geniculate nucleus (LGN) and visual cortex (V1) in carnivores and primates have found that a majority of neurons in LGN exhibit a center-surround organization, while V1 neurons exhibit strong orientation selectivity and, in many species, direction selectivity. Recent work in the mouse and the monkey has discovered previously unknown classes of orientation- and direction-selective neurons in LGN. Furthermore, some recent studies in the mouse report that many LGN cells exhibit pronounced orientation biases that are of comparable strength to the subthreshold inputs to V1 neurons. These results raise the possibility that, in rodents, orientation biases of individual LGN cells make a substantial contribution to cortical orientation selectivity. Alternatively, the size and contribution of orientation- or direction-selective channels from LGN to V1 may vary across mammals. To address this question, we examined orientation and direction selectivity in LGN and V1 neurons of a highly visual diurnal rodent: the gray squirrel. In the representation of central vision, only a few LGN neurons exhibited strong orientation or direction selectivity. Across the population, LGN neurons showed weak orientation biases and were much less selective for orientation compared with V1 neurons. Although direction selectivity was weak overall, LGN layers 3abc, which contain neurons that express calbindin, exhibited elevated direction selectivity index values compared with LGN layers 1 and 2. These results suggest that, for central visual fields, the contribution of orientation- and direction-selective channels from the LGN to V1 is small in the squirrel. As in other mammals, this small contribution is elevated in the calbindin-positive layers of the LGN PMID:25717157

All-optical mapping of barrel cortex circuits based on simultaneous voltage-sensitive dye imaging and channelrhodopsin-mediated photostimulation

PubMed Central

Lo, Shun Qiang; Koh, Dawn X. P.; Sng, Judy C. G.; Augustine, George J.

2015-01-01

Abstract. We describe an experimental approach that uses light to both control and detect neuronal activity in mouse barrel cortex slices: blue light patterned by a digital micromirror array system allowed us to photostimulate specific layers and columns, while a red-shifted voltage-sensitive dye was used to map out large-scale circuit activity. We demonstrate that such all-optical mapping can interrogate various circuits in somatosensory cortex by sequentially activating different layers and columns. Further, mapping in slices from whisker-deprived mice demonstrated that chronic sensory deprivation did not significantly alter feedforward inhibition driven by layer 5 pyramidal neurons. Further development of voltage-sensitive optical probes should allow this all-optical mapping approach to become an important and high-throughput tool for mapping circuit interactions in the brain. PMID:26158003

Molecular and behavioral profiling of Dbx1-derived neurons in the arcuate, lateral and ventromedial hypothalamic nuclei.

PubMed

Sokolowski, Katie; Tran, Tuyen; Esumi, Shigeyuki; Kamal, Yasmin; Oboti, Livio; Lischinsky, Julieta; Goodrich, Meredith; Lam, Andrew; Carter, Margaret; Nakagawa, Yasushi; Corbin, Joshua G

2016-05-21

Neurons in the hypothalamus function to regulate the state of the animal during both learned and innate behaviors, and alterations in hypothalamic development may contribute to pathological conditions such as anxiety, depression or obesity. Despite many studies of hypothalamic development and function, the link between embryonic development and innate behaviors remains unexplored. Here, focusing on the embryonically expressed homeodomain-containing gene Developing Brain Homeobox 1 (Dbx1), we explored the relationship between embryonic lineage, post-natal neuronal identity and lineage-specific responses to innate cues. We found that Dbx1 is widely expressed across multiple developing hypothalamic subdomains. Using standard and inducible fate-mapping to trace the Dbx1-derived neurons, we identified their contribution to specific neuronal subtypes across hypothalamic nuclei and further mapped their activation patterns in response to a series of well-defined innate behaviors. Dbx1-derived neurons occupy multiple postnatal hypothalamic nuclei including the lateral hypothalamus (LH), arcuate nucleus (Arc) and the ventral medial hypothalamus (VMH). Within these nuclei, Dbx1 (+) progenitors generate a large proportion of the Pmch-, Nesfatin-, Cart-, Hcrt-, Agrp- and ERα-expressing neuronal populations, and to a lesser extent the Pomc-, TH- and Aromatase-expressing populations. Inducible fate-mapping reveals distinct temporal windows for development of the Dbx1-derived LH and Arc populations, with Agrp(+) and Cart(+) populations in the Arc arising early (E7.5-E9.5), while Pmch(+) and Hcrt(+) populations in the LH derived from progenitors expressing Dbx1 later (E9.5-E11.5). Moreover, as revealed by c-Fos labeling, Dbx1-derived cells in male and female LH, Arc and VMH are responsive during mating and aggression. In contrast, Dbx1-lineage cells in the Arc and LH have a broader behavioral tuning, which includes responding to fasting and predator odor cues. We define a novel fate map of the hypothalamus with respect to Dbx1 expression in hypothalamic progenitor zones. We demonstrate that in a temporally regulated manner, Dbx1-derived neurons contribute to molecularly distinct neuronal populations in the LH, Arc and VMH that have been implicated in a variety of hypothalamic-driven behaviors. Consistent with this, Dbx1-derived neurons in the LH, Arc and VMH are activated during stress and other innate behavioral responses, implicating their involvement in these diverse behaviors.

Improved expression of halorhodopsin for light-induced silencing of neuronal activity

PubMed Central

Zhao, Shengli; Cunha, Catarina; Zhang, Feng; Liu, Qun; Gloss, Bernd; Deisseroth, Karl; Augustine, George J.; Feng, Guoping

2011-01-01

The ability to control and manipulate neuronal activity within an intact mammalian brain is of key importance for mapping functional connectivity and for dissecting the neural circuitry underlying behaviors. We have previously generated transgenic mice that express channelrhodopsin-2 for light-induced activation of neurons and mapping of neural circuits. Here we describe transgenic mice that express halorhodopsin (NpHR), a light-driven chloride pump, that can be used to silence neuronal activity via light. Using the Thy-1 promoter to target NpHR expression to neurons, we found that neurons in these mice expressed high levels of NpHR-YFP and that illumination of cortical pyramidal neurons expressing NpHR-YFP led to rapid, reversible photoinhibition of action potential firing in these cells. However, NpHR-YFP expression led to the formation of numerous intracellular blebs, which may disrupt neuronal function. Labeling of various subcellular markers indicated that the blebs arise from retention of NpHR-YFP in the endoplasmic reticulum. By improving the signal peptide sequence and adding an ER export signal to NpHR-YFP, we eliminated the formation of blebs and dramatically increased the membrane expression of NpHR-YFP. Thus, the improved version of NpHR should serve as an excellent tool for neuronal silencing in vitro and in vivo. PMID:18931914

Neuronal matrix metalloproteinase-9 is a determinant of selective neurodegeneration

PubMed Central

Kaplan, Artem; Spiller, Krista J.; Towne, Christopher; Kanning, Kevin C.; Choe, Ginn T.; Geber, Adam; Akay, Turgay; Aebischer, Patrick; Henderson, Christopher E.

2018-01-01

SUMMARY Selective neuronal loss is the hallmark of neurodegenerative diseases. In patients with amyotrophic lateral sclerosis (ALS), most motor neurons die but those innervating extraocular, pelvic sphincter and slow limb muscles exhibit selective resistance. We identified 18 genes that show >10-fold differential expression between resistant and vulnerable motor neurons. One of these, matrix metalloproteinase-9 (MMP-9), is expressed only by fast motor neurons, which are selectively vulnerable. In ALS model mice expressing mutant SOD1, reduction of MMP-9 function using gene ablation, viral gene therapy or pharmacological inhibition significantly delayed muscle denervation. In the presence of mutant SOD1, MMP-9 expressed by fast motor neurons themselves enhances activation of ER stress and is sufficient to trigger axonal die-back. These findings define MMP-9 as a candidate therapeutic target for ALS. The molecular basis of neuronal diversity thus provides novel insights into mechanisms of selective vulnerability to neurodegeneration. PMID:24462097

The Brain–to–Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions

PubMed Central

Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C.; Ali, Almas; Tamarina, Natalia; Philipson, Louis H.; Enquist, Lynn W.; Myers, Martin G.

2016-01-01

The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. PMID:27207534

The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

PubMed

Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

2016-09-01

The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

Adult neurogenesis is necessary to refine and maintain circuit specificity.

PubMed

Cummings, Diana M; Snyder, Jason S; Brewer, Michelle; Cameron, Heather A; Belluscio, Leonardo

2014-10-08

The circuitry of the olfactory bulb contains a precise anatomical map that links isofunctional regions within each olfactory bulb. This intrabulbar map forms perinatally and undergoes activity-dependent refinement during the first postnatal weeks. Although this map retains its plasticity throughout adulthood, its organization is remarkably stable despite the addition of millions of new neurons to this circuit. Here we show that the continuous supply of new neuroblasts from the subventricular zone is necessary for both the restoration and maintenance of this precise central circuit. Using pharmacogenetic methods to conditionally ablate adult neurogenesis in transgenic mice, we find that the influx of neuroblasts is required for recovery of intrabulbar map precision after disruption due to sensory block. We further demonstrate that eliminating adult-born interneurons in naive animals leads to an expansion of tufted cell axons that is identical to the changes caused by sensory block, thus revealing an essential role for new neurons in circuit maintenance under baseline conditions. These findings show, for the first time, that inhibiting adult neurogenesis alters the circuitry of projection neurons in brain regions that receive new interneurons and points to a critical role for adult-born neurons in stabilizing a brain circuit that exhibits high levels of plasticity. Copyright © 2014 the authors 0270-6474/14/3413801-10$15.00/0.

Mapping and Analysis of the Connectome of Sympathetic Premotor Neurons in the Rostral Ventrolateral Medulla of the Rat Using a Volumetric Brain Atlas

PubMed Central

Dempsey, Bowen; Le, Sheng; Turner, Anita; Bokiniec, Phil; Ramadas, Radhika; Bjaalie, Jan G.; Menuet, Clement; Neve, Rachael; Allen, Andrew M.; Goodchild, Ann K.; McMullan, Simon

2017-01-01

Spinally projecting neurons in the rostral ventrolateral medulla (RVLM) play a critical role in the generation of vasomotor sympathetic tone and are thought to receive convergent input from neurons at every level of the neuraxis; the factors that determine their ongoing activity remain unresolved. In this study we use a genetically restricted viral tracing strategy to definitively map their spatially diffuse connectome. We infected bulbospinal RVLM neurons with a recombinant rabies variant that drives reporter expression in monosynaptically connected input neurons and mapped their distribution using an MRI-based volumetric atlas and a novel image alignment and visualization tool that efficiently translates the positions of neurons captured in conventional photomicrographs to Cartesian coordinates. We identified prominent inputs from well-established neurohumoral and viscero-sympathetic sensory actuators, medullary autonomic and respiratory subnuclei, and supramedullary autonomic nuclei. The majority of inputs lay within the brainstem (88–94%), and included putative respiratory neurons in the pre-Bötzinger Complex and post-inspiratory complex that are therefore likely to underlie respiratory-sympathetic coupling. We also discovered a substantial and previously unrecognized input from the region immediately ventral to nucleus prepositus hypoglossi. In contrast, RVLM sympathetic premotor neurons were only sparsely innervated by suprapontine structures including the paraventricular nucleus, lateral hypothalamus, periaqueductal gray, and superior colliculus, and we found almost no evidence of direct inputs from the cortex or amygdala. Our approach can be used to quantify, standardize and share complete neuroanatomical datasets, and therefore provides researchers with a platform for presentation, analysis and independent reanalysis of connectomic data. PMID:28298886

Topographic mapping--the olfactory system.

PubMed

Imai, Takeshi; Sakano, Hitoshi; Vosshall, Leslie B

2010-08-01

Sensory systems must map accurate representations of the external world in the brain. Although the physical senses of touch and vision build topographic representations of the spatial coordinates of the body and the field of view, the chemical sense of olfaction maps discontinuous features of chemical space, comprising an extremely large number of possible odor stimuli. In both mammals and insects, olfactory circuits are wired according to the convergence of axons from sensory neurons expressing the same odorant receptor. Synapses are organized into distinctive spherical neuropils--the olfactory glomeruli--that connect sensory input with output neurons and local modulatory interneurons. Although there is a strong conservation of form in the olfactory maps of mammals and insects, they arise using divergent mechanisms. Olfactory glomeruli provide a unique solution to the problem of mapping discontinuous chemical space onto the brain.

Robust spatial memory maps in flickering neuronal networks: a topological model

NASA Astrophysics Data System (ADS)

Dabaghian, Yuri; Babichev, Andrey; Memoli, Facundo; Chowdhury, Samir; Rice University Collaboration; Ohio State University Collaboration

It is widely accepted that the hippocampal place cells provide a substrate of the neuronal representation of the environment--the ``cognitive map''. However, hippocampal network, as any other network in the brain is transient: thousands of hippocampal neurons die every day and the connections formed by these cells constantly change due to various forms of synaptic plasticity. What then explains the remarkable reliability of our spatial memories? We propose a computational approach to answering this question based on a couple of insights. First, we propose that the hippocampal cognitive map is fundamentally topological, and hence it is amenable to analysis by topological methods. We then apply several novel methods from homology theory, to understand how dynamic connections between cells influences the speed and reliability of spatial learning. We simulate the rat's exploratory movements through different environments and study how topological invariants of these environments arise in a network of simulated neurons with ``flickering'' connectivity. We find that despite transient connectivity the network of place cells produces a stable representation of the topology of the environment.

Brain/MINDS: brain-mapping project in Japan

PubMed Central

Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto

2015-01-01

There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas. PMID:25823872

Medial Habenula Output Circuit Mediated by α5 Nicotinic Receptor-Expressing GABAergic Neurons in the Interpeduncular Nucleus

PubMed Central

Hsu, Yun-Wei A.; Tempest, Lynne; Quina, Lely A.; Wei, Aguan D.; Zeng, Hongkui

2013-01-01

The Chrna5 gene encodes the α5 nicotinic acetylcholine receptor subunit, an “accessory” subunit of pentameric nicotinic receptors, that has been shown to play a role in nicotine-related behaviors in rodents and is genetically linked to smoking behavior in humans. Here we have used a BAC transgenic mouse line, α5GFP, to examine the cellular phenotype, connectivity, and function of α5-expressing neurons. Although the medial habenula (MHb) has been proposed as a site of α5 function, α5GFP is not detectable in the MHb, and α5 mRNA is expressed there only at very low levels. However, α5GFP is strongly expressed in a subset of neurons in the interpeduncular nucleus (IP), median raphe/paramedian raphe (MnR/PMnR), and dorsal tegmental area (DTg). Double-label fluorescence in situ hybridization reveals that these neurons are exclusively GABAergic. Transgenic and conventional tract tracing show that α5GFP neurons in the IP project principally to the MnR/PMnR and DTg/interfascicular dorsal raphe, both areas rich in serotonergic neurons. The α5GFP neurons in the IP are located in a region that receives cholinergic fiber inputs from the ventral MHb, and optogenetically assisted circuit mapping demonstrates a monosynaptic connection between these cholinergic neurons and α5GFP IP neurons. Selective inhibitors of both α4β2- and α3β4-containing nicotinic receptors were able to reduce nicotine-evoked inward currents in α5GFP neurons in the IP, suggesting a mixed nicotinic receptor profile in these cells. Together, these findings show that the α5-GABAergic interneurons form a link from the MHb to serotonergic brain centers, which is likely to mediate some of the behavioral effects of nicotine. PMID:24227714

Pharmacological characterization of potent and selective NaV1.7 inhibitors engineered from Chilobrachys jingzhao tarantula venom peptide JzTx-V.

PubMed

Moyer, Bryan D; Murray, Justin K; Ligutti, Joseph; Andrews, Kristin; Favreau, Philippe; Jordan, John B; Lee, Josie H; Liu, Dong; Long, Jason; Sham, Kelvin; Shi, Licheng; Stöcklin, Reto; Wu, Bin; Yin, Ruoyuan; Yu, Violeta; Zou, Anruo; Biswas, Kaustav; Miranda, Les P

2018-01-01

Identification of voltage-gated sodium channel NaV1.7 inhibitors for chronic pain therapeutic development is an area of vigorous pursuit. In an effort to identify more potent leads compared to our previously reported GpTx-1 peptide series, electrophysiology screening of fractionated tarantula venom discovered the NaV1.7 inhibitory peptide JzTx-V from the Chinese earth tiger tarantula Chilobrachys jingzhao. The parent peptide displayed nominal selectivity over the skeletal muscle NaV1.4 channel. Attribute-based positional scan analoging identified a key Ile28Glu mutation that improved NaV1.4 selectivity over 100-fold, and further optimization yielded the potent and selective peptide leads AM-8145 and AM-0422. NMR analyses revealed that the Ile28Glu substitution changed peptide conformation, pointing to a structural rationale for the selectivity gains. AM-8145 and AM-0422 as well as GpTx-1 and HwTx-IV competed for ProTx-II binding in HEK293 cells expressing human NaV1.7, suggesting that these NaV1.7 inhibitory peptides interact with a similar binding site. AM-8145 potently blocked native tetrodotoxin-sensitive (TTX-S) channels in mouse dorsal root ganglia (DRG) neurons, exhibited 30- to 120-fold selectivity over other human TTX-S channels and exhibited over 1,000-fold selectivity over other human tetrodotoxin-resistant (TTX-R) channels. Leveraging NaV1.7-NaV1.5 chimeras containing various voltage-sensor and pore regions, AM-8145 mapped to the second voltage-sensor domain of NaV1.7. AM-0422, but not the inactive peptide analog AM-8374, dose-dependently blocked capsaicin-induced DRG neuron action potential firing using a multi-electrode array readout and mechanically-induced C-fiber spiking in a saphenous skin-nerve preparation. Collectively, AM-8145 and AM-0422 represent potent, new engineered NaV1.7 inhibitory peptides derived from the JzTx-V scaffold with improved NaV selectivity and biological activity in blocking action potential firing in both DRG neurons and C-fibers.

Pharmacological characterization of potent and selective NaV1.7 inhibitors engineered from Chilobrachys jingzhao tarantula venom peptide JzTx-V

PubMed Central

Murray, Justin K.; Ligutti, Joseph; Andrews, Kristin; Favreau, Philippe; Jordan, John B.; Lee, Josie H.; Liu, Dong; Long, Jason; Sham, Kelvin; Shi, Licheng; Stöcklin, Reto; Wu, Bin; Yin, Ruoyuan; Yu, Violeta; Zou, Anruo; Biswas, Kaustav; Miranda, Les P.

2018-01-01

Identification of voltage-gated sodium channel NaV1.7 inhibitors for chronic pain therapeutic development is an area of vigorous pursuit. In an effort to identify more potent leads compared to our previously reported GpTx-1 peptide series, electrophysiology screening of fractionated tarantula venom discovered the NaV1.7 inhibitory peptide JzTx-V from the Chinese earth tiger tarantula Chilobrachys jingzhao. The parent peptide displayed nominal selectivity over the skeletal muscle NaV1.4 channel. Attribute-based positional scan analoging identified a key Ile28Glu mutation that improved NaV1.4 selectivity over 100-fold, and further optimization yielded the potent and selective peptide leads AM-8145 and AM-0422. NMR analyses revealed that the Ile28Glu substitution changed peptide conformation, pointing to a structural rationale for the selectivity gains. AM-8145 and AM-0422 as well as GpTx-1 and HwTx-IV competed for ProTx-II binding in HEK293 cells expressing human NaV1.7, suggesting that these NaV1.7 inhibitory peptides interact with a similar binding site. AM-8145 potently blocked native tetrodotoxin-sensitive (TTX-S) channels in mouse dorsal root ganglia (DRG) neurons, exhibited 30- to 120-fold selectivity over other human TTX-S channels and exhibited over 1,000-fold selectivity over other human tetrodotoxin-resistant (TTX-R) channels. Leveraging NaV1.7-NaV1.5 chimeras containing various voltage-sensor and pore regions, AM-8145 mapped to the second voltage-sensor domain of NaV1.7. AM-0422, but not the inactive peptide analog AM-8374, dose-dependently blocked capsaicin-induced DRG neuron action potential firing using a multi-electrode array readout and mechanically-induced C-fiber spiking in a saphenous skin-nerve preparation. Collectively, AM-8145 and AM-0422 represent potent, new engineered NaV1.7 inhibitory peptides derived from the JzTx-V scaffold with improved NaV selectivity and biological activity in blocking action potential firing in both DRG neurons and C-fibers. PMID:29723257

Spinal interneurons differentiate sequentially from those driving the fastest swimming movements in larval zebrafish to those driving the slowest ones.

PubMed

McLean, David L; Fetcho, Joseph R

2009-10-28

Studies of neuronal networks have revealed few general principles that link patterns of development with later functional roles. While investigating the neural control of movements, we recently discovered a topographic map in the spinal cord of larval zebrafish that relates the position of motoneurons and interneurons to their order of recruitment during swimming. Here, we show that the map reflects an orderly pattern of differentiation of neurons driving different movements. First, we use high-speed filming to show that large-amplitude swimming movements with bending along much of the body appear first, with smaller, regional swimming movements emerging later. Next, using whole-cell patch recordings, we demonstrate that the excitatory circuits that drive large-amplitude, fast swimming movements at larval stages are present and functional early on in embryos. Finally, we systematically assess the orderly emergence of spinal circuits according to swimming speed using transgenic fish expressing the photoconvertible protein Kaede to track neuronal differentiation in vivo. We conclude that a simple principle governs the development of spinal networks in which the neurons driving the fastest, most powerful swimming in larvae develop first with ones that drive increasingly weaker and slower larval movements layered on over time. Because the neurons are arranged by time of differentiation in the spinal cord, the result is a topographic map that represents the speed/strength of movements at which neurons are recruited and the temporal emergence of networks. This pattern may represent a general feature of neuronal network development throughout the brain and spinal cord.

Orientation selectivity of synaptic input to neurons in mouse and cat primary visual cortex.

PubMed

Tan, Andrew Y Y; Brown, Brandon D; Scholl, Benjamin; Mohanty, Deepankar; Priebe, Nicholas J

2011-08-24

Primary visual cortex (V1) is the site at which orientation selectivity emerges in mammals: visual thalamus afferents to V1 respond equally to all stimulus orientations, whereas their target V1 neurons respond selectively to stimulus orientation. The emergence of orientation selectivity in V1 has long served as a model for investigating cortical computation. Recent evidence for orientation selectivity in mouse V1 opens cortical computation to dissection by genetic and imaging tools, but also raises two essential questions: (1) How does orientation selectivity in mouse V1 neurons compare with that in previously described species? (2) What is the synaptic basis for orientation selectivity in mouse V1? A comparison of orientation selectivity in mouse and in cat, where such measures have traditionally been made, reveals that orientation selectivity in mouse V1 is weaker than in cat V1, but that spike threshold plays a similar role in narrowing selectivity between membrane potential and spike rate. To uncover the synaptic basis for orientation selectivity, we made whole-cell recordings in vivo from mouse V1 neurons, comparing neuronal input selectivity-based on membrane potential, synaptic excitation, and synaptic inhibition-to output selectivity based on spiking. We found that a neuron's excitatory and inhibitory inputs are selective for the same stimulus orientations as is its membrane potential response, and that inhibitory selectivity is not broader than excitatory selectivity. Inhibition has different dynamics than excitation, adapting more rapidly. In neurons with temporally modulated responses, the timing of excitation and inhibition was different in mice and cats.

Orientation Selectivity of Synaptic Input to Neurons in Mouse and Cat Primary Visual Cortex

PubMed Central

Tan (陈勇毅), Andrew Y. Y.; Brown, Brandon D.; Scholl, Benjamin; Mohanty, Deepankar; Priebe, Nicholas J.

2011-01-01

Primary visual cortex (V1) is the site at which orientation selectivity emerges in mammals: visual thalamus afferents to V1 respond equally to all stimulus orientations whereas their target V1 neurons respond selectively to stimulus orientation. The emergence of orientation selectivity in V1 has long served as a model for investigating cortical computation. Recent evidence for orientation selectivity in mouse V1 opens cortical computation to dissection by genetic and imaging tools, but also raises two essential questions: 1) how does orientation selectivity in mouse V1 neurons compare with that in previously described species? 2) what is the synaptic basis for orientation selectivity in mouse V1? A comparison of orientation selectivity in mouse and in cat, where such measures have traditionally been made, reveals that orientation selectivity in mouse V1 is weaker than in cat V1, but that spike threshold plays a similar role in narrowing selectivity between membrane potential and spike rate. To uncover the synaptic basis for orientation selectivity, we made whole-cell recordings in vivo from mouse V1 neurons, comparing neuronal input selectivity - based on membrane potential, synaptic excitation, and synaptic inhibition - to output selectivity based on spiking. We found that a neuron's excitatory and inhibitory inputs are selective for the same stimulus orientations as is its membrane potential response, and that inhibitory selectivity is not broader than excitatory selectivity. Inhibition has different dynamics than excitation, adapting more rapidly. In neurons with temporally modulated responses, the timing of excitation and inhibition was different in mice and cats. PMID:21865476

Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution.

PubMed

Chiang, Ann-Shyn; Lin, Chih-Yung; Chuang, Chao-Chun; Chang, Hsiu-Ming; Hsieh, Chang-Huain; Yeh, Chang-Wei; Shih, Chi-Tin; Wu, Jian-Jheng; Wang, Guo-Tzau; Chen, Yung-Chang; Wu, Cheng-Chi; Chen, Guan-Yu; Ching, Yu-Tai; Lee, Ping-Chang; Lin, Chih-Yang; Lin, Hui-Hao; Wu, Chia-Chou; Hsu, Hao-Wei; Huang, Yun-Ann; Chen, Jing-Yi; Chiang, Hsin-Jung; Lu, Chun-Fang; Ni, Ru-Fen; Yeh, Chao-Yuan; Hwang, Jenn-Kang

2011-01-11

Animal behavior is governed by the activity of interconnected brain circuits. Comprehensive brain wiring maps are thus needed in order to formulate hypotheses about information flow and also to guide genetic manipulations aimed at understanding how genes and circuits orchestrate complex behaviors. To assemble this map, we deconstructed the adult Drosophila brain into approximately 16,000 single neurons and reconstructed them into a common standardized framework to produce a virtual fly brain. We have constructed a mesoscopic map and found that it consists of 41 local processing units (LPUs), six hubs, and 58 tracts covering the whole Drosophila brain. Despite individual local variation, the architecture of the Drosophila brain shows invariance for both the aggregation of local neurons (LNs) within specific LPUs and for the connectivity of projection neurons (PNs) between the same set of LPUs. An open-access image database, named FlyCircuit, has been constructed for online data archiving, mining, analysis, and three-dimensional visualization of all single neurons, brain-wide LPUs, their wiring diagrams, and neural tracts. We found that the Drosophila brain is assembled from families of multiple LPUs and their interconnections. This provides an essential first step in the analysis of information processing within and between neurons in a complete brain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Synthesizing cognition in neuromorphic electronic systems

PubMed Central

Neftci, Emre; Binas, Jonathan; Rutishauser, Ueli; Chicca, Elisabetta; Indiveri, Giacomo; Douglas, Rodney J.

2013-01-01

The quest to implement intelligent processing in electronic neuromorphic systems lacks methods for achieving reliable behavioral dynamics on substrates of inherently imprecise and noisy neurons. Here we report a solution to this problem that involves first mapping an unreliable hardware layer of spiking silicon neurons into an abstract computational layer composed of generic reliable subnetworks of model neurons and then composing the target behavioral dynamics as a “soft state machine” running on these reliable subnets. In the first step, the neural networks of the abstract layer are realized on the hardware substrate by mapping the neuron circuit bias voltages to the model parameters. This mapping is obtained by an automatic method in which the electronic circuit biases are calibrated against the model parameters by a series of population activity measurements. The abstract computational layer is formed by configuring neural networks as generic soft winner-take-all subnetworks that provide reliable processing by virtue of their active gain, signal restoration, and multistability. The necessary states and transitions of the desired high-level behavior are then easily embedded in the computational layer by introducing only sparse connections between some neurons of the various subnets. We demonstrate this synthesis method for a neuromorphic sensory agent that performs real-time context-dependent classification of motion patterns observed by a silicon retina. PMID:23878215

Characterization of emergent synaptic topologies in noisy neural networks

NASA Astrophysics Data System (ADS)

Miller, Aaron James

Learned behaviors are one of the key contributors to an animal's ultimate survival. It is widely believed that the brain's microcircuitry undergoes structural changes when a new behavior is learned. In particular, motor learning, during which an animal learns a sequence of muscular movements, often requires precisely-timed coordination between muscles and becomes very natural once ingrained. Experiments show that neurons in the motor cortex exhibit precisely-timed spike activity when performing a learned motor behavior, and constituent stereotypical elements of the behavior can last several hundred milliseconds. The subject of this manuscript concerns how organized synaptic structures that produce stereotypical spike sequences emerge from random, dynamical networks. After a brief introduction in Chapter 1, we begin Chapter 2 by introducing a spike-timing-dependent plasticity (STDP) rule that defines how the activity of the network drives changes in network topology. The rule is then applied to idealized networks of leaky integrate-and-fire neurons (LIF). These neurons are not subjected to the variability that typically characterize neurons in vivo. In noiseless networks, synapses develop closed loops of strong connectivity that reproduce stereotypical, precisely-timed spike patterns from an initially random network. We demonstrate the characteristics of the asymptotic synaptic configuration are dependent on the statistics of the initial random network. The spike timings of the neurons simulated in Chapter 2 are generated exactly by a computationally economical, nonlinear mapping which is extended to LIF neurons injected with fluctuating current in Chapter 3. Development of an economical mapping that incorporates noise provides a practical solution to the long simulation times required to produce asymptotic synaptic topologies in networks with STDP in the presence of realistic neuronal variability. The mapping relies on generating numerical solutions to the dynamics of a LIF neuron subjected to Gaussian white noise (GWN). The system reduces to the Ornstein-Uhlenbeck first passage time problem, the solution of which we build into the mapping method of Chapter 2. We demonstrate that simulations using the stochastic mapping have reduced computation time compared to traditional Runge-Kutta methods by more than a factor of 150. In Chapter 4, we use the stochastic mapping to study the dynamics of emerging synaptic topologies in noisy networks. With the addition of membrane noise, networks with dynamical synapses can admit states in which the distribution of the synaptic weights is static under spontaneous activity, but the random connectivity between neurons is dynamical. The widely cited problem of instabilities in networks with STDP is avoided with the implementation of a synaptic decay and an activation threshold on each synapse. When such networks are presented with stimulus modeled by a focused excitatory current, chain-like networks can emerge with the addition of an axon-remodeling plasticity rule, a topological constraint on the connectivity modeling the finite resources available to each neuron. The emergent topologies are the result of an iterative stochastic process. The dynamics of the growth process suggest a strong interplay between the network topology and the spike sequences they produce during development. Namely, the existence of an embedded spike sequence alters the distribution of synaptic weights through the entire network. The roles of model parameters that affect the interplay between network structure and activity are elucidated. Finally, we propose two mathematical growth models, which are complementary, that capture the essence of the growth dynamics observed in simulations. In Chapter 5, we present an extension of the stochastic mapping that allows the possibility of neuronal cooperation. We demonstrate that synaptic topologies admitting stereotypical sequences can emerge in yet higher, biologically realistic levels of membrane potential variability when neurons cooperate to innervate shared targets. The structure that is most robust to the variability is that of a synfire chain. The principles of growth dynamics detailed in Chapter 4 are the same that sculpt the emergent synfire topologies. We conclude by discussing avenues for extensions of these results.

Learning and optimization with cascaded VLSI neural network building-block chips

NASA Technical Reports Server (NTRS)

Duong, T.; Eberhardt, S. P.; Tran, M.; Daud, T.; Thakoor, A. P.

1992-01-01

To demonstrate the versatility of the building-block approach, two neural network applications were implemented on cascaded analog VLSI chips. Weights were implemented using 7-b multiplying digital-to-analog converter (MDAC) synapse circuits, with 31 x 32 and 32 x 32 synapses per chip. A novel learning algorithm compatible with analog VLSI was applied to the two-input parity problem. The algorithm combines dynamically evolving architecture with limited gradient-descent backpropagation for efficient and versatile supervised learning. To implement the learning algorithm in hardware, synapse circuits were paralleled for additional quantization levels. The hardware-in-the-loop learning system allocated 2-5 hidden neurons for parity problems. Also, a 7 x 7 assignment problem was mapped onto a cascaded 64-neuron fully connected feedback network. In 100 randomly selected problems, the network found optimal or good solutions in most cases, with settling times in the range of 7-100 microseconds.

A Map of Anticipatory Activity in Mouse Motor Cortex.

PubMed

Chen, Tsai-Wen; Li, Nuo; Daie, Kayvon; Svoboda, Karel

2017-05-17

Activity in the mouse anterior lateral motor cortex (ALM) instructs directional movements, often seconds before movement initiation. It is unknown whether this preparatory activity is localized to ALM or widely distributed within motor cortex. Here we imaged activity across motor cortex while mice performed a whisker-based object localization task with a delayed, directional licking response. During tactile sensation and the delay epoch, object location was represented in motor cortex areas that are medial and posterior relative to ALM, including vibrissal motor cortex. Preparatory activity appeared first in deep layers of ALM, seconds before the behavioral response, and remained localized to ALM until the behavioral response. Later, widely distributed neurons represented the outcome of the trial. Cortical area was more predictive of neuronal selectivity than laminar location or axonal projection target. Motor cortex therefore represents sensory, motor, and outcome information in a spatially organized manner. Copyright © 2017 Elsevier Inc. All rights reserved.

A Mathematical Model for Storage and Recall of Images using Targeted Synchronization of Coupled Maps.

PubMed

Palaniyandi, P; Rangarajan, Govindan

2017-08-21

We propose a mathematical model for storage and recall of images using coupled maps. We start by theoretically investigating targeted synchronization in coupled map systems wherein only a desired (partial) subset of the maps is made to synchronize. A simple method is introduced to specify coupling coefficients such that targeted synchronization is ensured. The principle of this method is extended to storage/recall of images using coupled Rulkov maps. The process of adjusting coupling coefficients between Rulkov maps (often used to model neurons) for the purpose of storing a desired image mimics the process of adjusting synaptic strengths between neurons to store memories. Our method uses both synchronisation and synaptic weight modification, as the human brain is thought to do. The stored image can be recalled by providing an initial random pattern to the dynamical system. The storage and recall of the standard image of Lena is explicitly demonstrated.

Granger causality network reconstruction of conductance-based integrate-and-fire neuronal systems.

PubMed

Zhou, Douglas; Xiao, Yanyang; Zhang, Yaoyu; Xu, Zhiqin; Cai, David

2014-01-01

Reconstruction of anatomical connectivity from measured dynamical activities of coupled neurons is one of the fundamental issues in the understanding of structure-function relationship of neuronal circuitry. Many approaches have been developed to address this issue based on either electrical or metabolic data observed in experiment. The Granger causality (GC) analysis remains one of the major approaches to explore the dynamical causal connectivity among individual neurons or neuronal populations. However, it is yet to be clarified how such causal connectivity, i.e., the GC connectivity, can be mapped to the underlying anatomical connectivity in neuronal networks. We perform the GC analysis on the conductance-based integrate-and-fire (I&F) neuronal networks to obtain their causal connectivity. Through numerical experiments, we find that the underlying synaptic connectivity amongst individual neurons or subnetworks, can be successfully reconstructed by the GC connectivity constructed from voltage time series. Furthermore, this reconstruction is insensitive to dynamical regimes and can be achieved without perturbing systems and prior knowledge of neuronal model parameters. Surprisingly, the synaptic connectivity can even be reconstructed by merely knowing the raster of systems, i.e., spike timing of neurons. Using spike-triggered correlation techniques, we establish a direct mapping between the causal connectivity and the synaptic connectivity for the conductance-based I&F neuronal networks, and show the GC is quadratically related to the coupling strength. The theoretical approach we develop here may provide a framework for examining the validity of the GC analysis in other settings.

Granger Causality Network Reconstruction of Conductance-Based Integrate-and-Fire Neuronal Systems

PubMed Central

Zhou, Douglas; Xiao, Yanyang; Zhang, Yaoyu; Xu, Zhiqin; Cai, David

2014-01-01

Reconstruction of anatomical connectivity from measured dynamical activities of coupled neurons is one of the fundamental issues in the understanding of structure-function relationship of neuronal circuitry. Many approaches have been developed to address this issue based on either electrical or metabolic data observed in experiment. The Granger causality (GC) analysis remains one of the major approaches to explore the dynamical causal connectivity among individual neurons or neuronal populations. However, it is yet to be clarified how such causal connectivity, i.e., the GC connectivity, can be mapped to the underlying anatomical connectivity in neuronal networks. We perform the GC analysis on the conductance-based integrate-and-fire (IF) neuronal networks to obtain their causal connectivity. Through numerical experiments, we find that the underlying synaptic connectivity amongst individual neurons or subnetworks, can be successfully reconstructed by the GC connectivity constructed from voltage time series. Furthermore, this reconstruction is insensitive to dynamical regimes and can be achieved without perturbing systems and prior knowledge of neuronal model parameters. Surprisingly, the synaptic connectivity can even be reconstructed by merely knowing the raster of systems, i.e., spike timing of neurons. Using spike-triggered correlation techniques, we establish a direct mapping between the causal connectivity and the synaptic connectivity for the conductance-based IF neuronal networks, and show the GC is quadratically related to the coupling strength. The theoretical approach we develop here may provide a framework for examining the validity of the GC analysis in other settings. PMID:24586285

Cooperation-Controlled Learning for Explicit Class Structure in Self-Organizing Maps

PubMed Central

Kamimura, Ryotaro

2014-01-01

We attempt to demonstrate the effectiveness of multiple points of view toward neural networks. By restricting ourselves to two points of view of a neuron, we propose a new type of information-theoretic method called “cooperation-controlled learning.” In this method, individual and collective neurons are distinguished from one another, and we suppose that the characteristics of individual and collective neurons are different. To implement individual and collective neurons, we prepare two networks, namely, cooperative and uncooperative networks. The roles of these networks and the roles of individual and collective neurons are controlled by the cooperation parameter. As the parameter is increased, the role of cooperative networks becomes more important in learning, and the characteristics of collective neurons become more dominant. On the other hand, when the parameter is small, individual neurons play a more important role. We applied the method to the automobile and housing data from the machine learning database and examined whether explicit class boundaries could be obtained. Experimental results showed that cooperation-controlled learning, in particular taking into account information on input units, could be used to produce clearer class structure than conventional self-organizing maps. PMID:25309950

Neuronal matrix metalloproteinase-9 is a determinant of selective neurodegeneration.

PubMed

Kaplan, Artem; Spiller, Krista J; Towne, Christopher; Kanning, Kevin C; Choe, Ginn T; Geber, Adam; Akay, Turgay; Aebischer, Patrick; Henderson, Christopher E

2014-01-22

Selective neuronal loss is the hallmark of neurodegenerative diseases. In patients with amyotrophic lateral sclerosis (ALS), most motor neurons die but those innervating extraocular, pelvic sphincter, and slow limb muscles exhibit selective resistance. We identified 18 genes that show >10-fold differential expression between resistant and vulnerable motor neurons. One of these, matrix metalloproteinase-9 (MMP-9), is expressed only by fast motor neurons, which are selectively vulnerable. In ALS model mice expressing mutant superoxide dismutase (SOD1), reduction of MMP-9 function using gene ablation, viral gene therapy, or pharmacological inhibition significantly delayed muscle denervation. In the presence of mutant SOD1, MMP-9 expressed by fast motor neurons themselves enhances activation of ER stress and is sufficient to trigger axonal die-back. These findings define MMP-9 as a candidate therapeutic target for ALS. The molecular basis of neuronal diversity thus provides significant insights into mechanisms of selective vulnerability to neurodegeneration. Copyright © 2014 Elsevier Inc. All rights reserved.

Purα Repaired Expanded Hexanucleotide GGGGCC Repeat Noncoding RNA-Caused Neuronal Toxicity in Neuro-2a Cells.

PubMed

Shen, Jianying; Zhang, Yu; Zhao, Shi; Mao, Hong; Wang, Zhongjing; Li, Honglian; Xu, Zihui

2018-05-01

Expanded hexanucleotide GGGGCC repeat in a noncoding region of C9ORF72 is the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, its molecular pathogenesis remains unclear. In our previous study, the expanded GGGGCC repeats have been shown to be sufficient to cause neurodegeneration. In order to investigate the further role of expanded GGGGCC repeats in the neuron, the normal r(GGGGCC) 3 and mutant-type expanded r(GGGGCC) 30 expression vectors were transfected into Neuro-2a cells. Cell proliferation, dendrite development, and the proteins' levels of microtubule-associated protein-2 (MAP2) and cyclin-dependent kinase-5 (CDK5) were used to evaluate the cell toxicity of GGGGCC repeats on Neuro-2a cells. The results were shown that expression of expanded GGGGCC repeats caused neuronal cell toxicity in Neuro-2a cells, enhanced the expression of pMAP2 and pCDK5. Moreover, overexpression of Purα repaired expanded GGGGCC repeat-inducing neuronal toxicity in Neuro-2a cells and reduced the expression of pMAP2 and pCDK5. In all, our findings suggested that the expanded GGGGCC repeats might cause neurodegeneration through destroyed neuron cells. And the GGGGCC repeat-induced neuronal cell toxicity was inhibited by upregulation of Purα. We inferred that Purα inhibits expanded GGGGCC repeat-inducing neurodegeneration, which might reveal a novel mechanism of neurodegenerative diseases ALS and FTD.

Random waves in the brain: Symmetries and defect generation in the visual cortex

NASA Astrophysics Data System (ADS)

Schnabel, M.; Kaschube, M.; Löwel, S.; Wolf, F.

2007-06-01

How orientation maps in the visual cortex of the brain develop is a matter of long standing debate. Experimental and theoretical evidence suggests that their development represents an activity-dependent self-organization process. Theoretical analysis [1] exploring this hypothesis predicted that maps at an early developmental stage are realizations of Gaussian random fields exhibiting a rigorous lower bound for their densities of topological defects, called pinwheels. As a consequence, lower pinwheel densities, if observed in adult animals, are predicted to develop through the motion and annihilation of pinwheel pairs. Despite of being valid for a large class of developmental models this result depends on the symmetries of the models and thus of the predicted random field ensembles. In [1] invariance of the orientation map's statistical properties under independent space rotations and orientation shifts was assumed. However, full rotation symmetry appears to be broken by interactions of cortical neurons, e.g. selective couplings between groups of neurons with collinear orientation preferences [2]. A recently proposed new symmetry, called shift-twist symmetry [3], stating that spatial rotations have to occur together with orientation shifts in order to be an appropriate symmetry transformation, is more consistent with this organization. Here we generalize our random field approach to this important symmetry class. We propose a new class of shift-twist symmetric Gaussian random fields and derive the general correlation functions of this ensemble. It turns out that despite strong effects of the shift-twist symmetry on the structure of the correlation functions and on the map layout the lower bound on the pinwheel densities remains unaffected, predicting pinwheel annihilation in systems with low pinwheel densities.

D(2) receptors receive paracrine neurotransmission and are consistently targeted to a subset of synaptic structures in an identified neuron of the crustacean stomatogastric nervous system.

PubMed

Oginsky, Max F; Rodgers, Edmund W; Clark, Merry C; Simmons, Robert; Krenz, Wulf-Dieter C; Baro, Deborah J

2010-02-01

Dopamine (DA) modulates motor systems in phyla as diverse as nematodes and arthropods up through chordates. A comparison of dopaminergic systems across a broad phylogenetic range should reveal shared organizing principles. The pyloric network, located in the stomatogastric ganglion (STG), is an important model for neuromodulation of motor networks. The effects of DA on this network have been well characterized at the circuit and cellular levels in the spiny lobster, Panulirus interruptus. Here we provide the first data about the physical organization of the DA signaling system in the STG and the function of D(2) receptors in pyloric neurons. Previous studies showed that DA altered intrinsic firing properties and synaptic output in the pyloric dilator (PD) neuron, in part by reducing calcium currents and increasing outward potassium currents. We performed single cell reverse transcriptase-polymerase chain reaction (RT-PCR) experiments to show that PD neurons exclusively expressed a type 2 (D(2alphaPan)) DA receptor. This was confirmed by using confocal microscopy in conjunction with immunohistochemistry (IHC) on STG whole-mount preparations containing dye-filled PD neurons. Immunogold electron microscopy showed that surface receptors were concentrated in fine neurites/terminal swellings and vesicle-laden varicosities in the synaptic neuropil. Double-label IHC experiments with tyrosine hydroxylase antiserum suggested that the D(2alphaPan) receptors received volume neurotransmissions. Receptors were further mapped onto three-dimensional models of PD neurons built from Neurolucida tracings of confocal stacks from the IHC experiments. The data showed that D(2alphaPan) receptors were selectively targeted to approximately 40% of synaptic structures in any given PD neuron, and were nonuniformly distributed among neurites.

D2 Receptors Receive Paracrine Neurotransmission and Are Consistently Targeted to a Subset of Synaptic Structures in an Identified Neuron of the Crustacean Stomatogastric Nervous System

PubMed Central

Oginsky, Max F.; Rodgers, Edmund W.; Clark, Merry C.; Simmons, Robert; Krenz, Wulf-Dieter C.; Baro, Deborah J.

2014-01-01

Dopamine (DA) modulates motor systems in phyla as diverse as nematodes and arthropods up through chordates. A comparison of dopaminergic systems across a broad phylogenetic range should reveal shared organizing principles. The pyloric network, located in the stomatogastric ganglion (STG), is an important model for neuromodulation of motor networks. The effects of DA on this network have been well characterized at the circuit and cellular levels in the spiny lobster, Panulirus interruptus. Here we provide the first data about the physical organization of the DA signaling system in the STG and the function of D2 receptors in pyloric neurons. Previous studies showed that DA altered intrinsic firing properties and synaptic output in the pyloric dilator (PD) neuron, in part by reducing calcium currents and increasing outward potassium currents. We performed single cell reverse transcriptase-polymerase chain reaction (RT-PCR) experiments to show that PD neurons exclusively expressed a type 2 (D2αPan) DA receptor. This was confirmed by using confocal microscopy in conjunction with immunohistochemistry (IHC) on STG whole-mount preparations containing dye-filled PD neurons. Immunogold electron microscopy showed that surface receptors were concentrated in fine neurites/terminal swellings and vesicle-laden varicosities in the synaptic neuropil. Double-label IHC experiments with tyrosine hydroxylase antiserum suggested that the D2αPan receptors received volume neurotransmissions. Receptors were further mapped onto three-dimensional models of PD neurons built from Neurolucida tracings of confocal stacks from the IHC experiments. The data showed that D2αPan receptors were selectively targeted to approximately 40% of synaptic structures in any given PD neuron, and were nonuniformly distributed among neurites. PMID:19941347

The Molecular and Cellular Basis of Bitter Taste in Drosophila

PubMed Central

Weiss, Linnea A.; Dahanukar, Anupama; Kwon, Jae Young; Banerjee, Diya; Carlson, John R.

2011-01-01

Summary The extent of diversity among bitter-sensing neurons is a fundamental issue in the field of taste. Data are limited and conflicting as to whether bitter neurons are broadly tuned and uniform, resulting in indiscriminate avoidance of bitter stimuli, or diverse, allowing a more discerning evaluation of food sources. We provide a systematic analysis of how bitter taste is encoded by the major taste organ of the Drosophila head, the labellum. Each of 16 bitter compounds is tested physiologically against all 31 bitter neurons, revealing responses that are diverse in magnitude and dynamics. Four functional classes of bitter neurons are defined. Four corresponding classes are defined through expression analysis of all 68 Gr taste receptors. A receptor-to-neuron-to-tastant map is constructed. Misexpression of one receptor confers bitter responses as predicted by the map. These results reveal a degree of complexity that greatly expands the capacity of the system to encode bitter taste. PMID:21262465

System and method employing a self-organizing map load feature database to identify electric load types of different electric loads

DOEpatents

Lu, Bin; Harley, Ronald G.; Du, Liang; Yang, Yi; Sharma, Santosh K.; Zambare, Prachi; Madane, Mayura A.

2014-06-17

A method identifies electric load types of a plurality of different electric loads. The method includes providing a self-organizing map load feature database of a plurality of different electric load types and a plurality of neurons, each of the load types corresponding to a number of the neurons; employing a weight vector for each of the neurons; sensing a voltage signal and a current signal for each of the loads; determining a load feature vector including at least four different load features from the sensed voltage signal and the sensed current signal for a corresponding one of the loads; and identifying by a processor one of the load types by relating the load feature vector to the neurons of the database by identifying the weight vector of one of the neurons corresponding to the one of the load types that is a minimal distance to the load feature vector.

Calcium: A novel and efficient inducer of differentiation of adipose-derived stem cells into neuron-like cells.

PubMed

Goudarzi, Farjam; Tayebinia, Heidar; Karimi, Jamshid; Habibitabar, Elahe; Khodadadi, Iraj

2018-06-05

This study comparatively investigated the effectiveness of calcium and other well-known inducers such as isobutylmethylxanthine (IBMX) and insulin in differentiating human adipose-derived stem cells (ADSCs) into neuronal-like cells. ADSCs were immunophenotyped and differentiated into neuron-like cells with different combinations of calcium, IBMX, and insulin. Calcium mobilization across the membrane was determined. Differentiated cells were characterized by cell cycle profiling, staining of Nissl bodies, detecting the gene expression level of markers such as neuronal nuclear antigen (NeuN), microtubule associated protein 2 (MAP2), neuron-specific enolase (NSE), doublecortin, synapsin I, glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP) by quantitative real-time polymerase chain reaction (quantitative real-time polymerase chain reaction (qRT-PCR) and protein level by the immunofluorescence technique. Treatment with Ca + IBMX + Ins induced neuronal appearance and projection of neurite-like processes in the cells, accompanied with inhibition of proliferation and halt in the cell cycle. A significantly higher expression of MBP, GFAP, NeuN, NSE, synapsin 1, doublecortin, and MAP2 was detected in differentiated cells, confirming the advantages of Ca + IBMX + Ins to the other combinations of inducers. Here, we showed an efficient protocol for neuronal differentiation of ADSCs, and calcium fostered differentiation by augmenting the number of neuron-like cells and instantaneous increase in the expression of neuronal markers. © 2018 Wiley Periodicals, Inc.

