The Human Periallocortex: Layer Pattern in Presubiculum, Parasubiculum and Entorhinal Cortex. A Review

PubMed Central

Insausti, Ricardo; Muñoz-López, Mónica; Insausti, Ana M.; Artacho-Pérula, Emilio

2017-01-01

The cortical mantle is not homogeneous, so that three types of cortex can be distinguished: allocortex, periallocortex and isocortex. The main distinction among those three types is based on morphological differences, in particular the number of layers, overall organization, appearance, etc., as well as its connectivity. Additionally, in the phylogenetic scale, this classification is conserved among different mammals. The most primitive and simple cortex is the allocortex, which is characterized by the presence of three layers, with one cellular main layer; it is continued by the periallocortex, which presents six layers, although with enough differences in the layer pattern to separate three different fields: presubiculum (PrS), parasubiculum (PaS), and entorhinal cortex (EC). The closest part to the allocortex (represented by the subiculum) is the PrS, which shows outer (layers I–III) and inner (V–VI) principal layers (lamina principalis externa and lamina principalis interna), both separated by a cell poor band, parallel to the pial surface (layer IV or lamina dissecans). This layer organization is present throughout the anterior-posterior axis. The PaS continues the PrS, but its rostrocaudal extent is shorter than the PrS. The organization of the PaS shows the layer pattern more clearly than in the PrS. Up to six layers are recognizable in the PaS, with layer IV as lamina dissecans between superficial (layers I–III) and deep (V–VI) layers, as in the PrS. The EC presents even more clearly the layer pattern along both mediolateral and rostrocaudal extent. The layer pattern is a thick layer I, layer II in islands, layer III medium pyramids, layer IV as lamina dissecans (not present throughout the EC extent), layer V with dark and big pyramids and a multiform layer VI. The EC borders laterally the proisocortex (incomplete type of isocortex). Variations in the appearance of its layers justify the distinction of subfields in the EC, in particular in human and nonhuman primates. EC layers are not similar to those in the neocortex. The transition between the periallocortical EC and isocortex is not sharp, so that the proisocortex forms an intervening cortex, which fills the gap between the periallocortex and the isocortex. PMID:29046628

The Human Periallocortex: Layer Pattern in Presubiculum, Parasubiculum and Entorhinal Cortex. A Review.

PubMed

Insausti, Ricardo; Muñoz-López, Mónica; Insausti, Ana M; Artacho-Pérula, Emilio

2017-01-01

The cortical mantle is not homogeneous, so that three types of cortex can be distinguished: allocortex, periallocortex and isocortex. The main distinction among those three types is based on morphological differences, in particular the number of layers, overall organization, appearance, etc., as well as its connectivity. Additionally, in the phylogenetic scale, this classification is conserved among different mammals. The most primitive and simple cortex is the allocortex, which is characterized by the presence of three layers, with one cellular main layer; it is continued by the periallocortex, which presents six layers, although with enough differences in the layer pattern to separate three different fields: presubiculum (PrS), parasubiculum (PaS), and entorhinal cortex (EC). The closest part to the allocortex (represented by the subiculum) is the PrS, which shows outer (layers I-III) and inner (V-VI) principal layers ( lamina principalis externa and lamina principalis interna ), both separated by a cell poor band, parallel to the pial surface (layer IV or lamina dissecans ). This layer organization is present throughout the anterior-posterior axis. The PaS continues the PrS, but its rostrocaudal extent is shorter than the PrS. The organization of the PaS shows the layer pattern more clearly than in the PrS. Up to six layers are recognizable in the PaS, with layer IV as lamina dissecans between superficial (layers I-III) and deep (V-VI) layers, as in the PrS. The EC presents even more clearly the layer pattern along both mediolateral and rostrocaudal extent. The layer pattern is a thick layer I, layer II in islands, layer III medium pyramids, layer IV as lamina dissecans (not present throughout the EC extent), layer V with dark and big pyramids and a multiform layer VI. The EC borders laterally the proisocortex (incomplete type of isocortex). Variations in the appearance of its layers justify the distinction of subfields in the EC, in particular in human and nonhuman primates. EC layers are not similar to those in the neocortex. The transition between the periallocortical EC and isocortex is not sharp, so that the proisocortex forms an intervening cortex, which fills the gap between the periallocortex and the isocortex.

Cell structure and function in the visual cortex of the cat

PubMed Central

Kelly, J. P.; Van Essen, D. C.

1974-01-01

1. The organization of the visual cortex was studied with a technique that allows one to determine the physiology and morphology of individual cells. Micro-electrodes filled with the fluorescent dye Procion yellow were used to record intracellularly from cells in area 17 of the cat. The visual receptive field of each neurone was classified as simple, complex, or hypercomplex, and the cell was then stained by the iontophoretic injection of dye. 2. Fifty neurones were successfully examined in this way, and their structural features were compared to the varieties of cell types seen in Golgi preparations of area 17. The majority of simple units were stellate cells, whereas the majority of complex and hypercomplex units were pyramidal cells. Several neurones belonged to less common morphological types, such as double bouquet cells. Simple cells were concentrated in layer IV, hypercomplex cells in layer II + III, and complex cells in layers II + III, V and VI. 3. Electrically inexcitable cells that had high resting potentials but no impulse activity were stained and identified as glial cells. Glial cells responded to visual stimuli with slow graded depolarizations, and many of them showed a preference for a stimulus orientation similar to the optimal orientation for adjacent neurones. 4. The results show that there is a clear, but not absolute correlation between the major structural and functional classes of cells in the visual cortex. This approach, linking the physiological properties of a single cell to a given morphological type, will help in furthering our understanding of the cerebral cortex. ImagesPlate 4Plate 1Plate 2Plate 3 PMID:4136579

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

PubMed

Juric-Sekhar, Gordana; Kapur, Raj P; Glass, Ian A; Murray, Mitzi L; Parnell, Shawn E; Hevner, Robert F

2011-04-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

Neocortical layers I and II of the hedgehog (Erinaceus europaeus). I. Intrinsic organization.

PubMed

Valverde, F; Facal-Valverde, M V

1986-01-01

The intrinsic organization and interlaminar connections in neocortical layers I and II have been studied in adult hedgehogs (Erinaceus europaeus) using the Golgi method. Layer I contains a dense plexus of horizontal fibers, the terminal dendritic bouquets of pyramidal cells of layer II and of underlying layers, and varieties of intrinsic neurons. Four main types of cells were found in layer I. Small horizontal cells represent most probably persisting foetal horizontal cells described for other mammals. Large horizontal cells, tufted cells, and spinous horizontal cells were also found in this layer. Layer II contains primitive pyramidal cells representing the most outstanding feature of the neocortex of the hedgehog. Most pyramidal cells in layer II have two, three or more apical dendrites, richly covered by spines predominating over the basal dendrites. These cells resemble pyramidal cells found in the piriform cortex, hippocampus and other olfactory areas. It is suggested that the presence of these neurons reflects the retention of a primitive character in neocortical evolution. Cells with intrinsic axons were found among pyramidal cells in layer II. These have smooth dendrites penetrating layer I and local axons forming extremely complex terminal arborizations around the bodies and proximal dendritic portions of pyramidal cells. They most probably effect numerous axo-somatic contacts resembling basket cells. The similarity of some axonal terminals with the chandelier type of axonal arborization is discussed. Other varieties of cells located in deep cortical layers and having ascending axons for layers I and II were also studied. It is concluded that the two first neocortical layers represent a level of important integration in this primitive mammal.

Experience-dependent increase in spine calcium evoked by backpropagating action potentials in layer 2/3 pyramidal neurons in rat somatosensory cortex.

PubMed

Krieger, Patrik

2009-11-01

In spines on basal dendrites of layer 2/3 pyramidal neurons in somatosensory barrel cortex, calcium transients evoked by back-propagating action potentials (bAPs) were investigated (i) along the length of the basal dendrite, (ii) with postnatal development and (iii) with sensory deprivation during postnatal development. Layer 2/3 pyramidal neurons were investigated at three different ages. At all ages [postnatal day (P)8, P14, P21] the bAP-evoked calcium transient amplitude increased with distance from the soma with a peak at around 50 microm, followed by a gradual decline in amplitude. The effect of sensory deprivation on the bAP-evoked calcium was investigated using two different protocols. When all whiskers on one side of the rat snout were trimmed daily from P8 to P20-24 there was no difference in the bAP-evoked calcium transient between cells in the contralateral hemisphere, lacking sensory input from the whisker, and cells in the ipsilateral barrel cortex, with intact whisker activation. When, however, only the D-row whiskers on one side were trimmed the distribution of bAP-evoked calcium transients in spines was shifted towards larger amplitudes in cells located in the deprived D-column. In conclusion, (i) the bAP-evoked calcium transient gradient along the dendrite length is established at P8, (ii) the calcium transient increases in amplitude with age and (iii) this increase is enhanced in layer 2/3 pyramidal neurons located in a sensory-deprived barrel column that is bordered by non-deprived barrel columns.

Pronounced gradients of light, photosynthesis and O2 consumption in the tissue of the brown alga Fucus serratus.