Specific responses of human hippocampal neurons are associated with better memory.

PubMed

Suthana, Nanthia A; Parikshak, Neelroop N; Ekstrom, Arne D; Ison, Matias J; Knowlton, Barbara J; Bookheimer, Susan Y; Fried, Itzhak

2015-08-18

A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory.

Stochastic DT-MRI connectivity mapping on the GPU.

PubMed

McGraw, Tim; Nadar, Mariappan

2007-01-01

We present a method for stochastic fiber tract mapping from diffusion tensor MRI (DT-MRI) implemented on graphics hardware. From the simulated fibers we compute a connectivity map that gives an indication of the probability that two points in the dataset are connected by a neuronal fiber path. A Bayesian formulation of the fiber model is given and it is shown that the inversion method can be used to construct plausible connectivity. An implementation of this fiber model on the graphics processing unit (GPU) is presented. Since the fiber paths can be stochastically generated independently of one another, the algorithm is highly parallelizable. This allows us to exploit the data-parallel nature of the GPU fragment processors. We also present a framework for the connectivity computation on the GPU. Our implementation allows the user to interactively select regions of interest and observe the evolving connectivity results during computation. Results are presented from the stochastic generation of over 250,000 fiber steps per iteration at interactive frame rates on consumer-grade graphics hardware.

Unique Configurations of Compression and Truncation of Neuronal Activity Underlie l-DOPA-Induced Selection of Motor Patterns in Aplysia.

PubMed

Neveu, Curtis L; Costa, Renan M; Homma, Ryota; Nagayama, Shin; Baxter, Douglas A; Byrne, John H

2017-01-01

A key issue in neuroscience is understanding the ways in which neuromodulators such as dopamine modify neuronal activity to mediate selection of distinct motor patterns. We addressed this issue by applying either low or high concentrations of l-DOPA (40 or 250 μM) and then monitoring activity of up to 130 neurons simultaneously in the feeding circuitry of Aplysia using a voltage-sensitive dye (RH-155). l-DOPA selected one of two distinct buccal motor patterns (BMPs): intermediate (low l-DOPA) or bite (high l-DOPA) patterns. The selection of intermediate BMPs was associated with shortening of the second phase of the BMP (retraction), whereas the selection of bite BMPs was associated with shortening of both phases of the BMP (protraction and retraction). Selection of intermediate BMPs was also associated with truncation of individual neuron spike activity (decreased burst duration but no change in spike frequency or burst latency) in neurons active during retraction. In contrast, selection of bite BMPs was associated with compression of spike activity (decreased burst latency and duration and increased spike frequency) in neurons projecting through specific nerves, as well as increased spike frequency of protraction neurons. Finally, large-scale voltage-sensitive dye recordings delineated the spatial distribution of neurons active during BMPs and the modification of that distribution by the two concentrations of l-DOPA.

Unique Configurations of Compression and Truncation of Neuronal Activity Underlie l-DOPA–Induced Selection of Motor Patterns in Aplysia

PubMed Central

Homma, Ryota; Nagayama, Shin; Baxter, Douglas A.

2017-01-01

A key issue in neuroscience is understanding the ways in which neuromodulators such as dopamine modify neuronal activity to mediate selection of distinct motor patterns. We addressed this issue by applying either low or high concentrations of l-DOPA (40 or 250 μM) and then monitoring activity of up to 130 neurons simultaneously in the feeding circuitry of Aplysia using a voltage-sensitive dye (RH-155). l-DOPA selected one of two distinct buccal motor patterns (BMPs): intermediate (low l-DOPA) or bite (high l-DOPA) patterns. The selection of intermediate BMPs was associated with shortening of the second phase of the BMP (retraction), whereas the selection of bite BMPs was associated with shortening of both phases of the BMP (protraction and retraction). Selection of intermediate BMPs was also associated with truncation of individual neuron spike activity (decreased burst duration but no change in spike frequency or burst latency) in neurons active during retraction. In contrast, selection of bite BMPs was associated with compression of spike activity (decreased burst latency and duration and increased spike frequency) in neurons projecting through specific nerves, as well as increased spike frequency of protraction neurons. Finally, large-scale voltage-sensitive dye recordings delineated the spatial distribution of neurons active during BMPs and the modification of that distribution by the two concentrations of l-DOPA. PMID:29071298

Orientation selectivity in the visual cortex of the nine-banded armadillo

PubMed Central

Scholl, Benjamin; Rylee, Johnathan; Luci, Jeffrey J.; Priebe, Nicholas J.

2017-01-01

Orientation selectivity in primary visual cortex (V1) has been proposed to reflect a canonical computation performed by the neocortical circuitry. Although orientation selectivity has been reported in all mammals examined to date, the degree of selectivity and the functional organization of selectivity vary across mammalian clades. The differences in degree of orientation selectivity are large, from reports in marsupials that only a small subset of neurons are selective to studies in carnivores, in which it is rare to find a neuron lacking selectivity. Furthermore, the functional organization in cortex varies in that the primate and carnivore V1 is characterized by an organization in which nearby neurons share orientation preference while other mammals such as rodents and lagomorphs either lack or have only extremely weak clustering. To gain insight into the evolutionary emergence of orientation selectivity, we examined the nine-banded armadillo, a species within the early placental clade Xenarthra. Here we use a combination of neuroimaging, histological, and electrophysiological methods to identify the retinofugal pathways, locate V1, and for the first time examine the functional properties of V1 neurons in the armadillo (Dasypus novemcinctus) V1. Individual neurons were strongly sensitive to the orientation and often the direction of drifting gratings. We uncovered a wide range of orientation preferences but found a bias for horizontal gratings. The presence of strong orientation selectivity in armadillos suggests that the circuitry responsible for this computation is common to all placental mammals. NEW & NOTEWORTHY The current study shows that armadillo primary visual cortex (V1) neurons share the signature properties of V1 neurons of primates, carnivorans, and rodents. Furthermore, these neurons exhibit a degree of selectivity for stimulus orientation and motion direction similar to that found in primate V1. Our findings in armadillo visual cortex suggest that the functional properties of V1 neurons emerged early in the mammalian lineage, near the time of the divergence of marsupials. PMID:28053246

Name-calling in the hippocampus (and beyond): coming to terms with neuron types and properties.

PubMed

Hamilton, D J; Wheeler, D W; White, C M; Rees, C L; Komendantov, A O; Bergamino, M; Ascoli, G A

2017-03-01

Widely spread naming inconsistencies in neuroscience pose a vexing obstacle to effective communication within and across areas of expertise. This problem is particularly acute when identifying neuron types and their properties. Hippocampome.org is a web-accessible neuroinformatics resource that organizes existing data about essential properties of all known neuron types in the rodent hippocampal formation. Hippocampome.org links evidence supporting the assignment of a property to a type with direct pointers to quotes and figures. Mining this knowledge from peer-reviewed reports reveals the troubling extent of terminological ambiguity and undefined terms. Examples span simple cases of using multiple synonyms and acronyms for the same molecular biomarkers (or other property) to more complex cases of neuronal naming. New publications often use different terms without mapping them to previous terms. As a result, neurons of the same type are assigned disparate names, while neurons of different types are bestowed the same name. Furthermore, non-unique properties are frequently used as names, and several neuron types are not named at all. In order to alleviate this nomenclature confusion regarding hippocampal neuron types and properties, we introduce a new functionality of Hippocampome.org: a fully searchable, curated catalog of human and machine-readable definitions, each linked to the corresponding neuron and property terms. Furthermore, we extend our robust approach to providing each neuron type with an informative name and unique identifier by mapping all encountered synonyms and homonyms.

Sequencing the Connectome

PubMed Central

Zador, Anthony M.; Dubnau, Joshua; Oyibo, Hassana K.; Zhan, Huiqing; Cao, Gang; Peikon, Ian D.

2012-01-01

Connectivity determines the function of neural circuits. Historically, circuit mapping has usually been viewed as a problem of microscopy, but no current method can achieve high-throughput mapping of entire circuits with single neuron precision. Here we describe a novel approach to determining connectivity. We propose BOINC (“barcoding of individual neuronal connections”), a method for converting the problem of connectivity into a form that can be read out by high-throughput DNA sequencing. The appeal of using sequencing is that its scale—sequencing billions of nucleotides per day is now routine—is a natural match to the complexity of neural circuits. An inexpensive high-throughput technique for establishing circuit connectivity at single neuron resolution could transform neuroscience research. PMID:23109909

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

Synthesis of Novel Synthetic Vitamin K Analogues Prepared by Introduction of a Heteroatom and a Phenyl Group That Induce Highly Selective Neuronal Differentiation of Neuronal Progenitor Cells.

PubMed

Kimura, Kimito; Hirota, Yoshihisa; Kuwahara, Shigefumi; Takeuchi, Atsuko; Tode, Chisato; Wada, Akimori; Osakabe, Naomi; Suhara, Yoshitomo

2017-03-23

We synthesized novel vitamin K 2 analogues that incorporated a heteroatom and an aromatic ring in the side chain and evaluated their effect on the selective differentiation of neuronal progenitor cells into neurons in vitro. The results showed that a menaquinone-2 analogue bearing a p-fluoroaniline had the most potent activity, which was more than twice as great as the control. In addition, the neuronal selectivity was more than 3 times greater than the control.

A two-layered diffusion model traces the dynamics of information processing in the valuation-and-choice circuit of decision making.

PubMed

Piu, Pietro; Fargnoli, Francesco; Innocenti, Alessandro; Rufa, Alessandra

2014-01-01

A circuit of evaluation and selection of the alternatives is considered a reliable model in neurobiology. The prominent contributions of the literature to this topic are reported. In this study, valuation and choice of a decisional process during Two-Alternative Forced-Choice (TAFC) task are represented as a two-layered network of computational cells, where information accrual and processing progress in nonlinear diffusion dynamics. The evolution of the response-to-stimulus map is thus modeled by two linked diffusive modules (2LDM) representing the neuronal populations involved in the valuation-and-decision circuit of decision making. Diffusion models are naturally appropriate for describing accumulation of evidence over the time. This allows the computation of the response times (RTs) in valuation and choice, under the hypothesis of ex-Wald distribution. A nonlinear transfer function integrates the activities of the two layers. The input-output map based on the infomax principle makes the 2LDM consistent with the reinforcement learning approach. Results from simulated likelihood time series indicate that 2LDM may account for the activity-dependent modulatory component of effective connectivity between the neuronal populations. Rhythmic fluctuations of the estimate gain functions in the delta-beta bands also support the compatibility of 2LDM with the neurobiology of DM.

An Application of Self-Organizing Map for Multirobot Multigoal Path Planning with Minmax Objective.

PubMed

Faigl, Jan

2016-01-01

In this paper, Self-Organizing Map (SOM) for the Multiple Traveling Salesman Problem (MTSP) with minmax objective is applied to the robotic problem of multigoal path planning in the polygonal domain. The main difficulty of such SOM deployment is determination of collision-free paths among obstacles that is required to evaluate the neuron-city distances in the winner selection phase of unsupervised learning. Moreover, a collision-free path is also needed in the adaptation phase, where neurons are adapted towards the presented input signal (city) to the network. Simple approximations of the shortest path are utilized to address this issue and solve the robotic MTSP by SOM. Suitability of the proposed approximations is verified in the context of cooperative inspection, where cities represent sensing locations that guarantee to "see" the whole robots' workspace. The inspection task formulated as the MTSP-Minmax is solved by the proposed SOM approach and compared with the combinatorial heuristic GENIUS. The results indicate that the proposed approach provides competitive results to GENIUS and support applicability of SOM for robotic multigoal path planning with a group of cooperating mobile robots. The proposed combination of approximate shortest paths with unsupervised learning opens further applications of SOM in the field of robotic planning.

An Application of Self-Organizing Map for Multirobot Multigoal Path Planning with Minmax Objective

PubMed Central

Faigl, Jan

2016-01-01

In this paper, Self-Organizing Map (SOM) for the Multiple Traveling Salesman Problem (MTSP) with minmax objective is applied to the robotic problem of multigoal path planning in the polygonal domain. The main difficulty of such SOM deployment is determination of collision-free paths among obstacles that is required to evaluate the neuron-city distances in the winner selection phase of unsupervised learning. Moreover, a collision-free path is also needed in the adaptation phase, where neurons are adapted towards the presented input signal (city) to the network. Simple approximations of the shortest path are utilized to address this issue and solve the robotic MTSP by SOM. Suitability of the proposed approximations is verified in the context of cooperative inspection, where cities represent sensing locations that guarantee to “see” the whole robots' workspace. The inspection task formulated as the MTSP-Minmax is solved by the proposed SOM approach and compared with the combinatorial heuristic GENIUS. The results indicate that the proposed approach provides competitive results to GENIUS and support applicability of SOM for robotic multigoal path planning with a group of cooperating mobile robots. The proposed combination of approximate shortest paths with unsupervised learning opens further applications of SOM in the field of robotic planning. PMID:27340395

Nonlinear functional approximation with networks using adaptive neurons

NASA Technical Reports Server (NTRS)

Tawel, Raoul

1992-01-01

A novel mathematical framework for the rapid learning of nonlinear mappings and topological transformations is presented. It is based on allowing the neuron's parameters to adapt as a function of learning. This fully recurrent adaptive neuron model (ANM) has been successfully applied to complex nonlinear function approximation problems such as the highly degenerate inverse kinematics problem in robotics.

Stable learning of functional maps in self-organizing spiking neural networks with continuous synaptic plasticity

PubMed Central

Srinivasa, Narayan; Jiang, Qin

2013-01-01

This study describes a spiking model that self-organizes for stable formation and maintenance of orientation and ocular dominance maps in the visual cortex (V1). This self-organization process simulates three development phases: an early experience-independent phase, a late experience-independent phase and a subsequent refinement phase during which experience acts to shape the map properties. The ocular dominance maps that emerge accommodate the two sets of monocular inputs that arise from the lateral geniculate nucleus (LGN) to layer 4 of V1. The orientation selectivity maps that emerge feature well-developed iso-orientation domains and fractures. During the last two phases of development the orientation preferences at some locations appear to rotate continuously through ±180° along circular paths and referred to as pinwheel-like patterns but without any corresponding point discontinuities in the orientation gradient maps. The formation of these functional maps is driven by balanced excitatory and inhibitory currents that are established via synaptic plasticity based on spike timing for both excitatory and inhibitory synapses. The stability and maintenance of the formed maps with continuous synaptic plasticity is enabled by homeostasis caused by inhibitory plasticity. However, a prolonged exposure to repeated stimuli does alter the formed maps over time due to plasticity. The results from this study suggest that continuous synaptic plasticity in both excitatory neurons and interneurons could play a critical role in the formation, stability, and maintenance of functional maps in the cortex. PMID:23450808

Role of Ongoing, Intrinsic Activity of Neuronal Populations for Quantitative Neuroimaging of Functional Magnetic Resonance Imaging–Based Networks

PubMed Central

Herman, Peter; Sanganahalli, Basavaraju G.; Coman, Daniel; Blumenfeld, Hal; Rothman, Douglas L.

2011-01-01

Abstract A primary objective in neuroscience is to determine how neuronal populations process information within networks. In humans and animal models, functional magnetic resonance imaging (fMRI) is gaining increasing popularity for network mapping. Although neuroimaging with fMRI—conducted with or without tasks—is actively discovering new brain networks, current fMRI data analysis schemes disregard the importance of the total neuronal activity in a region. In task fMRI experiments, the baseline is differenced away to disclose areas of small evoked changes in the blood oxygenation level-dependent (BOLD) signal. In resting-state fMRI experiments, the spotlight is on regions revealed by correlations of tiny fluctuations in the baseline (or spontaneous) BOLD signal. Interpretation of fMRI-based networks is obscured further, because the BOLD signal indirectly reflects neuronal activity, and difference/correlation maps are thresholded. Since the small changes of BOLD signal typically observed in cognitive fMRI experiments represent a minimal fraction of the total energy/activity in a given area, the relevance of fMRI-based networks is uncertain, because the majority of neuronal energy/activity is ignored. Thus, another alternative for quantitative neuroimaging of fMRI-based networks is a perspective in which the activity of a neuronal population is accounted for by the demanded oxidative energy (CMRO2). In this article, we argue that network mapping can be improved by including neuronal energy/activity of both the information about baseline and small differences/fluctuations of BOLD signal. Thus, total energy/activity information can be obtained through use of calibrated fMRI to quantify differences of ΔCMRO2 and through resting-state positron emission tomography/magnetic resonance spectroscopy measurements for average CMRO2. PMID:22433047

A neuronal pathway that controls sperm ejection and storage in female Drosophila.

PubMed

Lee, Kang-Min; Daubnerová, Ivana; Isaac, R Elwyn; Zhang, Chen; Choi, Sekyu; Chung, Jongkyeong; Kim, Young-Joon

2015-03-16

In polyandrous females, sperm storage permits competition between sperm of different mates, and in some species females influence the relative fertilization success of competing sperm in favor of a preferred mate [1, 2]. In female Drosophila melanogaster, sperm competition is strongly influenced by the timing of sperm ejection from the uterus [3, 4]. Understanding how female behavior influences sperm competition requires knowledge of the neuronal mechanisms controlling sperm retention and storage, which is currently lacking. Here, we show that D. melanogaster females eject male ejaculates from the uterus 1-6 hr after mating with a stereotypic behavior regulated by a brain signaling pathway composed of diuretic hormone 44 (Dh44), a neuropeptide related to vertebrate corticotropin-releasing factor (CRF), and its receptor, Dh44R1. Suppression of Dh44 signals in the brain expedites sperm ejection from the uterus, resulting in marked reduction of sperm in the storage organs and decreased fecundity, whereas enhancement of Dh44 signals delays sperm expulsion. The Dh44 function was mapped to six neurons located in the pars intercerebralis of the brain together with a small subset of Dh44R1 neurons that express the sex-specific transcription factor doublesex. This study identifies a neuronal pathway by which females can control sperm retention and storage and provides new insight into how the female might exercise post-copulatory sexual selection. Copyright © 2015 Elsevier Ltd. All rights reserved.

(1)H-magnetic resonance spectroscopy ((1)H-MRS) in methamphetamine dependence and methamphetamine induced psychosis.

PubMed

Howells, Fleur M; Uhlmann, Anne; Temmingh, Henk; Sinclair, Heidi; Meintjes, Ernesta; Wilson, Don; Stein, Dan J

2014-03-01

Methamphetamine (MA) use has been shown to decrease n-acetyl-aspartate (NAA), a marker of neuronal integrity and viability, on (1)H magnetic resonance spectroscopy ((1)H-MRS). However, little work has compared (1)H-MRS in MA dependent individuals and MA dependent individuals with MA induced psychotic disorder (MAP). Twenty six participants with MA dependence (sixteen without psychosis, ten with psychosis - MAP) and nineteen healthy controls underwent 2D-chemical shift imaging (1)H-MRS, which included voxels in the anterior cingulate cortices (ACC), dorsolateral prefrontal cortices (DLPFC), and frontal white matter. We compared metabolite concentrations relative to phosphocreatine+creatine (PCr+Cr) for n-acetyl-aspartate (NAA), n-acetyl-aspartate+n-acetyl-aspartyl-glutamate (NAA+NAAG), glutamate (Glu), glutamate+glutamine (Glu+Gln), myo-inositol, and glycerophosphocholine+phosphocholine (GPC+PCh) across groups. The MA groups showed significantly decreased relative NAA metabolite concentrations for right ACC and right DLPFC, compared with control group. The MA dependent group only showed significantly decreased choline metabolites for right DLPFC, compared with control group. The MAP group's relative NAA metabolite concentrations were significantly correlated with age of initial use and duration of MA use, these correlates were not apparent in MA dependent group. MA use is associated with decreased neuronal integrity and viability, specifically in the right ACC and right DLPFC. MA dependence showed active neurodegeneration in the right DLPFC, this was not apparent in the MAP group and may be related to the use of antipsychotic medication in the MAP group. The effects of MA use in MAP suggest that age of initial use presents a mismatch of neuronal plasticity, in frontal white vs. gray matter and duration of use relates to decreased neuronal integrity and viability. Further study is warranted from this initial study of (1)H-MRS in MAP, in particular longitudinal assessment of these individuals both neurobiologically ((1)H-MRS) and clinically - to determine disease progression. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of feature-selective attention on neuronal responses in macaque area MT

PubMed Central

Chen, X.; Hoffmann, K.-P.; Albright, T. D.

2012-01-01

Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color). PMID:22170961

Effect of feature-selective attention on neuronal responses in macaque area MT.

PubMed

Chen, X; Hoffmann, K-P; Albright, T D; Thiele, A

2012-03-01

Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color).

The Temporal Tuning of the Drosophila Motion Detectors Is Determined by the Dynamics of Their Input Elements.

PubMed

Arenz, Alexander; Drews, Michael S; Richter, Florian G; Ammer, Georg; Borst, Alexander

2017-04-03

Detecting the direction of motion contained in the visual scene is crucial for many behaviors. However, because single photoreceptors only signal local luminance changes, motion detection requires a comparison of signals from neighboring photoreceptors across time in downstream neuronal circuits. For signals to coincide on readout neurons that thus become motion and direction selective, different input lines need to be delayed with respect to each other. Classical models of motion detection rely on non-linear interactions between two inputs after different temporal filtering. However, recent studies have suggested the requirement for at least three, not only two, input signals. Here, we comprehensively characterize the spatiotemporal response properties of all columnar input elements to the elementary motion detectors in the fruit fly, T4 and T5 cells, via two-photon calcium imaging. Between these input neurons, we find large differences in temporal dynamics. Based on this, computer simulations show that only a small subset of possible arrangements of these input elements maps onto a recently proposed algorithmic three-input model in a way that generates a highly direction-selective motion detector, suggesting plausible network architectures. Moreover, modulating the motion detection system by octopamine-receptor activation, we find the temporal tuning of T4 and T5 cells to be shifted toward higher frequencies, and this shift can be fully explained by the concomitant speeding of the input elements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Olfactory neuroblastoma in dogs and cats--a histological and immunohistochemical analysis.

PubMed

Brosinski, K; Janik, D; Polkinghorne, A; Von Bomhard, W; Schmahl, W

2012-01-01

Olfactory neuroblastoma (ONB) was identified in 13 dogs and nine cats. The tumours were subjected to microscopical examination and were graded using a human pathological grading system. In the canine and feline tumours there was more necrosis and higher mitotic activity (mitotic index and Ki67 labelling index) than reported in human ONB. Rosettes were a common feature of feline ONBs. A significant correlation was observed between the histological grade and the Ki67 labelling index. The histopathological diagnosis of ONB was confirmed immunohistochemically by demonstration of the neuronal marker neuron-specific enolase (NSE). Two other neuron-specific antibodies specific for microtubule-associated protein-2 (MAP-2) and neuronal nuclei antigen (NeuN) were evaluated. MAP-2 expression proved to have higher specificity than labelling for NSE. NeuN expression was less sensitive and of limited practical value. Copyright © 2011 Elsevier Ltd. All rights reserved.

Emergence of a Stable Cortical Map for Neuroprosthetic Control

PubMed Central

Ganguly, Karunesh; Carmena, Jose M.

2009-01-01

Cortical control of neuroprosthetic devices is known to require neuronal adaptations. It remains unclear whether a stable cortical representation for prosthetic function can be stored and recalled in a manner that mimics our natural recall of motor skills. Especially in light of the mixed evidence for a stationary neuron-behavior relationship in cortical motor areas, understanding this relationship during long-term neuroprosthetic control can elucidate principles of neural plasticity as well as improve prosthetic function. Here, we paired stable recordings from ensembles of primary motor cortex neurons in macaque monkeys with a constant decoder that transforms neural activity to prosthetic movements. Proficient control was closely linked to the emergence of a surprisingly stable pattern of ensemble activity, indicating that the motor cortex can consolidate a neural representation for prosthetic control in the presence of a constant decoder. The importance of such a cortical map was evident in that small perturbations to either the size of the neural ensemble or to the decoder could reversibly disrupt function. Moreover, once a cortical map became consolidated, a second map could be learned and stored. Thus, long-term use of a neuroprosthetic device is associated with the formation of a cortical map for prosthetic function that is stable across time, readily recalled, resistant to interference, and resembles a putative memory engram. PMID:19621062

Integrate and fire neural networks, piecewise contractive maps and limit cycles.

PubMed

Catsigeras, Eleonora; Guiraud, Pierre

2013-09-01

We study the global dynamics of integrate and fire neural networks composed of an arbitrary number of identical neurons interacting by inhibition and excitation. We prove that if the interactions are strong enough, then the support of the stable asymptotic dynamics consists of limit cycles. We also find sufficient conditions for the synchronization of networks containing excitatory neurons. The proofs are based on the analysis of the equivalent dynamics of a piecewise continuous Poincaré map associated to the system. We show that for efficient interactions the Poincaré map is piecewise contractive. Using this contraction property, we prove that there exist a countable number of limit cycles attracting all the orbits dropping into the stable subset of the phase space. This result applies not only to the Poincaré map under study, but also to a wide class of general n-dimensional piecewise contractive maps.

Activity-dependent and graded BACE1 expression in the olfactory epithelium is mediated by the retinoic acid metabolizing enzyme CYP26B1.

PubMed

Login, Hande; Butowt, Rafal; Bohm, Staffan

2015-07-01

It is well established that environmental influences play a key role in sculpting neuronal connectivity in the brain. One example is the olfactory sensory map of topographic axonal connectivity. While intrinsic odorant receptor signaling in olfactory sensory neurons (OSN) determines anterior-posterior counter gradients of the axonal guidance receptors Neuropilin-1 and Plexin-A1, little is known about stimulus-dependent gradients of protein expression, which correlates with the functional organization of the olfactory sensory map along its dorsomedial (DM)-ventrolateral (VL) axis. Deficiency of the Alzheimer's β-secretase BACE1, which is expressed in a DM(low)-VL(high) gradient, results in OSN axon targeting errors in a DM > VL and gene dose-dependent manner. We show that expression of BACE1 and the all-trans retinoic acid (RA)-degrading enzyme Cyp26B1 form DM-VL counter gradients in the olfactory epithelium. Analyses of mRNA and protein levels in OSNs after naris occlusion, in mice deficient in the olfactory cyclic nucleotide-gated channel and in relation to onset of respiration, show that BACE1 and Cyp26B1 expression in OSNs inversely depend on neuronal activity. Overexpression of a Cyp26B1 or presence of a dominant negative RA receptor transgene selectively in OSNs, inhibit BACE1 expression while leaving the DM(low)-VL(high) gradient of the axonal guidance protein Neuropilin-2 intact. We conclude that stimulus-dependent neuronal activity can control the expression of the RA catabolic enzyme Cyp26B1 and downstream genes such as BACE1. This result is pertinent to an understanding of the mechanisms by which a topographic pattern of connectivity is achieved and modified as a consequence of graded gene expression and sensory experience.

The Role of Visual Area V4 in the Discrimination of Partially Occluded Shapes

PubMed Central

Kosai, Yoshito; El-Shamayleh, Yasmine; Fyall, Amber M.

2014-01-01

The primate brain successfully recognizes objects, even when they are partially occluded. To begin to elucidate the neural substrates of this perceptual capacity, we measured the responses of shape-selective neurons in visual area V4 while monkeys discriminated pairs of shapes under varying degrees of occlusion. We found that neuronal shape selectivity always decreased with increasing occlusion level, with some neurons being notably more robust to occlusion than others. The responses of neurons that maintained their selectivity across a wider range of occlusion levels were often sufficiently sensitive to support behavioral performance. Many of these same neurons were distinctively selective for the curvature of local boundary features and their shape tuning was well fit by a model of boundary curvature (curvature-tuned neurons). A significant subset of V4 neurons also signaled the animal's upcoming behavioral choices; these decision signals had short onset latencies that emerged progressively later for higher occlusion levels. The time course of the decision signals in V4 paralleled that of shape selectivity in curvature-tuned neurons: shape selectivity in curvature-tuned neurons, but not others, emerged earlier than the decision signals. These findings provide evidence for the involvement of contour-based mechanisms in the segmentation and recognition of partially occluded objects, consistent with psychophysical theory. Furthermore, they suggest that area V4 participates in the representation of the relevant sensory signals and the generation of decision signals underlying discrimination. PMID:24948811

Dendrites Enable a Robust Mechanism for Neuronal Stimulus Selectivity.

PubMed

Cazé, Romain D; Jarvis, Sarah; Foust, Amanda J; Schultz, Simon R

2017-09-01

Hearing, vision, touch: underlying all of these senses is stimulus selectivity, a robust information processing operation in which cortical neurons respond more to some stimuli than to others. Previous models assume that these neurons receive the highest weighted input from an ensemble encoding the preferred stimulus, but dendrites enable other possibilities. Nonlinear dendritic processing can produce stimulus selectivity based on the spatial distribution of synapses, even if the total preferred stimulus weight does not exceed that of nonpreferred stimuli. Using a multi-subunit nonlinear model, we demonstrate that stimulus selectivity can arise from the spatial distribution of synapses. We propose this as a general mechanism for information processing by neurons possessing dendritic trees. Moreover, we show that this implementation of stimulus selectivity increases the neuron's robustness to synaptic and dendritic failure. Importantly, our model can maintain stimulus selectivity for a larger range of loss of synapses or dendrites than an equivalent linear model. We then use a layer 2/3 biophysical neuron model to show that our implementation is consistent with two recent experimental observations: (1) one can observe a mixture of selectivities in dendrites that can differ from the somatic selectivity, and (2) hyperpolarization can broaden somatic tuning without affecting dendritic tuning. Our model predicts that an initially nonselective neuron can become selective when depolarized. In addition to motivating new experiments, the model's increased robustness to synapses and dendrites loss provides a starting point for fault-resistant neuromorphic chip development.

Shape Selectivity of Middle Superior Temporal Sulcus Body Patch Neurons

PubMed Central

2017-01-01

Abstract Functional MRI studies in primates have demonstrated cortical regions that are strongly activated by visual images of bodies. The presence of such body patches in macaques allows characterization of the stimulus selectivity of their single neurons. Middle superior temporal sulcus body (MSB) patch neurons showed similar stimulus selectivity for natural, shaded, and textured images compared with their silhouettes, suggesting that shape is an important determinant of MSB responses. Here, we examined and modeled the shape selectivity of single MSB neurons. We measured the responses of single MSB neurons to a variety of shapes producing a wide range of responses. We used an adaptive stimulus sampling procedure, selecting and modifying shapes based on the responses of the neuron. Forty percent of shapes that produced the maximal response were rated by humans as animal-like, but the top shape of many MSB neurons was not judged as resembling a body. We fitted the shape selectivity of MSB neurons with a model that parameterizes shapes in terms of curvature and orientation of contour segments, with a pixel-based model, and with layers of units of convolutional neural networks (CNNs). The deep convolutional layers of CNNs provided the best goodness-of-fit, with a median explained explainable variance of the neurons’ responses of 77%. The goodness-of-fit increased along the convolutional layers’ hierarchy but was lower for the fully connected layers. Together with demonstrating the successful modeling of single unit shape selectivity with deep CNNs, the data suggest that semantic or category knowledge determines only slightly the single MSB neuron’s shape selectivity. PMID:28660250

Local domains of motor cortical activity revealed by fiber-optic calcium recordings in behaving nonhuman primates.

PubMed

Adelsberger, Helmuth; Zainos, Antonio; Alvarez, Manuel; Romo, Ranulfo; Konnerth, Arthur

2014-01-07

Brain mapping experiments involving electrical microstimulation indicate that the primary motor cortex (M1) directly regulates muscle contraction and thereby controls specific movements. Possibly, M1 contains a small circuit "map" of the body that is formed by discrete local networks that code for specific movements. Alternatively, movements may be controlled by distributed, larger-scale overlapping circuits. Because of technical limitations, it remained unclear how movement-determining circuits are organized in M1. Here we introduce a method that allows the functional mapping of small local neuronal circuits in awake behaving nonhuman primates. For this purpose, we combined optic-fiber-based calcium recordings of neuronal activity and cortical microstimulation. The method requires targeted bulk loading of synthetic calcium indicators (e.g., OGB-1 AM) for the staining of neuronal microdomains. The tip of a thin (200 µm) optical fiber can detect the coherent activity of a small cluster of neurons, but is insensitive to the asynchronous activity of individual cells. By combining such optical recordings with microstimulation at two well-separated sites of M1, we demonstrate that local cortical activity was tightly associated with distinct and stereotypical simple movements. Increasing stimulation intensity increased both the amplitude of the movements and the level of neuronal activity. Importantly, the activity remained local, without invading the recording domain of the second optical fiber. Furthermore, there was clear response specificity at the two recording sites in a trained behavioral task. Thus, the results provide support for movement control in M1 by local neuronal clusters that are organized in discrete cortical domains.

Spatial representation and cognitive modulation of response variability in the lateral intraparietal area priority map.

PubMed

Falkner, Annegret L; Goldberg, Michael E; Krishna, B Suresh

2013-10-09

The lateral intraparietal area (LIP) in the macaque contains a priority-based representation of the visual scene. We previously showed that the mean spike rate of LIP neurons is strongly influenced by spatially wide-ranging surround suppression in a manner that effectively sharpens the priority map. Reducing response variability can also improve the precision of LIP's priority map. We show that when a monkey plans a visually guided delayed saccade with an intervening distractor, variability (measured by the Fano factor) decreases both for neurons representing the saccade goal and for neurons representing the broad spatial surround. The reduction in Fano factor is maximal for neurons representing the saccade goal and steadily decreases for neurons representing more distant locations. LIP Fano factor changes are behaviorally significant: increasing expected reward leads to lower variability for the LIP representation of both the target and distractor locations, and trials with shorter latency saccades are associated with lower Fano factors in neurons representing the surround. Thus, the LIP Fano factor reflects both stimulus and behavioral engagement. Quantitative modeling shows that the interaction between mean spike count and target-receptive field (RF) distance in the surround during the predistractor epoch is multiplicative: the Fano factor increases more steeply with mean spike count further away from the RF. A negative-binomial model for LIP spike counts captures these findings quantitatively, suggests underlying mechanisms based on trial-by-trial variations in mean spike rate or burst-firing patterns, and potentially provides a principled framework to account simultaneously for the previously observed unsystematic relationships between spike rate and variability in different brain areas.

Task-Dependent Changes in Cross-Level Coupling between Single Neurons and Oscillatory Activity in Multiscale Networks

PubMed Central

Canolty, Ryan T.; Ganguly, Karunesh; Carmena, Jose M.

2012-01-01

Understanding the principles governing the dynamic coordination of functional brain networks remains an important unmet goal within neuroscience. How do distributed ensembles of neurons transiently coordinate their activity across a variety of spatial and temporal scales? While a complete mechanistic account of this process remains elusive, evidence suggests that neuronal oscillations may play a key role in this process, with different rhythms influencing both local computation and long-range communication. To investigate this question, we recorded multiple single unit and local field potential (LFP) activity from microelectrode arrays implanted bilaterally in macaque motor areas. Monkeys performed a delayed center-out reach task either manually using their natural arm (Manual Control, MC) or under direct neural control through a brain-machine interface (Brain Control, BC). In accord with prior work, we found that the spiking activity of individual neurons is coupled to multiple aspects of the ongoing motor beta rhythm (10–45 Hz) during both MC and BC, with neurons exhibiting a diversity of coupling preferences. However, here we show that for identified single neurons, this beta-to-rate mapping can change in a reversible and task-dependent way. For example, as beta power increases, a given neuron may increase spiking during MC but decrease spiking during BC, or exhibit a reversible shift in the preferred phase of firing. The within-task stability of coupling, combined with the reversible cross-task changes in coupling, suggest that task-dependent changes in the beta-to-rate mapping play a role in the transient functional reorganization of neural ensembles. We characterize the range of task-dependent changes in the mapping from beta amplitude, phase, and inter-hemispheric phase differences to the spike rates of an ensemble of simultaneously-recorded neurons, and discuss the potential implications that dynamic remapping from oscillatory activity to spike rate and timing may hold for models of computation and communication in distributed functional brain networks. PMID:23284276

Early valproic acid exposure alters functional organization in the primary visual cortex

PubMed Central

Pohl-Guimaraes, Fernanda; Krahe, Thomas E.; Medina, Alexandre E.

2018-01-01

Epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. The use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. Neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. Here we investigate the effects of early exposure to valproic acid (Val) and levetiracetam (Lev), commonly used antiepileptic drugs, on the development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets pups were exposed to Val (200 mg/kg), Lev (100 mg/kg) or saline every other day between postnatal day (P) 10 and P30, a period roughly equivalent to the third trimester of human gestation. Optical imaging of intrinsic signals or single-unit recordings were examined at P42–P84, when orientation selectivity in the ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in Val-but not Lev- or saline-treated animals. Moreover, single-unit recordings revealed that early Val treatment also reduced orientation selectivity at the cellular level. These findings indicate that Val exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in fetal anticonvulsant syndrome. PMID:21215743

Early valproic acid exposure alters functional organization in the primary visual cortex.

PubMed

Pohl-Guimaraes, Fernanda; Krahe, Thomas E; Medina, Alexandre E

2011-03-01

Epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. The use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. Neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. Here we investigate the effects of early exposure to valproic acid (Val) and levetiracetam (Lev), commonly used antiepileptic drugs, on the development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets pups were exposed to Val (200mg/kg), Lev (100mg/kg) or saline every other day between postnatal day (P) 10 and P30, a period roughly equivalent to the third trimester of human gestation. Optical imaging of intrinsic signals or single-unit recordings were examined at P42-P84, when orientation selectivity in the ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in Val- but not Lev- or saline-treated animals. Moreover, single-unit recordings revealed that early Val treatment also reduced orientation selectivity at the cellular level. These findings indicate that Val exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in fetal anticonvulsant syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Digital hardware implementation of a stochastic two-dimensional neuron model.

PubMed

Grassia, F; Kohno, T; Levi, T

2016-11-01

This study explores the feasibility of stochastic neuron simulation in digital systems (FPGA), which realizes an implementation of a two-dimensional neuron model. The stochasticity is added by a source of current noise in the silicon neuron using an Ornstein-Uhlenbeck process. This approach uses digital computation to emulate individual neuron behavior using fixed point arithmetic operation. The neuron model's computations are performed in arithmetic pipelines. It was designed in VHDL language and simulated prior to mapping in the FPGA. The experimental results confirmed the validity of the developed stochastic FPGA implementation, which makes the implementation of the silicon neuron more biologically plausible for future hybrid experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons

PubMed Central

Steinkellner, Thomas; Farino, Zachary J.; Sonders, Mark S.; Villeneuve, Michael; Freyberg, Robin J.; Przedborski, Serge; Lu, Wei; Hnasko, Thomas S.

2018-01-01

Parkinson’s disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here, we addressed the potential relationship between VGLUT expression and DA neuronal vulnerability by overexpressing VGLUT in DA neurons of flies and mice. In Drosophila, VGLUT overexpression led to loss of select DA neuron populations. Similarly, expression of VGLUT2 specifically in murine SNc DA neurons led to neuronal loss and Parkinsonian behaviors. Other neuronal cell types showed no such sensitivity, suggesting that DA neurons are distinctively vulnerable to VGLUT2 expression. Additionally, most DA neurons expressed VGLUT2 during development, and coexpression of VGLUT2 with DA markers increased following injury in the adult. Finally, conditional deletion of VGLUT2 made DA neurons more susceptible to Parkinsonian neurotoxins. These data suggest that the balance of VGLUT2 expression is a crucial determinant of DA neuron survival. Ultimately, manipulation of this VGLUT2-dependent process may represent an avenue for therapeutic development. PMID:29337309

A subconvulsive dose of kainate selectively compromises astrocytic metabolism in the mouse brain in vivo.

PubMed

Walls, Anne B; Eyjolfsson, Elvar M; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

2014-08-01

Despite the well-established use of kainate as a model for seizure activity and temporal lobe epilepsy, most studies have been performed at doses giving rise to general limbic seizures and have mainly focused on neuronal function. Little is known about the effect of lower doses of kainate on cerebral metabolism and particularly that associated with astrocytes. We investigated astrocytic and neuronal metabolism in the cerebral cortex of adult mice after treatment with saline (controls), a subconvulsive or a mildly convulsive dose of kainate. A combination of [1,2-(13)C]acetate and [1-(13)C]glucose was injected and subsequent nuclear magnetic resonance spectroscopy of cortical extracts was employed to distinctively map astrocytic and neuronal metabolism. The subconvulsive dose of kainate led to an instantaneous increase in the cortical lactate content, a subsequent reduction in the amount of [4,5-(13)C]glutamine and an increase in the calculated astrocytic TCA cycle activity. In contrast, the convulsive dose led to decrements in the cortical content and (13)C labeling of glutamate, glutamine, GABA, and aspartate. Evidence is provided that astrocytic metabolism is affected by a subconvulsive dose of kainate, whereas a higher dose is required to affect neuronal metabolism. The cerebral glycogen content was dose-dependently reduced by kainate supporting a role for glycogen during seizure activity.

A subconvulsive dose of kainate selectively compromises astrocytic metabolism in the mouse brain in vivo

PubMed Central

Walls, Anne B; Eyjolfsson, Elvar M; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

2014-01-01

Despite the well-established use of kainate as a model for seizure activity and temporal lobe epilepsy, most studies have been performed at doses giving rise to general limbic seizures and have mainly focused on neuronal function. Little is known about the effect of lower doses of kainate on cerebral metabolism and particularly that associated with astrocytes. We investigated astrocytic and neuronal metabolism in the cerebral cortex of adult mice after treatment with saline (controls), a subconvulsive or a mildly convulsive dose of kainate. A combination of [1,2-13C]acetate and [1-13C]glucose was injected and subsequent nuclear magnetic resonance spectroscopy of cortical extracts was employed to distinctively map astrocytic and neuronal metabolism. The subconvulsive dose of kainate led to an instantaneous increase in the cortical lactate content, a subsequent reduction in the amount of [4,5-13C]glutamine and an increase in the calculated astrocytic TCA cycle activity. In contrast, the convulsive dose led to decrements in the cortical content and 13C labeling of glutamate, glutamine, GABA, and aspartate. Evidence is provided that astrocytic metabolism is affected by a subconvulsive dose of kainate, whereas a higher dose is required to affect neuronal metabolism. The cerebral glycogen content was dose-dependently reduced by kainate supporting a role for glycogen during seizure activity. PMID:24824917

The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release

PubMed Central

2017-01-01

Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent vesicle-associated membrane protein 2-dependent vesicle fusion. Additionally, there was no difference in the ability of μ-opioid receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, and activation of the inhibitory designer receptor hM4Di on AgRP neurons did not affect sIPSCs recorded from POMC neurons. These approaches collectively indicate that AgRP neurons do not significantly contribute to the strong spontaneous GABA input to POMC neurons. Despite these observations, optogenetic stimulation of AgRP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron firing. Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant source of spontaneous GABA input to POMC neurons. Together, these results indicate that the relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need to consider different types of transmitter release in circuit mapping and physiologic regulation. SIGNIFICANCE STATEMENT Agouti-related peptide (AgRP) neurons play an important role in driving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding. Despite the importance of these two well characterized neuron types in maintaining metabolic homeostasis, communication between these cells remains poorly understood. To provide clarity to this circuit, we made electrophysiological recordings from mouse brain slices and found that AgRP neurons do not contribute spontaneously released GABA onto POMC neurons, although when activated with channelrhodopsin AgRP neurons inhibit POMC neurons through GABA-mediated transmission. These findings indicate that the relevance of AgRP to POMC neuron GABA connectivity depends on the state of AgRP neuron activity and suggest that different types of transmitter release should be considered when circuit mapping. PMID:28667175

The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release.

PubMed

Rau, Andrew R; Hentges, Shane T

2017-08-02

Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent vesicle-associated membrane protein 2-dependent vesicle fusion. Additionally, there was no difference in the ability of μ-opioid receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, and activation of the inhibitory designer receptor hM4Di on AgRP neurons did not affect sIPSCs recorded from POMC neurons. These approaches collectively indicate that AgRP neurons do not significantly contribute to the strong spontaneous GABA input to POMC neurons. Despite these observations, optogenetic stimulation of AgRP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron firing. Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant source of spontaneous GABA input to POMC neurons. Together, these results indicate that the relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need to consider different types of transmitter release in circuit mapping and physiologic regulation. SIGNIFICANCE STATEMENT Agouti-related peptide (AgRP) neurons play an important role in driving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding. Despite the importance of these two well characterized neuron types in maintaining metabolic homeostasis, communication between these cells remains poorly understood. To provide clarity to this circuit, we made electrophysiological recordings from mouse brain slices and found that AgRP neurons do not contribute spontaneously released GABA onto POMC neurons, although when activated with channelrhodopsin AgRP neurons inhibit POMC neurons through GABA-mediated transmission. These findings indicate that the relevance of AgRP to POMC neuron GABA connectivity depends on the state of AgRP neuron activity and suggest that different types of transmitter release should be considered when circuit mapping. Copyright © 2017 the authors 0270-6474/17/377362-11$15.00/0.

Rapid Long-Range Disynaptic Inhibition Explains the Formation of Cortical Orientation Maps

PubMed Central

Antolík, Ján

2017-01-01

Competitive interactions are believed to underlie many types of cortical processing, ranging from memory formation, attention and development of cortical functional organization (e.g., development of orientation maps in primary visual cortex). In the latter case, the competitive interactions happen along the cortical surface, with local populations of neurons reinforcing each other, while competing with those displaced more distally. This specific configuration of lateral interactions is however in stark contrast with the known properties of the anatomical substrate, i.e., excitatory connections (mediating reinforcement) having longer reach than inhibitory ones (mediating competition). No satisfactory biologically plausible resolution of this conflict between anatomical measures, and assumed cortical function has been proposed. Recently a specific pattern of delays between different types of neurons in cat cortex has been discovered, where direct mono-synaptic excitation has approximately the same delay, as the combined delays of the disynaptic inhibitory interactions between excitatory neurons (i.e., the sum of delays from excitatory to inhibitory and from inhibitory to excitatory neurons). Here we show that this specific pattern of delays represents a biologically plausible explanation for how short-range inhibition can support competitive interactions that underlie the development of orientation maps in primary visual cortex. We demonstrate this statement analytically under simplifying conditions, and subsequently show using network simulations that development of orientation maps is preserved when long-range excitation, direct inhibitory to inhibitory interactions, and moderate inequality in the delays between excitatory and inhibitory pathways is added. PMID:28408869

A New Tool for Local Manipulation of Neuronal Micro-Circuitry with Ions and Force

DTIC Science & Technology

2017-02-07

lifesci.ucsb.edu Final Report 7/30/2015-9/30/2016 3 neurons, memory , connectivity, microcircuitry 2/7/2017 Our goal is to compute the complete functional... memory trace. To date no functional connectivity map exists for living neurons at the resolution proposed here. In fact, a quantitative model of the...propagation signals are also present in cultures of human iPS-derived neurons and thus could be used to study axonal physiology in human disease models. 3

Strategies for mapping synaptic inputs on dendrites in vivo by combining two-photon microscopy, sharp intracellular recording, and pharmacology

PubMed Central

Levy, Manuel; Schramm, Adrien E.; Kara, Prakash

2012-01-01

Uncovering the functional properties of individual synaptic inputs on single neurons is critical for understanding the computational role of synapses and dendrites. Previous studies combined whole-cell patch recording to load neurons with a fluorescent calcium indicator and two-photon imaging to map subcellular changes in fluorescence upon sensory stimulation. By hyperpolarizing the neuron below spike threshold, the patch electrode ensured that changes in fluorescence associated with synaptic events were isolated from those caused by back-propagating action potentials. This technique holds promise for determining whether the existence of unique cortical feature maps across different species may be associated with distinct wiring diagrams. However, the use of whole-cell patch for mapping inputs on dendrites is challenging in large mammals, due to brain pulsations and the accumulation of fluorescent dye in the extracellular milieu. Alternatively, sharp intracellular electrodes have been used to label neurons with fluorescent dyes, but the current passing capabilities of these high impedance electrodes may be insufficient to prevent spiking. In this study, we tested whether sharp electrode recording is suitable for mapping functional inputs on dendrites in the cat visual cortex. We compared three different strategies for suppressing visually evoked spikes: (1) hyperpolarization by intracellular current injection, (2) pharmacological blockade of voltage-gated sodium channels by intracellular QX-314, and (3) GABA iontophoresis from a perisomatic electrode glued to the intracellular electrode. We found that functional inputs on dendrites could be successfully imaged using all three strategies. However, the best method for preventing spikes was GABA iontophoresis with low currents (5–10 nA), which minimally affected the local circuit. Our methods advance the possibility of determining functional connectivity in preparations where whole-cell patch may be impractical. PMID:23248588

Network inference from functional experimental data (Conference Presentation)

NASA Astrophysics Data System (ADS)

Desrosiers, Patrick; Labrecque, Simon; Tremblay, Maxime; Bélanger, Mathieu; De Dorlodot, Bertrand; Côté, Daniel C.

2016-03-01

Functional connectivity maps of neuronal networks are critical tools to understand how neurons form circuits, how information is encoded and processed by neurons, how memory is shaped, and how these basic processes are altered under pathological conditions. Current light microscopy allows to observe calcium or electrical activity of thousands of neurons simultaneously, yet assessing comprehensive connectivity maps directly from such data remains a non-trivial analytical task. There exist simple statistical methods, such as cross-correlation and Granger causality, but they only detect linear interactions between neurons. Other more involved inference methods inspired by information theory, such as mutual information and transfer entropy, identify more accurately connections between neurons but also require more computational resources. We carried out a comparative study of common connectivity inference methods. The relative accuracy and computational cost of each method was determined via simulated fluorescence traces generated with realistic computational models of interacting neurons in networks of different topologies (clustered or non-clustered) and sizes (10-1000 neurons). To bridge the computational and experimental works, we observed the intracellular calcium activity of live hippocampal neuronal cultures infected with the fluorescent calcium marker GCaMP6f. The spontaneous activity of the networks, consisting of 50-100 neurons per field of view, was recorded from 20 to 50 Hz on a microscope controlled by a homemade software. We implemented all connectivity inference methods in the software, which rapidly loads calcium fluorescence movies, segments the images, extracts the fluorescence traces, and assesses the functional connections (with strengths and directions) between each pair of neurons. We used this software to assess, in real time, the functional connectivity from real calcium imaging data in basal conditions, under plasticity protocols, and epileptic conditions.

FoxP2 brainstem neurons project to sodium appetite regulatory sites.

PubMed

Shin, Jung-Won; Geerling, Joel C; Stein, Matthew K; Miller, Rebecca L; Loewy, Arthur D

2011-09-01

The transcription factor Forkhead box protein 2 (FoxP2) is expressed in two cell groups of the brainstem that have been implicated in sodium appetite regulation: the pre-locus coeruleus (pre-LC) and parabrachial nucleus--external lateral-inner subdivision (PBel-inner). Because the connections of these two groups are unknown, neuroanatomical tracing methods were used to define their central projections. The pre-LC outputs were first analyzed using an anterograde axonal tracer--Phaseolus vulgaris leucoagglutinin (PHAL) to construct a brain map. Next, we examined whether the FoxP2 immunoreactive (FoxP2+) neurons of the pre-LC contribute to these projections using a retrograde neuronal tracer--cholera toxin β-subunit (CTb). CTb was injected into selected brain regions identified in the anterograde tracing study. One week later the rats were killed, and brainstem sections were processed by a double immunohistochemical procedure to determine whether the FoxP2+ neurons in the pre-LC and/or PBel-inner contained CTb. FoxP2+ pre-LC neurons project to: (1) ventral pallidum; (2) substantia innominata and bed nucleus of the stria terminalis; (3) paraventricular, central medial, parafascicular, and subparafascicular parvicellular thalamic nuclei; (4) paraventricular (PVH), lateral, perifornical, dorsomedial (DMH), and parasubthalamic hypothalamic nuclei; and (5) ventral tegmental area (VTA), periaqueductal gray matter (PAG), dorsal and central linear raphe nuclei. FoxP2+ PBel-inner neurons project to the PVH and DMH, with weaker connections to the LHA, VTA, and PAG. Both the pre-LC and PBel-inner project to central sites implicated in sodium appetite, and related issues, including foraging behavior, hedonic responses to salt intake, sodium balance, and cardiovascular regulation, are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Neurokinin-1 receptor antagonism attenuates neuronal activity triggered by stress-induced reinstatement of alcohol seeking.

PubMed

Schank, J R; Nelson, B S; Damadzic, R; Tapocik, J D; Yao, M; King, C E; Rowe, K E; Cheng, K; Rice, K C; Heilig, M

2015-12-01

Substance P (SP) and its cognate neurokinin-1 receptor (NK1R) are involved in alcohol-related behaviors. We have previously reported that NK1R antagonism attenuates stress-induced reinstatement of alcohol seeking and suppresses escalated alcohol self-administration, but does not affect primary reinforcement or cue-induced reinstatement. Here, we administered an NK1R antagonist or vehicle prior to footshock-induced reinstatement of alcohol seeking, and mapped the resulting neuronal activation using Fos immunohistochemistry. As expected, vehicle treated animals exposed to footshock showed induction of Fos immunoreactivity in several regions of the brain stress circuitry, including the amygdala (AMG), nucleus accumbens (NAC), dorsal raphe nucleus (DR), prefrontal cortex (PFC), and bed nucleus of the stria terminalis (BNST). NK1R antagonism selectively suppressed the stress-induced increase in Fos in the DR and NAC shell. In the DR, Fos-induction by stress largely overlapped with tryptophan hydroxylase (TrpH), indicating activation of serotonergic neurons. Of NAC shell neurons activated during stress-induced reinstatement of alcohol seeking, about 30% co-expressed dynorphin (DYN), while 70% co-expressed enkephalin (ENK). Few (<1%) activated NAC shell neurons coexpressed choline acetyltransferase (ChAT), which labels the cholinergic interneurons of this region. Infusion of the NK1R antagonist L822429 into the NAC shell blocked stress-induced reinstatement of alcohol seeking. In contrast, L822429 infusion into the DR had no effect, suggesting that the influence of NK1R signaling on neuronal activity in the DR is indirect. Taken together, our results outline a potential pathway through which endogenous NK1R activation mediates stress-induced alcohol seeking. Copyright © 2015 Elsevier Ltd. All rights reserved.

Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization

PubMed Central

2011-01-01

Background Calcitonin gene-related peptide (CGRP), a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD). Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD. Results Temporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ) capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X3 in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection. Conclusions Our results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD. PMID:22145886

Song Selectivity in the Pallial-Basal Ganglia Song Circuit of Zebra Finches Raised Without Tutor Song Exposure

PubMed Central

Kojima, Satoshi; Doupe, Allison J.

2008-01-01

Acoustic experience critically influences auditory cortical development as well as emergence of highly selective auditory neurons in the songbird sensorimotor circuit. In adult zebra finches, these “song-selective” neurons respond better to the bird's own song (BOS) than to songs of other conspecifics. Birds learn their songs by memorizing a tutor's song and then matching auditory feedback of their voice to the tutor song memory. Song-selective neurons in the pallial-basal ganglia circuit called the anterior forebrain pathway (AFP) reflect the development of BOS. However, during learning, they also respond strongly to tutor song and are compromised in their adult selectivity when birds are prevented from matching BOS to tutor, suggesting that selectivity depends on tutor song learning as well as sensorimotor matching of BOS feedback to the tutor song memory. We examined the contribution of sensory learning of tutor song to song selectivity by recording from AFP neurons in birds reared without exposure to adult conspecifics. We found that AFP neurons in these “isolate” birds had highly tuned responses to isolate BOS. The selectivity was as high, and in the striato-pallidal nucleus Area X, even higher than that in normal birds, due to abnormally weak responsiveness to conspecific song. These results demonstrate that sensory learning of tutor song is not necessary for BOS tuning of AFP neurons. Because isolate birds develop their song via sensorimotor learning, our data further illustrate the importance of individual sensorimotor learning for song selectivity and provide insight into possible functions of song-selective neurons. PMID:17625059

Activated actin-depolymerizing factor/cofilin sequesters phosphorylated microtubule-associated protein during the assembly of alzheimer-like neuritic cytoskeletal striations.

PubMed

Whiteman, Ineka T; Gervasio, Othon L; Cullen, Karen M; Guillemin, Gilles J; Jeong, Erica V; Witting, Paul K; Antao, Shane T; Minamide, Laurie S; Bamburg, James R; Goldsbury, Claire

2009-10-14

In Alzheimer's disease (AD), rod-like cofilin aggregates (cofilin-actin rods) and thread-like inclusions containing phosphorylated microtubule-associated protein (pMAP) tau form in the brain (neuropil threads), and the extent of their presence correlates with cognitive decline and disease progression. The assembly mechanism of these respective pathological lesions and the relationship between them is poorly understood, yet vital to understanding the causes of sporadic AD. We demonstrate that, during mitochondrial inhibition, activated actin-depolymerizing factor (ADF)/cofilin assemble into rods along processes of cultured primary neurons that recruit pMAP/tau and mimic neuropil threads. Fluorescence resonance energy transfer analysis revealed colocalization of cofilin-GFP (green fluorescent protein) and pMAP in rods, suggesting their close proximity within a cytoskeletal inclusion complex. The relationship between pMAP and cofilin-actin rods was further investigated using actin-modifying drugs and small interfering RNA knockdown of ADF/cofilin in primary neurons. The results suggest that activation of ADF/cofilin and generation of cofilin-actin rods is required for the subsequent recruitment of pMAP into the inclusions. Additionally, we were able to induce the formation of pMAP-positive ADF/cofilin rods by exposing cells to exogenous amyloid-beta (Abeta) peptides. These results reveal a common pathway for pMAP and cofilin accumulation in neuronal processes. The requirement of activated ADF/cofilin for the sequestration of pMAP suggests that neuropil thread structures in the AD brain may be initiated by elevated cofilin activation and F-actin bundling that can be caused by oxidative stress, mitochondrial dysfunction, or Abeta peptides, all suspected initiators of synaptic loss and neurodegeneration in AD.

A linear model fails to predict orientation selectivity of cells in the cat visual cortex.

PubMed Central

Volgushev, M; Vidyasagar, T R; Pei, X

1996-01-01

1. Postsynaptic potentials (PSPs) evoked by visual stimulation in simple cells in the cat visual cortex were recorded using in vivo whole-cell technique. Responses to small spots of light presented at different positions over the receptive field and responses to elongated bars of different orientations centred on the receptive field were recorded. 2. To test whether a linear model can account for orientation selectivity of cortical neurones, responses to elongated bars were compared with responses predicted by a linear model from the receptive field map obtained from flashing spots. 3. The linear model faithfully predicted the preferred orientation, but not the degree of orientation selectivity or the sharpness of orientation tuning. The ratio of optimal to non-optimal responses was always underestimated by the model. 4. Thus non-linear mechanisms, which can include suppression of non-optimal responses and/or amplification of optimal responses, are involved in the generation of orientation selectivity in the primary visual cortex. PMID:8930828

Hippocampal neuronal cells that accumulate α-synuclein fragments are more vulnerable to Aβ oligomer toxicity via mGluR5 – implications for dementia with Lewy bodies

PubMed Central

2014-01-01

Background In dementia with Lewy bodies (DLB) abnormal interactions between α-synuclein (α-syn) and beta amyloid (Aβ) result in selective degeneration of neurons in the neocortex, limbic system and striatum. However, factors rendering these neurons selectively vulnerable have not been fully investigated. The metabotropic glutamate receptor 5 (mGluR5) has been shown to be up regulated in DLB and might play a role as a mediator of the neurotoxic effects of Aβ and α-syn in vulnerable neuronal populations. In this context, the main objective of the present study was to investigate the role of mGluR5 as a mediator of the neurotoxic effects of α-syn and Aβ in the hippocampus. Results We generated double transgenic mice over-expressing amyloid precursor protein (APP) and α-syn under the mThy1 cassette and investigated the relationship between α-syn cleavage, Aβ, mGluR5 and neurodegeneration in the hippocampus. We found that compared to the single tg mice, the α-syn/APP tg mice displayed greater accumulation of α-syn and mGluR5 in the CA3 region of the hippocampus compared to the CA1 and other regions. This was accompanied by loss of CA3 (but not CA1) neurons in the single and α-syn/APP tg mice and greater loss of MAP 2 and synaptophysin in the CA3 in the α-syn/APP tg. mGluR5 gene transfer using a lentiviral vector into the hippocampus CA1 region resulted in greater α-syn accumulation and neurodegeneration in the single and α-syn/APP tg mice. In contrast, silencing mGluR5 with a lenti-shRNA protected neurons in the CA3 region of tg mice. In vitro, greater toxicity was observed in primary hippocampal neuronal cultures treated with Aβ oligomers and over-expressing α-syn; this effect was attenuated by down-regulating mGluR5 with an shRNA lentiviral vector. In α-syn-expressing neuronal cells lines, Aβ oligomers promoted increased intracellular calcium levels, calpain activation and α-syn cleavage resulting in caspase-3-dependent cell death. Treatment with pharmacological mGluR5 inhibitors such as 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) attenuated the toxic effects of Aβ in α-syn-expressing neuronal cells. Conclusions Together, these results support the possibility that vulnerability of hippocampal neurons to α-syn and Aβ might be mediated via mGluR5. Moreover, therapeutical interventions targeting mGluR5 might have a role in DLB. PMID:24885390

Network and neuronal membrane properties in hybrid networks reciprocally regulate selectivity to rapid thalamocortical inputs.

PubMed

Pesavento, Michael J; Pinto, David J

2012-11-01

Rapidly changing environments require rapid processing from sensory inputs. Varying deflection velocities of a rodent's primary facial vibrissa cause varying temporal neuronal activity profiles within the ventral posteromedial thalamic nucleus. Local neuron populations in a single somatosensory layer 4 barrel transform sparsely coded input into a spike count based on the input's temporal profile. We investigate this transformation by creating a barrel-like hybrid network with whole cell recordings of in vitro neurons from a cortical slice preparation, embedding the biological neuron in the simulated network by presenting virtual synaptic conductances via a conductance clamp. Utilizing the hybrid network, we examine the reciprocal network properties (local excitatory and inhibitory synaptic convergence) and neuronal membrane properties (input resistance) by altering the barrel population response to diverse thalamic input. In the presence of local network input, neurons are more selective to thalamic input timing; this arises from strong feedforward inhibition. Strongly inhibitory (damping) network regimes are more selective to timing and less selective to the magnitude of input but require stronger initial input. Input selectivity relies heavily on the different membrane properties of excitatory and inhibitory neurons. When inhibitory and excitatory neurons had identical membrane properties, the sensitivity of in vitro neurons to temporal vs. magnitude features of input was substantially reduced. Increasing the mean leak conductance of the inhibitory cells decreased the network's temporal sensitivity, whereas increasing excitatory leak conductance enhanced magnitude sensitivity. Local network synapses are essential in shaping thalamic input, and differing membrane properties of functional classes reciprocally modulate this effect.

Selective increase of in vivo firing frequencies in DA SN neurons after proteasome inhibition in the ventral midbrain.

PubMed

Subramaniam, Mahalakshmi; Kern, Beatrice; Vogel, Simone; Klose, Verena; Schneider, Gaby; Roeper, Jochen

2014-09-01

The impairment of protein degradation via the ubiquitin-proteasome system (UPS) is present in sporadic Parkinson's disease (PD), and might play a key role in selective degeneration of vulnerable dopamine (DA) neurons in the substantia nigra pars compacta (SN). Further evidence for a causal role of dysfunctional UPS in familial PD comes from mutations in parkin, which results in a loss of function of an E3-ubiquitin-ligase. In a mouse model, genetic inactivation of an essential component of the 26S proteasome lead to widespread neuronal degeneration including DA midbrain neurons and the formation of alpha-synuclein-positive inclusion bodies, another hallmark of PD. Studies using pharmacological UPS inhibition in vivo had more mixed results, varying from extensive degeneration to no loss of DA SN neurons. However, it is currently unknown whether UPS impairment will affect the neurophysiological functions of DA midbrain neurons. To answer this question, we infused a selective proteasome inhibitor into the ventral midbrain in vivo and recorded single DA midbrain neurons 2 weeks after the proteasome challenge. We found a selective increase in the mean in vivo firing frequencies of identified DA SN neurons in anesthetized mice, while those in the ventral tegmental area (VTA) were unaffected. Our results demonstrate that a single-hit UPS inhibition is sufficient to induce a stable and selective hyperexcitability phenotype in surviving DA SN neurons in vivo. This might imply that UPS dysfunction sensitizes DA SN neurons by enhancing 'stressful pacemaking'. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Selective attention in an insect visual neuron.

PubMed

Wiederman, Steven D; O'Carroll, David C

2013-01-21

Animals need attention to focus on one target amid alternative distracters. Dragonflies, for example, capture flies in swarms comprising prey and conspecifics, a feat that requires neurons to select one moving target from competing alternatives. Diverse evidence, from functional imaging and physiology to psychophysics, highlights the importance of such "competitive selection" in attention for vertebrates. Analogous mechanisms have been proposed in artificial intelligence and even in invertebrates, yet direct neural correlates of attention are scarce from all animal groups. Here, we demonstrate responses from an identified dragonfly visual neuron that perfectly match a model for competitive selection within limits of neuronal variability (r(2) = 0.83). Responses to individual targets moving at different locations within the receptive field differ in both magnitude and time course. However, responses to two simultaneous targets exclusively track those for one target alone rather than any combination of the pair. Irrespective of target size, contrast, or separation, this neuron selects one target from the pair and perfectly preserves the response, regardless of whether the "winner" is the stronger stimulus if presented alone. This neuron is amenable to electrophysiological recordings, providing neuroscientists with a new model system for studying selective attention. Copyright © 2013 Elsevier Ltd. All rights reserved.

All‐optical functional synaptic connectivity mapping in acute brain slices using the calcium integrator CaMPARI

PubMed Central

Sha, Fern; Johenning, Friedrich W.; Schreiter, Eric R.; Looger, Loren L.; Larkum, Matthew E.

2016-01-01

Key points The genetically encoded fluorescent calcium integrator calcium‐modulated photoactivatable ratiobetric integrator (CaMPARI) reports calcium influx induced by synaptic and neural activity. Its fluorescence is converted from green to red in the presence of violet light and calcium.The rate of conversion – the sensitivity to activity – is tunable and depends on the intensity of violet light.Synaptic activity and action potentials can independently initiate significant CaMPARI conversion.The level of conversion by subthreshold synaptic inputs is correlated to the strength of input, enabling optical readout of relative synaptic strength.When combined with optogenetic activation of defined presynaptic neurons, CaMPARI provides an all‐optical method to map synaptic connectivity. Abstract The calcium‐modulated photoactivatable ratiometric integrator (CaMPARI) is a genetically encoded calcium integrator that facilitates the study of neural circuits by permanently marking cells active during user‐specified temporal windows. Permanent marking enables measurement of signals from large swathes of tissue and easy correlation of activity with other structural or functional labels. One potential application of CaMPARI is labelling neurons postsynaptic to specific populations targeted for optogenetic stimulation, giving rise to all‐optical functional connectivity mapping. Here, we characterized the response of CaMPARI to several common types of neuronal calcium signals in mouse acute cortical brain slices. Our experiments show that CaMPARI is effectively converted by both action potentials and subthreshold synaptic inputs, and that conversion level is correlated to synaptic strength. Importantly, we found that conversion rate can be tuned: it is linearly related to light intensity. At low photoconversion light levels CaMPARI offers a wide dynamic range due to slower conversion rate; at high light levels conversion is more rapid and more sensitive to activity. Finally, we employed CaMPARI and optogenetics for functional circuit mapping in ex vivo acute brain slices, which preserve in vivo‐like connectivity of axon terminals. With a single light source, we stimulated channelrhodopsin‐2‐expressing long‐range posteromedial (POm) thalamic axon terminals in cortex and induced CaMPARI conversion in recipient cortical neurons. We found that POm stimulation triggers robust photoconversion of layer 5 cortical neurons and weaker conversion of layer 2/3 neurons. Thus, CaMPARI enables network‐wide, tunable, all‐optical functional circuit mapping that captures supra‐ and subthreshold depolarization. PMID:27861906

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

Stimulus features coded by single neurons of a macaque body category selective patch.

PubMed

Popivanov, Ivo D; Schyns, Philippe G; Vogels, Rufin

2016-04-26

Body category-selective regions of the primate temporal cortex respond to images of bodies, but it is unclear which fragments of such images drive single neurons' responses in these regions. Here we applied the Bubbles technique to the responses of single macaque middle superior temporal sulcus (midSTS) body patch neurons to reveal the image fragments the neurons respond to. We found that local image fragments such as extremities (limbs), curved boundaries, and parts of the torso drove the large majority of neurons. Bubbles revealed the whole body in only a few neurons. Neurons coded the features in a manner that was tolerant to translation and scale changes. Most image fragments were excitatory but for a few neurons both inhibitory and excitatory fragments (opponent coding) were present in the same image. The fragments we reveal here in the body patch with Bubbles differ from those suggested in previous studies of face-selective neurons in face patches. Together, our data indicate that the majority of body patch neurons respond to local image fragments that occur frequently, but not exclusively, in bodies, with a coding that is tolerant to translation and scale. Overall, the data suggest that the body category selectivity of the midSTS body patch depends more on the feature statistics of bodies (e.g., extensions occur more frequently in bodies) than on semantics (bodies as an abstract category).

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.

Optimality in mono- and multisensory map formation.

PubMed

Bürck, Moritz; Friedel, Paul; Sichert, Andreas B; Vossen, Christine; van Hemmen, J Leo

2010-07-01

In the struggle for survival in a complex and dynamic environment, nature has developed a multitude of sophisticated sensory systems. In order to exploit the information provided by these sensory systems, higher vertebrates reconstruct the spatio-temporal environment from each of the sensory systems they have at their disposal. That is, for each modality the animal computes a neuronal representation of the outside world, a monosensory neuronal map. Here we present a universal framework that allows to calculate the specific layout of the involved neuronal network by means of a general mathematical principle, viz., stochastic optimality. In order to illustrate the use of this theoretical framework, we provide a step-by-step tutorial of how to apply our model. In so doing, we present a spatial and a temporal example of optimal stimulus reconstruction which underline the advantages of our approach. That is, given a known physical signal transmission and rudimental knowledge of the detection process, our approach allows to estimate the possible performance and to predict neuronal properties of biological sensory systems. Finally, information from different sensory modalities has to be integrated so as to gain a unified perception of reality for further processing, e.g., for distinct motor commands. We briefly discuss concepts of multimodal interaction and how a multimodal space can evolve by alignment of monosensory maps.

Mapping of neuron soma size as an effective approach to delineate differences between neural populations.

PubMed

Lingley, Alexander J; Bowdridge, Joshua C; Farivar, Reza; Duffy, Kevin R

2018-04-30

A single histological marker applied to a slice of tissue often reveals myriad cytoarchitectonic characteristics that can obscure differences between neuron populations targeted for study. Isolation and measurement of a single feature from the tissue is possible through a variety of approaches, however, visualizing the data numerically or through graphs alone can preclude being able to identify important features and effects that are not obvious from direct observation of the tissue. We demonstrate an efficient, effective, and robust approach to quantify and visualize cytoarchitectural features in histologically prepared brain sections. We demonstrate that this approach is able to reveal small differences between populations of neurons that might otherwise have gone undiscovered. We used stereological methods to record the cross-sectional soma area and in situ position of neurons within sections of the cat, monkey, and human visual system. The two-dimensional coordinate of every measured cell was used to produce a scatter plot that recapitulated the natural spatial distribution of cells, and each point in the plot was color-coded according to its respective soma area. The final graphic display was a multi-dimensional map of neuron soma size that revealed subtle differences across neuron aggregations, permitted delineation of regional boundaries, and identified small differences between populations of neurons modified by a period of sensory deprivation. This approach to collecting and displaying cytoarchitectonic data is simple, efficient, and provides a means of investigating small differences between neuron populations. Copyright © 2018. Published by Elsevier B.V.

Cellular resolution circuit mapping with temporal-focused excitation of soma-targeted channelrhodopsin

PubMed Central

Baker, Christopher A; Elyada, Yishai M; Parra, Andres; Bolton, M McLean

2016-01-01

We describe refinements in optogenetic methods for circuit mapping that enable measurements of functional synaptic connectivity with single-neuron resolution. By expanding a two-photon beam in the imaging plane using the temporal focusing method and restricting channelrhodopsin to the soma and proximal dendrites, we are able to reliably evoke action potentials in individual neurons, verify spike generation with GCaMP6s, and determine the presence or absence of synaptic connections with patch-clamp electrophysiological recording. DOI: http://dx.doi.org/10.7554/eLife.14193.001 PMID:27525487

Evaluation of Techniques Used to Estimate Cortical Feature Maps

PubMed Central

Katta, Nalin; Chen, Thomas L.; Watkins, Paul V.; Barbour, Dennis L.

2011-01-01

Functional properties of neurons are often distributed nonrandomly within a cortical area and form topographic maps that reveal insights into neuronal organization and interconnection. Some functional maps, such as in visual cortex, are fairly straightforward to discern with a variety of techniques, while other maps, such as in auditory cortex, have resisted easy characterization. In order to determine appropriate protocols for establishing accurate functional maps in auditory cortex, artificial topographic maps were probed under various conditions, and the accuracy of estimates formed from the actual maps was quantified. Under these conditions, low-complexity maps such as sound frequency can be estimated accurately with as few as 25 total samples (e.g., electrode penetrations or imaging pixels) if neural responses are averaged together. More samples are required to achieve the highest estimation accuracy for higher complexity maps, and averaging improves map estimate accuracy even more than increasing sampling density. Undersampling without averaging can result in misleading map estimates, while undersampling with averaging can lead to the false conclusion of no map when one actually exists. Uniform sample spacing only slightly improves map estimation over nonuniform sample spacing typical of serial electrode penetrations. Tessellation plots commonly used to visualize maps estimated using nonuniform sampling are always inferior to linearly interpolated estimates, although differences are slight at higher sampling densities. Within primary auditory cortex, then, multiunit sampling with at least 100 samples would likely result in reasonable feature map estimates for all but the highest complexity maps and the highest variability that might be expected. PMID:21889537

Effects of inhibitory neurons on the quorum percolation model and dynamical extension with the Brette-Gerstner model

NASA Astrophysics Data System (ADS)

Fardet, Tanguy; Bottani, Samuel; Métens, Stéphane; Monceau, Pascal

2018-06-01

The Quorum Percolation model (QP) has been designed in the context of neurobiology to describe the initiation of activity bursts occurring in neuronal cultures from the point of view of statistical physics rather than from a dynamical synchronization approach. This paper aims at investigating an extension of the original QP model by taking into account the presence of inhibitory neurons in the cultures (IQP model). The first part of this paper is focused on an equivalence between the presence of inhibitory neurons and a reduction of the network connectivity. By relying on a simple topological argument, we show that the mean activation behavior of networks containing a fraction η of inhibitory neurons can be mapped onto purely excitatory networks with an appropriately modified wiring, provided that η remains in the range usually observed in neuronal cultures, namely η ⪅ 20%. As a striking result, we show that such a mapping enables to predict the evolution of the critical point of the IQP model with the fraction of inhibitory neurons. In a second part, we bridge the gap between the description of bursts in the framework of percolation and the temporal description of neural networks activity by showing how dynamical simulations of bursts with an adaptive exponential integrate-and-fire model lead to a mean description of bursts activation which is captured by Quorum Percolation.

Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

NASA Astrophysics Data System (ADS)

Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

2016-08-01

A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.

Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system.

PubMed

Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

2016-03-17

The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila.

A comparison of optimal MIMO linear and nonlinear models for brain machine interfaces

NASA Astrophysics Data System (ADS)

Kim, S.-P.; Sanchez, J. C.; Rao, Y. N.; Erdogmus, D.; Carmena, J. M.; Lebedev, M. A.; Nicolelis, M. A. L.; Principe, J. C.

2006-06-01

The field of brain-machine interfaces requires the estimation of a mapping from spike trains collected in motor cortex areas to the hand kinematics of the behaving animal. This paper presents a systematic investigation of several linear (Wiener filter, LMS adaptive filters, gamma filter, subspace Wiener filters) and nonlinear models (time-delay neural network and local linear switching models) applied to datasets from two experiments in monkeys performing motor tasks (reaching for food and target hitting). Ensembles of 100-200 cortical neurons were simultaneously recorded in these experiments, and even larger neuronal samples are anticipated in the future. Due to the large size of the models (thousands of parameters), the major issue studied was the generalization performance. Every parameter of the models (not only the weights) was selected optimally using signal processing and machine learning techniques. The models were also compared statistically with respect to the Wiener filter as the baseline. Each of the optimization procedures produced improvements over that baseline for either one of the two datasets or both.

Modularity in the Organization of Mouse Primary Visual Cortex

PubMed Central

Ji, Weiqing; Gămănuţ, Răzvan; Bista, Pawan; D’Souza, Rinaldo D.; Wang, Quanxin; Burkhalter, Andreas

2015-01-01

SUMMARY Layer 1 (L1) of primary visual cortex (V1) is the target of projections from many brain regions outside of V1. We found that inputs to the non-columnar mouse V1 from the dorsal lateral geniculate nucleus and feedback projections from multiple higher cortical areas to L1 are patchy. The patches are matched to a pattern of M2 muscarinic acetylcholine receptor expression at fixed locations of mouse, rat and monkey V1. Neurons in L2/3 aligned with M2-rich patches have high spatial acuity whereas cells in M2-poor zones exhibited high temporal acuity. Together M2+ and M2− zones form constant-size domains that are repeated across V1. Domains map subregions of the receptive field, such that multiple copies are contained within the point image. The results suggest that the modular network in mouse V1 selects spatiotemporally distinct clusters of neurons within the point image for top-down control and differential routing of inputs to cortical streams. PMID:26247867

A comparison of optimal MIMO linear and nonlinear models for brain-machine interfaces.

PubMed

Kim, S-P; Sanchez, J C; Rao, Y N; Erdogmus, D; Carmena, J M; Lebedev, M A; Nicolelis, M A L; Principe, J C

2006-06-01

The field of brain-machine interfaces requires the estimation of a mapping from spike trains collected in motor cortex areas to the hand kinematics of the behaving animal. This paper presents a systematic investigation of several linear (Wiener filter, LMS adaptive filters, gamma filter, subspace Wiener filters) and nonlinear models (time-delay neural network and local linear switching models) applied to datasets from two experiments in monkeys performing motor tasks (reaching for food and target hitting). Ensembles of 100-200 cortical neurons were simultaneously recorded in these experiments, and even larger neuronal samples are anticipated in the future. Due to the large size of the models (thousands of parameters), the major issue studied was the generalization performance. Every parameter of the models (not only the weights) was selected optimally using signal processing and machine learning techniques. The models were also compared statistically with respect to the Wiener filter as the baseline. Each of the optimization procedures produced improvements over that baseline for either one of the two datasets or both.

Visual Tuning Properties of Genetically Identified Layer 2/3 Neuronal Types in the Primary Visual Cortex of Cre-Transgenic Mice

PubMed Central

Zariwala, Hatim A.; Madisen, Linda; Ahrens, Kurt F.; Bernard, Amy; Lein, Edward S.; Jones, Allan R.; Zeng, Hongkui

2011-01-01

The putative excitatory and inhibitory cell classes within the mouse primary visual cortex V1 have different functional properties as studied using recording microelectrode. Excitatory neurons show high selectivity for the orientation angle of moving gratings while the putative inhibitory neurons show poor selectivity. However, the study of selectivity of the genetically identified interneurons and their subtypes remain controversial. Here we use novel Cre-driver and reporter mice to identify genetic subpopulations in vivo for two-photon calcium dye imaging: Wfs1(+)/Gad1(−) mice that labels layer 2/3 excitatory cell population and Pvalb(+)/Gad1(+) mice that labels a genetic subpopulation of inhibitory neurons. The cells in both mice were identically labeled with a tdTomato protein, visible in vivo, using a Cre-reporter line. We found that the Wfs1(+) cells exhibited visual tuning properties comparable to the excitatory population, i.e., high selectivity and tuning to the angle, direction, and spatial frequency of oriented moving gratings. The functional tuning of Pvalb(+) neurons was consistent with previously reported narrow-spiking interneurons in microelectrode studies, exhibiting poorer selectivity than the excitatory neurons. This study demonstrates the utility of Cre-transgenic mouse technology in selective targeting of subpopulations of neurons and makes them amenable to structural, functional, and connectivity studies. PMID:21283555

A role for the anterior insular cortex in the global neuronal workspace model of consciousness.

PubMed

Michel, Matthias

2017-03-01

According to the global neuronal workspace model of consciousness, consciousness results from the global broadcast of information throughout the brain. The global neuronal workspace is mainly constituted by a fronto-parietal network. The anterior insular cortex is part of this global neuronal workspace, but the function of this region has not yet been defined within the global neuronal workspace model of consciousness. In this review, I hypothesize that the anterior insular cortex implements a cross-modal priority map, the function of which is to determine priorities for the processing of information and subsequent entrance in the global neuronal workspace. Copyright © 2017 Elsevier Inc. All rights reserved.

Reflections on mirror neurons and speech perception.

PubMed

Lotto, Andrew J; Hickok, Gregory S; Holt, Lori L

2009-03-01

The discovery of mirror neurons, a class of neurons that respond when a monkey performs an action and also when the monkey observes others producing the same action, has promoted a renaissance for the Motor Theory (MT) of speech perception. This is because mirror neurons seem to accomplish the same kind of one to one mapping between perception and action that MT theorizes to be the basis of human speech communication. However, this seeming correspondence is superficial, and there are theoretical and empirical reasons to temper enthusiasm about the explanatory role mirror neurons might have for speech perception. In fact, rather than providing support for MT, mirror neurons are actually inconsistent with the central tenets of MT.

Reflections on mirror neurons and speech perception

PubMed Central

Lotto, Andrew J.; Hickok, Gregory S.; Holt, Lori L.

2010-01-01

The discovery of mirror neurons, a class of neurons that respond when a monkey performs an action and also when the monkey observes others producing the same action, has promoted a renaissance for the Motor Theory (MT) of speech perception. This is because mirror neurons seem to accomplish the same kind of one to one mapping between perception and action that MT theorizes to be the basis of human speech communication. However, this seeming correspondence is superficial, and there are theoretical and empirical reasons to temper enthusiasm about the explanatory role mirror neurons might have for speech perception. In fact, rather than providing support for MT, mirror neurons are actually inconsistent with the central tenets of MT. PMID:19223222

Neurons with object-centered spatial selectivity in macaque SEF: do they represent locations or rules?

PubMed

Tremblay, Léon; Gettner, Sonya N; Olson, Carl R

2002-01-01

In macaque monkeys performing a task that requires eye movements to the leftmost or rightmost of two dots in a horizontal array, some neurons in the supplementary eye field (SEF) fire differentially according to which side of the array is the target regardless of the array's location on the screen. We refer to these neurons as exhibiting selectivity for object-centered location. This form of selectivity might arise from involvement of the neurons in either of two processes: representing the locations of targets or representing the rules by which targets are selected. To distinguish between these possibilities, we monitored neuronal activity in the SEF of two monkeys performing a task that required the selection of targets by either an object-centered spatial rule or a color rule. On each trial, a sample array consisting of two side-by-side dots appeared; then a cue flashed on one dot; then the display vanished and a delay ensued. Next a target array consisting of two side-by-side dots appeared at an unpredictable location and another delay ensued; finally the monkey had to make an eye movement to one of the target dots. On some trials, the monkey had to select the dot on the same side as the cue (right or left). On other trials, he had to select the target of the same color as the cue (red or green). Neuronal activity robustly encoded the object-centered locations first of the cue and then of the target regardless of the whether the monkey was following a rule based on object-centered location or color. Neuronal activity was at most weakly affected by the type of rule the monkey was following (object-centered-location or color) or by the color of the cue and target (red or green). On trials involving a color rule, neuronal activity was moderately enhanced when the cue and target appeared on opposite sides of their respective arrays. We conclude that the general function of SEF neurons selective for object-centered location is to represent where the cue and target are in their respective arrays rather than to represent the rule for target selection.

Directional selectivity of afferent neurons in zebrafish neuromasts is regulated by Emx2 in presynaptic hair cells

PubMed Central

Ji, Young Rae; Warrier, Sunita; Jiang, Tao

2018-01-01

The orientation of hair bundles on top of sensory hair cells (HCs) in neuromasts of the lateral line system allows fish to detect direction of water flow. Each neuromast shows hair bundles arranged in two opposing directions and each afferent neuron innervates only HCs of the same orientation. Previously, we showed that this opposition is established by expression of Emx2 in half of the HCs, where it mediates hair bundle reversal (Jiang et al., 2017). Here, we show that Emx2 also regulates neuronal selection: afferent neurons innervate either Emx2-positive or negative HCs. In emx2 knockout and gain-of-function neuromasts, all HCs are unidirectional and the innervation patterns and physiological responses of the afferent neurons are dependent on the presence or absence of Emx2. Our results indicate that Emx2 mediates the directional selectivity of neuromasts by two distinct processes: regulating hair bundle orientation in HCs and selecting afferent neuronal targets. PMID:29671737

The development of cortical connections.

PubMed

Price, David J; Kennedy, Henry; Dehay, Colette; Zhou, Libing; Mercier, Marjorie; Jossin, Yves; Goffinet, André M; Tissir, Fadel; Blakey, Daniel; Molnár, Zoltán

2006-02-01

The cortex receives its major sensory input from the thalamus via thalamocortical axons, and cortical neurons are interconnected in complex networks by corticocortical and callosal axons. Our understanding of the mechanisms generating the circuitry that confers functional properties on cortical neurons and networks, although poor, has been advanced significantly by recent research on the molecular mechanisms of thalamocortical axonal guidance and ordering. Here we review recent advances in knowledge of how thalamocortical axons are guided and how they maintain order during that process. Several studies have shown the importance in this process of guidance molecules including Eph receptors and ephrins, members of the Wnt signalling pathway and members of a novel planar cell polarity pathway. Signalling molecules and transcription factors expressed with graded concentrations across the cortex are important in establishing cortical maps of the topography of sensory surfaces. Neural activity, both spontaneous and evoked, plays a role in refining thalamocortical connections but recent work has indicated that neural activity is less important than was previously thought for the development of some early maps. A strategy used widely in the development of corticocortical and callosal connections is the early overproduction of projections followed by selection after contact with the target structure. Here we discuss recent work in primates indicating that elimination of juvenile projections is not a major mechanism in the development of pathways feeding information forward to higher levels of cortical processing, although its use is common to developing feedback pathways.

Serum extravasation and cytoskeletal alterations following traumatic brain injury in rats. Comparison of lateral fluid percussion and cortical impact models.

PubMed

Hicks, R R; Baldwin, S A; Scheff, S W

1997-01-01

Disruption of the blood-brain barrier (BBB) and neuronal cytoskeletal damage were evaluated in two commonly used rat models of traumatic brain injury. Adult rats received a lateral cortical impact (CI) or lateral fluid percussion (FP) injury of mild or moderate severity or a sham procedure. Six hours after trauma, the brains were removed and analyzed with immunocytochemical techniques for alterations in the serum protein, IgG, and the cytoskeletal protein, microtubule-associated protein 2 (MAP2). Both models induced profound alterations in these proteins in the ipsilateral cortex and hippocampus compared to sham-injured controls. Following an injury of moderate severity, the CI injury resulted in greater IgG extravasation in the cortex and hippocampus than the FP injury. Conversely, after a mild injury, IgG extravasation in the hippocampus was greater for FP than CI. All of the animals in the CI group and most of the FP group showed a loss of MAP2 in the hippocampus. The specific subregions within the cortex and hippocampus that were affected by the injury varied between models, despite having identical impact sites. These data demonstrate that there are both similarities and differences between a CI and FP injury on vascular and neuronal cystoskeletal integrity, which should be considered when utilizing these animal models to study selected features of human head injury.

The why, what, where, when and how of goal-directed choice: neuronal and computational principles

PubMed Central

Verschure, Paul F. M. J.; Pennartz, Cyriel M. A.; Pezzulo, Giovanni

2014-01-01

The central problems that goal-directed animals must solve are: ‘What do I need and Why, Where and When can this be obtained, and How do I get it?' or the H4W problem. Here, we elucidate the principles underlying the neuronal solutions to H4W using a combination of neurobiological and neurorobotic approaches. First, we analyse H4W from a system-level perspective by mapping its objectives onto the Distributed Adaptive Control embodied cognitive architecture which sees the generation of adaptive action in the real world as the primary task of the brain rather than optimally solving abstract problems. We next map this functional decomposition to the architecture of the rodent brain to test its consistency. Following this approach, we propose that the mammalian brain solves the H4W problem on the basis of multiple kinds of outcome predictions, integrating central representations of needs and drives (e.g. hypothalamus), valence (e.g. amygdala), world, self and task state spaces (e.g. neocortex, hippocampus and prefrontal cortex, respectively) combined with multi-modal selection (e.g. basal ganglia). In our analysis, goal-directed behaviour results from a well-structured architecture in which goals are bootstrapped on the basis of predefined needs, valence and multiple learning, memory and planning mechanisms rather than being generated by a singular computation. PMID:25267825

Neurophysiological Organization of the Middle Face Patch in Macaque Inferior Temporal Cortex

PubMed Central

Aparicio, Paul L.; Issa, Elias B.

2016-01-01

While early cortical visual areas contain fine scale spatial organization of neuronal properties, such as orientation preference, the spatial organization of higher-level visual areas is less well understood. The fMRI demonstration of face-preferring regions in human ventral cortex and monkey inferior temporal cortex (“face patches”) raises the question of how neural selectivity for faces is organized. Here, we targeted hundreds of spatially registered neural recordings to the largest fMRI-identified face-preferring region in monkeys, the middle face patch (MFP), and show that the MFP contains a graded enrichment of face-preferring neurons. At its center, as much as 93% of the sites we sampled responded twice as strongly to faces than to nonface objects. We estimate the maximum neurophysiological size of the MFP to be ∼6 mm in diameter, consistent with its previously reported size under fMRI. Importantly, face selectivity in the MFP varied strongly even between neighboring sites. Additionally, extremely face-selective sites were ∼40 times more likely to be present inside the MFP than outside. These results provide the first direct quantification of the size and neural composition of the MFP by showing that the cortical tissue localized to the fMRI defined region consists of a very high fraction of face-preferring sites near its center, and a monotonic decrease in that fraction along any radial spatial axis. SIGNIFICANCE STATEMENT The underlying organization of neurons that give rise to the large spatial regions of activity observed with fMRI is not well understood. Neurophysiological studies that have targeted the fMRI identified face patches in monkeys have provided evidence for both large-scale clustering and a heterogeneous spatial organization. Here we used a novel x-ray imaging system to spatially map the responses of hundreds of sites in and around the middle face patch. We observed that face-selective signal localized to the middle face patch was characterized by a gradual spatial enrichment. Furthermore, strongly face-selective sites were ∼40 times more likely to be found inside the patch than outside of the patch. PMID:27810930

Neurophysiological Organization of the Middle Face Patch in Macaque Inferior Temporal Cortex.

PubMed

Aparicio, Paul L; Issa, Elias B; DiCarlo, James J

2016-12-14

While early cortical visual areas contain fine scale spatial organization of neuronal properties, such as orientation preference, the spatial organization of higher-level visual areas is less well understood. The fMRI demonstration of face-preferring regions in human ventral cortex and monkey inferior temporal cortex ("face patches") raises the question of how neural selectivity for faces is organized. Here, we targeted hundreds of spatially registered neural recordings to the largest fMRI-identified face-preferring region in monkeys, the middle face patch (MFP), and show that the MFP contains a graded enrichment of face-preferring neurons. At its center, as much as 93% of the sites we sampled responded twice as strongly to faces than to nonface objects. We estimate the maximum neurophysiological size of the MFP to be ∼6 mm in diameter, consistent with its previously reported size under fMRI. Importantly, face selectivity in the MFP varied strongly even between neighboring sites. Additionally, extremely face-selective sites were ∼40 times more likely to be present inside the MFP than outside. These results provide the first direct quantification of the size and neural composition of the MFP by showing that the cortical tissue localized to the fMRI defined region consists of a very high fraction of face-preferring sites near its center, and a monotonic decrease in that fraction along any radial spatial axis. The underlying organization of neurons that give rise to the large spatial regions of activity observed with fMRI is not well understood. Neurophysiological studies that have targeted the fMRI identified face patches in monkeys have provided evidence for both large-scale clustering and a heterogeneous spatial organization. Here we used a novel x-ray imaging system to spatially map the responses of hundreds of sites in and around the middle face patch. We observed that face-selective signal localized to the middle face patch was characterized by a gradual spatial enrichment. Furthermore, strongly face-selective sites were ∼40 times more likely to be found inside the patch than outside of the patch. Copyright © 2016 the authors 0270-6474/16/3612729-17$15.00/0.

Growing a hypercubical output space in a self-organizing feature map.

PubMed

Bauer, H U; Villmann, T

1997-01-01

Neural maps project data from an input space onto a neuron position in a (often lower dimensional) output space grid in a neighborhood preserving way, with neighboring neurons in the output space responding to neighboring data points in the input space. A map-learning algorithm can achieve an optimal neighborhood preservation only, if the output space topology roughly matches the effective structure of the data in the input space. We here present a growth algorithm, called the GSOM or growing self-organizing map, which enhances a widespread map self-organization process, Kohonen's self-organizing feature map (SOFM), by an adaptation of the output space grid during learning. The GSOM restricts the output space structure to the shape of a general hypercubical shape, with the overall dimensionality of the grid and its extensions along the different directions being subject of the adaptation. This constraint meets the demands of many larger information processing systems, of which the neural map can be a part. We apply our GSOM-algorithm to three examples, two of which involve real world data. Using recently developed methods for measuring the degree of neighborhood preservation in neural maps, we find the GSOM-algorithm to produce maps which preserve neighborhoods in a nearly optimal fashion.

Novel encoding and updating of positional, or directional, spatial cues are processed by distinct hippocampal subfields: Evidence for parallel information processing and the "what" stream.

PubMed

Hoang, Thu-Huong; Aliane, Verena; Manahan-Vaughan, Denise

2018-05-01

The specific roles of hippocampal subfields in spatial information processing and encoding are, as yet, unclear. The parallel map theory postulates that whereas the CA1 processes discrete environmental features (positional cues used to generate a "sketch map"), the dentate gyrus (DG) processes large navigation-relevant landmarks (directional cues used to generate a "bearing map"). Additionally, the two-streams hypothesis suggests that hippocampal subfields engage in differentiated processing of information from the "where" and the "what" streams. We investigated these hypotheses by analyzing the effect of exploration of discrete "positional" features and large "directional" spatial landmarks on hippocampal neuronal activity in rats. As an indicator of neuronal activity we measured the mRNA induction of the immediate early genes (IEGs), Arc and Homer1a. We observed an increase of this IEG mRNA in CA1 neurons of the distal neuronal compartment and in proximal CA3, after novel spatial exploration of discrete positional cues, whereas novel exploration of directional cues led to increases in IEG mRNA in the lower blade of the DG and in proximal CA3. Strikingly, the CA1 did not respond to directional cues and the DG did not respond to positional cues. Our data provide evidence for both the parallel map theory and the two-streams hypothesis and suggest a precise compartmentalization of the encoding and processing of "what" and "where" information occurs within the hippocampal subfields. © 2018 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

Magnetic resonance spectroscopy of current hand amputees reveals evidence for neuronal-level changes in former sensorimotor cortex

PubMed Central

Choi, In-Young; Lee, Phil; Peng, Huiling; Kaufman, Christina L.; Frey, Scott H.

2017-01-01

Deafferentation is accompanied by large-scale functional reorganization of maps in the primary sensory and motor areas of the hemisphere contralateral to injury. Animal models of deafferentation suggest a variety of cellular-level changes including depression of neuronal metabolism and even neuronal death. Whether similar neuronal changes contribute to patterns of reorganization within the contralateral sensorimotor cortex of chronic human amputees is uncertain. We used functional MRI-guided proton magnetic resonance spectroscopy to test the hypothesis that unilateral deafferentation is associated with lower levels of N-acetylaspartate (NAA, a putative marker of neuronal integrity) in the sensorimotor hand territory located contralateral to the missing hand in chronic amputees (n = 19) compared with the analogous hand territory of age- and sex-matched healthy controls (n = 28). We also tested whether former amputees [i.e., recipients of replanted (n = 3) or transplanted (n = 2) hands] exhibit NAA levels that are indistinguishable from controls, possible evidence for reversal of the effects of deafferentation. As predicted, relative to controls, current amputees exhibited lower levels of NAA that were negatively and significantly correlated with the time after amputation. Contrary to our prediction, NAA levels in both replanted and transplanted patients fell within the range of the current amputees. We suggest that lower levels of NAA in current amputees reflects altered neuronal integrity consequent to chronic deafferentation. Thus local changes in NAA levels may provide a means of assessing neuroplastic changes in deafferented cortex. Results from former amputees suggest that these changes may not be readily reversible through reafferentation. NEW & NOTEWORTHY This study is the first to use functional magnetic resonance-guided magnetic resonance spectroscopy to examine neurochemical mechanisms underlying functional reorganization in the primary somatosensory and motor cortices consequent to upper extremity amputation and its potential reversal through hand replantation or transplantation. We provide evidence for selective alteration of cortical neuronal integrity associated with amputation-related deafferentation that may not be reversible. PMID:28179478

Distinct sensory representations of wind and near-field sound in the Drosophila brain

PubMed Central

Yorozu, Suzuko; Wong, Allan; Fischer, Brian J.; Dankert, Heiko; Kernan, Maurice J.; Kamikouchi, Azusa; Ito, Kei; Anderson, David J.

2009-01-01

Behavioral responses to wind are thought to play a critical role in controlling the dispersal and population genetics of wild Drosophila species1,2, as well as their navigation in flight3, but their underlying neurobiological basis is unknown. We show that Drosophila melanogaster, like wild-caught Drosophila strains4, exhibits robust wind-induced suppression of locomotion (WISL), in response to air currents delivered at speeds normally encountered in nature1,2. Here we identify wind-sensitive neurons in Johnston’s Organ (JO), an antennal mechanosensory structure previously implicated in near-field sound detection (reviewed in5,6). Using Gal4 lines targeted to different subsets of JO neurons7, and a genetically encoded calcium indicator8, we show that wind and near-field sound (courtship song) activate distinct populations of JO neurons, which project to different regions of the antennal and mechanosensory motor center (AMMC) in the central brain. Selective genetic ablation of wind-sensitive JO neurons in the antenna abolishes WISL behavior, without impairing hearing. Different neuronal subsets within the wind-sensitive population, moreover, respond to different directions of arista deflection caused by airflow and project to different regions of the AMMC, providing a rudimentary map of wind-direction in the brain. Importantly, sound- and wind-sensitive JO neurons exhibit different intrinsic response properties: the former are phasically activated by small, bi-directional, displacements of the aristae, while the latter are tonically activated by unidirectional, static deflections of larger magnitude. These different intrinsic properties are well suited to the detection of oscillatory pulses of near-field sound and laminar airflow, respectively. These data identify wind-sensitive neurons in JO, a structure that has been primarily associated with hearing, and reveal how the brain can distinguish different types of air particle movements, using a common sensory organ. PMID:19279637

Fast targeted gene transfection and optogenetic modification of single neurons using femtosecond laser irradiation

PubMed Central

Antkowiak, Maciej; Torres-Mapa, Maria Leilani; Witts, Emily C.; Miles, Gareth B.; Dholakia, Kishan; Gunn-Moore, Frank J.

2013-01-01

A prevailing problem in neuroscience is the fast and targeted delivery of DNA into selected neurons. The development of an appropriate methodology would enable the transfection of multiple genes into the same cell or different genes into different neighboring cells as well as rapid cell selective functionalization of neurons. Here, we show that optimized femtosecond optical transfection fulfills these requirements. We also demonstrate successful optical transfection of channelrhodopsin-2 in single selected neurons. We extend the functionality of this technique for wider uptake by neuroscientists by using fast three-dimensional laser beam steering enabling an image-guided “point-and-transfect” user-friendly transfection of selected cells. A sub-second transfection timescale per cell makes this method more rapid by at least two orders of magnitude when compared to alternative single-cell transfection techniques. This novel technology provides the ability to carry out large-scale cell selective genetic studies on neuronal ensembles and perform rapid genetic programming of neural circuits. PMID:24257461

Fast targeted gene transfection and optogenetic modification of single neurons using femtosecond laser irradiation.