PubMed

Lichtenberg, Mads; Kühl, Michael

2015-08-01

Macroalgae live in an ever-changing light environment affected by wave motion, self-shading and light-scattering effects, and on the thallus scale, gradients of light and chemical parameters influence algal photosynthesis. However, the thallus microenvironment and internal gradients remain underexplored. In this study, microsensors were used to quantify gradients of light, O2 concentration, variable chlorophyll fluorescence, photosynthesis and O2 consumption as a function of irradiance in the cortex and medulla layers of Fucus serratus. The two cortex layers showed more efficient light utilization compared to the medulla, calculated both from electron transport rates through photosystem II and from photosynthesis-irradiance curves. At moderate irradiance, the upper cortex exhibited onset of photosynthetic saturation, whereas lower thallus layers exhibited net O2 consumption. O2 consumption rates in light varied with depth and irradiance and were more than two-fold higher than dark respiration. We show that the thallus microenvironment of F. serratus exhibits a highly stratified balance of production and consumption of O2 , and when the frond was held in a fixed position, high incident irradiance levels on the upper cortex did not saturate photosynthesis in the lower thallus layers. We discuss possible photoadaptive responses and consequences for optimizing photosynthetic activity on the basis of vertical differences in light attenuation coefficients. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Reevaluation of the Beam and Radial Hypotheses of Parallel Fiber Action in the Cerebellar Cortex

PubMed Central

Cramer, Samuel W.; Gao, Wangcai; Chen, Gang

2013-01-01

The role of parallel fibers (PFs) in cerebellar physiology remains controversial. Early studies inspired the “beam” hypothesis whereby granule cell (GC) activation results in PF-driven, postsynaptic excitation of beams of Purkinje cells (PCs). However, the “radial” hypothesis postulates that the ascending limb of the GC axon provides the dominant input to PCs and generates patch-like responses. Using optical imaging and single-cell recordings in the mouse cerebellar cortex in vivo, this study reexamines the beam versus radial controversy. Electrical stimulation of mossy fibers (MFs) as well as microinjection of NMDA in the granular layer generates beam-like responses with a centrally located patch-like response. Remarkably, ipsilateral forepaw stimulation evokes a beam-like response in Crus I. Discrete molecular layer lesions demonstrate that PFs contribute to the peripherally generated responses in Crus I. In contrast, vibrissal stimulation induces patch-like activation of Crus II and GABAA antagonists fail to convert this patch-like activity into a beam-like response, implying that molecular layer inhibition does not prevent beam-like responses. However, blocking excitatory amino acid transporters (EAATs) generates beam-like responses in Crus II. These beam-like responses are suppressed by focal inhibition of MF-GC synaptic transmission. Using EAAT4 reporter transgenic mice, we show that peripherally evoked patch-like responses in Crus II are aligned between parasagittal bands of EAAT4. This is the first study to demonstrate beam-like responses in the cerebellar cortex to peripheral, MF, and GC stimulation in vivo. Furthermore, the spatial pattern of the responses depends on extracellular glutamate and its local regulation by EAATs. PMID:23843513

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III

PubMed Central

Juric-Sekhar, Gordana; Kapur, Raj P.; Glass, Ian A.; Murray, Mitzi L.; Parnell, Shawn E.

2011-01-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria–lissencephaly. PMID:20857301

VGLUT1 and VGLUT2 mRNA expression in the primate auditory pathway

PubMed Central

Hackett, Troy A.; Takahata, Toru; Balaram, Pooja

2011-01-01

The vesicular glutamate transporters (VGLUTs) regulate storage and release of glutamate in the brain. In adult animals, the VGLUT1 and VGLUT2 isoforms are widely expressed and differentially distributed, suggesting that neural circuits exhibit distinct modes of glutamate regulation. Studies in rodents suggest that VGLUT1 and VGLUT2 mRNA expression patterns are partly complementary, with VGLUT1 expressed at higher levels in cortex and VGLUT2 prominent subcortically, but with overlapping distributions in some nuclei. In primates, VGLUT gene expression has not been previously studied in any part of the brain. The purposes of the present study were to document the regional expression of VGLUT1 and VGLUT2 mRNA in the auditory pathway through A1 in cortex, and to determine whether their distributions are comparable to rodents. In situ hybridization with antisense riboprobes revealed that VGLUT2 was strongly expressed by neurons in the cerebellum and most major auditory nuclei, including the dorsal and ventral cochlear nuclei, medial and lateral superior olivary nuclei, central nucleus of the inferior colliculus, sagulum, and all divisions of the medial geniculate. VGLUT1 was densely expressed in the hippocampus and ventral cochlear nuclei, and at reduced levels in other auditory nuclei. In auditory cortex, neurons expressing VGLUT1 were widely distributed in layers II – VI of the core, belt and parabelt regions. VGLUT2 was most strongly expressed by neurons in layers IIIb and IV, weakly by neurons in layers II – IIIa, and at very low levels in layers V – VI. The findings indicate that VGLUT2 is strongly expressed by neurons at all levels of the subcortical auditory pathway, and by neurons in the middle layers of cortex, whereas VGLUT1 is strongly expressed by most if not all glutamatergic neurons in auditory cortex and at variable levels among auditory subcortical nuclei. These patterns imply that VGLUT2 is the main vesicular glutamate transporter in subcortical and thalamocortical (TC) circuits, whereas VGLUT1 is dominant in cortico-cortical (CC) and cortico-thalamic (CT) systems of projections. The results also suggest that VGLUT mRNA expression patterns in primates are similar to rodents, and establishes a baseline for detailed studies of these transporters in selected circuits of the auditory system. PMID:21111036