PubMed

Antkowiak, Maciej; Torres-Mapa, Maria Leilani; Witts, Emily C; Miles, Gareth B; Dholakia, Kishan; Gunn-Moore, Frank J

2013-11-21

A prevailing problem in neuroscience is the fast and targeted delivery of DNA into selected neurons. The development of an appropriate methodology would enable the transfection of multiple genes into the same cell or different genes into different neighboring cells as well as rapid cell selective functionalization of neurons. Here, we show that optimized femtosecond optical transfection fulfills these requirements. We also demonstrate successful optical transfection of channelrhodopsin-2 in single selected neurons. We extend the functionality of this technique for wider uptake by neuroscientists by using fast three-dimensional laser beam steering enabling an image-guided "point-and-transfect" user-friendly transfection of selected cells. A sub-second transfection timescale per cell makes this method more rapid by at least two orders of magnitude when compared to alternative single-cell transfection techniques. This novel technology provides the ability to carry out large-scale cell selective genetic studies on neuronal ensembles and perform rapid genetic programming of neural circuits.

Stimulus features coded by single neurons of a macaque body category selective patch

PubMed Central

Popivanov, Ivo D.; Schyns, Philippe G.; Vogels, Rufin

2016-01-01

Body category-selective regions of the primate temporal cortex respond to images of bodies, but it is unclear which fragments of such images drive single neurons’ responses in these regions. Here we applied the Bubbles technique to the responses of single macaque middle superior temporal sulcus (midSTS) body patch neurons to reveal the image fragments the neurons respond to. We found that local image fragments such as extremities (limbs), curved boundaries, and parts of the torso drove the large majority of neurons. Bubbles revealed the whole body in only a few neurons. Neurons coded the features in a manner that was tolerant to translation and scale changes. Most image fragments were excitatory but for a few neurons both inhibitory and excitatory fragments (opponent coding) were present in the same image. The fragments we reveal here in the body patch with Bubbles differ from those suggested in previous studies of face-selective neurons in face patches. Together, our data indicate that the majority of body patch neurons respond to local image fragments that occur frequently, but not exclusively, in bodies, with a coding that is tolerant to translation and scale. Overall, the data suggest that the body category selectivity of the midSTS body patch depends more on the feature statistics of bodies (e.g., extensions occur more frequently in bodies) than on semantics (bodies as an abstract category). PMID:27071095

Changes in the Excitability of Neocortical Neurons in a Mouse Model of Amyotrophic Lateral Sclerosis Are Not Specific to Corticospinal Neurons and Are Modulated by Advancing Disease.

PubMed

Kim, Juhyun; Hughes, Ethan G; Shetty, Ashwin S; Arlotta, Paola; Goff, Loyal A; Bergles, Dwight E; Brown, Solange P

2017-09-13

Cell type-specific changes in neuronal excitability have been proposed to contribute to the selective degeneration of corticospinal neurons in amyotrophic lateral sclerosis (ALS) and to neocortical hyperexcitability, a prominent feature of both inherited and sporadic variants of the disease, but the mechanisms underlying selective loss of specific cell types in ALS are not known. We analyzed the physiological properties of distinct classes of cortical neurons in the motor cortex of hSOD1 G93A mice of both sexes and found that they all exhibit increases in intrinsic excitability that depend on disease stage. Targeted recordings and in vivo calcium imaging further revealed that neurons adapt their functional properties to normalize cortical excitability as the disease progresses. Although different neuron classes all exhibited increases in intrinsic excitability, transcriptional profiling indicated that the molecular mechanisms underlying these changes are cell type specific. The increases in excitability in both excitatory and inhibitory cortical neurons show that selective dysfunction of neuronal cell types cannot account for the specific vulnerability of corticospinal motor neurons in ALS. Furthermore, the stage-dependent alterations in neuronal function highlight the ability of cortical circuits to adapt as disease progresses. These findings show that both disease stage and cell type must be considered when developing therapeutic strategies for treating ALS. SIGNIFICANCE STATEMENT It is not known why certain classes of neurons preferentially die in different neurodegenerative diseases. It has been proposed that the enhanced excitability of affected neurons is a major contributor to their selective loss. We show using a mouse model of amyotrophic lateral sclerosis (ALS), a disease in which corticospinal neurons exhibit selective vulnerability, that changes in excitability are not restricted to this neuronal class and that excitability does not increase monotonically with disease progression. Moreover, although all neuronal cell types tested exhibited abnormal functional properties, analysis of their gene expression demonstrated cell type-specific responses to the ALS-causing mutation. These findings suggest that therapies for ALS may need to be tailored for different cell types and stages of disease. Copyright © 2017 the authors 0270-6474/17/379038-17$15.00/0.

Direct mapping of 19F in 19FDG-6P in brain tissue at subcellular resolution using soft X-ray fluorescence

NASA Astrophysics Data System (ADS)

Poitry-Yamate, C.; Gianoncelli, A.; Kourousias, G.; Kaulich, B.; Lepore, M.; Gruetter, R.; Kiskinova, M.

2013-10-01

Low energy x-ray fluorescence (LEXRF) detection was optimized for imaging cerebral glucose metabolism by mapping the fluorine LEXRF signal of 19F in 19FDG, trapped as intracellular 19F-deoxyglucose-6-phosphate (19FDG-6P) at 1μm spatial resolution from 3μm thick brain slices. 19FDG metabolism was evaluated in brain structures closely resembling the general cerebral cytoarchitecture following formalin fixation of brain slices and their inclusion in an epon matrix. 2-dimensional distribution maps of 19FDG-6P were placed in a cytoarchitectural and morphological context by simultaneous LEXRF mapping of N and O, and scanning transmission x-ray (STXM) imaging. A disproportionately high uptake and metabolism of glucose was found in neuropil relative to intracellular domains of the cell body of hypothalamic neurons, showing directly that neurons, like glial cells, also metabolize glucose. As 19F-deoxyglucose-6P is structurally identical to 18F-deoxyglucose-6P, LEXRF of subcellular 19F provides a link to in vivo 18FDG PET, forming a novel basis for understanding the physiological mechanisms underlying the 18FDG PET image, and the contribution of neurons and glia to the PET signal.

Neuromodulation: Selected approaches and challenges

PubMed Central

Parpura, Vladimir; Silva, Gabriel A.; Tass, Peter A.; Bennet, Kevin E.; Meyyappan, Meyya; Koehne, Jessica; Lee, Kendall H.; Andrews, Russell J.

2012-01-01

The brain operates through complex interactions in the flow of information and signal processing within neural networks. The “wiring” of such networks, being neuronal or glial, can physically and/or functionally go rogue in various pathological states. Neuromodulation, as a multidisciplinary venture, attempts to correct such faulty nets. In this review, selected approaches and challenges in neuromoduation are discussed. The use of water-dispersible carbon nanotubes have proven effective in modulation of neurite outgrowth in culture as well as in aiding regeneration after spinal cord injury in vivo. Studying neural circuits using computational biology and analytical engineering approaches brings to light geometrical mapping of dynamics within neural networks, much needed information for stimulation interventions in medical practice. Indeed, sophisticated desynchronization approaches used for brain stimulation have been successful in coaxing “misfiring” neuronal circuits to resume productive firing patterns in various human disorders. Devices have been developed for the real time measurement of various neurotransmitters as well as electrical activity in the human brain during electrical deep brain stimulation. Such devices can establish the dynamics of electrochemical changes in the brain during stimulation. With increasing application of nanomaterials in devices for electrical and chemical recording and stimulating in the brain, the era of cellular, and even intracellular, precision neuromodulation will soon be upon us. PMID:23190025

Emergence of Orientation Selectivity in the Mammalian Visual Pathway

PubMed Central

Scholl, Benjamin; Tan, Andrew Y. Y.; Corey, Joseph

2013-01-01

Orientation selectivity is a property of mammalian primary visual cortex (V1) neurons, yet its emergence along the visual pathway varies across species. In carnivores and primates, elongated receptive fields first appear in V1, whereas in lagomorphs such receptive fields emerge earlier, in the retina. Here we examine the mouse visual pathway and reveal the existence of orientation selectivity in lateral geniculate nucleus (LGN) relay cells. Cortical inactivation does not reduce this orientation selectivity, indicating that cortical feedback is not its source. Orientation selectivity is similar for LGN relay cells spiking and subthreshold input to V1 neurons, suggesting that cortical orientation selectivity is inherited from the LGN in mouse. In contrast, orientation selectivity of cat LGN relay cells is small relative to subthreshold inputs onto V1 simple cells. Together, these differences show that although orientation selectivity exists in visual neurons of both rodents and carnivores, its emergence along the visual pathway, and thus its underlying neuronal circuitry, is fundamentally different. PMID:23804085

Balanced increases in selectivity and tolerance produce constant sparseness along the ventral visual stream

PubMed Central

Rust, Nicole C.; DiCarlo, James J.

2012-01-01

While popular accounts suggest that neurons along the ventral visual processing stream become increasingly selective for particular objects, this appears at odds with the fact that inferior temporal cortical (IT) neurons are broadly tuned. To explore this apparent contradiction, we compared processing in two ventral stream stages (V4 and IT) in the rhesus macaque monkey. We confirmed that IT neurons are indeed more selective for conjunctions of visual features than V4 neurons, and that this increase in feature conjunction selectivity is accompanied by an increase in tolerance (“invariance”) to identity-preserving transformations (e.g. shifting, scaling) of those features. We report here that V4 and IT neurons are, on average, tightly matched in their tuning breadth for natural images (“sparseness”), and that the average V4 or IT neuron will produce a robust firing rate response (over 50% of its peak observed firing rate) to ~10% of all natural images. We also observed that sparseness was positively correlated with conjunction selectivity and negatively correlated with tolerance within both V4 and IT, consistent with selectivity-building and invariance-building computations that offset one another to produce sparseness. Our results imply that the conjunction-selectivity-building and invariance-building computations necessary to support object recognition are implemented in a balanced fashion to maintain sparseness at each stage of processing. PMID:22836252

Lack of huntingtin promotes neural stem cells differentiation into glial cells while neurons expressing huntingtin with expanded polyglutamine tracts undergo cell death.

PubMed

Conforti, Paola; Camnasio, Stefano; Mutti, Cesare; Valenza, Marta; Thompson, Morgan; Fossale, Elisa; Zeitlin, Scott; MacDonald, Marcy E; Zuccato, Chiara; Cattaneo, Elena

2013-02-01

Huntington's disease (HD) is a neurodegenerative disorder that affects muscle coordination and diminishes cognitive abilities. The genetic basis of the disease is an expansion of CAG repeats in the Huntingtin (Htt) gene. Here we aimed to generate a series of mouse neural stem (NS) cell lines that carried varying numbers of CAG repeats in the mouse Htt gene (Hdh CAG knock-in NS cells) or that had Hdh null alleles (Hdh knock-out NS cells). Towards this end, Hdh CAG knock-in mouse ES cell lines that carried an Htt gene with 20, 50, 111, or 140 CAG repeats or that were Htt null were neuralized and converted into self-renewing NS cells. The resulting NS cell lines were immunopositive for the neural stem cell markers NESTIN, SOX2, and BLBP and had similar proliferative rates and cell cycle distributions. After 14 days in vitro, wild-type NS cells gave rise to cultures composed of 70% MAP2(+) neurons and 30% GFAP(+) astrocytes. In contrast, NS cells with expanded CAG repeats underwent neuronal cell death, with only 38%±15% of the MAP2(+) cells remaining at the end of the differentiation period. Cell death was verified by increased caspase 3/7 activity on day 14 of the neuronal differentiation protocol. Interestingly, Hdh knock-out NS cells treated using the same neuronal differentiation protocol showed a dramatic increase in the number of GFAP(+) cells on day 14 (61%±20% versus 24%±10% in controls), and a massive decrease of MAP2(+) neurons (30%±11% versus 64%±17% in controls). Both Hdh CAG knock-in NS cells and Hdh knock-out NS cells showed reduced levels of Bdnf mRNA during neuronal differentiation, in agreement with data obtained previously in HD mouse models and in post-mortem brain samples from HD patients. We concluded that Hdh CAG knock-in and Hdh knock-out NS cells have potential as tools for investigating the roles of normal and mutant HTT in differentiated neurons and glial cells of the brain. Copyright © 2012 Elsevier Inc. All rights reserved.

[Relation between frequency modulation direction selectivity and forward masking of inferior collicular neurons: a study on in vivo intracellular recording in mice].

PubMed

Fu, Zi-Ying; Zeng, Hong; Tang, Jia; Li, Jie; Li, Juan; Chen, Qi-Cai

2013-06-25

It has been reported that the frequency modulation (FM) or FM direction sensitivity and forward masking of central auditory neurons are related with the neural inhibition, but there are some arguments, because no direct evidence of inhibitory synaptic input was obtained in previous studies using extracellular recording. In the present study, we studied the relation between FM direction sensitivity and forward masking of the inferior collicular (IC) neurons using in vivo intracellular recordings in 20 Mus musculus Km mice. Thirty seven with complete data among 93 neurons were analyzed and discussed. There was an inhibitory area which consisted of inhibitory postsynaptic potentials (IPSP) at high frequency side of frequency tuning of up-sweep FM (FMU) sensitive neurons (n = 12) and at low frequency side of frequency tuning of down-sweep FM (FMD) selective neurons (n = 8), while there was no any inhibitory area at both sides of frequency tuning of non-FM sweep direction (FMN) sensitive neurons (n = 17). Therefore, these results show that the inhibitory area at low or high frequency side of frequency tuning is one of the mechanisms for forming FM sweep direction sensitivity of IC neurons. By comparison of forward masking produced by FMU and FMD sound stimuli in FMU, FMD and FMN neurons, the selective FM sounds could produce stronger forward masking than the non-selective in FMU and FMD neurons, while there was no forward masking difference between FMU and FMD stimuli in the FMN neurons. We suggest that the post-action potential IPSP is a potential mechanism for producing stronger forward masking in FMU and FMD neurons.

Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection

PubMed Central

Bogacz, Rafal; Martin Moraud, Eduardo; Abdi, Azzedine; Magill, Peter J.; Baufreton, Jérôme

2016-01-01

The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes’ equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called ‘prototypic’ and ‘arkypallidal’ neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID:27389780

Learning to attend: modeling the shaping of selectivity in infero-temporal cortex in a categorization task.

PubMed

Szabo, Miruna; Deco, Gustavo; Fusi, Stefano; Del Giudice, Paolo; Mattia, Maurizio; Stetter, Martin

2006-05-01

Recent experiments on behaving monkeys have shown that learning a visual categorization task makes the neurons in infero-temporal cortex (ITC) more selective to the task-relevant features of the stimuli (Sigala and Logothetis in Nature 415 318-320, 2002). We hypothesize that such a selectivity modulation emerges from the interaction between ITC and other cortical area, presumably the prefrontal cortex (PFC), where the previously learned stimulus categories are encoded. We propose a biologically inspired model of excitatory and inhibitory spiking neurons with plastic synapses, modified according to a reward based Hebbian learning rule, to explain the experimental results and test the validity of our hypothesis. We assume that the ITC neurons, receiving feature selective inputs, form stronger connections with the category specific neurons to which they are consistently associated in rewarded trials. After learning, the top-down influence of PFC neurons enhances the selectivity of the ITC neurons encoding the behaviorally relevant features of the stimuli, as observed in the experiments. We conclude that the perceptual representation in visual areas like ITC can be strongly affected by the interaction with other areas which are devoted to higher cognitive functions.

Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity

PubMed Central

Yonehara, Keisuke; Fiscella, Michele; Drinnenberg, Antonia; Esposti, Federico; Trenholm, Stuart; Krol, Jacek; Franke, Felix; Scherf, Brigitte Gross; Kusnyerik, Akos; Müller, Jan; Szabo, Arnold; Jüttner, Josephine; Cordoba, Francisco; Reddy, Ashrithpal Police; Németh, János; Nagy, Zoltán Zsolt; Munier, Francis; Hierlemann, Andreas; Roska, Botond

2016-01-01

Summary Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease. Video Abstract PMID:26711119

Mapping whole-brain activity with cellular resolution by light-sheet microscopy and high-throughput image analysis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Silvestri, Ludovico; Rudinskiy, Nikita; Paciscopi, Marco; Müllenbroich, Marie Caroline; Costantini, Irene; Sacconi, Leonardo; Frasconi, Paolo; Hyman, Bradley T.; Pavone, Francesco S.

2016-03-01

Mapping neuronal activity patterns across the whole brain with cellular resolution is a challenging task for state-of-the-art imaging methods. Indeed, despite a number of technological efforts, quantitative cellular-resolution activation maps of the whole brain have not yet been obtained. Many techniques are limited by coarse resolution or by a narrow field of view. High-throughput imaging methods, such as light sheet microscopy, can be used to image large specimens with high resolution and in reasonable times. However, the bottleneck is then moved from image acquisition to image analysis, since many TeraBytes of data have to be processed to extract meaningful information. Here, we present a full experimental pipeline to quantify neuronal activity in the entire mouse brain with cellular resolution, based on a combination of genetics, optics and computer science. We used a transgenic mouse strain (Arc-dVenus mouse) in which neurons which have been active in the last hours before brain fixation are fluorescently labelled. Samples were cleared with CLARITY and imaged with a custom-made confocal light sheet microscope. To perform an automatic localization of fluorescent cells on the large images produced, we used a novel computational approach called semantic deconvolution. The combined approach presented here allows quantifying the amount of Arc-expressing neurons throughout the whole mouse brain. When applied to cohorts of mice subject to different stimuli and/or environmental conditions, this method helps finding correlations in activity between different neuronal populations, opening the possibility to infer a sort of brain-wide 'functional connectivity' with cellular resolution.

Cortical neurons of bats respond best to echoes from nearest targets when listening to natural biosonar multi-echo streams.

PubMed

Beetz, M Jerome; Hechavarría, Julio C; Kössl, Manfred

2016-10-27

Bats orientate in darkness by listening to echoes from their biosonar calls, a behaviour known as echolocation. Recent studies showed that cortical neurons respond in a highly selective manner when stimulated with natural echolocation sequences that contain echoes from single targets. However, it remains unknown how cortical neurons process echolocation sequences containing echo information from multiple objects. In the present study, we used echolocation sequences containing echoes from three, two or one object separated in the space depth as stimuli to study neuronal activity in the bat auditory cortex. Neuronal activity was recorded with multi-electrode arrays placed in the dorsal auditory cortex, where neurons tuned to target-distance are found. Our results show that target-distance encoding neurons are mostly selective to echoes coming from the closest object, and that the representation of echo information from distant objects is selectively suppressed. This suppression extends over a large part of the dorsal auditory cortex and may override possible parallel processing of multiple objects. The presented data suggest that global cortical suppression might establish a cortical "default mode" that allows selectively focusing on close obstacle even without active attention from the animals.

Cortical neurons of bats respond best to echoes from nearest targets when listening to natural biosonar multi-echo streams

PubMed Central

Beetz, M. Jerome; Hechavarría, Julio C.; Kössl, Manfred

2016-01-01

Bats orientate in darkness by listening to echoes from their biosonar calls, a behaviour known as echolocation. Recent studies showed that cortical neurons respond in a highly selective manner when stimulated with natural echolocation sequences that contain echoes from single targets. However, it remains unknown how cortical neurons process echolocation sequences containing echo information from multiple objects. In the present study, we used echolocation sequences containing echoes from three, two or one object separated in the space depth as stimuli to study neuronal activity in the bat auditory cortex. Neuronal activity was recorded with multi-electrode arrays placed in the dorsal auditory cortex, where neurons tuned to target-distance are found. Our results show that target-distance encoding neurons are mostly selective to echoes coming from the closest object, and that the representation of echo information from distant objects is selectively suppressed. This suppression extends over a large part of the dorsal auditory cortex and may override possible parallel processing of multiple objects. The presented data suggest that global cortical suppression might establish a cortical “default mode” that allows selectively focusing on close obstacle even without active attention from the animals. PMID:27786252

Localized Disruption of Narp in Medial Prefrontal Cortex Blocks Reinforcer Devaluation Performance

ERIC Educational Resources Information Center

Johnson, Alexander W.; Han, Sungho; Blouin, Ashley M.; Saini, Jasjit; Worley, Paul F.; During, Matthew J.; Holland, Peter C.; Baraban, Jay M.; Reti, Irving M.

2010-01-01

Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates [alpha]-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this…

Neurally Constrained Modeling of Perceptual Decision Making

ERIC Educational Resources Information Center

Purcell, Braden A.; Heitz, Richard P.; Cohen, Jeremiah Y.; Schall, Jeffrey D.; Logan, Gordon D.; Palmeri, Thomas J.

2010-01-01

Stochastic accumulator models account for response time in perceptual decision-making tasks by assuming that perceptual evidence accumulates to a threshold. The present investigation mapped the firing rate of frontal eye field (FEF) visual neurons onto perceptual evidence and the firing rate of FEF movement neurons onto evidence accumulation to…

A subharmonic dynamical bifurcation during in vitro epileptiform activity

NASA Astrophysics Data System (ADS)

Perez Velazquez, Jose L.; Khosravani, Houman

2004-06-01

Epileptic seizures are considered to result from a sudden change in the synchronization of firing neurons in brain neural networks. We have used an in vitro model of status epilepticus (SE) to characterize dynamical regimes underlying the observed seizure-like activity. Time intervals between spikes or bursts were used as the variable to construct first-return interpeak or interburst interval plots, for studying neuronal population activity during the transition to seizure, as well as within seizures. Return maps constructed for a brief epoch before seizures were used for approximating the local system dynamics during that time window. Analysis of the first-return maps suggests that intermittency is a dynamical regime underlying the observed epileptic activity. This type of analysis may be useful for understanding the collective dynamics of neuronal populations in the normal and pathological brain.

Shining light on neurons--elucidation of neuronal functions by photostimulation.

PubMed

Eder, Matthias; Zieglgänsberger, Walter; Dodt, Hans-Ulrich

2004-01-01

Many neuronal functions can be elucidated by techniques that allow for a precise stimulation of defined regions of a neuron and its afferents. Photolytic release of neurotransmitters from 'caged' derivates in the vicinity of visualized neurons in living brain slices meets this request. This technique allows the study of the subcellular distribution and properties of functional native neurotransmitter receptors. These are prerequisites for a detailed analysis of the expression and spatial specificity of synaptic plasticity. Photostimulation can further be used to fast map the synaptic connectivity between nearby and, more importantly, distant cells in a neuronal network. Here we give a personal review of some of the technical aspects of photostimulation and recent findings, which illustrate the advantages of this technique.

The Nanoscale Observation of the Three-Dimensional Structures of Neurosynapses, Membranous Conjunctions Between Cultured Hippocampal Neurons and Their Significance in the Development of Epilepsy.

PubMed

Sun, Lan; Jiang, Shuang; Tang, Xianhua; Zhang, Yingge; Qin, Luye; Jiang, Xia; Yu, Albert Cheung Hoi

2016-12-01

The nanoscale three-dimensional structures of neurosynapses are unknown, and the neuroanatomical basis of epilepsy remains to be elucidated. Here, we studied the nanoscale three-dimensional synapses between hippocampal neurons, and membranous conjunctions between neurons were found with atomic force microscopy (AFM) and confirmed by transmission electron microscope (TEM), and their pathophysiological significance was primarily investigated. The neurons and dendrites were marked by MAP-2, axons by neurofilament 200, and synapses by synapsin I immunological staining. In the synapsin I-positive neurite ends of the neurons positively stained with MAP-2 and neurofilament 200, neurosynapses with various nanoscale morphology and structure could be found by AFM. The neurosynapses had typical three-dimensional structures of synaptic triplet including the presynaptic neurite end, synaptic cleft of 30 ∼ 40 in chemical synapses and 2 ∼ 6 nm in electrical ones, the postsynaptic neurite or dendrite spine, the typical neurite end button, the distinct pre- and postsynaptic membranes, and the obvious thickening of the postsynaptic membranes or neurites. Some membranous connections including membrane-like junctions (MLJ) and fiber-tube links (FTL) without triplet structures and cleft were found between neurons. The development frequencies of the two membranous conjunctions increased while those of the synaptic conjunctions decreased between the neurons from Otx1 knock-out mice in comparison with those between the neurons from normal mice. These results suggested that the neuroanatomical basis of Otx1 knock-out epilepsy is the combination of the decreased synaptic conjunctions and the increased membranous conjunctions.

Central projections of gustatory receptor neurons in the medial and the lateral sensilla styloconica of Helicoverpa armigera larvae.

PubMed

Tang, Qing-Bo; Zhan, Huan; Cao, Huan; Berg, Bente G; Yan, Feng-Ming; Zhao, Xin-Cheng

2014-01-01

Food selection behavior of lepidopteran larvae is predominantly governed by the activation of taste neurons present in two sensilla styloconica located on the galea of the maxilla. In this study, we present the ultrastructure of the sensilla styloconica and the central projection pattern of their associated receptor neurons in larvae of the heliothine moth, Helicoverpa armigera. By means of light microscopy and scanning electron microscopy, the previous findings of two morphologically fairly similar sensilla comprising a socketed conic tip inserted into a large peg were confirmed. However, the peg size of the medial sensillum was found to be significantly bigger than that of the lateral sensillum. The sensory neurons derived from each sensillum styloconicum were mapped separately using anterograde staining experiments combined with confocal laser-scanning microscopy. For determining the afferents' target regions relative to each other, we reconstructed the labeled axons and placed them into a common reference framework. The sensory axons from both sensilla projected via the ipsilateral maxillary nerve to the suboesophageal ganglion and further through the ipsilateral circumoesophageal connective to the brain. In the suboesophageal ganglion, the sensory projections targeted two areas of the ipsilateral maxillary neuropil, one located in the ventrolateral neuromere and the other adjacent to the neuromere midline. In the brain, the axon terminals targeted the dorso-anterior area of the ipsilateral tritocerebrum. As confirmed by the three-dimensional reconstructions, the target regions of the neural projections originating from each of the two sensilla styloconica were identical.

Functional connectivity in the resting brain as biological correlate of the Affective Neuroscience Personality Scales.

PubMed

Deris, Nadja; Montag, Christian; Reuter, Martin; Weber, Bernd; Markett, Sebastian

2017-02-15

According to Jaak Panksepp's Affective Neuroscience Theory and the derived self-report measure, the Affective Neuroscience Personality Scales (ANPS), differences in the responsiveness of primary emotional systems form the basis of human personality. In order to investigate neuronal correlates of personality, the underlying neuronal circuits of the primary emotional systems were analyzed in the present fMRI-study by associating the ANPS to functional connectivity in the resting brain. N=120 healthy participants were invited for the present study. The results were reinvestigated in an independent, smaller sample of N=52 participants. A seed-based whole brain approach was conducted with seed-regions bilaterally in the basolateral and superficial amygdalae. The selection of seed-regions was based on meta-analytic data on affective processing and the Juelich histological atlas. Multiple regression analyses on the functional connectivity maps revealed associations with the SADNESS-scale in both samples. Functional resting-state connectivity between the left basolateral amygdala and a cluster in the postcentral gyrus, and between the right basolateral amygdala and clusters in the superior parietal lobe and subgyral in the parietal lobe was associated with SADNESS. No other ANPS-scale revealed replicable results. The present findings give first insights into the neuronal basis of the SADNESS-scale of the ANPS and support the idea of underlying neuronal circuits. In combination with previous research on genetic associations of the ANPS functional resting-state connectivity is discussed as a possible endophenotype of personality. Copyright © 2016 Elsevier Inc. All rights reserved.

Adaptation Shifts Preferred Orientation of Tuning Curve in the Mouse Visual Cortex

PubMed Central

Jeyabalaratnam, Jeyadarshan; Bharmauria, Vishal; Bachatene, Lyes; Cattan, Sarah; Angers, Annie; Molotchnikoff, Stéphane

2013-01-01

In frontalized mammals it has been demonstrated that adaptation produces shift of the peak of the orientation tuning curve of neuron following frequent or lengthier presentation of a non-preferred stimulus. Depending on the duration of adaptation the shift is attractive (toward the adapter) or repulsive (away from the adapter). Mouse exhibits a salt-and-pepper cortical organization of orientation maps, hence this species may respond differently to adaptation. To examine this question, we determined the effect of twelve minutes of adaptation to one particular orientation on neuronal orientation tuning curves in V1 of anesthetized mice. Multi-unit activity of neurons in V1 was recorded in a conventional fashion. Cells were stimulated with sine-wave drifting gratings whose orientation tilted in steps. Results revealed that similarly to cats and monkeys, majority of cells shifted their optimal orientation in the direction of the adapter while a small proportion exhibited a repulsive shift. Moreover, initially untuned cells showing poor tuning curves reacted to adaptation by displaying sharp orientation selectivity. It seems that modification of the cellular property following adaptation is a general phenomenon observed in all mammals in spite of the different organization pattern of the visual cortex. This study is of pertinence to comprehend the mechanistic pathways of brain plasticity. PMID:23717586

A face-selective ventral occipito-temporal map of the human brain with intracerebral potentials

PubMed Central

Jonas, Jacques; Jacques, Corentin; Liu-Shuang, Joan; Brissart, Hélène; Colnat-Coulbois, Sophie; Maillard, Louis; Rossion, Bruno

2016-01-01

Human neuroimaging studies have identified a network of distinct face-selective regions in the ventral occipito-temporal cortex (VOTC), with a right hemispheric dominance. To date, there is no evidence for this hemispheric and regional specialization with direct measures of brain activity. To address this gap in knowledge, we recorded local neurophysiological activity from 1,678 contact electrodes implanted in the VOTC of a large group of epileptic patients (n = 28). They were presented with natural images of objects at a rapid fixed rate (six images per second: 6 Hz), with faces interleaved as every fifth stimulus (i.e., 1.2 Hz). High signal-to-noise ratio face-selective responses were objectively (i.e., exactly at the face stimulation frequency) identified and quantified throughout the whole VOTC. Face-selective responses were widely distributed across the whole VOTC, but also spatially clustered in specific regions. Among these regions, the lateral section of the right middle fusiform gyrus showed the largest face-selective response by far, offering, to our knowledge, the first supporting evidence of two decades of neuroimaging observations with direct neural measures. In addition, three distinct regions with a high proportion of face-selective responses were disclosed in the right ventral anterior temporal lobe, a region that is undersampled in neuroimaging because of magnetic susceptibility artifacts. A high proportion of contacts responding only to faces (i.e., “face-exclusive” responses) were found in these regions, suggesting that they contain populations of neurons involved in dedicated face-processing functions. Overall, these observations provide a comprehensive mapping of visual category selectivity in the whole human VOTC with direct neural measures. PMID:27354526

Topographic organizations of taste-responsive neurons in the parabrachial nucleus of C57BL/6J mice: An electrophysiological mapping study.

PubMed

Tokita, K; Boughter, J D

2016-03-01

The activities of 178 taste-responsive neurons were recorded extracellularly from the parabrachial nucleus (PbN) in the anesthetized C57BL/6J mouse. Taste stimuli included those representative of five basic taste qualities, sweet, salty, sour, bitter and umami. Umami synergism was represented by all sucrose-best and sweet-sensitive sodium chloride-best neurons. Mediolaterally the PbN was divided into medial, brachium conjunctivum (BC) and lateral subdivisions while rostrocaudally the PbN was divided into rostral and caudal subdivisions for mapping and reconstruction of recording sites. Neurons in the medial and BC subdivisions had a significantly greater magnitude of response to sucrose and to the mixture of monopotassium glutamate and inosine monophosphate than those found in the lateral subdivision. In contrast, neurons in the lateral subdivision possessed a more robust response to quinine hydrochloride. Rostrocaudally no difference was found in the mean magnitude of response. Analysis on the distribution pattern of neuron types classified by their best stimulus revealed that the proportion of neuron types in the medial vs. lateral and BC vs. lateral subdivisions was significantly different, with a greater amount of sucrose-best neurons found medially and within the BC, and a greater amount of sodium chloride-, citric acid- and quinine hydrochloride-best neurons found laterally. There was no significant difference in the neuron-type distribution between rostral and caudal PbN. We also assessed breadth of tuning in these neurons by calculating entropy (H) and noise-to-signal (N/S) ratio. The mean N/S ratio of all neurons (0.43) was significantly lower than that of H value (0.64). Neurons in the caudal PbN had a significantly higher H value than in the rostral PbN. In contrast, mean N/S ratios were not different both mediolaterally and rostrocaudally. These results suggest that although there is overlap in taste quality representation in the mouse PbN, taste-responsive neurons still possessed a topographic organization. Published by Elsevier Ltd.

A Select Subset of Electron Transport Chain Genes Associated with Optic Atrophy Link Mitochondria to Axon Regeneration in Caenorhabditis elegans.

PubMed

Knowlton, Wendy M; Hubert, Thomas; Wu, Zilu; Chisholm, Andrew D; Jin, Yishi

2017-01-01

The role of mitochondria within injured neurons is an area of active interest since these organelles are vital for the production of cellular energy in the form of ATP. Using mechanosensory neurons of the nematode Caenorhabditis elegans to test regeneration after neuronal injury in vivo , we surveyed genes related to mitochondrial function for effects on axon regrowth after laser axotomy. Genes involved in mitochondrial transport, calcium uptake, mitophagy, or fission and fusion were largely dispensable for axon regrowth, with the exception of eat-3/Opa1 . Surprisingly, many genes encoding components of the electron transport chain were dispensable for regrowth, except for the iron-sulfur proteins gas-1, nduf-2.2, nduf-7 , and isp-1 , and the putative oxidoreductase rad-8 . In these mutants, axonal development was essentially normal and axons responded normally to injury by forming regenerative growth cones, but were impaired in subsequent axon extension. Overexpression of nduf-2.2 or isp-1 was sufficient to enhance regrowth, suggesting that mitochondrial function is rate-limiting in axon regeneration. Moreover, loss of function in isp-1 reduced the enhanced regeneration caused by either a gain-of-function mutation in the calcium channel EGL-19 or overexpression of the MAP kinase DLK-1. While the cellular function of RAD-8 remains unclear, our genetic analyses place rad-8 in the same pathway as other electron transport genes in axon regeneration. Unexpectedly, rad-8 regrowth defects were suppressed by altered function in the ubiquinone biosynthesis gene clk-1 . Furthermore, we found that inhibition of the mitochondrial unfolded protein response via deletion of atfs-1 suppressed the defective regrowth in nduf-2.2 mutants. Together, our data indicate that while axon regeneration is not significantly affected by general dysfunction of cellular respiration, it is sensitive to the proper functioning of a select subset of electron transport chain genes, or to the cellular adaptations used by neurons under conditions of injury.

A Select Subset of Electron Transport Chain Genes Associated with Optic Atrophy Link Mitochondria to Axon Regeneration in Caenorhabditis elegans

PubMed Central

Knowlton, Wendy M.; Hubert, Thomas; Wu, Zilu; Chisholm, Andrew D.; Jin, Yishi

2017-01-01

The role of mitochondria within injured neurons is an area of active interest since these organelles are vital for the production of cellular energy in the form of ATP. Using mechanosensory neurons of the nematode Caenorhabditis elegans to test regeneration after neuronal injury in vivo, we surveyed genes related to mitochondrial function for effects on axon regrowth after laser axotomy. Genes involved in mitochondrial transport, calcium uptake, mitophagy, or fission and fusion were largely dispensable for axon regrowth, with the exception of eat-3/Opa1. Surprisingly, many genes encoding components of the electron transport chain were dispensable for regrowth, except for the iron-sulfur proteins gas-1, nduf-2.2, nduf-7, and isp-1, and the putative oxidoreductase rad-8. In these mutants, axonal development was essentially normal and axons responded normally to injury by forming regenerative growth cones, but were impaired in subsequent axon extension. Overexpression of nduf-2.2 or isp-1 was sufficient to enhance regrowth, suggesting that mitochondrial function is rate-limiting in axon regeneration. Moreover, loss of function in isp-1 reduced the enhanced regeneration caused by either a gain-of-function mutation in the calcium channel EGL-19 or overexpression of the MAP kinase DLK-1. While the cellular function of RAD-8 remains unclear, our genetic analyses place rad-8 in the same pathway as other electron transport genes in axon regeneration. Unexpectedly, rad-8 regrowth defects were suppressed by altered function in the ubiquinone biosynthesis gene clk-1. Furthermore, we found that inhibition of the mitochondrial unfolded protein response via deletion of atfs-1 suppressed the defective regrowth in nduf-2.2 mutants. Together, our data indicate that while axon regeneration is not significantly affected by general dysfunction of cellular respiration, it is sensitive to the proper functioning of a select subset of electron transport chain genes, or to the cellular adaptations used by neurons under conditions of injury. PMID:28539870

Comparative mapping of serotonin-immunoreactive neurons in the central nervous systems of nudibranch molluscs.

PubMed

Newcomb, James M; Fickbohm, David J; Katz, Paul S

2006-11-20

The serotonergic systems in nudibranch molluscs were compared by mapping the locations of serotonin-immunoreactive (5-HT-ir) neurons in 11 species representing all four suborders of the nudibranch clade: Dendronotoidea (Tritonia diomedea, Tochuina tetraquetra, Dendronotus iris, Dendronotus frondosus, and Melibe leonina), Aeolidoidea (Hermissenda crassicornis and Flabellina trophina), Arminoidea (Dirona albolineata, Janolus fuscus, and Armina californica), and Doridoidea (Triopha catalinae). A nomenclature is proposed to standardize reports of cell location in species with differing brain morphologies. Certain patterns of 5-HT immunoreactivity were found to be consistent for all species, such as the presence of 5-HT-ir neurons in the pedal and cerebral ganglia. Also, particular clusters of 5-HT-ir neurons in the anterior and posterior regions of the dorsal surface of the cerebral ganglion were always present. However, there were interspecies differences in the number of 5-HT-ir neurons in each cluster, and some clusters even exhibited strong intraspecies variability that was only weakly correlated with brain size. Phylogenetic analysis suggests that the presence of particular classes of 5-HT-ir neurons exhibits a great deal of homoplasy. The conserved features of the nudibranch serotonergic system presumably represent the shared ancestral structure, whereas the derived characters suggest substantial independent evolutionary changes in the number and presence of serotonergic neurons. Although a number of studies have demonstrated phylogenetic variability of peptidergic systems, this study suggests that serotonergic systems may also exhibit a high degree of homoplasy in some groups of organisms.

Optical Probes for Neurobiological Sensing and Imaging.

PubMed

Kim, Eric H; Chin, Gregory; Rong, Guoxin; Poskanzer, Kira E; Clark, Heather A

2018-05-15

Fluorescent nanosensors and molecular probes are next-generation tools for imaging chemical signaling inside and between cells. Electrophysiology has long been considered the gold standard in elucidating neural dynamics with high temporal resolution and precision, particularly on the single-cell level. However, electrode-based techniques face challenges in illuminating the specific chemicals involved in neural cell activation with adequate spatial information. Measuring chemical dynamics is of fundamental importance to better understand synergistic interactions between neurons as well as interactions between neurons and non-neuronal cells. Over the past decade, significant technological advances in optical probes and imaging methods have enabled entirely new possibilities for studying neural cells and circuits at the chemical level. These optical imaging modalities have shown promise for combining chemical, temporal, and spatial information. This potential makes them ideal candidates to unravel the complex neural interactions at multiple scales in the brain, which could be complemented by traditional electrophysiological methods to obtain a full spatiotemporal picture of neurochemical dynamics. Despite the potential, only a handful of probe candidates have been utilized to provide detailed chemical information in the brain. To date, most live imaging and chemical mapping studies rely on fluorescent molecular indicators to report intracellular calcium (Ca 2+ ) dynamics, which correlates with neuronal activity. Methodological advances for monitoring a full array of chemicals in the brain with improved spatial, temporal, and chemical resolution will thus enable mapping of neurochemical circuits with finer precision. On the basis of numerous studies in this exciting field, we review the current efforts to develop and apply a palette of optical probes and nanosensors for chemical sensing in the brain. There is a strong impetus to further develop technologies capable of probing entire neurobiological units with high spatiotemporal resolution. Thus, we introduce selected applications for ion and neurotransmitter detection to investigate both neurons and non-neuronal brain cells. We focus on families of optical probes because of their ability to sense a wide array of molecules and convey spatial information with minimal damage to tissue. We start with a discussion of currently available molecular probes, highlight recent advances in genetically modified fluorescent probes for ions and small molecules, and end with the latest research in nanosensors for biological imaging. Customizable, nanoscale optical sensors that accurately and dynamically monitor the local environment with high spatiotemporal resolution could lead to not only new insights into the function of all cell types but also a broader understanding of how diverse neural signaling systems act in conjunction with neighboring cells in a spatially relevant manner.

Face-selective and auditory neurons in the primate orbitofrontal cortex.

PubMed

Rolls, Edmund T; Critchley, Hugo D; Browning, Andrew S; Inoue, Kazuo

2006-03-01

Neurons with responses selective for faces are described in the macaque orbitofrontal cortex. The neurons typically respond 2-13 times more to the best face than to the best non-face stimulus, and have response latencies which are typically in the range of 130-220 ms. Some of these face-selective neurons respond to identity, and others to facial expression. Some of the neurons do not have different responses to different views of a face, which is a useful property of neurons responding to face identity. Other neurons have view-dependent responses, and some respond to moving but not still heads. The neurons with face expression, face movement, or face view-dependent responses would all be useful as part of a system decoding and representing signals important in social interactions. The representation of face identity is also important in social interactions, for it provides some of the information needed in order to make different responses to different individuals. In addition, some orbitofrontal cortex neurons were shown to be tuned to auditory stimuli, including for some neurons, the sound of vocalizations. The findings are relevant to understanding the functions of the primate including human orbitofrontal cortex in normal behaviour, and to understanding the effects of damage to this region in humans.

A Role for SMN Exon 7 Splicing in the Selective Vulnerability of Motor Neurons in Spinal Muscular Atrophy

PubMed Central

Ruggiu, Matteo; McGovern, Vicki L.; Lotti, Francesco; Saieva, Luciano; Li, Darrick K.; Kariya, Shingo; Monani, Umrao R.; Burghes, Arthur H. M.

2012-01-01

Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by homozygous loss of the Survival Motor Neuron 1 (SMN1) gene. In the absence of SMN1, inefficient inclusion of exon 7 in transcripts from the nearly identical SMN2 gene results in ubiquitous SMN decrease but selective motor neuron degeneration. Here we investigated whether cell type-specific differences in the efficiency of exon 7 splicing contribute to the vulnerability of SMA motor neurons. We show that normal motor neurons express markedly lower levels of full-length SMN mRNA from SMN2 than do other cells in the spinal cord. This is due to inefficient exon 7 splicing that is intrinsic to motor neurons under normal conditions. We also find that SMN depletion in mammalian cells decreases exon 7 inclusion through a negative feedback loop affecting the splicing of its own mRNA. This mechanism is active in vivo and further decreases the efficiency of exon 7 inclusion specifically in motor neurons of severe-SMA mice. Consistent with expression of lower levels of full-length SMN, we find that SMN-dependent downstream molecular defects are exacerbated in SMA motor neurons. These findings suggest a mechanism to explain the selective vulnerability of motor neurons to loss of SMN1. PMID:22037760

Functional Maps of Mechanosensory Features in the Drosophila Brain.

PubMed

Patella, Paola; Wilson, Rachel I

2018-04-23

Johnston's organ is the largest mechanosensory organ in Drosophila. It contributes to hearing, touch, vestibular sensing, proprioception, and wind sensing. In this study, we used in vivo 2-photon calcium imaging and unsupervised image segmentation to map the tuning properties of Johnston's organ neurons (JONs) at the site where their axons enter the brain. We then applied the same methodology to study two key brain regions that process signals from JONs: the antennal mechanosensory and motor center (AMMC) and the wedge, which is downstream of the AMMC. First, we identified a diversity of JON response types that tile frequency space and form a rough tonotopic map. Some JON response types are direction selective; others are specialized to encode amplitude modulations over a specific range (dynamic range fractionation). Next, we discovered that both the AMMC and the wedge contain a tonotopic map, with a significant increase in tonotopy-and a narrowing of frequency tuning-at the level of the wedge. Whereas the AMMC tonotopic map is unilateral, the wedge tonotopic map is bilateral. Finally, we identified a subregion of the AMMC/wedge that responds preferentially to the coherent rotation of the two mechanical organs in the same angular direction, indicative of oriented steady air flow (directional wind). Together, these maps reveal the broad organization of the primary and secondary mechanosensory regions of the brain. They provide a framework for future efforts to identify the specific cell types and mechanisms that underlie the hierarchical re-mapping of mechanosensory information in this system. Copyright © 2018 Elsevier Ltd. All rights reserved.

Circuit mechanisms encoding odors and driving aging-associated behavioral declines in Caenorhabditis elegans.

PubMed

Leinwand, Sarah G; Yang, Claire J; Bazopoulou, Daphne; Chronis, Nikos; Srinivasan, Jagan; Chalasani, Sreekanth H

2015-09-22

Chemosensory neurons extract information about chemical cues from the environment. How is the activity in these sensory neurons transformed into behavior? Using Caenorhabditis elegans, we map a novel sensory neuron circuit motif that encodes odor concentration. Primary neurons, AWC(ON) and AWA, directly detect the food odor benzaldehyde (BZ) and release insulin-like peptides and acetylcholine, respectively, which are required for odor-evoked responses in secondary neurons, ASEL and AWB. Consistently, both primary and secondary neurons are required for BZ attraction. Unexpectedly, this combinatorial code is altered in aged animals: odor-evoked activity in secondary, but not primary, olfactory neurons is reduced. Moreover, experimental manipulations increasing neurotransmission from primary neurons rescues aging-associated neuronal deficits. Finally, we correlate the odor responsiveness of aged animals with their lifespan. Together, these results show how odors are encoded by primary and secondary neurons and suggest reduced neurotransmission as a novel mechanism driving aging-associated sensory neural activity and behavioral declines.

Circuit mechanisms encoding odors and driving aging-associated behavioral declines in Caenorhabditis elegans

PubMed Central

Leinwand, Sarah G; Yang, Claire J; Bazopoulou, Daphne; Chronis, Nikos; Srinivasan, Jagan; Chalasani, Sreekanth H

2015-01-01

Chemosensory neurons extract information about chemical cues from the environment. How is the activity in these sensory neurons transformed into behavior? Using Caenorhabditis elegans, we map a novel sensory neuron circuit motif that encodes odor concentration. Primary neurons, AWCON and AWA, directly detect the food odor benzaldehyde (BZ) and release insulin-like peptides and acetylcholine, respectively, which are required for odor-evoked responses in secondary neurons, ASEL and AWB. Consistently, both primary and secondary neurons are required for BZ attraction. Unexpectedly, this combinatorial code is altered in aged animals: odor-evoked activity in secondary, but not primary, olfactory neurons is reduced. Moreover, experimental manipulations increasing neurotransmission from primary neurons rescues aging-associated neuronal deficits. Finally, we correlate the odor responsiveness of aged animals with their lifespan. Together, these results show how odors are encoded by primary and secondary neurons and suggest reduced neurotransmission as a novel mechanism driving aging-associated sensory neural activity and behavioral declines. DOI: http://dx.doi.org/10.7554/eLife.10181.001 PMID:26394000

Discrete model of the olivo-cerebellar system: structure and dynamics

NASA Astrophysics Data System (ADS)

Maslennikov, O. V.; Nekorkin, V. I.

2012-08-01

We propose a discrete model of the olivo-cerebellar system. The model consists of three layers of interacting elements, namely, inferior olive neurons, Purkinje cells, and deep cerebellar nuclear neurons combined into a structure by axonal connections. Each element of the structure is described by a two-dimensional map with an individual set of parameters for each type of neurons. Dynamic properties of different types of neurons are described and spontaneous and stimulusinduced dynamics of the system is explored. Unlike the previously proposed models, this study takes into account the axonal interaction of neurons of different layers, as well as the interaction of the inferior olive neurons through electrical synapses with the property of plasticity. It is shown that the inclusion of these factors plays a significant role in the formation of spatio-temporal activity of the inferior olive neurons.

Shifting Topographic Activation and 5-HT1A-Receptor Mediated Inhibition of Dorsal Raphe Serotonin Neurons Produced by Nicotine Exposure and Withdrawal

PubMed Central

Sperling, Robin; Commons, Kathryn G.

2011-01-01

Nicotine activates serotonin (5-HT) neurons innervating the forebrain and this is thought to reduce anxiety. Nicotine withdrawal has also been associated with an activation of 5-HT neurotransmission, although withdrawal increases anxiety. In each case, 5-HT1A receptors have been implicated in the response. To determine if there are different subgroups of 5-HT cells activated during nicotine administration and withdrawal, we mapped the appearance of Fos, a marker of neuronal activation, in 5-HT cells of the dorsal and median raphe nuclei (DR and MR). To understand the role 5-HT1A receptor feedback inhibitory pathways on 5-HT cell activity during these conditions, we administered a selective 5-HT1A-receptor antagonist and measured novel disinhibited Fos expression within 5-HT cells. Using these approaches, we found evidence that acute nicotine activates 5-HT neurons rostrally and in the lateral wings of the DR while there is 5-HT1A dependent inhibition of cells located ventrally both at rostral and mid levels. Previous chronic nicotine exposure did not modify the pattern of Fos activation produced by acute nicotine, but increased 5-HT1A-dependent inhibition of 5-HT cells in the caudal DR. This pattern was nearly reversed during nicotine withdrawal when there was evidence for caudal activation and mid- and rostral-5-HT1A-dependent inhibition. These results suggest that the distinct behavioral states produced by nicotine exposure and withdrawal correlate with reciprocal rostral-caudal patterns of activation and 5-HT1A-mediated inhibition of DR 5-HT neurons. The complimentary patterns of activation and inhibition suggest that 5-HT1A receptors may help shape distinct topographic patterns of activation within the DR. PMID:21501256

Feature selection for the classification of traced neurons.

PubMed

López-Cabrera, José D; Lorenzo-Ginori, Juan V

2018-06-01

The great availability of computational tools to calculate the properties of traced neurons leads to the existence of many descriptors which allow the automated classification of neurons from these reconstructions. This situation determines the necessity to eliminate irrelevant features as well as making a selection of the most appropriate among them, in order to improve the quality of the classification obtained. The dataset used contains a total of 318 traced neurons, classified by human experts in 192 GABAergic interneurons and 126 pyramidal cells. The features were extracted by means of the L-measure software, which is one of the most used computational tools in neuroinformatics to quantify traced neurons. We review some current feature selection techniques as filter, wrapper, embedded and ensemble methods. The stability of the feature selection methods was measured. For the ensemble methods, several aggregation methods based on different metrics were applied to combine the subsets obtained during the feature selection process. The subsets obtained applying feature selection methods were evaluated using supervised classifiers, among which Random Forest, C4.5, SVM, Naïve Bayes, Knn, Decision Table and the Logistic classifier were used as classification algorithms. Feature selection methods of types filter, embedded, wrappers and ensembles were compared and the subsets returned were tested in classification tasks for different classification algorithms. L-measure features EucDistanceSD, PathDistanceSD, Branch_pathlengthAve, Branch_pathlengthSD and EucDistanceAve were present in more than 60% of the selected subsets which provides evidence about their importance in the classification of this neurons. Copyright © 2018 Elsevier B.V. All rights reserved.

Transient Cnp expression by early progenitors causes Cre-Lox-based reporter lines to map profoundly different fates.

PubMed

Tognatta, Reshmi; Sun, Wenjing; Goebbels, Sandra; Nave, Klaus-Armin; Nishiyama, Akiko; Schoch, Susanne; Dimou, Leda; Dietrich, Dirk

2017-02-01

NG2 expressing oligodendroglial precursor cells are ubiquitous in the central nervous system and the only cell type cycling throughout life. Previous fate mapping studies have remained inconsistent regarding the question whether NG2 cells are capable of generating certain types of neurons. Here, we use CNP-Cre mice to map the fate of a sub-population of NG2 cells assumed to be close to differentiation. When crossing these mice with the ROSA26/YFP Cre-reporter line we discovered large numbers of reporter-expressing pyramidal neurons in the piriform and dorsal cortex. In contrast, when using Z/EG reporter mice to track the fate of Cnp-expressing NG2 cells only oligodendroglial cells were found reporter positive. Using BrdU-based birth dating protocols and inducible NG2CreER:ROSA26/YFP mice we show that YFP positive neurons are generated from radial glial cells and that these radial glial cells display temporary and low level activity of certain oligodendroglial genes sufficient to recombine the Cre-inducible reporter gene in ROSA26/YFP but not in Z/EG mice. Taken together, we did not obtain evidence for generation of neurons from NG2 cells. Our results suggest that with an appropriate reporter system Cnp activity can be used to define a proliferative subpopulation of NG2 cells committed to generate oligodendrocytes. However, the strikingly different results obtained from ROSA26/YFP versus Z/EG mice demonstrate that the choice of Cre-reporter line can be of crucial importance for fate mapping studies and other applications of the Cre-lox technology. GLIA 2017;65:342-359. © 2016 Wiley Periodicals, Inc.

Bidirectional Modulation of Intrinsic Excitability in Rat Prelimbic Cortex Neuronal Ensembles and Non-Ensembles after Operant Learning.

PubMed

Whitaker, Leslie R; Warren, Brandon L; Venniro, Marco; Harte, Tyler C; McPherson, Kylie B; Beidel, Jennifer; Bossert, Jennifer M; Shaham, Yavin; Bonci, Antonello; Hope, Bruce T

2017-09-06

Learned associations between environmental stimuli and rewards drive goal-directed learning and motivated behavior. These memories are thought to be encoded by alterations within specific patterns of sparsely distributed neurons called neuronal ensembles that are activated selectively by reward-predictive stimuli. Here, we use the Fos promoter to identify strongly activated neuronal ensembles in rat prelimbic cortex (PLC) and assess altered intrinsic excitability after 10 d of operant food self-administration training (1 h/d). First, we used the Daun02 inactivation procedure in male FosLacZ-transgenic rats to ablate selectively Fos-expressing PLC neurons that were active during operant food self-administration. Selective ablation of these neurons decreased food seeking. We then used male FosGFP-transgenic rats to assess selective alterations of intrinsic excitability in Fos-expressing neuronal ensembles (FosGFP + ) that were activated during food self-administration and compared these with alterations in less activated non-ensemble neurons (FosGFP - ). Using whole-cell recordings of layer V pyramidal neurons in an ex vivo brain slice preparation, we found that operant self-administration increased excitability of FosGFP + neurons and decreased excitability of FosGFP - neurons. Increased excitability of FosGFP + neurons was driven by increased steady-state input resistance. Decreased excitability of FosGFP - neurons was driven by increased contribution of small-conductance calcium-activated potassium (SK) channels. Injections of the specific SK channel antagonist apamin into PLC increased Fos expression but had no effect on food seeking. Overall, operant learning increased intrinsic excitability of PLC Fos-expressing neuronal ensembles that play a role in food seeking but decreased intrinsic excitability of Fos - non-ensembles. SIGNIFICANCE STATEMENT Prefrontal cortex activity plays a critical role in operant learning, but the underlying cellular mechanisms are unknown. Using the chemogenetic Daun02 inactivation procedure, we found that a small number of strongly activated Fos-expressing neuronal ensembles in rat PLC play an important role in learned operant food seeking. Using GFP expression to identify Fos-expressing layer V pyramidal neurons in prelimbic cortex (PLC) of FosGFP-transgenic rats, we found that operant food self-administration led to increased intrinsic excitability in the behaviorally relevant Fos-expressing neuronal ensembles, but decreased intrinsic excitability in Fos - neurons using distinct cellular mechanisms. Copyright © 2017 the authors 0270-6474/17/378845-12$15.00/0.

Mapping Neuronal Activation and the Influence of Adrenergic Signaling during Contextual Memory Retrieval

ERIC Educational Resources Information Center

Zhang, Wei-Ping; Guzowski, John F.; Thomas, Steven A.

2005-01-01

We recently described a critical role for adrenergic signaling in the hippocampus during contextual and spatial memory retrieval. To determine which neurons are activated by contextual memory retrieval and its sequelae in the presence and absence of adrenergic signaling, transcriptional imaging for the immediate-early gene "Arc" was used in…

Distribution and co-localization of choline acetyltransferase and p75 neurotrophin receptors in the sheep basal forebrain: implications for the use of a specific cholinergic immunotoxin.

PubMed

Ferreira, G; Meurisse, M; Tillet, Y; Lévy, F

2001-01-01

The basal forebrain cholinergic system is involved in different forms of memory. To study its role in social memory in sheep, an immunotoxin, ME20.4 immunoglobulin G (IgG)-saporin, was developed that is specific to basal forebrain cholinergic neurons bearing the p75 neurotrophin receptor. The distribution of sheep cholinergic neurons was mapped with an antibody against choline acetyltransferase. To assess the localization of the p75 receptor on basal forebrain cholinergic neurons, the distribution of p75 receptor-immunoreactive neurons with ME20.4 IgG was examined, and a double-labeling study with antibodies against choline acetyltransferase and p75 receptor was undertaken. The loss of basal forebrain cholinergic neurons and acetylcholinesterase fibers in basal forebrain projection areas was assessed in ewes that had received intracerebroventricular injections of the immunotoxin (50, 100 or 150 microg) alone, as well as, in some of the ewes treated with the highest dose, with bilateral immunotoxin injections in the nucleus basalis (11 microg/side). Results indicated that choline acetyltransferase- and p75 receptor-immunoreactive cells had similar distributions in the medial septum, the vertical and horizontal limbs of the band of Broca, and the nucleus basalis. The double-labeling procedure revealed that 100% of the cholinergic neurons are also p75 receptor positive in the medial septum and in the vertical and horizontal limbs of the band of Broca, and 82% in the nucleus basalis. Moreover, 100% of the p75 receptor-immunoreactive cells of these four nuclei were cholinergic. Combined immunotoxin injections into ventricles and the nucleus basalis produced a near complete loss (80-95%) of basal forebrain cholinergic neurons and acetylcholinesterase-positive fibers in the hippocampus, olfactory bulb and entorhinal cortex. This study provides the first anatomical data concerning the basal forebrain cholinergic system in ungulates. The availability of a selective cholinergic immunotoxin effective in sheep provides a new tool to probe the involvement of basal forebrain cholinergic neurons in cognitive processes in this species.

Local structure of subcellular input retinotopy in an identified visual interneuron

NASA Astrophysics Data System (ADS)

Zhu, Ying; Gabbiani, Fabrizio; Fabrizio Gabbiani's lab Team

2015-03-01

How does the spatial layout of the projections that a neuron receives impact its synaptic integration and computation? What is the mapping topography of subcellular wiring at the single neuron level? The LGMD (lobula giant movement detector) neuron in the locust is an identified neuron that responds preferentially to objects approaching on a collision course. It receives excitatory inputs from the entire visual hemifield through calcium-permeable nicotinic acetylcholine receptors. Previous work showed that the projection from the locust compound eye to the LGMD preserved retinotopy down to the level of a single ommatidium (facet) by employing in vivo widefield calcium imaging. Because widefield imaging relies on global excitation of the preparation and has a relatively low resolution, previous work could not investigate this retinotopic mapping at the level of individual thin dendritic branches. Our current work employs a custom-built two-photon microscope with sub-micron resolution in conjunction with a single-facet stimulation setup that provides visual stimuli to the single ommatidium of locust adequate to explore the local structure of this retinotopy at a finer level. We would thank NIMH for funding this research.

BlastNeuron for Automated Comparison, Retrieval and Clustering of 3D Neuron Morphologies.

PubMed

Wan, Yinan; Long, Fuhui; Qu, Lei; Xiao, Hang; Hawrylycz, Michael; Myers, Eugene W; Peng, Hanchuan

2015-10-01

Characterizing the identity and types of neurons in the brain, as well as their associated function, requires a means of quantifying and comparing 3D neuron morphology. Presently, neuron comparison methods are based on statistics from neuronal morphology such as size and number of branches, which are not fully suitable for detecting local similarities and differences in the detailed structure. We developed BlastNeuron to compare neurons in terms of their global appearance, detailed arborization patterns, and topological similarity. BlastNeuron first compares and clusters 3D neuron reconstructions based on global morphology features and moment invariants, independent of their orientations, sizes, level of reconstruction and other variations. Subsequently, BlastNeuron performs local alignment between any pair of retrieved neurons via a tree-topology driven dynamic programming method. A 3D correspondence map can thus be generated at the resolution of single reconstruction nodes. We applied BlastNeuron to three datasets: (1) 10,000+ neuron reconstructions from a public morphology database, (2) 681 newly and manually reconstructed neurons, and (3) neurons reconstructions produced using several independent reconstruction methods. Our approach was able to accurately and efficiently retrieve morphologically and functionally similar neuron structures from large morphology database, identify the local common structures, and find clusters of neurons that share similarities in both morphology and molecular profiles.

Contribution of correlated noise and selective decoding to choice probability measurements in extrastriate visual cortex.

PubMed

Gu, Yong; Angelaki, Dora E; DeAngelis, Gregory C

2014-07-01

Trial by trial covariations between neural activity and perceptual decisions (quantified by choice Probability, CP) have been used to probe the contribution of sensory neurons to perceptual decisions. CPs are thought to be determined by both selective decoding of neural activity and by the structure of correlated noise among neurons, but the respective roles of these factors in creating CPs have been controversial. We used biologically-constrained simulations to explore this issue, taking advantage of a peculiar pattern of CPs exhibited by multisensory neurons in area MSTd that represent self-motion. Although models that relied on correlated noise or selective decoding could both account for the peculiar pattern of CPs, predictions of the selective decoding model were substantially more consistent with various features of the neural and behavioral data. While correlated noise is essential to observe CPs, our findings suggest that selective decoding of neuronal signals also plays important roles.

Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2.

PubMed

Ruane, Peter T; Gumy, Laura F; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J; Hoogenraad, Casper C; Allan, Victoria J

2016-06-07

Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members, the exact mechanism for the peripheral localization of APC remains unclear. Here we show that the heavy chain of kinesin-1 directly interacts with the APC C-terminus, contributing to the peripheral localisation of APC in fibroblasts. In rat hippocampal neurons the kinesin-1 binding domain of APC is required for its axon tip enrichment. Moreover, we demonstrate that APC requires interactions with both kinesin-2 and kinesin-1 for this localisation. Underlining the importance of the kinesin-1 association, neurons expressing APC lacking kinesin-1-binding domain have shorter axons. The identification of this novel kinesin-1-APC interaction highlights the complexity and significance of APC localisation in neurons.

Superior colliculus neurons encode a visual saliency map during free viewing of natural dynamic video

NASA Astrophysics Data System (ADS)

White, Brian J.; Berg, David J.; Kan, Janis Y.; Marino, Robert A.; Itti, Laurent; Munoz, Douglas P.

2017-01-01

Models of visual attention postulate the existence of a saliency map whose function is to guide attention and gaze to the most conspicuous regions in a visual scene. Although cortical representations of saliency have been reported, there is mounting evidence for a subcortical saliency mechanism, which pre-dates the evolution of neocortex. Here, we conduct a strong test of the saliency hypothesis by comparing the output of a well-established computational saliency model with the activation of neurons in the primate superior colliculus (SC), a midbrain structure associated with attention and gaze, while monkeys watched video of natural scenes. We find that the activity of SC superficial visual-layer neurons (SCs), specifically, is well-predicted by the model. This saliency representation is unlikely to be inherited from fronto-parietal cortices, which do not project to SCs, but may be computed in SCs and relayed to other areas via tectothalamic pathways.

Orientation selectivity and the functional clustering of synaptic inputs in primary visual cortex

PubMed Central

Wilson, Daniel E.; Whitney, David E.; Scholl, Benjamin; Fitzpatrick, David

2016-01-01

The majority of neurons in primary visual cortex are tuned for stimulus orientation, but the factors that account for the range of orientation selectivities exhibited by cortical neurons remain unclear. To address this issue, we used in vivo 2-photon calcium imaging to characterize the orientation tuning and spatial arrangement of synaptic inputs to the dendritic spines of individual pyramidal neurons in layer 2/3 of ferret visual cortex. The summed synaptic input to individual neurons reliably predicted the neuron’s orientation preference, but did not account for differences in orientation selectivity among neurons. These differences reflected a robust input-output nonlinearity that could not be explained by spike threshold alone, and was strongly correlated with the spatial clustering of co-tuned synaptic inputs within the dendritic field. Dendritic branches with more co-tuned synaptic clusters exhibited greater rates of local dendritic calcium events supporting a prominent role for functional clustering of synaptic inputs in dendritic nonlinearities that shape orientation selectivity. PMID:27294510

Tuning In to Sound: Frequency-Selective Attentional Filter in Human Primary Auditory Cortex

PubMed Central

Da Costa, Sandra; van der Zwaag, Wietske; Miller, Lee M.; Clarke, Stephanie

2013-01-01

Cocktail parties, busy streets, and other noisy environments pose a difficult challenge to the auditory system: how to focus attention on selected sounds while ignoring others? Neurons of primary auditory cortex, many of which are sharply tuned to sound frequency, could help solve this problem by filtering selected sound information based on frequency-content. To investigate whether this occurs, we used high-resolution fMRI at 7 tesla to map the fine-scale frequency-tuning (1.5 mm isotropic resolution) of primary auditory areas A1 and R in six human participants. Then, in a selective attention experiment, participants heard low (250 Hz)- and high (4000 Hz)-frequency streams of tones presented at the same time (dual-stream) and were instructed to focus attention onto one stream versus the other, switching back and forth every 30 s. Attention to low-frequency tones enhanced neural responses within low-frequency-tuned voxels relative to high, and when attention switched the pattern quickly reversed. Thus, like a radio, human primary auditory cortex is able to tune into attended frequency channels and can switch channels on demand. PMID:23365225

Calpeptin is neuroprotective against acrylamide-induced neuropathy in rats.

PubMed

Su, Benyu; Guan, Qiangdong; Wang, Miaomiao; Liu, Ning; Wei, Xiaomin; Wang, Shue; Yang, Xiwei; Jiang, Wenchong; Xu, Mengmeng; Yu, Sufang

2018-05-01

The aim of this study is to explore the potent neuroprotective effect of calpeptin (CP) on neuron damage induced by acrylamide (ACR) and its mechanism. Behavioural indicators such as hind limb splay, rota-rod performance, and gait analysis were assessed weekly to evaluate neurobehavioural changes after ACR and/or CP administration. The histopathological alterations and the changes of μ-calpain, m-calpain, microtubule-associated protein 2 (MAP2), and α-tubulin and β-tubulin protein levels in spinal cord were determined. Results showed that after administration of 30 mg/kg ACR, decreased body weight, attenuated neurobehavioural function, injury of motor neuron, increased protein levels of m-calpain and β-tubulin, suppressed MAP2 protein level, and no significant changes of μ-calpain and α-tubulin protein levels were observed compared with the control group rats. After administration of 200 μg/kg CP, partially restored body weight and neurobehavioural function, improvement of motor neuron injury, decreased protein levels of m- calpain and β-tubulin, and reversed effects of MAP2 protein level were observed compared with the ACR group rats. Our results suggested that CP alleviates neuropathy induced by ACR in rats. The calpain's overactivation causes the degrading of MAP2 and eventually leads to the destruction of microtubules (MTs), which may be one of the mechanisms of cytoskeletal damage induced by ACR. Copyright © 2018 Elsevier B.V. All rights reserved.

Neural representation of cost-benefit selections in rat anterior cingulate cortex in self-paced decision making.

PubMed

Wang, Shuai; Shi, Yi; Li, Bao-Ming

2017-03-01

The anterior cingulate cortex (ACC) is crucial for decision making which involves the processing of cost-benefit information. Our previous study has shown that ACC is essential for self-paced decision making. However, it is unclear how ACC neurons represent cost-benefit selections during the decision-making process. In the present study, we trained rats on the same "Do More Get More" (DMGM) task as in our previous work. In each trial, the animals stand upright and perform a sustained nosepoke of their own will to earn a water reward, with the amount of reward positively correlated to the duration of the nosepoke (i.e., longer nosepokes earn larger rewards). We then recorded ACC neuronal activity on well-trained rats while they were performing the DMGM task. Our results show that (1) approximately 3/5 ACC neurons (296/496, 59.7%) exhibited changes in firing frequency that were temporally locked with the main events of the DMGM task; (2) about 1/5 ACC neurons (101/496, 20.4%) or 1/3 of the event-modulated neurons (101/296, 34.1%) showed differential firing rate changes for different cost-benefit selections; and (3) many ACC neurons exhibited linear encoding of the cost-benefit selections in the DMGM task events. These results suggest that ACC neurons are engaged in encoding cost-benefit information, thus represent the selections in self-paced decision making. Copyright © 2016 Elsevier Inc. All rights reserved.

Suckling induced activation pattern in the brain of rat pups.

PubMed

Barna, János; Renner, Eva; Arszovszki, Antónia; Cservenák, Melinda; Kovács, Zsolt; Palkovits, Miklós; Dobolyi, Arpád

2018-06-01

The aim of the study was to understand the effects of suckling on the brain of the pups by mapping their brain activation pattern in response to suckling. The c-fos method was applied to identify activated neurons. Fasted rat pups were returned to their mothers for suckling and sacrificed 2 hours later for Fos immunohistochemistry. Double labeling was also performed to characterize some of the activated neurons. For comparison, another group of fasted pups were given dry food before Fos mapping. After suckling, we found an increase in the number of Fos-immunoreactive neurons in the insular and somatosensory cortices, central amygdaloid nucleus (CAm), paraventricular (PVN) and supraoptic hypothalamic nuclei, lateral parabrachial nucleus (LPB), nucleus of the solitary tract (NTS), and the area postrema. Double labeling experiments demonstrated the activation of calcitonin gene-related peptide-ir (CGRP-ir) neurons in the LPB, corticotropin-releasing hormone-ir (CRH-ir) but not oxytocin-ir neurons in the PVN, and noradrenergic neurons in the NTS. In the CAm, Fos-ir neurons did not contain CRH but were apposed to CGRP-ir fiber terminals. Refeeding with dry food-induced Fos activation in all brain areas activated by suckling. The degree of activation was higher following dry food consumption than suckling in the insular cortex, and lower in the supraoptic nucleus and the NTS. Furthermore, the accumbens, arcuate, and dorsomedial hypothalamic nuclei, and the lateral hypothalamic area, which were not activated by suckling, showed activation by dry food. Neurons in a number of brain areas are activated during suckling, and may participate in the signaling of satiety, taste perception, reward, food, and salt balance regulation.

SenseLab

PubMed Central

Crasto, Chiquito J.; Marenco, Luis N.; Liu, Nian; Morse, Thomas M.; Cheung, Kei-Hoi; Lai, Peter C.; Bahl, Gautam; Masiar, Peter; Lam, Hugo Y.K.; Lim, Ernest; Chen, Huajin; Nadkarni, Prakash; Migliore, Michele; Miller, Perry L.; Shepherd, Gordon M.

2009-01-01

This article presents the latest developments in neuroscience information dissemination through the SenseLab suite of databases: NeuronDB, CellPropDB, ORDB, OdorDB, OdorMapDB, ModelDB and BrainPharm. These databases include information related to: (i) neuronal membrane properties and neuronal models, and (ii) genetics, genomics, proteomics and imaging studies of the olfactory system. We describe here: the new features for each database, the evolution of SenseLab’s unifying database architecture and instances of SenseLab database interoperation with other neuroscience online resources. PMID:17510162

Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase.

PubMed

Block, M L; Wu, X; Pei, Z; Li, G; Wang, T; Qin, L; Wilson, B; Yang, J; Hong, J S; Veronesi, B

2004-10-01

The contributing role of environmental factors to the development of Parkinson's disease has become increasingly evident. We report that mesencephalic neuron-glia cultures treated with diesel exhaust particles (DEP; 0.22 microM) (5-50 microg/ml) resulted in a dose-dependent decrease in dopaminergic (DA) neurons, as determined by DA-uptake assay and tyrosine-hydroxylase immunocytochemistry (ICC). The selective toxicity of DEP for DA neurons was demonstrated by the lack of DEP effect on both GABA uptake and Neu-N immunoreactive cell number. The critical role of microglia was demonstrated by the failure of neuron-enriched cultures to exhibit DEP-induced DA neurotoxicity, where DEP-induced DA neuron death was reinstated with the addition of microglia to neuron-enriched cultures. OX-42 ICC staining of DEP treated neuron-glia cultures revealed changes in microglia morphology indicative of activation. Intracellular reactive oxygen species and superoxide were produced from enriched-microglia cultures in response to DEP. Neuron-glia cultures from NADPH oxidase deficient (PHOX-/-) mice were insensitive to DEP neurotoxicity when compared with control mice (PHOX+/+). Cytochalasin D inhibited DEP-induced superoxide production in enriched-microglia cultures, implying that DEP must be phagocytized by microglia to produce superoxide. Together, these in vitro data indicate that DEP selectively damages DA neurons through the phagocytic activation of microglial NADPH oxidase and consequent oxidative insult.

A neurotransmitter transporter encoded by the Drosophila inebriated gene

PubMed Central

Soehnge, Holly; Huang, Xi; Becker, Marie; Whitley, Penn; Conover, Diana; Stern, Michael

1996-01-01

Behavioral and electrophysiological studies on mutants defective in the Drosophila inebriated (ine) gene demonstrated increased excitability of the motor neuron. In this paper, we describe the cloning and sequence analysis of ine. Mutations in ine were localized on cloned DNA by restriction mapping and restriction fragment length polymorphism (RFLP) mapping of ine mutants. DNA from the ine region was then used to isolate an ine cDNA. In situ hybridization of ine transcripts to developing embryos revealed expression of this gene in several cell types, including the posterior hindgut, Malpighian tubules, anal plate, garland cells, and a subset of cells in the central nervous system. The ine cDNA contains an open reading frame of 658 amino acids with a high degree of sequence similarity to members of the Na+/Cl−-dependent neurotransmitter transporter family. Members of this family catalyze the rapid reuptake of neurotransmitters released into the synapse and thereby play key roles in controlling neuronal function. We conclude that ine mutations cause increased excitability of the Drosophila motor neuron by causing the defective reuptake of the substrate neurotransmitter of the ine transporter and thus overstimulation of the motor neuron by this neurotransmitter. From this observation comes a unique opportunity to perform a genetic dissection of the regulation of excitability of the Drosophila motor neuron. PMID:8917579

Spiking, Bursting, and Population Dynamics in a Network of Growth Transform Neurons.

PubMed

Gangopadhyay, Ahana; Chakrabartty, Shantanu

2018-06-01

This paper investigates the dynamical properties of a network of neurons, each of which implements an asynchronous mapping based on polynomial growth transforms. In the first part of this paper, we present a geometric approach for visualizing the dynamics of the network where each of the neurons traverses a trajectory in a dual optimization space, whereas the network itself traverses a trajectory in an equivalent primal optimization space. We show that as the network learns to solve basic classification tasks, different choices of primal-dual mapping produce unique but interpretable neural dynamics like noise shaping, spiking, and bursting. While the proposed framework is general enough, in this paper, we demonstrate its use for designing support vector machines (SVMs) that exhibit noise-shaping properties similar to those of modulators, and for designing SVMs that learn to encode information using spikes and bursts. It is demonstrated that the emergent switching, spiking, and burst dynamics produced by each neuron encodes its respective margin of separation from a classification hyperplane whose parameters are encoded by the network population dynamics. We believe that the proposed growth transform neuron model and the underlying geometric framework could serve as an important tool to connect well-established machine learning algorithms like SVMs to neuromorphic principles like spiking, bursting, population encoding, and noise shaping.

Human-Specific Histone Methylation Signatures at Transcription Start Sites in Prefrontal Neurons

PubMed Central

Cheung, Iris; Bharadwaj, Rahul; Chou, Hsin-Jung; Houston, Isaac B.; Peter, Cyril J.; Mitchell, Amanda C.; Yao, Wei-Dong; Myers, Richard H.; Chen, Jiang-fan; Preuss, Todd M.; Rogaev, Evgeny I.; Jensen, Jeffrey D.; Weng, Zhiping; Akbarian, Schahram

2012-01-01

Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility genes. Regulatory sequences at DPP10 and additional loci carried a strong footprint of hominid adaptation, including elevated nucleotide substitution rates and regulatory motifs absent in other primates (including archaic hominins), with evidence for selective pressures during more recent evolution and adaptive fixations in modern populations. Chromosome conformation capture at two neurodevelopmental disease loci, 2q14.1 and 16p11.2, revealed higher order chromatin structures resulting in physical contact of multiple human-specific H3K4me3 peaks spaced 0.5–1 Mb apart, in conjunction with a novel cis-bound antisense RNA linked to Polycomb repressor proteins and downregulated DPP10 expression. Therefore, coordinated epigenetic regulation via newly derived TSS chromatin could play an important role in the emergence of human-specific gene expression networks in brain that contribute to cognitive functions and neurological disease susceptibility in modern day humans. PMID:23185133

Sharp wave ripples during learning stabilize hippocampal spatial map

PubMed Central

Roux, Lisa; Hu, Bo; Eichler, Ronny; Stark, Eran; Buzsáki, György

2017-01-01

Cognitive representation of the environment requires a stable hippocampal map but the mechanisms maintaining map representation are unknown. Because sharp wave-ripples (SPW-R) orchestrate both retrospective and prospective spatial information, we hypothesized that disrupting neuronal activity during SPW-Rs affects spatial representation. Mice learned daily a new set of three goal locations on a multi-well maze. We used closed-loop SPW-R detection at goal locations to trigger optogenetic silencing of a subset of CA1 pyramidal neurons. Control place cells (non-silenced or silenced outside SPW-Rs) largely maintained the location of their place fields after learning and showed increased spatial information content. In contrast, the place fields of SPW-R-silenced place cells remapped, and their spatial information remained unaltered. SPW-R silencing did not impact the firing rates or the proportions of place cells. These results suggest that interference with SPW-R-associated activity during learning prevents the stabilization and refinement of the hippocampal map. PMID:28394323

Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility

PubMed Central

Murray, Andrew J.; Woloszynowska-Fraser, Marta U.; Ansel-Bollepalli, Laura; Cole, Katy L. H.; Foggetti, Angelica; Crouch, Barry; Riedel, Gernot; Wulff, Peer

2015-01-01

Dysfunction of parvalbumin (PV)-positive GABAergic interneurons (PVIs) within the prefrontal cortex (PFC) has been implicated in schizophrenia pathology. It is however unclear, how impaired signaling of these neurons may contribute to PFC dysfunction. To identify how PVIs contribute to PFC-dependent behaviors we inactivated PVIs in the PFC in mice using region- and cell-type-selective expression of tetanus toxin light chain (TeLC) and compared the functional consequences of this manipulation with non-cell-type-selective perturbations of the same circuitry. By sampling for behavioral alterations that map onto distinct symptom categories in schizophrenia, we show that dysfunction of PVI signaling in the PFC specifically produces deficits in the cognitive domain, but does not give rise to PFC-dependent correlates of negative or positive symptoms. Our results suggest that distinct aspects of the complex symptomatology of PFC dysfunction in schizophrenia can be attributed to specific prefrontal circuit elements. PMID:26608841

Neural networks for vertical microcode compaction

NASA Astrophysics Data System (ADS)

Chu, Pong P.

1992-09-01

Neural networks provide an alternative way to solve complex optimization problems. Instead of performing a program of instructions sequentially as in a traditional computer, neural network model explores many competing hypotheses simultaneously using its massively parallel net. The paper shows how to use the neural network approach to perform vertical micro-code compaction for a micro-programmed control unit. The compaction procedure includes two basic steps. The first step determines the compatibility classes and the second step selects a minimal subset to cover the control signals. Since the selection process is an NP- complete problem, to find an optimal solution is impractical. In this study, we employ a customized neural network to obtain the minimal subset. We first formalize this problem, and then define an `energy function' and map it to a two-layer fully connected neural network. The modified network has two types of neurons and can always obtain a valid solution.

Effect of Interocular Delay on Disparity-Selective V1 Neurons: Relationship to Stereoacuity and the Pulfrich Effect

PubMed Central

Read, Jenny C. A.; Cumming, Bruce G.

2006-01-01

The temporal properties of disparity-sensitive neurons place important temporal constraints on stereo matching. We examined these constraints by measuring the responses of disparity-selective neurons in striate cortex of awake behaving monkeys to random-dot stereograms that contained interocular delays. Disparity selectivity was gradually abolished by increasing interocular delay (when the delay exceeds the integration time, the inputs from the 2 eyes become uncorrelated). The amplitude of the disparity-selective response was a Gaussian function of interocular delay, with a mean of 16 ms (±5 ms, SD). Psychophysical measures of stereoacuity, in both monkey and human observers, showed a closely similar dependency on time, suggesting that temporal integration in V1 neurons is what determines psychophysical matching constraints over time. There was a slight but consistent asymmetry in the neuronal responses, as if the optimum stimulus is one in which the right stimulus leads by about 4 ms. Because all recordings were made in the left hemisphere, this probably reflects nasotemporal differences in conduction times; psychophysical data are compatible with this interpretation. In only a few neurons (5/72), interocular delay caused a change in the preferred disparity. Such tilted disparity/delay profiles have been invoked previously to explain depth perception in the stroboscopic version of the Pulfrich effect (and other variants). However, the great majority of the neurons did not show tilted disparity/delay profiles. This suggests that either the activity of these neurons is ignored when viewing Pulfrich stimuli, or that current theories relating neuronal properties to perception in the Pulfrich effect need to be reevaluated. PMID:15788521

[Long-term memory, neurogenesis and novelty signal].

PubMed

Sokolova, E N; Nezlina, N I

2003-01-01

In accordance with the advanced hypothesis the long-term memory is a collection of "gnostic units" selectively tuned to experienced events. The long-term memory is continuously supplemented by new neurons differentiated from stem cells during neurogenesis (particularly, in adults). The transformation of neuronal progenitors into event-selective gnostic units is accomplished with participation of hippocampal "novelty neurons" emphasizing information inputs to be stored in the long-term memory. The formation of the gnostic units is preceded by informational processes occurring in the ventral ("what?") and dorsal ("where?") systems. The formation of a new gnostic unit selectively tuned to a particular event is a result of combination of feature-detector excitation and novelty signal generated by hippocampal novelty neurons.

Neuropeptide Mapping of Dimmed Cells of Adult Drosophila Brain

NASA Astrophysics Data System (ADS)

Diesner, Max; Predel, Reinhard; Neupert, Susanne

2018-05-01

Neuropeptides are structurally highly diverse messenger molecules that act as regulators of many physiological processes such as development, metabolism, reproduction or behavior in general. Differentiation of neuropeptidergic cells often corresponds with the presence of the transcription factor DIMMED. In the central nervous system of the fruit fly Drosophila melanogaster, DIMMED commonly occurs in neuroendocrine neurons that release peptides as neurohormones but also in interneurons with complex branching patterns. Fly strains with green fluorescence protein (GFP)-expressing dimmed cells make it possible to systematically analyze the processed neuropeptides in these cells. In this study, we mapped individual GFP-expressing neurons of adult D. melanogaster from the dimmed ( c929)>GFP line. Using single cell mass spectrometry, we analyzed 10 types of dimmed neurons from the brain/gnathal ganglion. These cells included neuroendocrine cells with projection into the retrocerebral complex but also a number of large interneurons. Resulting mass spectra not only provided comprehensive data regarding mature products from 13 neuropeptide precursors but also evidence for the cellular co-localization of neuropeptides from different neuropeptide genes. The results can be implemented in a neuroanatomical map of the D. melanogaster brain. [Figure not available: see fulltext.

Neuropeptide Mapping of Dimmed Cells of Adult Drosophila Brain

NASA Astrophysics Data System (ADS)

Diesner, Max; Predel, Reinhard; Neupert, Susanne

2018-01-01

Neuropeptides are structurally highly diverse messenger molecules that act as regulators of many physiological processes such as development, metabolism, reproduction or behavior in general. Differentiation of neuropeptidergic cells often corresponds with the presence of the transcription factor DIMMED. In the central nervous system of the fruit fly Drosophila melanogaster, DIMMED commonly occurs in neuroendocrine neurons that release peptides as neurohormones but also in interneurons with complex branching patterns. Fly strains with green fluorescence protein (GFP)-expressing dimmed cells make it possible to systematically analyze the processed neuropeptides in these cells. In this study, we mapped individual GFP-expressing neurons of adult D. melanogaster from the dimmed (c929)>GFP line. Using single cell mass spectrometry, we analyzed 10 types of dimmed neurons from the brain/gnathal ganglion. These cells included neuroendocrine cells with projection into the retrocerebral complex but also a number of large interneurons. Resulting mass spectra not only provided comprehensive data regarding mature products from 13 neuropeptide precursors but also evidence for the cellular co-localization of neuropeptides from different neuropeptide genes. The results can be implemented in a neuroanatomical map of the D. melanogaster brain. [Figure not available: see fulltext.

Topographical maps as complex networks

NASA Astrophysics Data System (ADS)

da Fontoura Costa, Luciano; Diambra, Luis

2005-02-01

The neuronal networks in the mammalian cortex are characterized by the coexistence of hierarchy, modularity, short and long range interactions, spatial correlations, and topographical connections. Particularly interesting, the latter type of organization implies special demands on developing systems in order to achieve precise maps preserving spatial adjacencies, even at the expense of isometry. Although the object of intensive biological research, the elucidation of the main anatomic-functional purposes of the ubiquitous topographical connections in the mammalian brain remains an elusive issue. The present work reports on how recent results from complex network formalism can be used to quantify and model the effect of topographical connections between neuronal cells over the connectivity of the network. While the topographical mapping between two cortical modules is achieved by connecting nearest cells from each module, four kinds of network models are adopted for implementing intramodular connections, including random, preferential-attachment, short-range, and long-range networks. It is shown that, though spatially uniform and simple, topographical connections between modules can lead to major changes in the network properties in some specific cases, depending on intramodular connections schemes, fostering more effective intercommunication between the involved neuronal cells and modules. The possible implications of such effects on cortical operation are discussed.

Neuropeptide Mapping of Dimmed Cells of Adult Drosophila Brain.

PubMed

Diesner, Max; Predel, Reinhard; Neupert, Susanne

2018-05-01

Neuropeptides are structurally highly diverse messenger molecules that act as regulators of many physiological processes such as development, metabolism, reproduction or behavior in general. Differentiation of neuropeptidergic cells often corresponds with the presence of the transcription factor DIMMED. In the central nervous system of the fruit fly Drosophila melanogaster, DIMMED commonly occurs in neuroendocrine neurons that release peptides as neurohormones but also in interneurons with complex branching patterns. Fly strains with green fluorescence protein (GFP)-expressing dimmed cells make it possible to systematically analyze the processed neuropeptides in these cells. In this study, we mapped individual GFP-expressing neurons of adult D. melanogaster from the dimmed (c929)>GFP line. Using single cell mass spectrometry, we analyzed 10 types of dimmed neurons from the brain/gnathal ganglion. These cells included neuroendocrine cells with projection into the retrocerebral complex but also a number of large interneurons. Resulting mass spectra not only provided comprehensive data regarding mature products from 13 neuropeptide precursors but also evidence for the cellular co-localization of neuropeptides from different neuropeptide genes. The results can be implemented in a neuroanatomical map of the D. melanogaster brain. Graphical Abstract ᅟ.

Selective Modulation of K+ Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons.

PubMed

Zhao, Chen; Su, Min; Wang, Yingzi; Li, Xinmeng; Zhang, Yongxue; Du, Xiaona; Zhang, Hailin

2017-01-01

The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K + channel modulators.

Selective Modulation of K+ Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons

PubMed Central

Zhao, Chen; Su, Min; Wang, Yingzi; Li, Xinmeng; Zhang, Yongxue; Du, Xiaona; Zhang, Hailin

2017-01-01

The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K+ channel modulators. PMID:29311835

Presynaptic Partners of Dorsal Raphe Serotonergic and GABAergic Neurons

PubMed Central

Weissbourd, Brandon; Ren, Jing; DeLoach, Katherine E.; Guenthner, Casey J.; Miyamichi, Kazunari; Luo, Liqun

2016-01-01

SUMMARY The serotonin system powerfully modulates physiology and behavior in health and disease, yet the circuit mechanisms underlying serotonin neuron activity are poorly understood. The major source of forebrain serotonergic innervation is from the dorsal raphe nucleus (DR), which contains both serotonin and GABA neurons. Using viral tracing combined with electrophysiology, we found that GABA and serotonin neurons in the DR receive excitatory, inhibitory, and peptidergic inputs from the same specific brain regions. Embedded in this overall similarity are important differences. Serotonin neurons are more likely to receive synaptic inputs from anterior neocortex while GABA neurons receive disproportionally higher input from the central amygdala. Local input mapping revealed extensive serotonin-serotonin as well as GABA-serotonin connectivity with a distinct spatial organization. Covariance analysis suggests heterogeneity of both serotonin and GABA neurons with respect to the inputs they receive. These analyses provide a foundation for further functional dissection of the serotonin system. PMID:25102560

Mapping sensory circuits by anterograde trans-synaptic transfer of recombinant rabies virus

PubMed Central

Zampieri, Niccolò; Jessell, Thomas M.; Murray, Andrew J.

2014-01-01

Summary Primary sensory neurons convey information from the external world to relay circuits within the central nervous system (CNS), but the identity and organization of the neurons that process incoming sensory information remains sketchy. Within the CNS viral tracing techniques that rely on retrograde trans-synaptic transfer provide a powerful tool for delineating circuit organization. Viral tracing of the circuits engaged by primary sensory neurons has, however, been hampered by the absence of a genetically tractable anterograde transfer system. In this study we demonstrate that rabies virus can infect sensory neurons in the somatosensory system, is subject to anterograde trans-synaptic transfer from primary sensory to spinal target neurons, and can delineate output connectivity with third-order neurons. Anterograde trans-synaptic transfer is a feature shared by other classes of primary sensory neurons, permitting the identification and potentially the manipulation of neural circuits processing sensory feedback within the mammalian CNS. PMID:24486087

Cortical processing of dynamic sound envelope transitions.

PubMed

Zhou, Yi; Wang, Xiaoqin

2010-12-08

Slow envelope fluctuations in the range of 2-20 Hz provide important segmental cues for processing communication sounds. For a successful segmentation, a neural processor must capture envelope features associated with the rise and fall of signal energy, a process that is often challenged by the interference of background noise. This study investigated the neural representations of slowly varying envelopes in quiet and in background noise in the primary auditory cortex (A1) of awake marmoset monkeys. We characterized envelope features based on the local average and rate of change of sound level in envelope waveforms and identified envelope features to which neurons were selective by reverse correlation. Our results showed that envelope feature selectivity of A1 neurons was correlated with the degree of nonmonotonicity in their static rate-level functions. Nonmonotonic neurons exhibited greater feature selectivity than monotonic neurons in quiet and in background noise. The diverse envelope feature selectivity decreased spike-timing correlation among A1 neurons in response to the same envelope waveforms. As a result, the variability, but not the average, of the ensemble responses of A1 neurons represented more faithfully the dynamic transitions in low-frequency sound envelopes both in quiet and in background noise.

Linearly Additive Shape and Color Signals in Monkey Inferotemporal Cortex

PubMed Central

McMahon, David B. T.; Olson, Carl R.

2009-01-01

How does the brain represent a red circle? One possibility is that there is a specialized and possibly time-consuming process whereby the attributes of shape and color, carried by separate populations of neurons in low-order visual cortex, are bound together into a unitary neural representation. Another possibility is that neurons in high-order visual cortex are selective, by virtue of their bottom-up input from low-order visual areas, for particular conjunctions of shape and color. A third possibility is that they simply sum shape and color signals linearly. We tested these ideas by measuring the responses of inferotemporal cortex neurons to sets of stimuli in which two attributes—shape and color—varied independently. We find that a few neurons exhibit conjunction selectivity but that in most neurons the influences of shape and color sum linearly. Contrary to the idea of conjunction coding, few neurons respond selectively to a particular combination of shape and color. Contrary to the idea that binding requires time, conjunction signals, when present, occur as early as feature signals. We argue that neither conjunction selectivity nor a specialized feature binding process is necessary for the effective representation of shape–color combinations. PMID:19144745

Linearly additive shape and color signals in monkey inferotemporal cortex.

PubMed

McMahon, David B T; Olson, Carl R

2009-04-01

How does the brain represent a red circle? One possibility is that there is a specialized and possibly time-consuming process whereby the attributes of shape and color, carried by separate populations of neurons in low-order visual cortex, are bound together into a unitary neural representation. Another possibility is that neurons in high-order visual cortex are selective, by virtue of their bottom-up input from low-order visual areas, for particular conjunctions of shape and color. A third possibility is that they simply sum shape and color signals linearly. We tested these ideas by measuring the responses of inferotemporal cortex neurons to sets of stimuli in which two attributes-shape and color-varied independently. We find that a few neurons exhibit conjunction selectivity but that in most neurons the influences of shape and color sum linearly. Contrary to the idea of conjunction coding, few neurons respond selectively to a particular combination of shape and color. Contrary to the idea that binding requires time, conjunction signals, when present, occur as early as feature signals. We argue that neither conjunction selectivity nor a specialized feature binding process is necessary for the effective representation of shape-color combinations.

Rapid acquisition of novel interface control by small ensembles of arbitrarily selected primary motor cortex neurons

PubMed Central

Law, Andrew J.; Rivlis, Gil

2014-01-01

Pioneering studies demonstrated that novel degrees of freedom could be controlled individually by directly encoding the firing rate of single motor cortex neurons, without regard to each neuron's role in controlling movement of the native limb. In contrast, recent brain-computer interface work has emphasized decoding outputs from large ensembles that include substantially more neurons than the number of degrees of freedom being controlled. To bridge the gap between direct encoding by single neurons and decoding output from large ensembles, we studied monkeys controlling one degree of freedom by comodulating up to four arbitrarily selected motor cortex neurons. Performance typically exceeded random quite early in single sessions and then continued to improve to different degrees in different sessions. We therefore examined factors that might affect performance. Performance improved with larger ensembles. In contrast, other factors that might have reflected preexisting synaptic architecture—such as the similarity of preferred directions—had little if any effect on performance. Patterns of comodulation among ensemble neurons became more consistent across trials as performance improved over single sessions. Compared with the ensemble neurons, other simultaneously recorded neurons showed less modulation. Patterns of voluntarily comodulated firing among small numbers of arbitrarily selected primary motor cortex (M1) neurons thus can be found and improved rapidly, with little constraint based on the normal relationships of the individual neurons to native limb movement. This rapid flexibility in relationships among M1 neurons may in part underlie our ability to learn new movements and improve motor skill. PMID:24920030

Spatially Distributed Dendritic Resonance Selectively Filters Synaptic Input

PubMed Central

Segev, Idan; Shamma, Shihab

2014-01-01

An important task performed by a neuron is the selection of relevant inputs from among thousands of synapses impinging on the dendritic tree. Synaptic plasticity enables this by strenghtening a subset of synapses that are, presumably, functionally relevant to the neuron. A different selection mechanism exploits the resonance of the dendritic membranes to preferentially filter synaptic inputs based on their temporal rates. A widely held view is that a neuron has one resonant frequency and thus can pass through one rate. Here we demonstrate through mathematical analyses and numerical simulations that dendritic resonance is inevitably a spatially distributed property; and therefore the resonance frequency varies along the dendrites, and thus endows neurons with a powerful spatiotemporal selection mechanism that is sensitive both to the dendritic location and the temporal structure of the incoming synaptic inputs. PMID:25144440

Optodynamic simulation of β-adrenergic receptor signalling

PubMed Central

Siuda, Edward R.; McCall, Jordan G.; Al-Hasani, Ream; Shin, Gunchul; Il Park, Sung; Schmidt, Martin J.; Anderson, Sonya L.; Planer, William J.; Rogers, John A.; Bruchas, Michael R.

2015-01-01

Optogenetics has provided a revolutionary approach to dissecting biological phenomena. However, the generation and use of optically active GPCRs in these contexts is limited and it is unclear how well an opsin-chimera GPCR might mimic endogenous receptor activity. Here we show that a chimeric rhodopsin/β2 adrenergic receptor (opto-β2AR) is similar in dynamics to endogenous β2AR in terms of: cAMP generation, MAP kinase activation and receptor internalization. In addition, we develop and characterize a novel toolset of optically active, functionally selective GPCRs that can bias intracellular signalling cascades towards either G-protein or arrestin-mediated cAMP and MAP kinase pathways. Finally, we show how photoactivation of opto-β2AR in vivo modulates neuronal activity and induces anxiety-like behavioural states in both fiber-tethered and wireless, freely moving animals when expressed in brain regions known to contain β2ARs. These new GPCR approaches enhance the utility of optogenetics and allow for discrete spatiotemporal control of GPCR signalling in vitro and in vivo. PMID:26412387

Optodynamic simulation of β-adrenergic receptor signalling.

PubMed

Siuda, Edward R; McCall, Jordan G; Al-Hasani, Ream; Shin, Gunchul; Il Park, Sung; Schmidt, Martin J; Anderson, Sonya L; Planer, William J; Rogers, John A; Bruchas, Michael R

2015-09-28

Optogenetics has provided a revolutionary approach to dissecting biological phenomena. However, the generation and use of optically active GPCRs in these contexts is limited and it is unclear how well an opsin-chimera GPCR might mimic endogenous receptor activity. Here we show that a chimeric rhodopsin/β2 adrenergic receptor (opto-β2AR) is similar in dynamics to endogenous β2AR in terms of: cAMP generation, MAP kinase activation and receptor internalization. In addition, we develop and characterize a novel toolset of optically active, functionally selective GPCRs that can bias intracellular signalling cascades towards either G-protein or arrestin-mediated cAMP and MAP kinase pathways. Finally, we show how photoactivation of opto-β2AR in vivo modulates neuronal activity and induces anxiety-like behavioural states in both fiber-tethered and wireless, freely moving animals when expressed in brain regions known to contain β2ARs. These new GPCR approaches enhance the utility of optogenetics and allow for discrete spatiotemporal control of GPCR signalling in vitro and in vivo.

Local-learning-based neuron selection for grasping gesture prediction in motor brain machine interfaces

NASA Astrophysics Data System (ADS)

Xu, Kai; Wang, Yiwen; Wang, Yueming; Wang, Fang; Hao, Yaoyao; Zhang, Shaomin; Zhang, Qiaosheng; Chen, Weidong; Zheng, Xiaoxiang

2013-04-01

Objective. The high-dimensional neural recordings bring computational challenges to movement decoding in motor brain machine interfaces (mBMI), especially for portable applications. However, not all recorded neural activities relate to the execution of a certain movement task. This paper proposes to use a local-learning-based method to perform neuron selection for the gesture prediction in a reaching and grasping task. Approach. Nonlinear neural activities are decomposed into a set of linear ones in a weighted feature space. A margin is defined to measure the distance between inter-class and intra-class neural patterns. The weights, reflecting the importance of neurons, are obtained by minimizing a margin-based exponential error function. To find the most dominant neurons in the task, 1-norm regularization is introduced to the objective function for sparse weights, where near-zero weights indicate irrelevant neurons. Main results. The signals of only 10 neurons out of 70 selected by the proposed method could achieve over 95% of the full recording's decoding accuracy of gesture predictions, no matter which different decoding methods are used (support vector machine and K-nearest neighbor). The temporal activities of the selected neurons show visually distinguishable patterns associated with various hand states. Compared with other algorithms, the proposed method can better eliminate the irrelevant neurons with near-zero weights and provides the important neuron subset with the best decoding performance in statistics. The weights of important neurons converge usually within 10-20 iterations. In addition, we study the temporal and spatial variation of neuron importance along a period of one and a half months in the same task. A high decoding performance can be maintained by updating the neuron subset. Significance. The proposed algorithm effectively ascertains the neuronal importance without assuming any coding model and provides a high performance with different decoding models. It shows better robustness of identifying the important neurons with noisy signals presented. The low demand of computational resources which, reflected by the fast convergence, indicates the feasibility of the method applied in portable BMI systems. The ascertainment of the important neurons helps to inspect neural patterns visually associated with the movement task. The elimination of irrelevant neurons greatly reduces the computational burden of mBMI systems and maintains the performance with better robustness.