VGLUT1 and VGLUT2 mRNA expression in the primate auditory pathway.

PubMed

Hackett, Troy A; Takahata, Toru; Balaram, Pooja

2011-04-01

The vesicular glutamate transporters (VGLUTs) regulate the storage and release of glutamate in the brain. In adult animals, the VGLUT1 and VGLUT2 isoforms are widely expressed and differentially distributed, suggesting that neural circuits exhibit distinct modes of glutamate regulation. Studies in rodents suggest that VGLUT1 and VGLUT2 mRNA expression patterns are partly complementary, with VGLUT1 expressed at higher levels in the cortex and VGLUT2 prominent subcortically, but with overlapping distributions in some nuclei. In primates, VGLUT gene expression has not been previously studied in any part of the brain. The purposes of the present study were to document the regional expression of VGLUT1 and VGLUT2 mRNA in the auditory pathway through A1 in the cortex, and to determine whether their distributions are comparable to rodents. In situ hybridization with antisense riboprobes revealed that VGLUT2 was strongly expressed by neurons in the cerebellum and most major auditory nuclei, including the dorsal and ventral cochlear nuclei, medial and lateral superior olivary nuclei, central nucleus of the inferior colliculus, sagulum, and all divisions of the medial geniculate. VGLUT1 was densely expressed in the hippocampus and ventral cochlear nuclei, and at reduced levels in other auditory nuclei. In the auditory cortex, neurons expressing VGLUT1 were widely distributed in layers II-VI of the core, belt and parabelt regions. VGLUT2 was expressed most strongly by neurons in layers IIIb and IV, weakly by neurons in layers II-IIIa, and at very low levels in layers V-VI. The findings indicate that VGLUT2 is strongly expressed by neurons at all levels of the subcortical auditory pathway, and by neurons in the middle layers of the cortex, whereas VGLUT1 is strongly expressed by most if not all glutamatergic neurons in the auditory cortex and at variable levels among auditory subcortical nuclei. These patterns imply that VGLUT2 is the main vesicular glutamate transporter in subcortical and thalamocortical (TC) circuits, whereas VGLUT1 is dominant in corticocortical (CC) and corticothalamic (CT) systems of projections. The results also suggest that VGLUT mRNA expression patterns in primates are similar to rodents, and establish a baseline for detailed studies of these transporters in selected circuits of the auditory system. Copyright © 2010 Elsevier B.V. All rights reserved.

Sonic Hedgehog Expression in Corticofugal Projection Neurons Directs Cortical Microcircuit Formation

PubMed Central

Harwell, Corey C.; Parker, Philip R.L.; Gee, Steven M.; Okada, Ami; McConnell, Susan K.; Kreitzer, Anatol C.; Kriegstein, Arnold R.

2012-01-01

SUMMARY The precise connectivity of inputs and outputs is critical for cerebral cortex function; however, the cellular mechanisms that establish these connections are poorly understood. Here, we show that the secreted molecule Sonic Hedgehog (Shh) is involved in synapse formation of a specific cortical circuit. Shh is expressed in layer V corticofugal projection neurons and the Shh receptor, Brother of CDO (Boc), is expressed in local and callosal projection neurons of layer II/III that synapse onto the subcortical projection neurons. Layer V neurons of mice lacking functional Shh exhibit decreased synapses. Conversely, the loss of functional Boc leads to a reduction in the strength of synaptic connections onto layer Vb, but not layer II/III, pyramidal neurons. These results demonstrate that Shh is expressed in postsynaptic target cells while Boc is expressed in a complementary population of presynaptic input neurons, and they function to guide the formation of cortical microcircuitry. PMID:22445340

Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex.