Exploiting the gain-modulation mechanism in parieto-motor neurons: application to visuomotor transformations and embodied simulation.

PubMed

Mahé, Sylvain; Braud, Raphaël; Gaussier, Philippe; Quoy, Mathias; Pitti, Alexandre

2015-02-01

The so-called self-other correspondence problem in imitation demands to find the transformation that maps the motor dynamics of one partner to our own. This requires a general purpose sensorimotor mechanism that transforms an external fixation-point (partner's shoulder) reference frame to one's own body-centered reference frame. We propose that the mechanism of gain-modulation observed in parietal neurons may generally serve these types of transformations by binding the sensory signals across the modalities with radial basis functions (tensor products) on the one hand and by permitting the learning of contextual reference frames on the other hand. In a shoulder-elbow robotic experiment, gain-field neurons (GF) intertwine the visuo-motor variables so that their amplitude depends on them all. In situations of modification of the body-centered reference frame, the error detected in the visuo-motor mapping can serve then to learn the transformation between the robot's current sensorimotor space and the new one. These situations occur for instance when we turn the head on its axis (visual transformation), when we use a tool (body modification), or when we interact with a partner (embodied simulation). Our results defend the idea that the biologically-inspired mechanism of gain modulation found in parietal neurons can serve as a basic structure for achieving nonlinear mapping in spatial tasks as well as in cooperative and social functions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional Maps of Neocortical Local Circuitry

PubMed Central

Thomson, Alex M.; Lamy, Christophe

2007-01-01

This review aims to summarize data obtained with different techniques to provide a functional map of the local circuit connections made by neocortical neurones, a reference for those interested in cortical circuitry and the numerical information required by those wishing to model the circuit. A brief description of the main techniques used to study circuitry is followed by outline descriptions of the major classes of neocortical excitatory and inhibitory neurones and the connections that each layer makes with other cortical and subcortical regions. Maps summarizing the projection patterns of each class of neurone within the local circuit and tables of the properties of these local circuit connections are provided. This review relies primarily on anatomical studies that have identified the classes of neurones and their local and long distance connections and on paired intracellular and whole-cell recordings which have documented the properties of the connections between them. A large number of different types of synaptic connections have been described, but for some there are only a few published examples and for others the details that can only be obtained with paired recordings and dye-filling are lacking. A further complication is provided by the range of species, technical approaches and age groups used in these studies. Wherever possible the range of available data are summarised and compared. To fill some of the more obvious gaps for the less well-documented cases, data obtained with other methods are also summarized. PMID:18982117

Unbalanced neuronal circuits in addiction.

PubMed

Volkow, Nora D; Wang, Gen-Jack; Tomasi, Dardo; Baler, Ruben D

2013-08-01

Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it. Published by Elsevier Ltd.

Knowledge Representation and Data Mining of Neuronal Morphologies Using Neuroinformatics Tools and Formal Ontologies

ERIC Educational Resources Information Center

Polavaram, Sridevi

2016-01-01

Neuroscience can greatly benefit from using novel methods in computer science and informatics, which enable knowledge discovery in unexpected ways. Currently one of the biggest challenges in Neuroscience is to map the functional circuitry of the brain. The applications of this goal range from understanding structural reorganization of neurons to…

Double-Labeled Metabolic Maps of Memory.

ERIC Educational Resources Information Center

John, E. R.; And Others

1986-01-01

Reviews a study which sought to obtain a quantitative metabolic map of the neurons mediating a specific memory. Research results support notions of cooperative processes in which nonrandom behavior of high ensembles of neural elements mediates the integration and processing of information and the retrieval of memory. (ML)

Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system

PubMed Central

Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

2016-01-01

The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila. DOI: http://dx.doi.org/10.7554/eLife.13715.001 PMID:26987017

Homeostatic circuits selectively gate food cue responses in insular cortex

PubMed Central

Livneh, Yoav; Ramesh, Rohan n.; Burgess, christian R.; Levandowski, Kirsten M.; Madara, Joseph c.; Fenselau, henning; Goldey, Glenn J.; Diaz, Veronica E.; Jikomes, nick; Resch, Jon M.; Lowell, Bradford B.; Andermann, Mark L.

2017-01-01

Physiological needs bias perception and attention to relevant sensory cues. This process is ‘hijacked’ by drug addiction, causing cue-induced cravings and relapse. Similarly, its dysregulation contributes to failed diets, obesity, and eating disorders. Neuroimaging studies in humans have implicated insular cortex in these phenomena. However, it remains unclear how ‘cognitive’ cortical representations of motivationally relevant cues are biased by subcortical circuits that drive specific motivational states. Here we develop a microprism-based cellular imaging approach to monitor visual cue responses in the insular cortex of behaving mice across hunger states. Insular cortex neurons demonstrate food- cue-biased responses that are abolished during satiety. Unexpectedly, while multiple satiety-related visceral signals converge in insular cortex, chemogenetic activation of hypothalamic ‘hunger neurons’ (expressing agouti-related peptide (AgRP)) bypasses these signals to restore hunger-like response patterns in insular cortex. Circuit mapping and pathway-specific manipulations uncover a pathway from AgRP neurons to insular cortex via the paraventricular thalamus and basolateral amygdala. These results reveal a neural basis for state-specific biased processing of motivationally relevant cues. PMID:28614299

Neural Processing of Target Distance by Echolocating Bats: Functional Roles of the Auditory Midbrain

PubMed Central

Wenstrup, Jeffrey J.; Portfors, Christine V.

2011-01-01

Using their biological sonar, bats estimate distance to avoid obstacles and capture moving prey. The primary distance cue is the delay between the bat's emitted echolocation pulse and the return of an echo. The mustached bat's auditory midbrain (inferior colliculus, IC) is crucial to the analysis of pulse-echo delay. IC neurons are selective for certain delays between frequency modulated (FM) elements of the pulse and echo. One role of the IC is to create these “delay-tuned”, “FM-FM” response properties through a series of spectro-temporal integrative interactions. A second major role of the midbrain is to project target distance information to many parts of the brain. Pathways through auditory thalamus undergo radical reorganization to create highly ordered maps of pulse-echo delay in auditory cortex, likely contributing to perceptual features of target distance analysis. FM-FM neurons in IC also project strongly to pre-motor centers including the pretectum and the pontine nuclei. These pathways may contribute to rapid adjustments in flight, body position, and sonar vocalizations that occur as a bat closes in on a target. PMID:21238485

A genome-wide scan for signatures of directional selection in domesticated pigs.

PubMed

Moon, Sunjin; Kim, Tae-Hun; Lee, Kyung-Tai; Kwak, Woori; Lee, Taeheon; Lee, Si-Woo; Kim, Myung-Jick; Cho, Kyuho; Kim, Namshin; Chung, Won-Hyong; Sung, Samsun; Park, Taesung; Cho, Seoae; Groenen, Martien Am; Nielsen, Rasmus; Kim, Yuseob; Kim, Heebal

2015-02-25

Animal domestication involved drastic phenotypic changes driven by strong artificial selection and also resulted in new populations of breeds, established by humans. This study aims to identify genes that show evidence of recent artificial selection during pig domestication. Whole-genome resequencing of 30 individual pigs from domesticated breeds, Landrace and Yorkshire, and 10 Asian wild boars at ~16-fold coverage was performed resulting in over 4.3 million SNPs for 19,990 genes. We constructed a comprehensive genome map of directional selection by detecting selective sweeps using an F ST-based approach that detects directional selection in lineages leading to the domesticated breeds and using a haplotype-based test that detects ongoing selective sweeps within the breeds. We show that candidate genes under selection are significantly enriched for loci implicated in quantitative traits important to pig reproduction and production. The candidate gene with the strongest signals of directional selection belongs to group III of the metabolomics glutamate receptors, known to affect brain functions associated with eating behavior, suggesting that loci under strong selection include loci involved in behaviorial traits in domesticated pigs including tameness. We show that a significant proportion of selection signatures coincide with loci that were previously inferred to affect phenotypic variation in pigs. We further identify functional enrichment related to behavior, such as signal transduction and neuronal activities, for those targets of selection during domestication in pigs.

The effect of face inversion for neurons inside and outside fMRI-defined face-selective cortical regions

PubMed Central

Van Belle, Goedele; Vanduffel, Wim; Rossion, Bruno; Vogels, Rufin

2014-01-01

It is widely believed that face processing in the primate brain occurs in a network of category-selective cortical regions. Combined functional MRI (fMRI)-single-cell recording studies in macaques have identified high concentrations of neurons that respond more to faces than objects within face-selective patches. However, cells with a preference for faces over objects are also found scattered throughout inferior temporal (IT) cortex, raising the question whether face-selective cells inside and outside of the face patches differ functionally. Here, we compare the properties of face-selective cells inside and outside of face-selective patches in the IT cortex by means of an image manipulation that reliably disrupts behavior toward face processing: inversion. We recorded IT neurons from two fMRI-defined face-patches (ML and AL) and a region outside of the face patches (herein labeled OUT) during upright and inverted face stimulation. Overall, turning faces upside down reduced the firing rate of face-selective cells. However, there were differences among the recording regions. First, the reduced neuronal response for inverted faces was independent of stimulus position, relative to fixation, in the face-selective patches (ML and AL) only. Additionally, the effect of inversion for face-selective cells in ML, but not those in AL or OUT, was impervious to whether the neurons were initially searched for using upright or inverted stimuli. Collectively, these results show that face-selective cells differ in their functional characteristics depending on their anatomicofunctional location, suggesting that upright faces are preferably coded by face-selective cells inside but not outside of the fMRI-defined face-selective regions of the posterior IT cortex. PMID:25520434

The effects of visual stimulation and selective visual attention on rhythmic neuronal synchronization in macaque area V4.

PubMed

Fries, Pascal; Womelsdorf, Thilo; Oostenveld, Robert; Desimone, Robert

2008-04-30

Selective attention lends relevant sensory input priority access to higher-level brain areas and ultimately to behavior. Recent studies have suggested that those neurons in visual areas that are activated by an attended stimulus engage in enhanced gamma-band (30-70 Hz) synchronization compared with neurons activated by a distracter. Such precise synchronization could enhance the postsynaptic impact of cells carrying behaviorally relevant information. Previous studies have used the local field potential (LFP) power spectrum or spike-LFP coherence (SFC) to indirectly estimate spike synchronization. Here, we directly demonstrate zero-phase gamma-band coherence among spike trains of V4 neurons. This synchronization was particularly evident during visual stimulation and enhanced by selective attention, thus confirming the pattern inferred from LFP power and SFC. We therefore investigated the time course of LFP gamma-band power and found rapid dynamics consistent with interactions of top-down spatial and feature attention with bottom-up saliency. In addition to the modulation of synchronization during visual stimulation, selective attention significantly changed the prestimulus pattern of synchronization. Attention inside the receptive field of the recorded neuronal population enhanced gamma-band synchronization and strongly reduced alpha-band (9-11 Hz) synchronization in the prestimulus period. These results lend further support for a functional role of rhythmic neuronal synchronization in attentional stimulus selection.

Choline metabolism as a basis for the selective vulnerability of cholinergic neurons

NASA Technical Reports Server (NTRS)

Wurtman, R. J.

1992-01-01

The unique propensity of cholinergic neurons to use choline for two purposes--ACh and membrane phosphatidylcholine synthesis--may contribute to their selective vulnerability in Alzheimer's disease and other cholinergic neurodegenerative disorders. When physiologically active, the neurons use free choline taken from the 'reservoir' in membrane phosphatidylcholine to synthesize ACh; this can lead to an actual decrease in the quantity of membrane per cell. Alzheimer's disease (but not Down's syndrome, or other neurodegenerative disorders) is associated with characteristic neurochemical lesions involving choline and ethanolamine: brain levels of these compounds are diminished, while those of glycerophosphocholine and glycerophosphoethanolamine (breakdown products of their respective membrane phosphatides) are increased, both in cholinergic and noncholinergic brain regions. Perhaps this metabolic disturbance and the tendency of cholinergic neurons to 'export' choline--in the form of ACh--underlie the selective vulnerability of the neurons. Resulting changes in membrane composition could abnormally expose intramembraneous proteins such as amyloid precursor protein to proteases.

Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

PubMed

Okaty, Benjamin W; Freret, Morgan E; Rood, Benjamin D; Brust, Rachael D; Hennessy, Morgan L; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N; Dymecki, Susan M

2015-11-18

Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. Copyright © 2015 Elsevier Inc. All rights reserved.

Tangential migration of corridor guidepost neurons contributes to anxiety circuits.

PubMed

Tinterri, Andrea; Deck, Marie; Keita, Maryama; Mailhes, Caroline; Rubin, Anna Noren; Kessaris, Nicoletta; Lokmane, Ludmilla; Bielle, Franck; Garel, Sonia

2018-02-15

In mammals, thalamic axons are guided internally toward their neocortical target by corridor (Co) neurons that act as axonal guideposts. The existence of Co-like neurons in non-mammalian species, in which thalamic axons do not grow internally, raised the possibility that Co cells might have an ancestral role. Here, we investigated the contribution of corridor (Co) cells to mature brain circuits using a combination of genetic fate-mapping and assays in mice. We unexpectedly found that Co neurons contribute to striatal-like projection neurons in the central extended amygdala. In particular, Co-like neurons participate in specific nuclei of the bed nucleus of the stria terminalis, which plays essential roles in anxiety circuits. Our study shows that Co neurons possess an evolutionary conserved role in anxiety circuits independently from an acquired guidepost function. It furthermore highlights that neurons can have multiple sequential functions during brain wiring and supports a general role of tangential migration in the building of subpallial circuits. © 2017 Wiley Periodicals, Inc.

Cell-type specific circuit connectivity of hippocampal CA1 revealed through Cre-dependent rabies tracing

PubMed Central

Sun, Yanjun; Nguyen, Amanda; Nguyen, Joseph; Le, Luc; Saur, Dieter; Choi, Jiwon; Callaway, Edward M.; Xu, Xiangmin

2014-01-01

Summary We applied a new Cre-dependent, genetically modified rabies-based tracing system to map direct synaptic connections to CA1 excitatory and inhibitory neuron types in mouse hippocampus. We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, entorhinal cortex and the medial septum (MS), and unexpectedly also from the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons while inhibitory CA1 neurons receive a great majority of input from GABAergic MS neurons; both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 PV+ interneurons versus SOM+ interneurons showed similar strengths of input from the subiculum, but PV+ interneurons receive much stronger input than SOM+ neurons from CA3, entorhinal cortex and MS. Differential input from CA3 to specific CA1 cell types was also demonstrated functionally using laser scanning photostimulation and whole cell recordings. PMID:24656815

Multi-Scale Molecular Deconstruction of the Serotonin Neuron System

PubMed Central

Okaty, Benjamin W.; Freret, Morgan E.; Rood, Benjamin D.; Brust, Rachael D.; Hennessy, Morgan L.; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N.; Dymecki, Susan M.

2016-01-01

Summary Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-Seq to deconstruct the mouse 5HT system at multiple levels of granularity—from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal: principles underlying system organization, novel 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers new subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. PMID:26549332

Central Projections of Gustatory Receptor Neurons in the Medial and the Lateral Sensilla Styloconica of Helicoverpa armigera Larvae

PubMed Central

Tang, Qing-Bo; Zhan, Huan; Cao, Huan; Berg, Bente G.; Yan, Feng-Ming; Zhao, Xin-Cheng

2014-01-01

Food selection behavior of lepidopteran larvae is predominantly governed by the activation of taste neurons present in two sensilla styloconica located on the galea of the maxilla. In this study, we present the ultrastructure of the sensilla styloconica and the central projection pattern of their associated receptor neurons in larvae of the heliothine moth, Helicoverpa armigera. By means of light microscopy and scanning electron microscopy, the previous findings of two morphologically fairly similar sensilla comprising a socketed conic tip inserted into a large peg were confirmed. However, the peg size of the medial sensillum was found to be significantly bigger than that of the lateral sensillum. The sensory neurons derived from each sensillum styloconicum were mapped separately using anterograde staining experiments combined with confocal laser-scanning microscopy. For determining the afferents’ target regions relative to each other, we reconstructed the labeled axons and placed them into a common reference framework. The sensory axons from both sensilla projected via the ipsilateral maxillary nerve to the suboesophageal ganglion and further through the ipsilateral circumoesophageal connective to the brain. In the suboesophageal ganglion, the sensory projections targeted two areas of the ipsilateral maxillary neuropil, one located in the ventrolateral neuromere and the other adjacent to the neuromere midline. In the brain, the axon terminals targeted the dorso-anterior area of the ipsilateral tritocerebrum. As confirmed by the three-dimensional reconstructions, the target regions of the neural projections originating from each of the two sensilla styloconica were identical. PMID:24740428

The opponent channel population code of sound location is an efficient representation of natural binaural sounds.

PubMed

Młynarski, Wiktor

2015-05-01

In mammalian auditory cortex, sound source position is represented by a population of broadly tuned neurons whose firing is modulated by sounds located at all positions surrounding the animal. Peaks of their tuning curves are concentrated at lateral position, while their slopes are steepest at the interaural midline, allowing for the maximum localization accuracy in that area. These experimental observations contradict initial assumptions that the auditory space is represented as a topographic cortical map. It has been suggested that a "panoramic" code has evolved to match specific demands of the sound localization task. This work provides evidence suggesting that properties of spatial auditory neurons identified experimentally follow from a general design principle- learning a sparse, efficient representation of natural stimuli. Natural binaural sounds were recorded and served as input to a hierarchical sparse-coding model. In the first layer, left and right ear sounds were separately encoded by a population of complex-valued basis functions which separated phase and amplitude. Both parameters are known to carry information relevant for spatial hearing. Monaural input converged in the second layer, which learned a joint representation of amplitude and interaural phase difference. Spatial selectivity of each second-layer unit was measured by exposing the model to natural sound sources recorded at different positions. Obtained tuning curves match well tuning characteristics of neurons in the mammalian auditory cortex. This study connects neuronal coding of the auditory space with natural stimulus statistics and generates new experimental predictions. Moreover, results presented here suggest that cortical regions with seemingly different functions may implement the same computational strategy-efficient coding.

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex.

PubMed

Major, Alex J; Vijayraghavan, Susheel; Everling, Stefan

2018-01-31

Acetylcholine is released in the prefrontal cortex (PFC) and is a key modulator of cognitive performance in primates. Cholinergic stimulation has been shown to have beneficial effects on performance of cognitive tasks, and cholinergic receptors are being actively explored as promising targets for ameliorating cognitive deficits in Alzheimer's disease. We hypothesized that cholinergic stimulation of PFC during performance of a cognitive task would augment neuronal activity and neuronal coding of task attributes. We iontophoretically applied the general cholinergic receptor agonist carbachol onto neurons in dorsolateral PFC (DLPFC) of male rhesus macaques performing rule-guided prosaccades and antisaccades, a well established oculomotor task for testing cognitive control. Carbachol application had heterogeneous effects on neuronal excitability, with both excitation and suppression observed in significant proportions. Contrary to our prediction, neurons with rule-selective activity exhibited a reduction in selectivity during carbachol application. Cholinergic stimulation disrupted rule selectivity regardless of whether it had suppressive or excitatory effects on these neurons. In addition, cholinergic stimulation excited putative pyramidal neurons, whereas the activity of putative interneurons remained unchanged. Moreover, cholinergic stimulation attenuated saccade direction selectivity in putative pyramidal neurons due to nonspecific increases in activity. Our results suggest excessive cholinergic stimulation has detrimental effects on DLPFC representations of task attributes. These findings delineate the complexity and heterogeneity of neuromodulation of cerebral cortex by cholinergic stimulation, an area of active exploration with respect to the development of cognitive enhancers. SIGNIFICANCE STATEMENT The neurotransmitter acetylcholine is known to be important for cognitive processes in the prefrontal cortex. Removal of acetylcholine from prefrontal cortex can disrupt short-term memory performance and is reminiscent of Alzheimer's disease, which is characterized by degeneration of acetylcholine-producing neurons. Stimulation of cholinergic receptors is being explored to create cognitive enhancers for the treatment of Alzheimer's disease and other psychiatric diseases. Here, we stimulated cholinergic receptors in prefrontal cortex and examined its effects on neurons that are engaged in cognitive behavior. Surprisingly, cholinergic stimulation decreased neurons' ability to discriminate between rules. This work suggests that overstimulation of acetylcholine receptors could disrupt neuronal processing during cognition and is relevant to the design of cognitive enhancers based on stimulating the cholinergic system. Copyright © 2018 the authors 0270-6474/18/381137-14$15.00/0.

Orientation-selective aVLSI spiking neurons.

PubMed

Liu, S C; Kramer, J; Indiveri, G; Delbrück, T; Burg, T; Douglas, R

2001-01-01

We describe a programmable multi-chip VLSI neuronal system that can be used for exploring spike-based information processing models. The system consists of a silicon retina, a PIC microcontroller, and a transceiver chip whose integrate-and-fire neurons are connected in a soft winner-take-all architecture. The circuit on this multi-neuron chip approximates a cortical microcircuit. The neurons can be configured for different computational properties by the virtual connections of a selected set of pixels on the silicon retina. The virtual wiring between the different chips is effected by an event-driven communication protocol that uses asynchronous digital pulses, similar to spikes in a neuronal system. We used the multi-chip spike-based system to synthesize orientation-tuned neurons using both a feedforward model and a feedback model. The performance of our analog hardware spiking model matched the experimental observations and digital simulations of continuous-valued neurons. The multi-chip VLSI system has advantages over computer neuronal models in that it is real-time, and the computational time does not scale with the size of the neuronal network.

Shape encoding consistency across colors in primate V4

PubMed Central

Bushnell, Brittany N.

2012-01-01

Neurons in primate cortical area V4 are sensitive to the form and color of visual stimuli. To determine whether form selectivity remains consistent across colors, we studied the responses of single V4 neurons in awake monkeys to a set of two-dimensional shapes presented in two different colors. For each neuron, we chose two colors that were visually distinct and that evoked reliable and different responses. Across neurons, the correlation coefficient between responses in the two colors ranged from −0.03 to 0.93 (median 0.54). Neurons with highly consistent shape responses, i.e., high correlation coefficients, showed greater dispersion in their responses to the different shapes, i.e., greater shape selectivity, and also tended to have less eccentric receptive field locations; among shape-selective neurons, shape consistency ranged from 0.16 to 0.93 (median 0.63). Consistency of shape responses was independent of the physical difference between the stimulus colors used and the strength of neuronal color tuning. Finally, we found that our measurement of shape response consistency was strongly influenced by the number of stimulus repeats: consistency estimates based on fewer than 10 repeats were substantially underestimated. In conclusion, our results suggest that neurons that are likely to contribute to shape perception and discrimination exhibit shape responses that are largely consistent across colors, facilitating the use of simpler algorithms for decoding shape information from V4 neuronal populations. PMID:22673324

The Histamine H1 Receptor Participates in the Increased Dorsal Telencephalic Neurogenesis in Embryos from Diabetic Rats.

PubMed

Solís, Karina H; Méndez, Laura I; García-López, Guadalupe; Díaz, Néstor F; Portillo, Wendy; De Nova-Ocampo, Mónica; Molina-Hernández, Anayansi

2017-01-01

Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E) 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H 1 receptor (H 1 R) which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H 1 R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2) and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H 1 R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H 1 R expression by qRT-PCR and Western blot and, finally, we tested H 1 R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers) and partially reverted the increased level of MAP2 protein at E14, concluding that H 1 R have an important role in the increased neurogenesis within the dorsal telencephalon of embryos from diabetic rats. This study opens new perspective on the participation of HA and H 1 R receptor in early corticogenesis in health and disease.

The Histamine H1 Receptor Participates in the Increased Dorsal Telencephalic Neurogenesis in Embryos from Diabetic Rats

PubMed Central

Solís, Karina H.; Méndez, Laura I.; García-López, Guadalupe; Díaz, Néstor F.; Portillo, Wendy; De Nova-Ocampo, Mónica; Molina-Hernández, Anayansi

2017-01-01

Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E) 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H1 receptor (H1R) which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H1R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2) and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H1R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H1R expression by qRT-PCR and Western blot and, finally, we tested H1R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers) and partially reverted the increased level of MAP2 protein at E14, concluding that H1R have an important role in the increased neurogenesis within the dorsal telencephalon of embryos from diabetic rats. This study opens new perspective on the participation of HA and H1R receptor in early corticogenesis in health and disease. PMID:29311766

Estimating Fast Neural Input Using Anatomical and Functional Connectivity

PubMed Central

Eriksson, David

2016-01-01

In the last 20 years there has been an increased interest in estimating signals that are sent between neurons and brain areas. During this time many new methods have appeared for measuring those signals. Here we review a wide range of methods for which connected neurons can be identified anatomically, by tracing axons that run between the cells, or functionally, by detecting if the activity of two neurons are correlated with a short lag. The signals that are sent between the neurons are represented by the activity in the neurons that are connected to the target population or by the activity at the corresponding synapses. The different methods not only differ in the accuracy of the signal measurement but they also differ in the type of signal being measured. For example, unselective recording of all neurons in the source population encompasses more indirect pathways to the target population than if one selectively record from the neurons that project to the target population. Infact, this degree of selectivity is similar to that of optogenetic perturbations; one can perturb selectively or unselectively. Thus it becomes possible to match a given signal measurement method with a signal perturbation method, something that allows for an exact input control to any neuronal population. PMID:28066189

Involvement of Infralimbic Prefrontal Cortex but not Lateral Habenula in Dopamine Attenuation After Chronic Mild Stress.

PubMed

Moreines, Jared L; Owrutsky, Zoe L; Grace, Anthony A

2017-03-01

Emerging evidence supports a role for dopamine in major depressive disorder (MDD). We recently reported fewer spontaneously active ventral tegmental area (VTA) dopamine neurons (ie, reduced dopamine neuron population activity) in the chronic mild stress (CMS) rodent model of MDD. In this study, we examined the role of two brain regions that have been implicated in MDD in humans, the infralimbic prefrontal cortex (ILPFC)-that is, rodent homolog of Brodmann area 25 (BA25), and the lateral habenula (LHb) in the CMS-induced attenuation of dopamine neuron activity. The impact of activating the ILPFC or LHb was evaluated using single-unit extracellular recordings of identified VTA dopamine neurons. The involvement of each region in dopamine neuron attenuation following 5-7 weeks of CMS was then evaluated by selective inactivation. Activation of either ILPFC or LHb in normal rats potently suppressed dopamine neuron population activity, but in unique patterns. ILPFC activation selectively inhibited dopamine neurons in medial VTA, which were most impacted by CMS. Conversely, LHb activation selectively inhibited dopamine neurons in lateral VTA, which were unaffected by CMS. Moreover, only ILPFC inactivation restored dopamine neuron population activity to normal levels following CMS; LHb inactivation had no restorative effect. These data suggest that, in the CMS model of MDD, the ILPFC is the primary driver of diminished dopamine neuron responses. These findings support a neural substrate for ILPFC/BA25 linking affective and motivational circuitry dysfunction in MDD.

Wnt1 from cochlear schwann cells enhances neuronal differentiation of transplanted neural stem cells in a rat spiral ganglion neuron degeneration model.

PubMed

He, Ya; Zhang, Peng-Zhi; Sun, Dong; Mi, Wen-Juan; Zhang, Xin-Yi; Cui, Yong; Jiang, Xing-Wang; Mao, Xiao-Bo; Qiu, Jian-Hua

2014-04-01

Although neural stem cell (NSC) transplantation is widely expected to become a therapy for nervous system degenerative diseases and injuries, the low neuronal differentiation rate of NSCs transplanted into the inner ear is a major obstacle for the successful treatment of spiral ganglion neuron (SGN) degeneration. In this study, we validated whether the local microenvironment influences the neuronal differentiation of transplanted NSCs in the inner ear. Using a rat SGN degeneration model, we demonstrated that transplanted NSCs were more likely to differentiate into microtubule-associated protein 2 (MAP2)-positive neurons in SGN-degenerated cochleae than in control cochleae. Using real-time quantitative PCR and an immunofluorescence assay, we also proved that the expression of Wnt1 (a ligand of Wnt signaling) increases significantly in Schwann cells in the SGN-degenerated cochlea. We further verified that NSC cultures express receptors and signaling components for Wnts. Based on these expression patterns, we hypothesized that Schwann cell-derived Wnt1 and Wnt signaling might be involved in the regulation of the neuronal differentiation of transplanted NSCs. We verified our hypothesis in vitro using a coculture system. We transduced a lentiviral vector expressing Wnt1 into cochlear Schwann cell cultures and cocultured them with NSC cultures. The coculture with Wnt1-expressing Schwann cells resulted in a significant increase in the percentage of NSCs that differentiated into MAP2-positive neurons, whereas this differentiation-enhancing effect was prevented by Dkk1 (an inhibitor of the Wnt signaling pathway). These results suggested that Wnt1 derived from cochlear Schwann cells enhanced the neuronal differentiation of transplanted NSCs through Wnt signaling pathway activation. Alterations of the microenvironment deserve detailed investigation because they may help us to conceive effective strategies to overcome the barrier of the low differentiation rate of transplanted NSCs.

Viral-genetic tracing of the input-output organization of a central noradrenaline circuit.

PubMed

Schwarz, Lindsay A; Miyamichi, Kazunari; Gao, Xiaojing J; Beier, Kevin T; Weissbourd, Brandon; DeLoach, Katherine E; Ren, Jing; Ibanes, Sandy; Malenka, Robert C; Kremer, Eric J; Luo, Liqun

2015-08-06

Deciphering how neural circuits are anatomically organized with regard to input and output is instrumental in understanding how the brain processes information. For example, locus coeruleus noradrenaline (also known as norepinephrine) (LC-NE) neurons receive input from and send output to broad regions of the brain and spinal cord, and regulate diverse functions including arousal, attention, mood and sensory gating. However, it is unclear how LC-NE neurons divide up their brain-wide projection patterns and whether different LC-NE neurons receive differential input. Here we developed a set of viral-genetic tools to quantitatively analyse the input-output relationship of neural circuits, and applied these tools to dissect the LC-NE circuit in mice. Rabies-virus-based input mapping indicated that LC-NE neurons receive convergent synaptic input from many regions previously identified as sending axons to the locus coeruleus, as well as from newly identified presynaptic partners, including cerebellar Purkinje cells. The 'tracing the relationship between input and output' method (or TRIO method) enables trans-synaptic input tracing from specific subsets of neurons based on their projection and cell type. We found that LC-NE neurons projecting to diverse output regions receive mostly similar input. Projection-based viral labelling revealed that LC-NE neurons projecting to one output region also project to all brain regions we examined. Thus, the LC-NE circuit overall integrates information from, and broadcasts to, many brain regions, consistent with its primary role in regulating brain states. At the same time, we uncovered several levels of specificity in certain LC-NE sub-circuits. These tools for mapping output architecture and input-output relationship are applicable to other neuronal circuits and organisms. More broadly, our viral-genetic approaches provide an efficient intersectional means to target neuronal populations based on cell type and projection pattern.

Orientation-Selective Retinal Circuits in Vertebrates.

PubMed

Antinucci, Paride; Hindges, Robert

2018-01-01

Visual information is already processed in the retina before it is transmitted to higher visual centers in the brain. This includes the extraction of salient features from visual scenes, such as motion directionality or contrast, through neurons belonging to distinct neural circuits. Some retinal neurons are tuned to the orientation of elongated visual stimuli. Such 'orientation-selective' neurons are present in the retinae of most, if not all, vertebrate species analyzed to date, with species-specific differences in frequency and degree of tuning. In some cases, orientation-selective neurons have very stereotyped functional and morphological properties suggesting that they represent distinct cell types. In this review, we describe the retinal cell types underlying orientation selectivity found in various vertebrate species, and highlight their commonalities and differences. In addition, we discuss recent studies that revealed the cellular, synaptic and circuit mechanisms at the basis of retinal orientation selectivity. Finally, we outline the significance of these findings in shaping our current understanding of how this fundamental neural computation is implemented in the visual systems of vertebrates.

Contribution of correlated noise and selective decoding to choice probability measurements in extrastriate visual cortex

PubMed Central

Gu, Yong; Angelaki, Dora E; DeAngelis, Gregory C

2014-01-01

Trial by trial covariations between neural activity and perceptual decisions (quantified by choice Probability, CP) have been used to probe the contribution of sensory neurons to perceptual decisions. CPs are thought to be determined by both selective decoding of neural activity and by the structure of correlated noise among neurons, but the respective roles of these factors in creating CPs have been controversial. We used biologically-constrained simulations to explore this issue, taking advantage of a peculiar pattern of CPs exhibited by multisensory neurons in area MSTd that represent self-motion. Although models that relied on correlated noise or selective decoding could both account for the peculiar pattern of CPs, predictions of the selective decoding model were substantially more consistent with various features of the neural and behavioral data. While correlated noise is essential to observe CPs, our findings suggest that selective decoding of neuronal signals also plays important roles. DOI: http://dx.doi.org/10.7554/eLife.02670.001 PMID:24986734

A fast BK-type KCa current acts as a postsynaptic modulator of temporal selectivity for communication signals.

PubMed

Kohashi, Tsunehiko; Carlson, Bruce A

2014-01-01

Temporal patterns of spiking often convey behaviorally relevant information. Various synaptic mechanisms and intrinsic membrane properties can influence neuronal selectivity to temporal patterns of input. However, little is known about how synaptic mechanisms and intrinsic properties together determine the temporal selectivity of neuronal output. We tackled this question by recording from midbrain electrosensory neurons in mormyrid fish, in which the processing of temporal intervals between communication signals can be studied in a reduced in vitro preparation. Mormyrids communicate by varying interpulse intervals (IPIs) between electric pulses. Within the midbrain posterior exterolateral nucleus (ELp), the temporal patterns of afferent spike trains are filtered to establish single-neuron IPI tuning. We performed whole-cell recording from ELp neurons in a whole-brain preparation and examined the relationship between intrinsic excitability and IPI tuning. We found that spike frequency adaptation of ELp neurons was highly variable. Postsynaptic potentials (PSPs) of strongly adapting (phasic) neurons were more sharply tuned to IPIs than weakly adapting (tonic) neurons. Further, the synaptic filtering of IPIs by tonic neurons was more faithfully converted into variation in spiking output, particularly at short IPIs. Pharmacological manipulation under current- and voltage-clamp revealed that tonic firing is mediated by a fast, large-conductance Ca(2+)-activated K(+) (KCa) current (BK) that speeds up action potential repolarization. These results suggest that BK currents can shape the temporal filtering of sensory inputs by modifying both synaptic responses and PSP-to-spike conversion. Slow SK-type KCa currents have previously been implicated in temporal processing. Thus, both fast and slow KCa currents can fine-tune temporal selectivity.

Neuronal correlate of visual associative long-term memory in the primate temporal cortex

NASA Astrophysics Data System (ADS)

Miyashita, Yasushi

1988-10-01

In human long-term memory, ideas and concepts become associated in the learning process1. No neuronal correlate for this cognitive function has so far been described, except that memory traces are thought to be localized in the cerebral cortex; the temporal lobe has been assigned as the site for visual experience because electric stimulation of this area results in imagery recall,2 and lesions produce deficits in visual recognition of objects3-9. We previously reported that in the anterior ventral temporal cortex of monkeys, individual neurons have a sustained activity that is highly selective for a few of the 100 coloured fractal patterns used in a visual working-memory task10. Here I report the development of this selectivity through repeated trials involving the working memory. The few patterns for which a neuron was conjointly selective were frequently related to each other through stimulus-stimulus association imposed during training. The results indicate that the selectivity acquired by these cells represents a neuronal correlate of the associative long-term memory of pictures.

The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes

PubMed Central

McClelland, Shawn; Brennan, Gary P; Dubé, Celine; Rajpara, Seeta; Iyer, Shruti; Richichi, Cristina; Bernard, Christophe; Baram, Tallie Z

2014-01-01

The mechanisms generating epileptic neuronal networks following insults such as severe seizures are unknown. We have previously shown that interfering with the function of the neuron-restrictive silencer factor (NRSF/REST), an important transcription factor that influences neuronal phenotype, attenuated development of this disorder. In this study, we found that epilepsy-provoking seizures increased the low NRSF levels in mature hippocampus several fold yet surprisingly, provoked repression of only a subset (∼10%) of potential NRSF target genes. Accordingly, the repressed gene-set was rescued when NRSF binding to chromatin was blocked. Unexpectedly, genes selectively repressed by NRSF had mid-range binding frequencies to the repressor, a property that rendered them sensitive to moderate fluctuations of NRSF levels. Genes selectively regulated by NRSF during epileptogenesis coded for ion channels, receptors, and other crucial contributors to neuronal function. Thus, dynamic, selective regulation of NRSF target genes may play a role in influencing neuronal properties in pathological and physiological contexts. DOI: http://dx.doi.org/10.7554/eLife.01267.001 PMID:25117540

The role of the parafascicular complex (CM-Pf) of the human thalamus in the neuronal mechanisms of selective attention.

PubMed

Raeva, S N

2006-03-01

The reactions of 93 neurons in the parafascicular complex (CM-Pf) of the human thalamus were studied by microelectrode recording during stereotaxic neurosurgical operations in patients with spastic torticollis. High reactivity was demonstrated for two previously classified types of neurons with identical irregular (type A) and bursting Ca2+ -dependent (type B) activities in response to presentation of relevant verbal stimuli evoking selective attention in humans. Concordant changes in the network activity of A and B neurons were observed, in the form of linked activatory-inhibitory patterns of responses and the appearance, at the moment of presentation of an imperative morpheme of the command stimulus, of rapidly occurring intercellular interactions consisting of local synchronization with simultaneously developing rhythmic oscillatory (3-4 Hz) activity. Data are presented on the existence of a direct connection between these neuronal rearrangements and activation of selective attention, providing evidence for the involvement of the thalamic parafascicular complex (CM-Pf) in the mechanisms of selective attention and processing of relevant verbal information during the preparative period of voluntary actions.

Image statistics underlying natural texture selectivity of neurons in macaque V4

PubMed Central

Okazawa, Gouki; Tajima, Satohiro; Komatsu, Hidehiko

2015-01-01

Our daily visual experiences are inevitably linked to recognizing the rich variety of textures. However, how the brain encodes and differentiates a plethora of natural textures remains poorly understood. Here, we show that many neurons in macaque V4 selectively encode sparse combinations of higher-order image statistics to represent natural textures. We systematically explored neural selectivity in a high-dimensional texture space by combining texture synthesis and efficient-sampling techniques. This yielded parameterized models for individual texture-selective neurons. The models provided parsimonious but powerful predictors for each neuron’s preferred textures using a sparse combination of image statistics. As a whole population, the neuronal tuning was distributed in a way suitable for categorizing textures and quantitatively predicts human ability to discriminate textures. Together, we suggest that the collective representation of visual image statistics in V4 plays a key role in organizing the natural texture perception. PMID:25535362

Selective and graded coding of reward-uncertainty by neurons in the primate anterodorsal septal region

PubMed Central

Monosov, Ilya E.; Hikosaka, Okihide

2014-01-01

Natural environments are uncertain. Uncertainty of emotional outcomes can induce anxiety and raise vigilance, promote and signal the opportunity for learning, modulate economic choice, and regulate risk seeking. Here we demonstrate that a subset of neurons in the anterodorsal region of the primate septum (ADS) are primarily devoted to processing uncertainty in a highly specific manner. Those neurons were selectively activated by visual cues indicating probabilistic delivery of reward (e.g. 25%, 50%, 75% reward) and did not respond to cues indicating certain outcomes (0% and 100% reward). The average ADS uncertainty response was graded with the magnitude of reward uncertainty, and selectively signaled uncertainty about rewards rather than punishments. The selective and graded information about reward uncertainty encoded by many neurons in the ADS may underlie uncertainty-modulation of value- and sensorimotor- related areas to regulate goal-directed behavior. PMID:23666181

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

Neuroengineering control and regulation of behavior

NASA Astrophysics Data System (ADS)

Wróbel, A.; Radzewicz, C.; Mankiewicz, L.; Hottowy, P.; Knapska, E.; Konopka, W.; Kublik, E.; Radwańska, K.; Waleszczyk, W. J.; Wójcik, D. K.

2014-11-01

To monitor neuronal circuits involved in emotional modulation of sensory processing we proposed a plan to establish novel research techniques combining recent biological, technical and analytical discoveries. The project was granted by National Science Center and we started to build a new experimental model for studying the selected circuits of genetically marked and behaviorally activated neurons. To achieve this goal we will combine the pioneering, interdisciplinary expertise of four Polish institutions: (i) the Nencki Institute of Experimental Biology (Polish Academy of Sciences) will deliver the expertise on genetically modified mice and rats, mapping of the neuronal circuits activated by behavior, monitoring complex behaviors measured in the IntelliCage system, electrophysiological brain activity recordings by multielectrodes in behaving animals, analysis and modeling of behavioral and electrophysiological data; (ii) the AGH University of Science and Technology (Faculty of Physics and Applied Computer Sciences) will use its experience in high-throughput electronics to build multichannel systems for recording the brain activity of behaving animals; (iii) the University of Warsaw (Faculty of Physics) and (iv) the Center for Theoretical Physics (Polish Academy of Sciences) will construct optoelectronic device for remote control of opto-animals produced in the Nencki Institute based on the unique experience in laser sources, studies of light propagation and its interaction with condensed media, wireless medical robotic systems, fast readout opto-electronics with control software and micromechanics.

Short-Term Depression, Temporal Summation, and Onset Inhibition Shape Interval Tuning in Midbrain Neurons

PubMed Central

Baker, Christa A.

2014-01-01

A variety of synaptic mechanisms can contribute to single-neuron selectivity for temporal intervals in sensory stimuli. However, it remains unknown how these mechanisms interact to establish single-neuron sensitivity to temporal patterns of sensory stimulation in vivo. Here we address this question in a circuit that allows us to control the precise temporal patterns of synaptic input to interval-tuned neurons in behaviorally relevant ways. We obtained in vivo intracellular recordings under multiple levels of current clamp from midbrain neurons in the mormyrid weakly electric fish Brienomyrus brachyistius during stimulation with electrosensory pulse trains. To reveal the excitatory and inhibitory inputs onto interval-tuned neurons, we then estimated the synaptic conductances underlying responses. We found short-term depression in excitatory and inhibitory pathways onto all interval-tuned neurons. Short-interval selectivity was associated with excitation that depressed less than inhibition at short intervals, as well as temporally summating excitation. Long-interval selectivity was associated with long-lasting onset inhibition. We investigated tuning after separately nullifying the contributions of temporal summation and depression, and found the greatest diversity of interval selectivity among neurons when both mechanisms were at play. Furthermore, eliminating the effects of depression decreased sensitivity to directional changes in interval. These findings demonstrate that variation in depression and summation of excitation and inhibition helps to establish tuning to behaviorally relevant intervals in communication signals, and that depression contributes to neural coding of interval sequences. This work reveals for the first time how the interplay between short-term plasticity and temporal summation mediates the decoding of temporal sequences in awake, behaving animals. PMID:25339741

Inhibition of Lithium-Sensitive Phosphatase BPNT-1 Causes Selective Neuronal Dysfunction in C. elegans.

PubMed

Meisel, Joshua D; Kim, Dennis H

2016-07-25

Lithium has been a mainstay for the treatment of bipolar disorder, yet the molecular mechanisms underlying its action remain enigmatic. Bisphosphate 3'-nucleotidase (BPNT-1) is a lithium-sensitive phosphatase that catalyzes the breakdown of cytosolic 3'-phosphoadenosine 5'-phosphate (PAP), a byproduct of sulfation reactions utilizing the universal sulfate group donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) [1-3]. Loss of BPNT-1 leads to the toxic accumulation of PAP in yeast and non-neuronal cell types in mice [4, 5]. Intriguingly, BPNT-1 is expressed throughout the mammalian brain [4], and it has been hypothesized that inhibition of BPNT-1 could contribute to the effects of lithium on behavior [5]. Here, we show that loss of BPNT-1 in Caenorhabditis elegans results in the selective dysfunction of two neurons, the bilaterally symmetric pair of ASJ chemosensory neurons. As a result, BPNT-1 mutants are defective in behaviors dependent on the ASJ neurons, such as dauer exit and pathogen avoidance. Acute treatment with lithium also causes dysfunction of the ASJ neurons, and we show that this effect is reversible and mediated specifically through inhibition of BPNT-1. Finally, we show that the selective effect of lithium on the nervous system is due in part to the limited expression of the cytosolic sulfotransferase SSU-1 in the ASJ neuron pair. Our data suggest that lithium, through inhibition of BPNT-1 in the nervous system, can cause selective toxicity to specific neurons, resulting in corresponding effects on behavior of C. elegans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pattern Separation, Pattern Completion, and New Neuronal Codes within a Continuous CA3 Map

ERIC Educational Resources Information Center

Leutgeb, Stefan; Leutgeb, Jill K.

2007-01-01

The hippocampal CA3 subregion is critical for rapidly encoding new memories, which suggests that neuronal computations are implemented in its circuitry that cannot be performed elsewhere in the hippocampus or in the neocortex. Recording studies show that CA3 cells are bound to a large degree to a spatial coordinate system, while CA1 cells can…

Understanding neurodynamical systems via Fuzzy Symbolic Dynamics.

PubMed

Dobosz, Krzysztof; Duch, Włodzisław

2010-05-01

Neurodynamical systems are characterized by a large number of signal streams, measuring activity of individual neurons, local field potentials, aggregated electrical (EEG) or magnetic potentials (MEG), oxygen use (fMRI) or activity of simulated neurons. Various basis set decomposition techniques are used to analyze such signals, trying to discover components that carry meaningful information, but these techniques tell us little about the global activity of the whole system. A novel technique called Fuzzy Symbolic Dynamics (FSD) is introduced to help in understanding of the multidimensional dynamical system's behavior. It is based on a fuzzy partitioning of the signal space that defines a non-linear mapping of the system's trajectory to the low-dimensional space of membership function activations. This allows for visualization of the trajectory showing various aspects of observed signals that may be difficult to discover looking at individual components, or to notice otherwise. FSD mapping can be applied to raw signals, transformed signals (for example, ICA components), or to signals defined in the time-frequency domain. To illustrate the method two FSD visualizations are presented: a model system with artificial radial oscillatory sources, and the output layer (50 neurons) of Respiratory Rhythm Generator (RRG) composed of 300 spiking neurons. 2009 Elsevier Ltd. All rights reserved.

An image registration pipeline for analysis of transsynaptic tracing in mice

NASA Astrophysics Data System (ADS)

Kutten, Kwame S.; Eacker, Stephen M.; Dawson, Valina L.; Dawson, Ted M.; Ratnanather, Tilak; Miller, Michael I.

2016-03-01

Parkinson's Disease (PD) is a movement disorder characterized by the loss of dopamine neurons in the substantia nigra pars compacta (SNpc) and norepinephrine neurons in the locus coeruleus (LC). To further understand the pathophysiology of PD, the input neurons of the SNpc and LC will be transsynapticly traced in mice using a fluorescent recombinant rabies virus (RbV) and imaged using serial two-photon tomography (STP). A mapping between these images and a brain atlas must be found to accurately determine the locations of input neurons in the brain. Therefore a registration pipeline to align the Allen Reference Atlas (ARA) to these types of images was developed. In the preprocessing step, a brain mask was generated from the transsynaptic tracing images using simple morphological operators. The masks were then registered to the ARA using Large Deformation Diffeomorphic Metric Mapping (LDDMM), an algorithm specialized for calculating anatomically realistic transforms between images. The pipeline was then tested on an STP scan of a mouse brain labeled by an adeno-associated virus (AAV). Based on qualitative evaluation of the registration results, the pipeline was found to be sufficient for use with transsynaptic RbV tracing.

A neural-network-based approach to the double traveling salesman problem.

PubMed

Plebe, Alessio; Anile, Angelo Marcello

2002-02-01

The double traveling salesman problem is a variation of the basic traveling salesman problem where targets can be reached by two salespersons operating in parallel. The real problem addressed by this work concerns the optimization of the harvest sequence for the two independent arms of a fruit-harvesting robot. This application poses further constraints, like a collision-avoidance function. The proposed solution is based on a self-organizing map structure, initialized with as many artificial neurons as the number of targets to be reached. One of the key components of the process is the combination of competitive relaxation with a mechanism for deleting and creating artificial neurons. Moreover, in the competitive relaxation process, information about the trajectory connecting the neurons is combined with the distance of neurons from the target. This strategy prevents tangles in the trajectory and collisions between the two tours. Results of tests indicate that the proposed approach is efficient and reliable for harvest sequence planning. Moreover, the enhancements added to the pure self-organizing map concept are of wider importance, as proved by a traveling salesman problem version of the program, simplified from the double version for comparison.

Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers.

PubMed

Rhee, Ho Sung; Closser, Michael; Guo, Yuchun; Bashkirova, Elizaveta V; Tan, G Christopher; Gifford, David K; Wichterle, Hynek

2016-12-21

Generic spinal motor neuron identity is established by cooperative binding of programming transcription factors (TFs), Isl1 and Lhx3, to motor-neuron-specific enhancers. How expression of effector genes is maintained following downregulation of programming TFs in maturing neurons remains unknown. High-resolution exonuclease (ChIP-exo) mapping revealed that the majority of enhancers established by programming TFs are rapidly deactivated following Lhx3 downregulation in stem-cell-derived hypaxial motor neurons. Isl1 is released from nascent motor neuron enhancers and recruited to new enhancers bound by clusters of Onecut1 in maturing neurons. Synthetic enhancer reporter assays revealed that Isl1 operates as an integrator factor, translating the density of Lhx3 or Onecut1 binding sites into transient enhancer activity. Importantly, independent Isl1/Lhx3- and Isl1/Onecut1-bound enhancers contribute to sustained expression of motor neuron effector genes, demonstrating that outwardly stable expression of terminal effector genes in postmitotic neurons is controlled by a dynamic relay of stage-specific enhancers. Copyright © 2016 Elsevier Inc. All rights reserved.

In vivo imaging of neuronal calcium during electrode implantation: Spatial and temporal mapping of damage and recovery.

PubMed

Eles, James R; Vazquez, Alberto L; Kozai, Takashi D Y; Cui, X Tracy

2018-08-01

Implantable electrode devices enable long-term electrophysiological recordings for brain-machine interfaces and basic neuroscience research. Implantation of these devices, however, leads to neuronal damage and progressive neural degeneration that can lead to device failure. The present study uses in vivo two-photon microscopy to study the calcium activity and morphology of neurons before, during, and one month after electrode implantation to determine how implantation trauma injures neurons. We show that implantation leads to prolonged, elevated calcium levels in neurons within 150 μm of the electrode interface. These neurons show signs of mechanical distortion and mechanoporation after implantation, suggesting that calcium influx is related to mechanical trauma. Further, calcium-laden neurites develop signs of axonal injury at 1-3 h post-insert. Over the first month after implantation, physiological neuronal calcium activity increases, suggesting that neurons may be recovering. By defining the mechanisms of neuron damage after electrode implantation, our results suggest new directions for therapies to improve electrode longevity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin★

PubMed Central

Wang, Qian; Liu, Chen; Uchida, Aki; Chuang, Jen-Chieh; Walker, Angela; Liu, Tiemin; Osborne-Lawrence, Sherri; Mason, Brittany L.; Mosher, Christina; Berglund, Eric D.; Elmquist, Joel K.; Zigman, Jeffrey M.

2013-01-01

The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreERT2 transgenic mouse model that allows spatiotemporally-controlled re-expression of physiological levels of ghrelin receptors (GHSRs) specifically in AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP neuron-selective GHSR re-expression partially restored the orexigenic response to administered ghrelin and fully restored the lowered blood glucose levels observed upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron-selective GHSR expression was linked to glucagon rises and hepatic gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP neurons are not solely responsible for ghrelin's orexigenic effects but are sufficient to mediate ghrelin's effects on glycemia. PMID:24567905

Functional identification of a neurocircuit regulating blood glucose

PubMed Central

Meek, Thomas H.; Nelson, Jarrell T.; Matsen, Miles E.; Dorfman, Mauricio D.; Guyenet, Stephan J.; Damian, Vincent; Allison, Margaret B.; Scarlett, Jarrad M.; Nguyen, Hong T.; Thaler, Joshua P.; Olson, David P.; Myers, Martin G.; Schwartz, Michael W.; Morton, Gregory J.

2016-01-01

Previous studies implicate the hypothalamic ventromedial nucleus (VMN) in glycemic control. Here, we report that selective inhibition of the subset of VMN neurons that express the transcription factor steroidogenic-factor 1 (VMNSF1 neurons) blocks recovery from insulin-induced hypoglycemia whereas, conversely, activation of VMNSF1 neurons causes diabetes-range hyperglycemia. Moreover, this hyperglycemic response is reproduced by selective activation of VMNSF1 fibers projecting to the anterior bed nucleus of the stria terminalis (aBNST), but not to other brain areas innervated by VMNSF1 neurons. We also report that neurons in the lateral parabrachial nucleus (LPBN), a brain area that is also implicated in the response to hypoglycemia, make synaptic connections with the specific subset of glucoregulatory VMNSF1 neurons that project to the aBNST. These results collectively establish a physiological role in glucose homeostasis for VMNSF1 neurons and suggest that these neurons are part of an ascending glucoregulatory LPBN→VMNSF1→aBNST neurocircuit. PMID:27001850

Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin.

PubMed

Wang, Qian; Liu, Chen; Uchida, Aki; Chuang, Jen-Chieh; Walker, Angela; Liu, Tiemin; Osborne-Lawrence, Sherri; Mason, Brittany L; Mosher, Christina; Berglund, Eric D; Elmquist, Joel K; Zigman, Jeffrey M

2014-02-01

The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreER(T2) transgenic mouse model that allows spatiotemporally-controlled re-expression of physiological levels of ghrelin receptors (GHSRs) specifically in AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP neuron-selective GHSR re-expression partially restored the orexigenic response to administered ghrelin and fully restored the lowered blood glucose levels observed upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron-selective GHSR expression was linked to glucagon rises and hepatic gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP neurons are not solely responsible for ghrelin's orexigenic effects but are sufficient to mediate ghrelin's effects on glycemia.

Spinal muscular atrophy: Selective motor neuron loss and global defect in the assembly of ribonucleoproteins.

PubMed

Beattie, Christine E; Kolb, Stephen J

2018-08-15

Spinal muscular atrophy is caused by deletions or mutations in the SMN1 gene that result in reduced expression of the SMN protein. The SMN protein is an essential molecular chaperone that is required for the biogenesis of multiple ribonucleoprotein (RNP) complexes including spliceosomal small nuclear RNPs (snRNPs). Reductions in SMN expression result in a reduced abundance of snRNPs and to downstream RNA splicing alterations. SMN is also present in axons and dendrites and appears to have important roles in the formation of neuronal mRNA-protein complexes during development or neuronal repair. Thus, SMA is an exemplar, selective motor neuron disorder that is caused by defects in fundamental RNA processing events. A detailed molecular understanding of how motor neurons fail, and why other neurons do not, in SMA will yield important principals about motor neuron maintenance and neuronal specificity in neurodegenerative diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

GABAergic neurons in ferret visual cortex participate in functionally specific networks

PubMed Central

Wilson, Daniel E.; Smith, Gordon B.; Jacob, Amanda; Walker, Theo; Dimidschstein, Jordane; Fishell, Gord J.; Fitzpatrick, David

2017-01-01

Summary Functional circuits in the visual cortex require the coordinated activity of excitatory and inhibitory neurons. Molecular genetic approaches in the mouse have led to the ‘local nonspecific pooling principle’ of inhibitory connectivity, in which inhibitory neurons are untuned for stimulus features due to the random pooling of local inputs. However, it remains unclear whether this principle generalizes to species with a columnar organization of feature selectivity such as carnivores, primates, and humans. Here we use virally-mediated GABAergic-specific GCaMP6f expression to demonstrate that inhibitory neurons in ferret visual cortex respond robustly and selectively to oriented stimuli. We find that the tuning of inhibitory neurons is inconsistent with the local non-specific pooling of excitatory inputs, and that inhibitory neurons exhibit orientation-specific noise correlations with local and distant excitatory neurons. These findings challenge the generality of the non-specific pooling principle for inhibitory neurons, suggesting different rules for functional excitatory-inhibitory interactions in non-murine species. PMID:28279352

Adaptive Neuron Model: An architecture for the rapid learning of nonlinear topological transformations

NASA Technical Reports Server (NTRS)

Tawel, Raoul (Inventor)

1994-01-01

A method for the rapid learning of nonlinear mappings and topological transformations using a dynamically reconfigurable artificial neural network is presented. This fully-recurrent Adaptive Neuron Model (ANM) network was applied to the highly degenerate inverse kinematics problem in robotics, and its performance evaluation is bench-marked. Once trained, the resulting neuromorphic architecture was implemented in custom analog neural network hardware and the parameters capturing the functional transformation downloaded onto the system. This neuroprocessor, capable of 10(exp 9) ops/sec, was interfaced directly to a three degree of freedom Heathkit robotic manipulator. Calculation of the hardware feed-forward pass for this mapping was benchmarked at approximately 10 microsec.

Exact computation of the maximum-entropy potential of spiking neural-network models.

PubMed

Cofré, R; Cessac, B

2014-05-01

Understanding how stimuli and synaptic connectivity influence the statistics of spike patterns in neural networks is a central question in computational neuroscience. The maximum-entropy approach has been successfully used to characterize the statistical response of simultaneously recorded spiking neurons responding to stimuli. However, in spite of good performance in terms of prediction, the fitting parameters do not explain the underlying mechanistic causes of the observed correlations. On the other hand, mathematical models of spiking neurons (neuromimetic models) provide a probabilistic mapping between the stimulus, network architecture, and spike patterns in terms of conditional probabilities. In this paper we build an exact analytical mapping between neuromimetic and maximum-entropy models.

Bistability induces episodic spike communication by inhibitory neurons in neuronal networks.

PubMed

Kazantsev, V B; Asatryan, S Yu

2011-09-01

Bistability is one of the important features of nonlinear dynamical systems. In neurodynamics, bistability has been found in basic Hodgkin-Huxley equations describing the cell membrane dynamics. When the neuron is clamped near its threshold, the stable rest potential may coexist with the stable limit cycle describing periodic spiking. However, this effect is often neglected in network computations where the neurons are typically reduced to threshold firing units (e.g., integrate-and-fire models). We found that the bistability may induce spike communication by inhibitory coupled neurons in the spiking network. The communication is realized in the form of episodic discharges with synchronous (correlated) spikes during the episodes. A spiking phase map is constructed to describe the synchronization and to estimate basic spike phase locking modes.

A new era for functional labeling of neurons: activity-dependent promoters have come of age

PubMed Central

Kawashima, Takashi; Okuno, Hiroyuki; Bito, Haruhiko

2014-01-01

Genetic labeling of neurons with a specific response feature is an emerging technology for precise dissection of brain circuits that are functionally heterogeneous at the single-cell level. While immediate early gene mapping has been widely used for decades to identify brain regions which are activated by external stimuli, recent characterization of the promoter and enhancer elements responsible for neuronal activity-dependent transcription have opened new avenues for live imaging of active neurons. Indeed, these advancements provided the basis for a growing repertoire of novel experiments to address the role of active neuronal networks in cognitive behaviors. In this review, we summarize the current literature on the usage and development of activity-dependent promoters and discuss the future directions of this expanding new field. PMID:24795570

Mapping visual stimuli to perceptual decisions via sparse decoding of mesoscopic neural activity.

PubMed

Sajda, Paul

2010-01-01

In this talk I will describe our work investigating sparse decoding of neural activity, given a realistic mapping of the visual scene to neuronal spike trains generated by a model of primary visual cortex (V1). We use a linear decoder which imposes sparsity via an L1 norm. The decoder can be viewed as a decoding neuron (linear summation followed by a sigmoidal nonlinearity) in which there are relatively few non-zero synaptic weights. We find: (1) the best decoding performance is for a representation that is sparse in both space and time, (2) decoding of a temporal code results in better performance than a rate code and is also a better fit to the psychophysical data, (3) the number of neurons required for decoding increases monotonically as signal-to-noise in the stimulus decreases, with as little as 1% of the neurons required for decoding at the highest signal-to-noise levels, and (4) sparse decoding results in a more accurate decoding of the stimulus and is a better fit to psychophysical performance than a distributed decoding, for example one imposed by an L2 norm. We conclude that sparse coding is well-justified from a decoding perspective in that it results in a minimum number of neurons and maximum accuracy when sparse representations can be decoded from the neural dynamics.

Pheromone detection by mammalian vomeronasal neurons.

PubMed

Zufall, Frank; Kelliher, Kevin R; Leinders-Zufall, Trese

2002-08-01

The vomeronasal organ (VNO) of mammals plays an essential role in the perception of chemical stimuli of social nature including pheromone-like signals but direct evidence for the transduction of pheromones by vomeronasal sensory neurons has been lacking. The recent development of electrophysiological and optical imaging methods using confocal microscopy has enabled researchers to systematically analyze sensory responses in large populations of mouse vomeronasal neurons. These experiments revealed that vomeronasal neurons are surprisingly sensitive and highly discriminative detectors of volatile, urinary metabolites that have pheromonal activity in recipient mice. Functional mapping studies of pheromone receptor activation have uncovered the basic principles of sensory processing by vomeronasal neurons and revealed striking differences in the neural mechanisms by which chemosensory information is detected by receptor neurons in the VNO and the main olfactory epithelium. These advances offer the opportunity to decipher the logic of mammalian pheromonal communication. Copyright 2002 Wiley-Liss, Inc.

Differential regulation of amyloid-. beta. -protein mRNA expression within hippocampal neuronal subpopulations in Alzheimer disease

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

Higgins, G.A.; Lewis, D.A.; Bahmanyar, S.

1988-02-01

The authors have mapped the neuroanatomical distribution of amyloid-..beta..-protein mRNA within neuronal subpopulations of the hippocampal formation in the cynomolgus monkey (Macaca fascicularis), normal aged human, and patients with Alzheimer disease. Amyloid-..beta..-protein mRNA appears to be expressed in all hippocampal neurons, but at different levels of abundance. In the central nervous system of monkey and normal aged human, image analysis shows that neurons of the dentate gyrus and cornu Ammonis fields contain a 2.5-times-greater hybridization signal than is present in neurons of the subiculum and entorhinal cortex. In contrast, in the Alzheimer disease hippocampal formation, the levels of amyloid-..beta..-protein mRNAmore » in the cornu Ammonis field 3 and parasubiculum are equivalent. These findings suggest that within certain neuronal subpopulations cell type-specific regulation of amyloid-..beta..-protein gene expression may be altered in Alzheimer disease.« less

Regional TNFα mapping in the brain reveals the striatum as a neuroinflammatory target after ventricular fibrillation cardiac arrest in rats☆

PubMed Central

Janata, Andreas; Magnet, Ingrid A.M.; Uray, Thomas; Stezoski, Jason P.; Janesko-Feldman, Keri; Tisherman, Samuel A.; Kochanek, Patrick M.; Drabek, Tomas

2014-01-01

Cardiac arrest (CA) triggers neuroinflammation that could play a role in a delayed neuronal death. In our previously established rat model of ventricular fibrillation (VF) CA characterized by extensive neuronal death, we tested the hypothesis that individual brain regions have specific neuroinflammatory responses, as reflected by regional brain tissue levels of tumor necrosis factor (TNF)α and other cytokines. In a prospective study, rats were randomized to 6 min (CA6), 8 min (CA8) or 10 min (CA10) of VF CA, or sham group. Cortex, striatum, hippocampus and cerebellum were evaluated for TNFα and interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 and interferon gamma at 3 h, 6 h or 14 d after CA by ELISA and Luminex. Immunohistochemistry was used to determine the cell source of TNFα. CA resulted in a selective TNFα response with significant regional and temporal differences. At 3 h after CA, TNFα-levels increased in all regions depending on the duration of the insult. The most pronounced increase was observed in striatum that showed 20-fold increase in CA10 vs. sham, and 3-fold increase vs. CA6 or CA8 group, respectively (p < 0.01). TNFα levels in striatum decreased between 3 h and 6 h, but increased in other regions between 3 h and 14 d. TNFα levels remained twofold higher in CA6 vs. shams across brain regions at 14 d (p < 0.01). In contrast to pronounced TNFα response, other cytokines showed only a minimal increase in CA6 and CA8 groups vs. sham in all brain regions with the exception that IL-1β increased twofold in cerebellum and striatum (p < 0.01). TNFα colocalized with neurons. In conclusion, CA produced a duration-dependent acute TNFα response, with dramatic increase in the striatum where TNFα colocalized with neurons. Increased TNFα levels persist for at least two weeks. This TNFα surge contrasts the lack of an acute increase in other cytokines in brain after CA. Given that striatum is a selectively vulnerable brain region, our data suggest possible role of neuronal TNFα in striatum after CA and identify therapeutic targets for future experiments. PMID:24530249

Coupling an aVLSI neuromorphic vision chip to a neurotrophic model of synaptic plasticity: the development of topography.

PubMed

Elliott, Terry; Kramer, Jörg

2002-10-01

We couple a previously studied, biologically inspired neurotrophic model of activity-dependent competitive synaptic plasticity and neuronal development to a neuromorphic retina chip. Using this system, we examine the development and refinement of a topographic mapping between an array of afferent neurons (the retinal ganglion cells) and an array of target neurons. We find that the plasticity model can indeed drive topographic refinement in the presence of afferent activity patterns generated by a real-world device. We examine the resilience of the developing system to the presence of high levels of noise by adjusting the spontaneous firing rate of the silicon neurons.

[Perception and selectivity of sound duration in the central auditory midbrain].

PubMed

Wang, Xin; Li, An-An; Wu, Fei-Jian

2010-08-25

Sound duration plays important role in acoustic communication. Information of acoustic signal is mainly encoded in the amplitude and frequency spectrum of different durations. Duration selective neurons exist in the central auditory system including inferior colliculus (IC) of frog, bat, mouse and chinchilla, etc., and they are important in signal recognition and feature detection. Two generally accepted models, which are "coincidence detector model" and "anti-coincidence detector model", have been raised to explain the mechanism of neural selective responses to sound durations based on the study of IC neurons in bats. Although they are different in details, they both emphasize the importance of synaptic integration of excitatory and inhibitory inputs, and are able to explain the responses of most duration-selective neurons. However, both of the hypotheses need to be improved since other sound parameters, such as spectral pattern, amplitude and repetition rate, could affect the duration selectivity of the neurons. The dynamic changes of sound parameters are believed to enable the animal to effectively perform recognition of behavior related acoustic signals. Under free field sound stimulation, we analyzed the neural responses in the IC and auditory cortex of mouse and bat to sounds with different duration, frequency and amplitude, using intracellular or extracellular recording techniques. Based on our work and previous studies, this article reviews the properties of duration selectivity in central auditory system and discusses the mechanisms of duration selectivity and the effect of other sound parameters on the duration coding of auditory neurons.

Long-term memory, neurogenesis, and signal novelty.

PubMed

Sokolov, E N; Nezlina, N I

2004-10-01

According to our suggested hypothesis, long-term memory is a collection of "gnostic units," selectively tuned to past events. The formation of long-term memory occurs with the involvement of constantly appearing new neurons which differentiate from stem cells during the process of neurogenesis, in particular in adults. Conversion of precursor neurons into "gnostic units" selective in relation to ongoing events, supplemented by the involvement of hippocampal "novelty neurons," which increase the flow of information needing to be fixed in long-term memory. "Gnostic units" form before the informational processes occurring in the ventral ("what?") and dorsal ("where?") systems. Formation of new "gnostic units" selectively tuned to a particular event results from the combination of excitation of the detector for stimulus characteristics and the novelty signal generated by "novelty neurons" in the hippocampus.

Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2

PubMed Central

Ruane, Peter T.; Gumy, Laura F.; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J.; Hoogenraad, Casper C.; Allan, Victoria J.

2016-01-01

Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members, the exact mechanism for the peripheral localization of APC remains unclear. Here we show that the heavy chain of kinesin-1 directly interacts with the APC C-terminus, contributing to the peripheral localisation of APC in fibroblasts. In rat hippocampal neurons the kinesin-1 binding domain of APC is required for its axon tip enrichment. Moreover, we demonstrate that APC requires interactions with both kinesin-2 and kinesin-1 for this localisation. Underlining the importance of the kinesin-1 association, neurons expressing APC lacking kinesin-1-binding domain have shorter axons. The identification of this novel kinesin-1-APC interaction highlights the complexity and significance of APC localisation in neurons. PMID:27272132

A neural circuit for gamma-band coherence across the retinotopic map in mouse visual cortex

PubMed Central

Hakim, Richard; Shamardani, Kiarash

2018-01-01

Cortical gamma oscillations have been implicated in a variety of cognitive, behavioral, and circuit-level phenomena. However, the circuit mechanisms of gamma-band generation and synchronization across cortical space remain uncertain. Using optogenetic patterned illumination in acute brain slices of mouse visual cortex, we define a circuit composed of layer 2/3 (L2/3) pyramidal cells and somatostatin (SOM) interneurons that phase-locks ensembles across the retinotopic map. The network oscillations generated here emerge from non-periodic stimuli, and are stimulus size-dependent, coherent across cortical space, narrow band (30 Hz), and depend on SOM neuron but not parvalbumin (PV) neuron activity; similar to visually induced gamma oscillations observed in vivo. Gamma oscillations generated in separate cortical locations exhibited high coherence as far apart as 850 μm, and lateral gamma entrainment depended on SOM neuron activity. These data identify a circuit that is sufficient to mediate long-range gamma-band coherence in the primary visual cortex. PMID:29480803

Mapping social behavior-induced brain activation at cellular resolution in the mouse

PubMed Central

Kim, Yongsoo; Venkataraju, Kannan Umadevi; Pradhan, Kith; Mende, Carolin; Taranda, Julian; Turaga, Srinivas C.; Arganda-Carreras, Ignacio; Ng, Lydia; Hawrylycz, Michael J.; Rockland, Kathleen; Seung, H. Sebastian; Osten, Pavel

2014-01-01

Understanding how brain activation mediates behaviors is a central goal of systems neuroscience. Here we apply an automated method for mapping brain activation in the mouse in order to probe how sex-specific social behaviors are represented in the male brain. Our method uses the immediate early gene c-fos, a marker of neuronal activation, visualized by serial two-photon tomography: the c-fos-GFP-positive neurons are computationally detected, their distribution is registered to a reference brain and a brain atlas, and their numbers are analyzed by statistical tests. Our results reveal distinct and shared female and male interaction-evoked patterns of male brain activation representing sex discrimination and social recognition. We also identify brain regions whose degree of activity correlates to specific features of social behaviors and estimate the total numbers and the densities of activated neurons per brain areas. Our study opens the door to automated screening of behavior-evoked brain activation in the mouse. PMID:25558063

Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism.

PubMed

Kim, Yongsoo; Yang, Guangyu Robert; Pradhan, Kith; Venkataraju, Kannan Umadevi; Bota, Mihail; García Del Molino, Luis Carlos; Fitzgerald, Greg; Ram, Keerthi; He, Miao; Levine, Jesse Maurica; Mitra, Partha; Huang, Z Josh; Wang, Xiao-Jing; Osten, Pavel

2017-10-05

The stereotyped features of neuronal circuits are those most likely to explain the remarkable capacity of the brain to process information and govern behaviors, yet it has not been possible to comprehensively quantify neuronal distributions across animals or genders due to the size and complexity of the mammalian brain. Here we apply our quantitative brain-wide (qBrain) mapping platform to document the stereotyped distributions of mainly inhibitory cell types. We discover an unexpected cortical organizing principle: sensory-motor areas are dominated by output-modulating parvalbumin-positive interneurons, whereas association, including frontal, areas are dominated by input-modulating somatostatin-positive interneurons. Furthermore, we identify local cell type distributions with more cells in the female brain in 10 out of 11 sexually dimorphic subcortical areas, in contrast to the overall larger brains in males. The qBrain resource can be further mined to link stereotyped aspects of neuronal distributions to known and unknown functions of diverse brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

Normal movement selectivity in autism.

PubMed

Dinstein, Ilan; Thomas, Cibu; Humphreys, Kate; Minshew, Nancy; Behrmann, Marlene; Heeger, David J

2010-05-13

It has been proposed that individuals with autism have difficulties understanding the goals and intentions of others because of a fundamental dysfunction in the mirror neuron system. Here, however, we show that individuals with autism exhibited not only normal fMRI responses in mirror system areas during observation and execution of hand movements but also exhibited typical movement-selective adaptation (repetition suppression) when observing or executing the same movement repeatedly. Movement selectivity is a defining characteristic of neurons involved in movement perception, including mirror neurons, and, as such, these findings argue against a mirror system dysfunction in autism. Copyright 2010 Elsevier Inc. All rights reserved.

A novel function of the cell polarity-regulating kinase PAR-1/MARK in dendritic spines

PubMed Central

Hayashi, Kenji; Suzuki, Atsushi; Ohno, Shigeo

2011-01-01

Dendritic spines are postsynaptic structures that receive excitatory synaptic signals from presynaptic terminals in neurons. Because the morphology of spines has been considered to be a crucial factor for the efficiency of synaptic transmission, understanding the mechanisms regulating their morphology is important for neuroscience. Actin filaments and their regulatory proteins are known to actively maintain spine morphology; recent studies have also shown an essential role of microtubules (MTs). Live imaging of the plus-ends of MTs in mature neurons revealed that MTs stochastically enter spines and mediate accumulation of p140Cap, which regulates reorganization of actin filaments. However, the molecular mechanism by which MT dynamics is controlled has remained largely unknown. A cell polarity-regulating serine/threonine kinase, partitioning-defective 1 (PAR-1), phosphorylates classical MAPs and inhibits their binding to MTs. Because the interaction of MAPs with MTs can decrease MT dynamic instability, PAR-1 is supposed to activate MT dynamics through its MAP/MT affinity-regulating kinase (MARK) activity, although there is not yet any direct evidence for this. Here, we review recent findings on the localization of PAR-1b in the dendrites of mouse hippocampal neurons, and its novel function in the maintenance of mature spine morphology by regulating MT dynamics. PMID:22545177

A novel function of the cell polarity-regulating kinase PAR-1/MARK in dendritic spines.

PubMed

Hayashi, Kenji; Suzuki, Atsushi; Ohno, Shigeo

2011-11-01

Dendritic spines are postsynaptic structures that receive excitatory synaptic signals from presynaptic terminals in neurons. Because the morphology of spines has been considered to be a crucial factor for the efficiency of synaptic transmission, understanding the mechanisms regulating their morphology is important for neuroscience. Actin filaments and their regulatory proteins are known to actively maintain spine morphology; recent studies have also shown an essential role of microtubules (MTs). Live imaging of the plus-ends of MTs in mature neurons revealed that MTs stochastically enter spines and mediate accumulation of p140Cap, which regulates reorganization of actin filaments. However, the molecular mechanism by which MT dynamics is controlled has remained largely unknown. A cell polarity-regulating serine/threonine kinase, partitioning-defective 1 (PAR-1), phosphorylates classical MAPs and inhibits their binding to MTs. Because the interaction of MAPs with MTs can decrease MT dynamic instability, PAR-1 is supposed to activate MT dynamics through its MAP/MT affinity-regulating kinase (MARK) activity, although there is not yet any direct evidence for this. Here, we review recent findings on the localization of PAR-1b in the dendrites of mouse hippocampal neurons, and its novel function in the maintenance of mature spine morphology by regulating MT dynamics.

Rapid changes in phospho-MAP/tau epitopes during neuronal stress: cofilin-actin rods primarily recruit microtubule binding domain epitopes.

PubMed

Whiteman, Ineka T; Minamide, Laurie S; Goh, De Lian; Bamburg, James R; Goldsbury, Claire

2011-01-01

Abnormal mitochondrial function is a widely reported contributor to neurodegenerative disease including Alzheimer's disease (AD), however, a mechanistic link between mitochondrial dysfunction and the initiation of neuropathology remains elusive. In AD, one of the earliest hallmark pathologies is neuropil threads comprising accumulated hyperphosphorylated microtubule-associated protein (MAP) tau in neurites. Rod-like aggregates of actin and its associated protein cofilin (AC rods) also occur in AD. Using a series of antibodies--AT270, AT8, AT100, S214, AT180, 12E8, S396, S404 and S422--raised against different phosphoepitopes on tau, we characterize the pattern of expression and re-distribution in neurites of these phosphoepitope labels during mitochondrial inhibition. Employing chick primary neuron cultures, we demonstrate that epitopes recognized by the monoclonal antibody 12E8, are the only species rapidly recruited into AC rods. These results were recapitulated with the actin depolymerizing drug Latrunculin B, which induces AC rods and a concomitant increase in the 12E8 signal measured on Western blot. This suggests that AC rods may be one way in which MAP redistribution and phosphorylation is influenced in neurons during mitochondrial stress and potentially in the early pathogenesis of AD.

Using Immediate-Early Genes to Map Hippocampal Subregional Functions

ERIC Educational Resources Information Center

Kubik, Stepan; Miyashita, Teiko; Guzowski, John F.

2007-01-01

Different functions have been suggested for the hippocampus and its subdivisions along both transversal and longitudinal axes. Expression of immediate-early genes (IEGs) has been used to map specific functions onto neuronal activity in different areas of the brain including the hippocampus (IEG imaging). Here we review IEG studies on hippocampal…

Sensory neurons that detect stretch and nutrients in the digestive system

PubMed Central

Williams, Erika K.; Chang, Rui B.; Strochlic, David E.; Umans, Benjamin D.; Lowell, Bradford B.; Liberles, Stephen D.

2016-01-01

SUMMARY Neural inputs from internal organs are essential for normal autonomic function. The vagus nerve is a key body-brain connection that monitors the digestive, cardiovascular, and respiratory systems. Within the gastrointestinal tract, vagal sensory neurons detect gut hormones and organ distension. Here, we investigate the molecular diversity of vagal sensory neurons and their roles in sensing gastrointestinal inputs. Genetic approaches allowed targeted investigation of gut-to-brain afferents involved in homeostatic responses to ingested nutrients (GPR65 neurons) and mechanical distension of the stomach and intestine (GLP1R neurons). Optogenetics, in vivo ganglion imaging, and genetically guided anatomical mapping provide direct links between neuron identity, peripheral anatomy, central anatomy, conduction velocity, response properties in vitro and in vivo, and physiological function. These studies clarify the roles of vagal afferents in mediating particular gut hormone responses. Moreover, genetic control over gut-to-brain neurons provides a molecular framework for understanding neural control of gastrointestinal physiology. PMID:27238020

A hypothalamic circuit for the circadian control of aggression.

PubMed

Todd, William D; Fenselau, Henning; Wang, Joshua L; Zhang, Rong; Machado, Natalia L; Venner, Anne; Broadhurst, Rebecca Y; Kaur, Satvinder; Lynagh, Timothy; Olson, David P; Lowell, Bradford B; Fuller, Patrick M; Saper, Clifford B

2018-05-01

'Sundowning' in dementia and Alzheimer's disease is characterized by early-evening agitation and aggression. While such periodicity suggests a circadian origin, whether the circadian clock directly regulates aggressive behavior is unknown. We demonstrate that a daily rhythm in aggression propensity in male mice is gated by GABAergic subparaventricular zone (SPZ GABA ) neurons, the major postsynaptic targets of the central circadian clock, the suprachiasmatic nucleus. Optogenetic mapping revealed that SPZ GABA neurons receive input from vasoactive intestinal polypeptide suprachiasmatic nucleus neurons and innervate neurons in the ventrolateral part of the ventromedial hypothalamus (VMH), which is known to regulate aggression. Additionally, VMH-projecting dorsal SPZ neurons are more active during early day than early night, and acute chemogenetic inhibition of SPZ GABA transmission phase-dependently increases aggression. Finally, SPZ GABA -recipient central VMH neurons directly innervate ventrolateral VMH neurons, and activation of this intra-VMH circuit drove attack behavior. Altogether, we reveal a functional polysynaptic circuit by which the suprachiasmatic nucleus clock regulates aggression.

En1 is necessary for survival of neurons in the ventral nuclei of the lateral lemniscus.

PubMed

Altieri, Stefanie C; Zhao, Tianna; Jalabi, Walid; Romito-DiGiacomo, Rita R; Maricich, Stephen M

2016-11-01

The ventral nuclei of the lateral lemniscus (VNLL) are part of the central auditory system thought to participate in temporal sound processing. While the timing and location of VNLL neurogenesis have been determined, the genetic factors that regulate VNLL neuron development are unknown. Here, we use genetic fate-mapping techniques to demonstrate that all glycinergic and glycinergic/GABAergic VNLL neurons derive from a cellular lineage that expresses the homeobox transcription factor Engrailed 1 (En1). We also show that En1 deletion does not affect migration or adoption of a neuronal cell fate but does lead to VNLL neuron death during development. Furthermore, En1 deletion blocks expression of the transcription factor FoxP1 in a subset of VNLL neurons. Together, these data identify En1 as a gene important for VNLL neuron development and survival. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1266-1274, 2016. © 2016 Wiley Periodicals, Inc.

Hippocampal neuronal subtypes develop abnormal dendritic arbors in the presence of Fragile X astrocytes.

PubMed

Jacobs, S; Cheng, C; Doering, L C

2016-06-02

Astrocytes are now recognized as key players in the neurobiology of neurodevelopmental disorders such as Fragile X syndrome. However, the nature of Fragile X astrocyte-mediated control of dendrite development in subtypes of hippocampal neurons is not yet known. We used a co-culture procedure in which wildtype primary hippocampal neurons were cultured with astrocytes from either a wildtype or Fragile X mouse, for either 7, 14 or 21 days. The neurons were processed for immunocytochemistry with the dendritic marker MAP2, classified by morphological criteria into one of five neuronal subtypes, and subjected to Sholl analyses. Both linear and semi-log methods of Sholl analyses were applied to the neurons in order to provide an in depth analysis of the dendritic arborizations. We found that Fragile X astrocytes affect the development of dendritic arborization of all subtypes of wildtype hippocampal neurons. Furthermore, we show that hippocampal neurons with spiny stellate neuron morphology exhibit the most pervasive developmental delays, with significant dendritic arbor alterations persisting at 21 days in culture. The results further dictate the critical role astrocytes play in governing neuronal morphology including altered dendrite development in Fragile X. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Dynamic representation of partially occluded objects in primate prefrontal and visual cortex

PubMed Central

Choi, Hannah; Shea-Brown, Eric

2017-01-01

Successful recognition of partially occluded objects is presumed to involve dynamic interactions between brain areas responsible for vision and cognition, but neurophysiological evidence for the involvement of feedback signals is lacking. Here, we demonstrate that neurons in the ventrolateral prefrontal cortex (vlPFC) of monkeys performing a shape discrimination task respond more strongly to occluded than unoccluded stimuli. In contrast, neurons in visual area V4 respond more strongly to unoccluded stimuli. Analyses of V4 response dynamics reveal that many neurons exhibit two transient response peaks, the second of which emerges after vlPFC response onset and displays stronger selectivity for occluded shapes. We replicate these findings using a model of V4/vlPFC interactions in which occlusion-sensitive vlPFC neurons feed back to shape-selective V4 neurons, thereby enhancing V4 responses and selectivity to occluded shapes. These results reveal how signals from frontal and visual cortex could interact to facilitate object recognition under occlusion. PMID:28925354

Reprogramming of orientation columns in visual cortex: a domino effect

PubMed Central

Bachatene, Lyes; Bharmauria, Vishal; Cattan, Sarah; Rouat, Jean; Molotchnikoff, Stéphane

2015-01-01

Cortical organization rests upon the fundamental principle that neurons sharing similar properties are co-located. In the visual cortex, neurons are organized into orientation columns. In a column, most neurons respond optimally to the same axis of an oriented edge, that is, the preferred orientation. This orientation selectivity is believed to be absolute in adulthood. However, in a fully mature brain, it has been established that neurons change their selectivity following sensory experience or visual adaptation. Here, we show that after applying an adapter away from the tested cells, neurons whose receptive fields were located remotely from the adapted site also exhibit a novel selectivity in spite of the fact that they were not adapted. These results indicate a robust reconfiguration and remapping of the orientation domains with respect to each other thus removing the possibility of an orientation hole in the new hypercolumn. These data suggest that orientation columns transcend anatomy, and are almost strictly functionally dynamic. PMID:25801392

Species and Sex Differences in the Morphogenic Response of Primary Rodent Neurons to 3,3′-Dichlorobiphenyl (PCB 11)

PubMed Central

Sethi, Sunjay; Keil, Kimberly P.

2017-01-01

PCB 11 is an emerging global pollutant that we recently showed promotes axonal and dendritic growth in primary rat neuronal cell cultures. Here, we address the influence of sex and species on neuronal responses to PCB 11. Neuronal morphology was quantified in sex-specific primary hippocampal and cortical neuron-glia co-cultures derived from neonatal C57BL/6J mice and Sprague Dawley rats exposed for 48 h to vehicle (0.1% DMSO) or PCB 11 at concentrations ranging from 1 fM to 1 nM. Total axonal length was quantified in tau-1 immunoreactive neurons at day in vitro (DIV) 2; dendritic arborization was assessed by Sholl analysis at DIV 9 in neurons transfected with MAP2B-FusRed. In mouse cultures, PCB 11 enhanced dendritic arborization in female, but not male, hippocampal neurons and male, but not female, cortical neurons. In rat cultures, PCB 11 promoted dendritic arborization in male and female hippocampal and cortical neurons. PCB 11 also increased axonal growth in mouse and rat neurons of both sexes and neuronal cell types. These data demonstrate that PCB 11 exerts sex-specific effects on neuronal morphogenesis that vary depending on species, neurite type, and neuronal cell type. These findings have significant implications for risk assessment of this emerging developmental neurotoxicant. PMID:29295518

Species and Sex Differences in the Morphogenic Response of Primary Rodent Neurons to 3,3'-Dichlorobiphenyl (PCB 11).

PubMed

Sethi, Sunjay; Keil, Kimberly P; Lein, Pamela J

2017-12-23

PCB 11 is an emerging global pollutant that we recently showed promotes axonal and dendritic growth in primary rat neuronal cell cultures. Here, we address the influence of sex and species on neuronal responses to PCB 11. Neuronal morphology was quantified in sex-specific primary hippocampal and cortical neuron-glia co-cultures derived from neonatal C57BL/6J mice and Sprague Dawley rats exposed for 48 h to vehicle (0.1% DMSO) or PCB 11 at concentrations ranging from 1 fM to 1 nM. Total axonal length was quantified in tau-1 immunoreactive neurons at day in vitro (DIV) 2; dendritic arborization was assessed by Sholl analysis at DIV 9 in neurons transfected with MAP2B-FusRed. In mouse cultures, PCB 11 enhanced dendritic arborization in female, but not male, hippocampal neurons and male, but not female, cortical neurons. In rat cultures, PCB 11 promoted dendritic arborization in male and female hippocampal and cortical neurons. PCB 11 also increased axonal growth in mouse and rat neurons of both sexes and neuronal cell types. These data demonstrate that PCB 11 exerts sex-specific effects on neuronal morphogenesis that vary depending on species, neurite type, and neuronal cell type. These findings have significant implications for risk assessment of this emerging developmental neurotoxicant.

Role of PTP1B in POMC neurons during chronic high-fat diet: sex differences in regulation of liver lipids and glucose tolerance.

PubMed

Aberdein, Nicola; Dambrino, Robert J; do Carmo, Jussara M; Wang, Zhen; Mitchell, Laura E; Drummond, Heather A; Hall, John E

2018-03-01

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin receptor signaling and may contribute to leptin resistance in diet-induced obesity. Although PTP1B inhibition has been suggested as a potential weight loss therapy, the role of specific neuronal PTP1B signaling in cardiovascular and metabolic regulation and the importance of sex differences in this regulation are still unclear. In this study, we investigated the impact of proopiomelanocortin (POMC) neuronal PTP1B deficiency in cardiometabolic regulation in male and female mice fed a high-fat diet (HFD). When compared with control mice (PTP1B flox/flox ), male and female mice deficient in POMC neuronal PTP1B (PTP1B flox/flox /POMC-Cre) had attenuated body weight gain (males: -18%; females: -16%) and fat mass (males: -33%; female: -29%) in response to HFD. Glucose tolerance was improved by 40%, and liver lipid accumulation was reduced by 40% in PTP1B/POMC-Cre males but not in females. When compared with control mice, deficiency of POMC neuronal PTP1B did not alter mean arterial pressure (MAP) in male or female mice (males: 112 ± 1 vs. 112 ± 1 mmHg in controls; females: 106 ± 3 vs. 109 ± 3 mmHg in controls). Deficiency of POMC neuronal PTP1B also did not alter MAP response to acute stress in males or females compared with control mice (males: Δ32 ± 0 vs. Δ29 ± 4 mmHg; females: Δ22 ± 2 vs. Δ27 ± 4 mmHg). These data demonstrate that POMC-specific PTP1B deficiency improved glucose tolerance and attenuated diet-induced fatty liver only in male mice and attenuated weight gain in males and females but did not enhance the MAP and HR responses to a HFD or to acute stress.

[Orienting reflex: "targeting reaction" and "searchlight of attention"].

PubMed

Sokolov, E N; Nezlina, N I; Polianskiĭ, V B; Evtikhin, D V

2001-01-01

The concept of orienting reflex based on the principle of vector coding of cognitive and executive processes is proposed. The orienting reflex to non-signal and signal stimuli is a set of orienting reactions: motor, autonomic, neuronal, and subjective emphasizing new and significant stimuli. Two basic mechanisms can be identified within the orienting reflex: a "targeting reaction" and a "searchlight of attention". In the visual system the first one consists in a foveation of a target stimulus. The foveation is performed with participation of premotor neurons excited by saccadic command neurons of the superior colliculi. The "searchlight of attention" is based on the resonance of gamma-oscillations in the reticular thalamus selectively enhancing responses of cortical neurons (involuntary attention). The novelty signal is generated in novelty neurons of the hippocampus, which are selectively tuned to a repeatedly presented standard stimulus. The selective tuning is caused by the depression of plastic synapses representing a "neuronal model" of the standard stimulus. A mismatch of the novel stimulus with the established neuronal model gives rise to a "novelty signal" enhancing the novel input. The novelty signal inhibits current conditioned reflexes (external inhibition) contributing to redirecting the behavior. By triggering the expression of early genes the novelty signal initiates the formation of the long-term memory connected with neoneurogenesis.

Spatial and Feature-Based Attention in a Layered Cortical Microcircuit Model

PubMed Central

Wagatsuma, Nobuhiko; Potjans, Tobias C.; Diesmann, Markus; Sakai, Ko; Fukai, Tomoki

2013-01-01

Directing attention to the spatial location or the distinguishing feature of a visual object modulates neuronal responses in the visual cortex and the stimulus discriminability of subjects. However, the spatial and feature-based modes of attention differently influence visual processing by changing the tuning properties of neurons. Intriguingly, neurons' tuning curves are modulated similarly across different visual areas under both these modes of attention. Here, we explored the mechanism underlying the effects of these two modes of visual attention on the orientation selectivity of visual cortical neurons. To do this, we developed a layered microcircuit model. This model describes multiple orientation-specific microcircuits sharing their receptive fields and consisting of layers 2/3, 4, 5, and 6. These microcircuits represent a functional grouping of cortical neurons and mutually interact via lateral inhibition and excitatory connections between groups with similar selectivity. The individual microcircuits receive bottom-up visual stimuli and top-down attention in different layers. A crucial assumption of the model is that feature-based attention activates orientation-specific microcircuits for the relevant feature selectively, whereas spatial attention activates all microcircuits homogeneously, irrespective of their orientation selectivity. Consequently, our model simultaneously accounts for the multiplicative scaling of neuronal responses in spatial attention and the additive modulations of orientation tuning curves in feature-based attention, which have been observed widely in various visual cortical areas. Simulations of the model predict contrasting differences between excitatory and inhibitory neurons in the two modes of attentional modulations. Furthermore, the model replicates the modulation of the psychophysical discriminability of visual stimuli in the presence of external noise. Our layered model with a biologically suggested laminar structure describes the basic circuit mechanism underlying the attention-mode specific modulations of neuronal responses and visual perception. PMID:24324628

Amygdala connections with jaw, tongue and laryngo-pharyngeal premotor neurons.

PubMed

Van Daele, D J; Fazan, V P S; Agassandian, K; Cassell, M D

2011-03-17

As the central nucleus (CE) is the only amygdaloid nucleus to send axons to the pons and medulla, it is thought to be involved in the expression of conditioned responses by accessing hindbrain circuitry generating stereotypic responses to aversive stimuli. Responses to aversive oral stimuli include gaping and tongue protrusion generated by central pattern generators and other premotor neurons in the ponto-medullary reticular formation. We investigated central nucleus connections with the reticular formation by identifying premotor reticular formation neurons through the retrograde trans-synaptic transport of pseudorabies virus (PRV) inoculated into masseter, genioglossus, thyroarytenoid or inferior constrictor muscles in combination with anterograde labeling of CE axons with biotinylated dextran amine. Three dimensional mapping of PRV infected premotor neurons revealed specific clusters of these neurons associated with different oro-laryngo-pharyngeal muscles, particularly in the parvicellular reticular formation. CE axon terminals were concentrated in certain parvicellular clusters but overall putative contacts were identified with premotor neurons associated with all four oro-laryngo-pharyngeal muscles investigated. We also mapped the retrograde trans-synaptic spread of PRV through the various nuclei of the amygdaloid complex. Medial CE was the first amygdala structure infected (4 days post-inoculation) with trans-synaptic spread to the lateral CE and the caudomedial parvicellular basolateral nucleus by day 5 post-inoculation. Infected neurons were only very rarely found in the lateral capsular CE and the lateral nucleus and then at only the latest time points. The data demonstrate that the CE is directly connected with clusters of reticular premotor neurons that may represent complex pattern generators and/or switching elements for the generation of stereotypic oral and laryngo-pharyngeal movements during aversive oral stimulation. Serial connections through the amygdaloid complex linked with the oro-laryngo-pharyngeal musculature appear quite distinct from those believed to sub-serve fear responses, suggesting there are distinct "channels" for the acquisition and expression of particular conditioned behaviors. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

PubMed

Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytokines and cytokine networks target neurons to modulate long-term potentiation

PubMed Central

Prieto, G. Aleph; Cotman, Carl W.

2017-01-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. PMID:28377062

Cellular identification of water gustatory receptor neurons and their central projection pattern in Drosophila

PubMed Central

Inoshita, Tsuyoshi; Tanimura, Teiichi

2006-01-01

Water perception is important for insects, because they are particularly vulnerable to water loss because their body size is small. In Drosophila, gustatory receptor neurons are located at the base of the taste sensilla on the labellum, tarsi, and wing margins. One of the gustatory receptor neurons in typical sensilla is known to respond to water. To reveal the neural mechanisms of water perception in Drosophila, it is necessary to identify water receptor neurons and their projection patterns. We used a Gal4 enhancer trap strain in which GAL4 is expressed in a single gustatory receptor neuron in each sensillum on the labellum. We investigated the function of these neurons by expressing the upstream activating sequence transgenes, shibirets1, tetanus toxin light chain, or diphtheria toxin A chain. Results from the proboscis extension reflex test and electrophysiological recordings indicated that the GAL4-expressing neurons respond to water. We show here that the water receptor neurons project to a specific region in the subesophageal ganglion, thus revealing the water taste sensory map in Drosophila. PMID:16415164

Toward functional classification of neuronal types.

PubMed

Sharpee, Tatyana O

2014-09-17

How many types of neurons are there in the brain? This basic neuroscience question remains unsettled despite many decades of research. Classification schemes have been proposed based on anatomical, electrophysiological, or molecular properties. However, different schemes do not always agree with each other. This raises the question of whether one can classify neurons based on their function directly. For example, among sensory neurons, can a classification scheme be devised that is based on their role in encoding sensory stimuli? Here, theoretical arguments are outlined for how this can be achieved using information theory by looking at optimal numbers of cell types and paying attention to two key properties: correlations between inputs and noise in neural responses. This theoretical framework could help to map the hierarchical tree relating different neuronal classes within and across species. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevention of posttraumatic axon sprouting by blocking CRMP2-mediated neurite outgrowth and tubulin polymerization

PubMed Central

Wilson, Sarah M.; Xiong, Wenhui; Wang, Yuying; Ping, Xingjie; Head, Jessica D.; Brittain, Joel M.; Gagare, Pravin D.; Ramachandran, P. Veeraraghavan; Jin, Xiaoming; Khanna, Rajesh

2012-01-01

Epileptogenesis following traumatic brain injury (TBI) is likely due to a combination of increased excitability, disinhibition, and increased excitatory connectivity via aberrant axon sprouting. Targeting these pathways could be beneficial in the prevention and treatment of posttraumatic epilepsy. Here, we tested this possibility using the novel anticonvulsant (R)-N-benzyl 2-acetamido-3-methoxypropionamide ((R)-lacosamide (LCM) which acts on both voltage-gated sodium channels and collapsin response mediator protein 2 (CRMP2), an axonal growth/guidance protein. LCM inhibited CRMP2-mediated neurite outgrowth, an effect phenocopied by CRMP2 knockdown. Mutation of LCM binding sites in CRMP2 reduced the neurite inhibitory effect of LCM by ~8-fold. LCM also reduced CRMP2-mediated tubulin polymerization. Thus, LCM selectively impairs CRMP2-mediated microtubule polymerization which underlies its neurite outgrowth and branching. To determine whether LCM inhibits axon sprouting in vivo, LCM was injected into rats subjected to partial cortical isolation, an animal model of posttraumatic epileptogenesis that exhibits axon sprouting in cortical pyramidal neurons. Two weeks following injury, excitatory synaptic connectivity of cortical layer V pyramidal neurons was mapped using patch clamp recordings and laser scanning photostimulation of caged glutamate. In comparison to injured control animals, there was a significant decrease in the map size of excitatory synaptic connectivity in LCM-treated rats, suggesting that LCM treatment prevented enhanced excitatory synaptic connectivity due to posttraumatic axon sprouting. These findings suggest, for the first time, that LCM’s mode of action involves interactions with CRMP2 to inhibit posttraumatic axon sprouting. PMID:22433297

Cytoarchitecture of the spinal cord of the postnatal (P4) mouse.

PubMed

Sengul, Gulgun; Puchalski, Ralph B; Watson, Charles

2012-05-01

Interpretation of the new wealth of gene expression and molecular mechanisms in the developing mouse spinal cord requires an accurate anatomical base on which data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4 mouse to facilitate direct comparison with the adult specimens and to contribute to studies of the development of the mouse spinal cord. This study presents the anatomy of the spinal cord of the P4 C57Bl/6J mouse using Nissl and acetyl cholinesterase-stained sections. It includes a detailed map of the laminar organization of selected spinal cord segments and a description of named cell groups of the spinal cord such as the central cervical (CeCv), lateral spinal nucleus, lateral cervical, and dorsal nuclei. The motor neuron groups have also been identified according to the muscle groups they are likely to supply. General features of Rexed's laminae of the P4 spinal cord showed similarities to that of the adult (P56). However, certain differences were observed with regard to the extent of laminae and location of certain cell groups, such as the dorsal nucleus having a more dispersed structure and a more ventral and medial position or the CeCv being located in the medial part of lamina 5 in contrast to the adult where it is located in lamina 7. Motor neuron pools appeared to be more tightly packed in the P4 spinal cord. The dorsal horn was relatively larger and there was more white matter in the P56 spinal cord. Copyright © 2012 Wiley Periodicals, Inc.

Orientation-Selective Retinal Circuits in Vertebrates

PubMed Central

Antinucci, Paride; Hindges, Robert

2018-01-01

Visual information is already processed in the retina before it is transmitted to higher visual centers in the brain. This includes the extraction of salient features from visual scenes, such as motion directionality or contrast, through neurons belonging to distinct neural circuits. Some retinal neurons are tuned to the orientation of elongated visual stimuli. Such ‘orientation-selective’ neurons are present in the retinae of most, if not all, vertebrate species analyzed to date, with species-specific differences in frequency and degree of tuning. In some cases, orientation-selective neurons have very stereotyped functional and morphological properties suggesting that they represent distinct cell types. In this review, we describe the retinal cell types underlying orientation selectivity found in various vertebrate species, and highlight their commonalities and differences. In addition, we discuss recent studies that revealed the cellular, synaptic and circuit mechanisms at the basis of retinal orientation selectivity. Finally, we outline the significance of these findings in shaping our current understanding of how this fundamental neural computation is implemented in the visual systems of vertebrates. PMID:29467629

Novelty-Sensitive Dopaminergic Neurons in the Human Substantia Nigra Predict Success of Declarative Memory Formation.

PubMed

Kamiński, Jan; Mamelak, Adam N; Birch, Kurtis; Mosher, Clayton P; Tagliati, Michele; Rutishauser, Ueli

2018-05-07

The encoding of information into long-term declarative memory is facilitated by dopamine. This process depends on hippocampal novelty signals, but it remains unknown how midbrain dopaminergic neurons are modulated by declarative-memory-based information. We recorded individual substantia nigra (SN) neurons and cortical field potentials in human patients performing a recognition memory task. We found that 25% of SN neurons were modulated by stimulus novelty. Extracellular waveform shape and anatomical location indicated that these memory-selective neurons were putatively dopaminergic. The responses of memory-selective neurons appeared 527 ms after stimulus onset, changed after a single trial, and were indicative of recognition accuracy. SN neurons phase locked to frontal cortical theta-frequency oscillations, and the extent of this coordination predicted successful memory formation. These data reveal that dopaminergic neurons in the human SN are modulated by memory signals and demonstrate a progression of information flow in the hippocampal-basal ganglia-frontal cortex loop for memory encoding. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Software for Brain Network Simulations: A Comparative Study

PubMed Central

Tikidji-Hamburyan, Ruben A.; Narayana, Vikram; Bozkus, Zeki; El-Ghazawi, Tarek A.

2017-01-01

Numerical simulations of brain networks are a critical part of our efforts in understanding brain functions under pathological and normal conditions. For several decades, the community has developed many software packages and simulators to accelerate research in computational neuroscience. In this article, we select the three most popular simulators, as determined by the number of models in the ModelDB database, such as NEURON, GENESIS, and BRIAN, and perform an independent evaluation of these simulators. In addition, we study NEST, one of the lead simulators of the Human Brain Project. First, we study them based on one of the most important characteristics, the range of supported models. Our investigation reveals that brain network simulators may be biased toward supporting a specific set of models. However, all simulators tend to expand the supported range of models by providing a universal environment for the computational study of individual neurons and brain networks. Next, our investigations on the characteristics of computational architecture and efficiency indicate that all simulators compile the most computationally intensive procedures into binary code, with the aim of maximizing their computational performance. However, not all simulators provide the simplest method for module development and/or guarantee efficient binary code. Third, a study of their amenability for high-performance computing reveals that NEST can almost transparently map an existing model on a cluster or multicore computer, while NEURON requires code modification if the model developed for a single computer has to be mapped on a computational cluster. Interestingly, parallelization is the weakest characteristic of BRIAN, which provides no support for cluster computations and limited support for multicore computers. Fourth, we identify the level of user support and frequency of usage for all simulators. Finally, we carry out an evaluation using two case studies: a large network with simplified neural and synaptic models and a small network with detailed models. These two case studies allow us to avoid any bias toward a particular software package. The results indicate that BRIAN provides the most concise language for both cases considered. Furthermore, as expected, NEST mostly favors large network models, while NEURON is better suited for detailed models. Overall, the case studies reinforce our general observation that simulators have a bias in the computational performance toward specific types of the brain network models. PMID:28775687

Differential Receptive Field Properties of Parvalbumin and Somatostatin Inhibitory Neurons in Mouse Auditory Cortex.

PubMed

Li, Ling-Yun; Xiong, Xiaorui R; Ibrahim, Leena A; Yuan, Wei; Tao, Huizhong W; Zhang, Li I

2015-07-01

Cortical inhibitory circuits play important roles in shaping sensory processing. In auditory cortex, however, functional properties of genetically identified inhibitory neurons are poorly characterized. By two-photon imaging-guided recordings, we specifically targeted 2 major types of cortical inhibitory neuron, parvalbumin (PV) and somatostatin (SOM) expressing neurons, in superficial layers of mouse auditory cortex. We found that PV cells exhibited broader tonal receptive fields with lower intensity thresholds and stronger tone-evoked spike responses compared with SOM neurons. The latter exhibited similar frequency selectivity as excitatory neurons. The broader/weaker frequency tuning of PV neurons was attributed to a broader range of synaptic inputs and stronger subthreshold responses elicited, which resulted in a higher efficiency in the conversion of input to output. In addition, onsets of both the input and spike responses of SOM neurons were significantly delayed compared with PV and excitatory cells. Our results suggest that PV and SOM neurons engage in auditory cortical circuits in different manners: while PV neurons may provide broadly tuned feedforward inhibition for a rapid control of ascending inputs to excitatory neurons, the delayed and more selective inhibition from SOM neurons may provide a specific modulation of feedback inputs on their distal dendrites. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity.

PubMed

Li, Qingyun; Barish, Scott; Okuwa, Sumie; Maciejewski, Abigail; Brandt, Alicia T; Reinhold, Dominik; Jones, Corbin D; Volkan, Pelin Cayirlioglu

2016-01-01

Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, the olfactory environment is detected by 50 different olfactory receptor neuron (ORN) classes that are clustered in combinations within distinct sensilla subtypes. Each sensilla subtype houses stereotypically clustered 1-4 ORN identities that arise through asymmetric divisions from a single multipotent sensory organ precursor (SOP). How each class of SOPs acquires a unique differentiation potential that accounts for ORN diversity is unknown. Previously, we reported a critical component of SOP diversification program, Rotund (Rn), increases ORN diversity by generating novel developmental trajectories from existing precursors within each independent sensilla type lineages. Here, we show that Rn, along with BarH1/H2 (Bar), Bric-à-brac (Bab), Apterous (Ap) and Dachshund (Dac), constitutes a transcription factor (TF) network that patterns the developing olfactory tissue. This network was previously shown to pattern the segmentation of the leg, which suggests that this network is functionally conserved. In antennal imaginal discs, precursors with diverse ORN differentiation potentials are selected from concentric rings defined by unique combinations of these TFs along the proximodistal axis of the developing antennal disc. The combinatorial code that demarcates each precursor field is set up by cross-regulatory interactions among different factors within the network. Modifications of this network lead to predictable changes in the diversity of sensilla subtypes and ORN pools. In light of our data, we propose a molecular map that defines each unique SOP fate. Our results highlight the importance of the early prepatterning gene regulatory network as a modulator of SOP and terminally differentiated ORN diversity. Finally, our model illustrates how conserved developmental strategies are used to generate neuronal diversity.

The Opponent Channel Population Code of Sound Location Is an Efficient Representation of Natural Binaural Sounds

PubMed Central

Młynarski, Wiktor

2015-01-01

In mammalian auditory cortex, sound source position is represented by a population of broadly tuned neurons whose firing is modulated by sounds located at all positions surrounding the animal. Peaks of their tuning curves are concentrated at lateral position, while their slopes are steepest at the interaural midline, allowing for the maximum localization accuracy in that area. These experimental observations contradict initial assumptions that the auditory space is represented as a topographic cortical map. It has been suggested that a “panoramic” code has evolved to match specific demands of the sound localization task. This work provides evidence suggesting that properties of spatial auditory neurons identified experimentally follow from a general design principle- learning a sparse, efficient representation of natural stimuli. Natural binaural sounds were recorded and served as input to a hierarchical sparse-coding model. In the first layer, left and right ear sounds were separately encoded by a population of complex-valued basis functions which separated phase and amplitude. Both parameters are known to carry information relevant for spatial hearing. Monaural input converged in the second layer, which learned a joint representation of amplitude and interaural phase difference. Spatial selectivity of each second-layer unit was measured by exposing the model to natural sound sources recorded at different positions. Obtained tuning curves match well tuning characteristics of neurons in the mammalian auditory cortex. This study connects neuronal coding of the auditory space with natural stimulus statistics and generates new experimental predictions. Moreover, results presented here suggest that cortical regions with seemingly different functions may implement the same computational strategy-efficient coding. PMID:25996373

Two symmetry-breaking mechanisms for the development of orientation selectivity in a neural system

NASA Astrophysics Data System (ADS)

Cho, Myoung Won; Chun, Min Young

2015-11-01

Orientation selectivity is a remarkable feature of the neurons located in the primary visual cortex. Provided that the visual neurons acquire orientation selectivity through activity-dependent Hebbian learning, the development process could be understood as a kind of symmetry-breaking phenomenon in the view of physics. This paper examines the key mechanisms of the orientation selectivity development process. Be found that at least two different mechanisms, which lead to the development of orientation selectivity by breaking the radial symmetry in receptive fields. The first is a simultaneous symmetry-breaking mechanism occurring based on the competition between neighboring neurons, and the second is a spontaneous one occurring based on the nonlinearity in interactions. Only the second mechanism leads to the formation of a columnar pattern whose characteristics is in accord with those observed in an animal experiment.

Neurons responsive to face-view in the primate ventrolateral prefrontal cortex.

PubMed

Romanski, L M; Diehl, M M

2011-08-25

Studies have indicated that temporal and prefrontal brain regions process face and vocal information. Face-selective and vocalization-responsive neurons have been demonstrated in the ventrolateral prefrontal cortex (VLPFC) and some prefrontal cells preferentially respond to combinations of face and corresponding vocalizations. These studies suggest VLPFC in nonhuman primates may play a role in communication that is similar to the role of inferior frontal regions in human language processing. If VLPFC is involved in communication, information about a speaker's face including identity, face-view, gaze, and emotional expression might be encoded by prefrontal neurons. In the following study, we examined the effect of face-view in ventrolateral prefrontal neurons by testing cells with auditory, visual, and a set of human and monkey faces rotated through 0°, 30°, 60°, 90°, and -30°. Prefrontal neurons responded selectively to either the identity of the face presented (human or monkey) or to the specific view of the face/head, or to both identity and face-view. Neurons which were affected by the identity of the face most often showed an increase in firing in the second part of the stimulus period. Neurons that were selective for face-view typically preferred forward face-view stimuli (0° and 30° rotation). The neurons which were selective for forward face-view were also auditory responsive compared to other neurons which responded to other views or were unselective which were not auditory responsive. Our analysis showed that the human forward face (0°) was decoded better and also contained the most information relative to other face-views. Our findings confirm a role for VLPFC in the processing and integration of face and vocalization information and add to the growing body of evidence that the primate ventrolateral prefrontal cortex plays a prominent role in social communication and is an important model in understanding the cellular mechanisms of communication. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Neurons responsive to face-view in the Primate Ventrolateral Prefrontal Cortex

PubMed Central

Romanski, Lizabeth M.; Diehl, Maria M.

2011-01-01

Studies have indicated that temporal and prefrontal brain regions process face and vocal information. Face-selective and vocalization-responsive neurons have been demonstrated in the ventrolateral prefrontal cortex (VLPFC) and some prefrontal cells preferentially respond to combinations of face and corresponding vocalizations. These studies suggest VLPFC in non-human primates may play a role in communication that is similar to the role of inferior frontal regions in human language processing. If VLPFC is involved in communication, information about a speaker's face including identity, face-view, gaze and emotional expression might be encoded by prefrontal neurons. In the following study, we examined the effect of face-view in ventrolateral prefrontal neurons by testing cells with auditory, visual, and a set of human and monkey faces rotated through 0°, 30°, 60°, 90°, and −30°. Prefrontal neurons responded selectively to either the identity of the face presented (human or monkey) or to the specific view of the face/head, or to both identity and face-view. Neurons which were affected by the identity of the face most often showed an increase in firing in the second part of the stimulus period. Neurons that were selective for face-view typically preferred forward face-view stimuli (0° and 30° rotation). The neurons which were selective for forward face-view were also auditory responsive compared to other neurons which responded to other views or were unselective which were not auditory responsive. Our analysis showed that the human forward face (0°) was decoded better and also contained the most information relative to other face-views. Our findings confirm a role for VLPFC in the processing and integration of face and vocalization information and add to the growing body of evidence that the primate ventrolateral prefrontal cortex plays a prominent role in social communication and is an important model in understanding the cellular mechanisms of communication. PMID:21605632

Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice

PubMed Central

Liu, Yang; Huang, Ying; Liu, Tiemin; Wu, Hua; Cui, Huxing

2016-01-01

Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia. PMID:27111742

Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice.

PubMed

Liu, Yang; Huang, Ying; Liu, Tiemin; Wu, Hua; Cui, Huxing; Gautron, Laurent

2016-06-01

Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia.

Selective ablation of dorsal horn NK1 expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones.

PubMed

Rahman, Wahida; Suzuki, Rie; Hunt, Stephen P; Dickenson, Anthony H

2008-06-01

Activity in descending systems from the brainstem modulates nociceptive transmission through the dorsal horn. Intrathecal injection of the neurotoxin saporin conjugated to SP (SP-SAP) into the lumbar spinal cord results in the selective ablation of NK(1) receptor expressing (NK(1)+ve) neurones in the superficial dorsal horn (lamina I/III). Loss of these NK(1)+ve neurones attenuates excitability of deep dorsal horn neurones due to a disruption of both intrinsic spinal circuits and a spino-bulbo-spinal loop, which activates a descending excitatory drive, mediated through spinal 5HT(3) receptors. Descending inhibitory pathways also modulate spinal activity and hence control the level of nociceptive transmission relayed to higher centres. To ascertain the spinal origins of the major descending noradrenergic inhibitory pathway we studied the effects of a selective alpha2-adrenoceptor antagonist, atipamezole, on neuronal activity in animals pre-treated with SP-SAP. Intrathecal application of atipamezole dose dependently facilitated the mechanically evoked neuronal responses of deep dorsal horn neurones to low intensity von Frey hairs (5-15 g) and noxious thermal (45-50 degrees C) evoked responses in SAP control animals indicating a physiological alpha2-adrenoceptor control. This facilitatory effect of atipamezole was lost in the SP-SAP treated group. These data suggest that activity within noradrenergic pathways have a dependence on dorsal horn NK(1)+ve cells. Further, noradrenergic descending inhibition may in part be driven by lamina I/III (NK(1)+ve) cells, and mediated via spinal alpha2-adrenoceptor activation. Since the same neuronal population drives descending facilitation and inhibition, the reduced excitability of lamina V/VI WDR neurones seen after loss of these NK(1)+ve neurones indicates a dominant role of descending facilitation.

Encoding of Target Detection during Visual Search by Single Neurons in the Human Brain.

PubMed

Wang, Shuo; Mamelak, Adam N; Adolphs, Ralph; Rutishauser, Ueli

2018-06-08

Neurons in the primate medial temporal lobe (MTL) respond selectively to visual categories such as faces, contributing to how the brain represents stimulus meaning. However, it remains unknown whether MTL neurons continue to encode stimulus meaning when it changes flexibly as a function of variable task demands imposed by goal-directed behavior. While classically associated with long-term memory, recent lesion and neuroimaging studies show that the MTL also contributes critically to the online guidance of goal-directed behaviors such as visual search. Do such tasks modulate responses of neurons in the MTL, and if so, do their responses mirror bottom-up input from visual cortices or do they reflect more abstract goal-directed properties? To answer these questions, we performed concurrent recordings of eye movements and single neurons in the MTL and medial frontal cortex (MFC) in human neurosurgical patients performing a memory-guided visual search task. We identified a distinct population of target-selective neurons in both the MTL and MFC whose response signaled whether the currently fixated stimulus was a target or distractor. This target-selective response was invariant to visual category and predicted whether a target was detected or missed behaviorally during a given fixation. The response latencies, relative to fixation onset, of MFC target-selective neurons preceded those in the MTL by ∼200 ms, suggesting a frontal origin for the target signal. The human MTL thus represents not only fixed stimulus identity, but also task-specified stimulus relevance due to top-down goal relevance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neural-Network Computer Transforms Coordinates

NASA Technical Reports Server (NTRS)

Josin, Gary M.

1990-01-01

Numerical simulation demonstrated ability of conceptual neural-network computer to generalize what it has "learned" from few examples. Ability to generalize achieved with even simple neural network (relatively few neurons) and after exposure of network to only few "training" examples. Ability to obtain fairly accurate mappings after only few training examples used to provide solutions to otherwise intractable mapping problems.

Selective optogenetic stimulation of the retrotrapezoid nucleus in sleeping rats activates breathing without changing blood pressure or causing arousal or sighs

PubMed Central

Burke, Peter G. R.; Kanbar, Roy; Viar, Kenneth E.; Stornetta, Ruth L.

2015-01-01

Combined optogenetic activation of the retrotrapezoid nucleus (RTN; a CO2/proton-activated brainstem nucleus) with nearby catecholaminergic neurons (C1 and A5), or selective C1 neuron stimulation, increases blood pressure (BP) and breathing, causes arousal from non-rapid eye movement (non-REM) sleep, and triggers sighs. Here we wished to determine which of these physiological responses are elicited when RTN neurons are selectively activated. The left rostral RTN and nearby A5 neurons were transduced with channelrhodopsin-2 (ChR2+) using a lentiviral vector. Very few C1 cells were transduced. BP, breathing, EEG, and neck EMG were monitored. During non-REM sleep, photostimulation of ChR2+ neurons (20s, 2-20 Hz) instantly increased V̇e without changing BP (13 rats). V̇e and BP were unaffected by light in nine control (ChR2−) rats. Photostimulation produced no sighs and caused arousal (EEG desynchronization) more frequently in ChR2+ than ChR2− rats (62 ± 5% of trials vs. 25 ± 2%; P < 0.0001). Six ChR2+ rats then received spinal injections of a saporin-based toxin that spared RTN neurons but destroyed surrounding catecholaminergic neurons. Photostimulation of the ChR2+ neurons produced the same ventilatory stimulation before and after lesion, but arousal was no longer elicited. Overall (all ChR2+ rats combined), ΔV̇e correlated with the number of ChR2+ RTN neurons whereas arousal probability correlated with the number of ChR2+ catecholaminergic neurons. In conclusion, RTN neurons activate breathing powerfully and, unlike the C1 cells, have minimal effects on BP and have a weak arousal capability at best. A5 neuron stimulation produces little effect on breathing and BP but does appear to facilitate arousal. PMID:25858492

LGR5/GPR49 is implicated in motor neuron specification in nervous system.

PubMed

Song, Shao-jun; Mao, Xing-gang; Wang, Chao; Han, An-guo; Yan, Ming; Xue, Xiao-yan

2015-01-01

The biological roles of stem cell marker LGR5, the receptor for the Wnt-agonistic R-spondins, for nervous system are poorly known. Bioinformatics analysis in normal human brain tissues revealed that LGR5 is closely related with neuron development and functions. Interestingly, LGR5 and its ligands R-spondins (RSPO2 and RSPO3) are specifically highly expressed in projection motor neurons in the spinal cord, brain stem and cerebral. Inhibition of Notch activity in neural stem cells (NSCs) increased the percentage of neuronal cells and promoted LGR5 expression, while activation of Notch signal decreased neuronal cells and inhibited the LGR5 expression. Furthermore, knockdown of LGR5 inhibited the expression of neuronal markers MAP2, NeuN, GAP43, SYP and CHRM3, and also reduced the expression of genes that program the identity of motor neurons, including Isl1, Lhx3, PHOX2A, TBX20 and NEUROG2. Our data demonstrated that LGR5 is highly expressed in motor neurons in nervous system and is involved in their development by regulating transcription factors that program motor neuron identity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Age of Enlightenment: Evolving Opportunities in Brain Research Through Optical Manipulation of Neuronal Activity

PubMed Central

Jerome, Jason; Heck, Detlef H.

2011-01-01

Optical manipulation of neuronal activity has rapidly developed into the most powerful and widely used approach to study mechanisms related to neuronal connectivity over a range of scales. Since the early use of single site uncaging to map network connectivity, rapid technological development of light modulation techniques has added important new options, such as fast scanning photostimulation, massively parallel control of light stimuli, holographic uncaging, and two-photon stimulation techniques. Exciting new developments in optogenetics complement neurotransmitter uncaging techniques by providing cell-type specificity and in vivo usability, providing optical access to the neural substrates of behavior. Here we review the rapid evolution of methods for the optical manipulation of neuronal activity, emphasizing crucial recent developments. PMID:22275886

The age of enlightenment: evolving opportunities in brain research through optical manipulation of neuronal activity.

PubMed

Jerome, Jason; Heck, Detlef H

2011-01-01

Optical manipulation of neuronal activity has rapidly developed into the most powerful and widely used approach to study mechanisms related to neuronal connectivity over a range of scales. Since the early use of single site uncaging to map network connectivity, rapid technological development of light modulation techniques has added important new options, such as fast scanning photostimulation, massively parallel control of light stimuli, holographic uncaging, and two-photon stimulation techniques. Exciting new developments in optogenetics complement neurotransmitter uncaging techniques by providing cell-type specificity and in vivo usability, providing optical access to the neural substrates of behavior. Here we review the rapid evolution of methods for the optical manipulation of neuronal activity, emphasizing crucial recent developments.

Prenatal choline deficiency decreases the cross-sectional area of cholinergic neurons in the medial septal nucleus.

PubMed

McKeon-O'Malley, Catherine; Siwek, Donald; Lamoureux, Jeffrey A; Williams, Christina L; Kowall, Neil W

2003-07-11

Levels of dietary choline in utero influence postnatal cognitive performance. To better understand this phenomenon, forebrain cholinergic neurons were studied in the 8-9 month old offspring of dams fed a control or choline-deficient diet from EDs 11-17. Serial sections were immunostained with antibodies against p75, a cholinergic marker. Neuronal morphology was analyzed in the basal forebrain, a heterogeneous area composed of several structures including the medial septal nucleus (MSN), nucleus of the diagonal band (DB), and the nucleus basalis of Meynert (NB). Neuronal cross-sectional areas were selectively reduced in the MSN of choline-deficient animals, compared to controls, but cell counts were not altered. Our findings suggest that cholinergic medial septal neurons may be selectively vulnerable to in utero choline deficiency.

Novel Models of Visual Topographic Map Alignment in the Superior Colliculus

PubMed Central

El-Ghazawi, Tarek A.; Triplett, Jason W.

2016-01-01

The establishment of precise neuronal connectivity during development is critical for sensing the external environment and informing appropriate behavioral responses. In the visual system, many connections are organized topographically, which preserves the spatial order of the visual scene. The superior colliculus (SC) is a midbrain nucleus that integrates visual inputs from the retina and primary visual cortex (V1) to regulate goal-directed eye movements. In the SC, topographically organized inputs from the retina and V1 must be aligned to facilitate integration. Previously, we showed that retinal input instructs the alignment of V1 inputs in the SC in a manner dependent on spontaneous neuronal activity; however, the mechanism of activity-dependent instruction remains unclear. To begin to address this gap, we developed two novel computational models of visual map alignment in the SC that incorporate distinct activity-dependent components. First, a Correlational Model assumes that V1 inputs achieve alignment with established retinal inputs through simple correlative firing mechanisms. A second Integrational Model assumes that V1 inputs contribute to the firing of SC neurons during alignment. Both models accurately replicate in vivo findings in wild type, transgenic and combination mutant mouse models, suggesting either activity-dependent mechanism is plausible. In silico experiments reveal distinct behaviors in response to weakening retinal drive, providing insight into the nature of the system governing map alignment depending on the activity-dependent strategy utilized. Overall, we describe novel computational frameworks of visual map alignment that accurately model many aspects of the in vivo process and propose experiments to test them. PMID:28027309

Fine and distributed subcellular retinotopy of excitatory inputs to the dendritic tree of a collision-detecting neuron

PubMed Central

Zhu, Ying

2016-01-01

Individual neurons in several sensory systems receive synaptic inputs organized according to subcellular topographic maps, yet the fine structure of this topographic organization and its relation to dendritic morphology have not been studied in detail. Subcellular topography is expected to play a role in dendritic integration, particularly when dendrites are extended and active. The lobula giant movement detector (LGMD) neuron in the locust visual system is known to receive topographic excitatory inputs on part of its dendritic tree. The LGMD responds preferentially to objects approaching on a collision course and is thought to implement several interesting dendritic computations. To study the fine retinotopic mapping of visual inputs onto the excitatory dendrites of the LGMD, we designed a custom microscope allowing visual stimulation at the native sampling resolution of the locust compound eye while simultaneously performing two-photon calcium imaging on excitatory dendrites. We show that the LGMD receives a distributed, fine retinotopic projection from the eye facets and that adjacent facets activate overlapping portions of the same dendritic branches. We also demonstrate that adjacent retinal inputs most likely make independent synapses on the excitatory dendrites of the LGMD. Finally, we show that the fine topographic mapping can be studied using dynamic visual stimuli. Our results reveal the detailed structure of the dendritic input originating from individual facets on the eye and their relation to that of adjacent facets. The mapping of visual space onto the LGMD's dendrites is expected to have implications for dendritic computation. PMID:27009157

Simultaneous imaging of neural activity in three dimensions

PubMed Central

Quirin, Sean; Jackson, Jesse; Peterka, Darcy S.; Yuste, Rafael

2014-01-01

We introduce a scanless optical method to image neuronal activity in three dimensions simultaneously. Using a spatial light modulator and a custom-designed phase mask, we illuminate and collect light simultaneously from different focal planes and perform calcium imaging of neuronal activity in vitro and in vivo. This method, combining structured illumination with volume projection imaging, could be used as a technological platform for brain activity mapping. PMID:24772066

Potential roles of the interaction between model V1 neurons with orientation-selective and non-selective surround inhibition in contour detection

PubMed Central

Yang, Kai-Fu; Li, Chao-Yi; Li, Yong-Jie

2015-01-01

Both the neurons with orientation-selective and with non-selective surround inhibition have been observed in the primary visual cortex (V1) of primates and cats. Though the inhibition coming from the surround region (named as non-classical receptive field, nCRF) has been considered playing critical role in visual perception, the specific role of orientation-selective and non-selective inhibition in the task of contour detection is less known. To clarify above question, we first carried out computational analysis of the contour detection performance of V1 neurons with different types of surround inhibition, on the basis of which we then proposed two integrated models to evaluate their role in this specific perceptual task by combining the two types of surround inhibition with two different ways. The two models were evaluated with synthetic images and a set of challenging natural images, and the results show that both of the integrated models outperform the typical models with orientation-selective or non-selective inhibition alone. The findings of this study suggest that V1 neurons with different types of center–surround interaction work in cooperative and adaptive ways at least when extracting organized structures from cluttered natural scenes. This work is expected to inspire efficient phenomenological models for engineering applications in field of computational machine-vision. PMID:26136664

Potential roles of the interaction between model V1 neurons with orientation-selective and non-selective surround inhibition in contour detection.

PubMed

Yang, Kai-Fu; Li, Chao-Yi; Li, Yong-Jie

2015-01-01

Both the neurons with orientation-selective and with non-selective surround inhibition have been observed in the primary visual cortex (V1) of primates and cats. Though the inhibition coming from the surround region (named as non-classical receptive field, nCRF) has been considered playing critical role in visual perception, the specific role of orientation-selective and non-selective inhibition in the task of contour detection is less known. To clarify above question, we first carried out computational analysis of the contour detection performance of V1 neurons with different types of surround inhibition, on the basis of which we then proposed two integrated models to evaluate their role in this specific perceptual task by combining the two types of surround inhibition with two different ways. The two models were evaluated with synthetic images and a set of challenging natural images, and the results show that both of the integrated models outperform the typical models with orientation-selective or non-selective inhibition alone. The findings of this study suggest that V1 neurons with different types of center-surround interaction work in cooperative and adaptive ways at least when extracting organized structures from cluttered natural scenes. This work is expected to inspire efficient phenomenological models for engineering applications in field of computational machine-vision.

Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases

PubMed Central

Engstrom, Anna; Wang, Hao; Xia, Zhengui

2015-01-01

Adult hippocampal neurogenesis is the process whereby adult neural precursor cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate adult-born, functional neurons in the hippocampus. This process is modulated by various extracellular and intracellular stimuli, and the adult-born neurons have been implicated in hippocampus-dependent learning and memory. However, studies on how neurotoxic agents affect this process and the underlying mechanisms are limited. The goal of this study was to determine whether lead, a heavy metal, directly impairs critical processes in adult neurogenesis and to characterize the underlying signaling pathways using primary cultured SGZ-aNPCs isolated from adult mice. We report here that lead significantly increases apoptosis and inhibits proliferation in SGZ-aNPCs. In addition, lead significantly impairs spontaneous neuronal differentiation and maturation. Furthermore, we found that activation of the c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase signaling pathways are important for lead cytotoxicity. Our data suggest that lead can directly act on adult neural stem cells and impair critical processes in adult hippocampal neurogenesis, which may contribute to its neurotoxicity and adverse effects on cognition in adults. PMID:25967738

Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases.

PubMed

Engstrom, Anna; Wang, Hao; Xia, Zhengui

2015-08-01

Adult hippocampal neurogenesis is the process whereby adult neural precursor cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate adult-born, functional neurons in the hippocampus. This process is modulated by various extracellular and intracellular stimuli, and the adult-born neurons have been implicated in hippocampus-dependent learning and memory. However, studies on how neurotoxic agents affect this process and the underlying mechanisms are limited. The goal of this study was to determine whether lead, a heavy metal, directly impairs critical processes in adult neurogenesis and to characterize the underlying signaling pathways using primary cultured SGZ-aNPCs isolated from adult mice. We report here that lead significantly increases apoptosis and inhibits proliferation in SGZ-aNPCs. In addition, lead significantly impairs spontaneous neuronal differentiation and maturation. Furthermore, we found that activation of the c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase signaling pathways are important for lead cytotoxicity. Our data suggest that lead can directly act on adult neural stem cells and impair critical processes in adult hippocampal neurogenesis, which may contribute to its neurotoxicity and adverse effects on cognition in adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

Overexpression of MAP2 and NF-H Associated with Dendritic Pathology in the Spinal Cord of Mice Infected with Rabies Virus

PubMed Central

Santamaría, Gerardo; Torres-Fernández, Orlando

2018-01-01

Rabies is a viral infection that targets the nervous system, specifically neurons. The clinical manifestations of the disease are dramatic and their outcome fatal; paradoxically, conventional histopathological descriptions reveal only subtle changes in the affected nervous tissue. Some researchers have considered that the pathophysiology of rabies is based more on biochemical changes than on structural alterations, as is the case with some psychiatric diseases. However, we believe that it has been necessary to resort to other methods that allow us to analyze the effect of the infection on neurons. The Golgi technique is the gold standard for studying the morphology of all the components of a neuron and the cytoskeletal proteins are the structural support of dendrites and axons. We have previously shown, in the mouse cerebral cortex and now with this work in spinal cord, that rabies virus generates remarkable alterations in the morphological pattern of the neurons and that this effect is associated with the increase in the expression of two cytoskeletal proteins (MAP2 and NF-H). It is necessary to deepen the investigation of the pathogenesis of rabies in order to find therapeutic alternatives to a disease to which the World Health Organization classifies as a neglected disease. PMID:29509660

Fragile X Mental Retardation Protein Restricts Small Dye Iontophoresis Entry into Central Neurons

PubMed Central

2017-01-01

Fragile X mental retardation protein (FMRP) loss causes Fragile X syndrome (FXS), a major disorder characterized by autism, intellectual disability, hyperactivity, and seizures. FMRP is both an RNA- and channel-binding regulator, with critical roles in neural circuit formation and function. However, it remains unclear how these FMRP activities relate to each other and how dysfunction in their absence underlies FXS neurological symptoms. In testing circuit level defects in the Drosophila FXS model, we discovered a completely unexpected and highly robust neuronal dye iontophoresis phenotype in the well mapped giant fiber (GF) circuit. Controlled dye injection into the GF interneuron results in a dramatic increase in dye uptake in neurons lacking FMRP. Transgenic wild-type FMRP reintroduction rescues the mutant defect, demonstrating a specific FMRP requirement. This phenotype affects only small dyes, but is independent of dye charge polarity. Surprisingly, the elevated dye iontophoresis persists in shaking B mutants that eliminate gap junctions and dye coupling among GF circuit neurons. We therefore used a wide range of manipulations to investigate the dye uptake defect, including timed injection series, pharmacology and ion replacement, and optogenetic activity studies. The results show that FMRP strongly limits the rate of dye entry via a cytosolic mechanism. This study reveals an unexpected new phenotype in a physical property of central neurons lacking FMRP that could underlie aspects of FXS disruption of neural function. SIGNIFICANCE STATEMENT FXS is a leading heritable cause of intellectual disability and autism spectrum disorders. Although researchers established the causal link with FMRP loss >;25 years ago, studies continue to reveal diverse FMRP functions. The Drosophila FXS model is key to discovering new FMRP roles, because of its genetic malleability and individually identified neuron maps. Taking advantage of a well characterized Drosophila neural circuit, we discovered that neurons lacking FMRP take up dramatically more current-injected small dye. After examining many neuronal properties, we determined that this dye defect is cytoplasmic and occurs due to a highly elevated dye iontophoresis rate. We also report several new factors affecting neuron dye uptake. Understanding how FMRP regulates iontophoresis should reveal new molecular factors underpinning FXS dysfunction. PMID:28887386

Birthdating of myenteric neuron subtypes in the small intestine of the mouse.

PubMed

Bergner, Annette J; Stamp, Lincon A; Gonsalvez, David G; Allison, Margaret B; Olson, David P; Myers, Martin G; Anderson, Colin R; Young, Heather M

2014-02-15

There are many different types of enteric neurons. Previous studies have identified the time at which some enteric neuron subtypes are born (exit the cell cycle) in the mouse, but the birthdates of some major enteric neuron subtypes are still incompletely characterized or unknown. We combined 5-ethynynl-2'-deoxyuridine (EdU) labeling with antibody markers that identify myenteric neuron subtypes to determine when neuron subtypes are born in the mouse small intestine. We found that different neurochemical classes of enteric neuron differed in their birthdates; serotonin neurons were born first with peak cell cycle exit at E11.5, followed by neurofilament-M neurons, calcitonin gene-related peptide neurons (peak cell cycle exit for both at embryonic day [E]12.5-E13.5), tyrosine hydroxylase neurons (E15.5), nitric oxide synthase 1 (NOS1) neurons (E15.5), and calretinin neurons (postnatal day [P]0). The vast majority of myenteric neurons had exited the cell cycle by P10. We did not observe any EdU+/NOS1+ myenteric neurons in the small intestine of adult mice following EdU injection at E10.5 or E11.5, which was unexpected, as previous studies have shown that NOS1 neurons are present in E11.5 mice. Studies using the proliferation marker Ki67 revealed that very few NOS1 neurons in the E11.5 and E12.5 gut were proliferating. However, Cre-lox-based genetic fate-mapping revealed a small subpopulation of myenteric neurons that appears to express NOS1 only transiently. Together, our results confirm a relationship between enteric neuron subtype and birthdate, and suggest that some enteric neurons exhibit neurochemical phenotypes during development that are different from their mature phenotype. Copyright © 2013 Wiley Periodicals, Inc.

Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways.

PubMed

Kim, Jisung; Lee, Siyoung; Choi, Bo-Ryoung; Yang, Hee; Hwang, Youjin; Park, Jung Han Yoon; LaFerla, Frank M; Han, Jung-Soo; Lee, Ki Won; Kim, Jiyoung

2017-02-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways. Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane. Sulforaphane enhanced neuronal BDNF expression and increased levels of neuronal and synaptic molecules such as MAP2, synaptophysin, and PSD-95 in primary cortical neurons and 3 × Tg-AD mice. Sulforaphane elevated levels of synaptic TrkB signaling pathway components, including CREB, CaMKII, ERK, and Akt in both primary cortical neurons and 3 × Tg-AD mice. Sulforaphane increased global acetylation of histone 3 (H3) and H4, inhibited HDAC activity, and decreased the level of HDAC2 in primary cortical neurons. Chromatin immunoprecipitation analysis revealed that sulforaphane increased acetylated H3 and H4 at BDNF promoters, suggesting that sulforaphane regulates BDNF expression via HDAC inhibition. These findings suggest that sulforaphane has the potential to prevent neuronal disorders such as Alzheimer's disease by epigenetically enhancing neuronal BDNF expression and its TrkB signaling pathways. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bursting Transition Dynamics Within the Pre-Bötzinger Complex

NASA Astrophysics Data System (ADS)

Duan, Lixia; Chen, Xi; Tang, Xuhui; Su, Jianzhong

The pre-Bötzinger complex of the mammalian brain stem plays a crucial role in the respiratory rhythms generation. Neurons within the pre-Bötzinger complex have been found experimentally to yield different firing activities. In this paper, we study the spiking and bursting activities related to the respiratory rhythms in the pre-Bötzinger complex based on a mathematical model proposed by Butera. Using the one-dimensional first recurrence map induced by dynamics, we investigate the different bursting patterns and their transition of the pre-Bötzinger complex neurons based on the Butera model, after we derived a one-dimensional map from the dynamical characters of the differential equations, and we obtained conditions for the transition of different bursting patterns. These analytical results were verified through numerical simulations. We conclude that the one-dimensional map contains similar rhythmic patterns as the Butera model and can be used as a simpler modeling tool to study fast-slow models like pre-Bötzinger complex neural circuit.

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

Switches for multiple behavioral states and a viral-based approach to non-invasive whole-brain cargo delivery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Gradinaru, Viviana

2017-05-01

Over the past years we have worked on: (1) Viral-based approaches to non-invasive whole-brain cargo delivery: Genetically-encoded tools that can be used to visualize, monitor, and modulate mammalian neurons are revolutionizing neuroscience. These tools are particularly powerful in rodents and invertebrate models where intersectional transgenic strategies are available to restrict their expression to defined cell populations. However, use of genetic tools in non-transgenic animals is often hindered by the lack of vectors capable of safe, efficient, and specific delivery to the desired cellular targets. To begin to address these challenges, we have developed an in vivo Cre-based selection platform (CREATE) for identifying adeno-associated viruses (AAVs) that more efficiently transduce genetically defined cell populations. Our platform's novelty and power arises from the additional selective pressure imparted by a recovery step that amplifies only those capsid variants that have functionally transduced a genetically-defined, Cre-expressing target cell population. The Cre-dependent capsid recovery works within heterogeneous tissue samples without the need for additional steps such as selective capsid recovery approaches that require cell sorting or secondary adenovirus infection. As a first test of the CREATE platform, we selected for viruses that transduced the brain after intravascular delivery and found a novel vector, AAV-PHP.B, that is 40- to 90-fold more efficient at transducing the brain than the current standard, AAV9. AAV-PHP.B transduces most neuronal types and glia across the brain. We also demonstrate here how whole-body tissue clearing can facilitate transduction maps of systemically delivered genes. Since CNS disorders are notoriously challenging due to the restrictive nature of the blood brain barrier our discovery that recombinant vectors can be engineered to overcome this barrier is enabling for the whole field. With the exciting advances in gene editing via the CRISPR-Cas, RNA interference and gene replacement strategies, the availability of potent gene delivery methods provided by vectors such as our reported AAV-PHP.B is key to advancing the field of genome engineering. • Deverman BE, Pravdo P, Simpson B, Banerjee A, Kumar, S.R., Chan K, Wu WL, Yang B, Gradinaru V. Cre-Dependent Capsid Selection Yields AAVs for Global Gene Transfer to the Adult Brain. Nature Biotechnol. 2016 Feb 34(2):204-9. PMID: 26829320 • Yang B, Treweek JB, Kulkarni RP, Deverman BE, Chen CK, Lubeck E, Shah S, Cai L, Gradinaru V. Single-cell phenotyping within transparent intact tissue through whole-body clearing. Cell. 2014 Aug 14;158(4):945-58. PMCID: PMC4153367. (2) The mesopontine tegmentum, including the pedunculopontine and laterodorsal tegmental nuclei (PPN and LDT), provides major cholinergic inputs to midbrain and regulates locomotion and reward. To delineate the underlying projection-specific circuit mechanisms, we employed optogenetics to control mesopontine cholinergic neurons at somata and at divergent projections within distinct midbrain areas. Bidirectional manipulation of PPN cholinergic cell bodies exerted opposing effects on locomotor behavior and reinforcement learning. These motor and reward effects were separable via limiting photostimulation to PPN cholinergic terminals in the ventral substantia nigra pars compacta (vSNc) or to the ventral tegmental area (VTA), respectively. LDT cholinergic neurons also form connections with vSNc and VTA neurons; however, although photo-excitation of LDT cholinergic terminals in the VTA caused positive reinforcement, LDT-to-vSNc modulation did not alter locomotion or reward. Therefore, the selective targeting of projection-specific mesopontine cholinergic pathways may offer increased benefit in treating movement and addiction disorders. • Xiao C, Cho JR, Zhou C, Treweek BJ, Chan K, McKinney SL, Yang B, and Gradinaru V. Cholinergic Mesopontine Signals Govern Locomotion and Reward Through Dissociable Midbrain Pathways. Neuron 2016 Apr 20;90(2)33-47. PMCID: PMC4840478

Brain serotonin transporter density and aggression in abstinent methamphetamine abusers.

PubMed

Sekine, Yoshimoto; Ouchi, Yasuomi; Takei, Nori; Yoshikawa, Etsuji; Nakamura, Kazuhiko; Futatsubashi, Masami; Okada, Hiroyuki; Minabe, Yoshio; Suzuki, Katsuaki; Iwata, Yasuhide; Tsuchiya, Kenji J; Tsukada, Hideo; Iyo, Masaomi; Mori, Norio

2006-01-01

In animals, methamphetamine is known to have a neurotoxic effect on serotonin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. It remains unknown whether methamphetamine damages serotonin neurons in humans. To investigate the status of brain serotonin neurons and their possible relationship with clinical characteristics in currently abstinent methamphetamine abusers. Case-control analysis. A hospital research center. Twelve currently abstinent former methamphetamine abusers (5 women and 7 men) and 12 age-, sex-, and education-matched control subjects recruited from the community. The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated using positron emission tomography and trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652). Estimates were derived from region-of-interest and statistical parametric mapping methods, followed by within-case analysis using the measures of clinical variables. The duration of methamphetamine use, the magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [(11)C](+)McN-5652 distribution volume. Methamphetamine abusers showed increased levels of aggression compared with controls. Region-of-interest and statistical parametric mapping analyses revealed that the serotonin transporter density in global brain regions (eg, the midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in methamphetamine abusers than in control subjects, and this reduction was significantly inversely correlated with the duration of methamphetamine use. Furthermore, statistical parametric mapping analyses indicated that the density in the orbitofrontal, temporal, and anterior cingulate areas was closely associated with the magnitude of aggression in methamphetamine abusers. Protracted abuse of methamphetamine may reduce the density of the serotonin transporter in the brain, leading to elevated aggression, even in currently abstinent abusers.

Fast and singular muscle responses initiate the startle response of Pantodon buchholzi (Osteoglossomorpha).

PubMed

Starosciak, A K; Kalola, R P; Perkins, K P; Riley, J A; Saidel, W M

2008-01-01

The startle response of Pantodon buchholzi, the African butterfly fish, is a complete or incomplete ballistic jump resulting from abduction of the pectoral fins. This study analyzed the neuromuscular basis for such a jump by recording in vivo electromyograms (emgs) from the muscles of abduction, the muscularis abductor superficialis (MAS) and the muscularis abductor profundus (MAP). The motor neurons innervating the MAS muscle were localized by retrograde transport of biocytin. The latency between stimulus and the evoked emg in the MAS was less than 5 ms; the latency of the MAP was about 6.5 ms. A single emg was recorded per jump. High speed video demonstrated that onset of a startle movement began within 10 ms of the onset of fin abduction. The emg associated with this movement is short (<2 ms) and followed by a variably-shaped, slower and smaller potential of 10-30 ms duration. The brief period between stimulus and startle response of Pantodon suggests a Mauthner neuron-related response, only with the behavior occurring in the vertical plane. The MAS may act only in a startle response, whereas the MAP might have a role in other behaviors. Elicited jumping habituates after a single trial. Electrophysiological evidence is presented indicating that the innervating motor neurons are suppressed for seconds following a stimulus. The neurons innervating the MAS are located at the medullary-spinal cord junction and possess an average radius of approximately 17.9 mum. These fish have been historically described as 'fresh water' flying fish. As a single emg occurs per startle response, repetitive pectoral activity generating flying cannot be supported. Pantodon 'flight' is ballistic. Copyright 2007 S. Karger AG, Basel.

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

Combined ICA-LORETA analysis of mismatch negativity.

PubMed

Marco-Pallarés, J; Grau, C; Ruffini, G

2005-04-01

A major challenge for neuroscience is to map accurately the spatiotemporal patterns of activity of the large neuronal populations that are believed to underlie computing in the human brain. To study a specific example, we selected the mismatch negativity (MMN) brain wave (an event-related potential, ERP) because it gives an electrophysiological index of a "primitive intelligence" capable of detecting changes, even abstract ones, in a regular auditory pattern. ERPs have a temporal resolution of milliseconds but appear to result from mixed neuronal contributions whose spatial location is not fully understood. Thus, it is important to separate these sources in space and time. To tackle this problem, a two-step approach was designed combining the independent component analysis (ICA) and low-resolution tomography (LORETA) algorithms. Here we implement this approach to analyze the subsecond spatiotemporal dynamics of MMN cerebral sources using trial-by-trial experimental data. We show evidence that a cerebral computation mechanism underlies MMN. This mechanism is mediated by the orchestrated activity of several spatially distributed brain sources located in the temporal, frontal, and parietal areas, which activate at distinct time intervals and are grouped in six main statistically independent components.

Autism and the mirror neuron system: insights from learning and teaching

PubMed Central

Vivanti, Giacomo; Rogers, Sally J.

2014-01-01

Individuals with autism have difficulties in social learning domains which typically involve mirror neuron system (MNS) activation. However, the precise role of the MNS in the development of autism and its relevance to treatment remain unclear. In this paper, we argue that three distinct aspects of social learning are critical for advancing knowledge in this area: (i) the mechanisms that allow for the implicit mapping of and learning from others' behaviour, (ii) the motivation to attend to and model conspecifics and (iii) the flexible and selective use of social learning. These factors are key targets of the Early Start Denver Model, an autism treatment approach which emphasizes social imitation, dyadic engagement, verbal and non-verbal communication and affect sharing. Analysis of the developmental processes and treatment-related changes in these different aspects of social learning in autism can shed light on the nature of the neuropsychological mechanisms underlying social learning and positive treatment outcomes in autism. This knowledge in turn may assist in developing more successful pedagogic approaches to autism spectrum disorder. Thus, intervention research can inform the debate on relations among neuropsychology of social learning, the role of the MNS, and educational practice in autism. PMID:24778379

Autism and the mirror neuron system: insights from learning and teaching.

PubMed

Vivanti, Giacomo; Rogers, Sally J

2014-01-01

Individuals with autism have difficulties in social learning domains which typically involve mirror neuron system (MNS) activation. However, the precise role of the MNS in the development of autism and its relevance to treatment remain unclear. In this paper, we argue that three distinct aspects of social learning are critical for advancing knowledge in this area: (i) the mechanisms that allow for the implicit mapping of and learning from others' behaviour, (ii) the motivation to attend to and model conspecifics and (iii) the flexible and selective use of social learning. These factors are key targets of the Early Start Denver Model, an autism treatment approach which emphasizes social imitation, dyadic engagement, verbal and non-verbal communication and affect sharing. Analysis of the developmental processes and treatment-related changes in these different aspects of social learning in autism can shed light on the nature of the neuropsychological mechanisms underlying social learning and positive treatment outcomes in autism. This knowledge in turn may assist in developing more successful pedagogic approaches to autism spectrum disorder. Thus, intervention research can inform the debate on relations among neuropsychology of social learning, the role of the MNS, and educational practice in autism.

Computational model of cerebral blood flow redistribution during cortical spreading depression

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Y.; Verveyko, Darya V.; Postnov, Dmitry E.

2016-04-01

In recent decades modelling studies on cortical spreading depression (CSD) and migraine waves successfully contributed to formation of modern view on these fundamental phenomena of brain physiology. However, due to the extreme complexity of object under study (brain cortex) and the diversity of involved physiological pathways, the development of new mathematical models of CSD is still a very relevant and challenging research problem. In our study we follow the functional modelling approach aimed to map the action of known physiological pathways to the specific nonlinear mechanisms that govern formation and evolution of CSD wave patterns. Specifically, we address the role of cerebral blood flow (CBF) redistribution that is caused by excessive neuronal activity by means of neurovascular coupling and mediates a spatial pattern of oxygen and glucose delivery. This in turn changes the local metabolic status of neural tissue. To build the model we simplify the web of known cell-to-cell interactions within a neurovascular unit by selecting the most relevant ones, such as local neuron-induced elevation of extracellular potassium concentration and biphasic response of arteriole radius. We propose the lumped description of distance-dependent hemodynamic coupling that fits the most recent experimental findings.

Mapping human temporal and parietal neuronal population activity and functional coupling during mathematical cognition

PubMed Central

Daitch, Amy L.; Foster, Brett L.; Schrouff, Jessica; Rangarajan, Vinitha; Kaşikçi, Itır; Gattas, Sandra; Parvizi, Josef

2016-01-01

Brain areas within the lateral parietal cortex (LPC) and ventral temporal cortex (VTC) have been shown to code for abstract quantity representations and for symbolic numerical representations, respectively. To explore the fast dynamics of activity within each region and the interaction between them, we used electrocorticography recordings from 16 neurosurgical subjects implanted with grids of electrodes over these two regions and tracked the activity within and between the regions as subjects performed three different numerical tasks. Although our results reconfirm the presence of math-selective hubs within the VTC and LPC, we report here a remarkable heterogeneity of neural responses within each region at both millimeter and millisecond scales. Moreover, we show that the heterogeneity of response profiles within each hub mirrors the distinct patterns of functional coupling between them. Our results support the existence of multiple bidirectional functional loops operating between discrete populations of neurons within the VTC and LPC during the visual processing of numerals and the performance of arithmetic functions. These findings reveal information about the dynamics of numerical processing in the brain and also provide insight into the fine-grained functional architecture and connectivity within the human brain. PMID:27821758