PubMed

Leguey, Ignacio; Bielza, Concha; Larrañaga, Pedro; Kastanauskaite, Asta; Rojo, Concepción; Benavides-Piccione, Ruth; DeFelipe, Javier

2016-09-01

The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Localization of the peroxisome proliferator-activated receptor in the brain.

PubMed

Kainu, T; Wikström, A C; Gustafsson, J A; Pelto-Huikko, M

1994-12-20

This paper describes the localization of the alpha-type peroxisome proliferator-activated receptor (PPAR alpha) in the rat brain using immunocytochemistry and in situ hybridization. Expression of PPAR alpha mRNA was highest in the granular cells of the cerebellar cortex and in the dentate gyrus, with a somewhat lower expression in areas CA1-CA4 of the hippocampus. PPAR alpha mRNA was also found in some neurones of the cerebral cortex (layers II-IV) and the molecular layer of the cerebellar cortex, and in the olfactory tubercle. Immunocytochemistry revealed nuclear PPAR alpha-immunoreactivity (-IR) in the same areas as seen with the in situ hybridization. Furthermore, PPAR alpha-IR was also localized in oligodendrocytes, whereas the other glial cell types appeared to lack PPAR alpha. These results suggest that peroxisome proliferators and chemicals acting similarly have effects on discrete populations of neurones. The presence of PPAR alpha in oligodendrocytes lends further support to the suggestion that peroxisomes are important in the assembly and degradation of myelin.

TRH regulates action potential shape in cerebral cortex pyramidal neurons.

PubMed

Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

2014-07-07

Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

The cholinergic basal forebrain in the ferret and its inputs to the auditory cortex

PubMed Central

Bajo, Victoria M; Leach, Nicholas D; Cordery, Patricia M; Nodal, Fernando R; King, Andrew J

2014-01-01

Cholinergic inputs to the auditory cortex can modulate sensory processing and regulate stimulus-specific plasticity according to the behavioural state of the subject. In order to understand how acetylcholine achieves this, it is essential to elucidate the circuitry by which cholinergic inputs influence the cortex. In this study, we described the distribution of cholinergic neurons in the basal forebrain and their inputs to the auditory cortex of the ferret, a species used increasingly in studies of auditory learning and plasticity. Cholinergic neurons in the basal forebrain, visualized by choline acetyltransferase and p75 neurotrophin receptor immunocytochemistry, were distributed through the medial septum, diagonal band of Broca, and nucleus basalis magnocellularis. Epipial tracer deposits and injections of the immunotoxin ME20.4-SAP (monoclonal antibody specific for the p75 neurotrophin receptor conjugated to saporin) in the auditory cortex showed that cholinergic inputs originate almost exclusively in the ipsilateral nucleus basalis. Moreover, tracer injections in the nucleus basalis revealed a pattern of labelled fibres and terminal fields that resembled acetylcholinesterase fibre staining in the auditory cortex, with the heaviest labelling in layers II/III and in the infragranular layers. Labelled fibres with small en-passant varicosities and simple terminal swellings were observed throughout all auditory cortical regions. The widespread distribution of cholinergic inputs from the nucleus basalis to both primary and higher level areas of the auditory cortex suggests that acetylcholine is likely to be involved in modulating many aspects of auditory processing. PMID:24945075

Motor Training Promotes Both Synaptic and Intrinsic Plasticity of Layer II/III Pyramidal Neurons in the Primary Motor Cortex

PubMed Central

Kida, Hiroyuki; Tsuda, Yasumasa; Ito, Nana; Yamamoto, Yui; Owada, Yuji; Kamiya, Yoshinori; Mitsushima, Dai

2016-01-01

Motor skill training induces structural plasticity at dendritic spines in the primary motor cortex (M1). To further analyze both synaptic and intrinsic plasticity in the layer II/III area of M1, we subjected rats to a rotor rod test and then prepared acute brain slices. Motor skill consistently improved within 2 days of training. Voltage clamp analysis showed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate (AMPA/NMDA) ratios and miniature EPSC amplitudes in 1-day trained rats compared with untrained rats, suggesting increased postsynaptic AMPA receptors in the early phase of motor learning. Compared with untrained controls, 2-days trained rats showed significantly higher miniature EPSC amplitude and frequency. Paired-pulse analysis further demonstrated lower rates in 2-days trained rats, suggesting increased presynaptic glutamate release during the late phase of learning. One-day trained rats showed decreased miniature IPSC frequency and increased paired-pulse analysis of evoked IPSC, suggesting a transient decrease in presynaptic γ-aminobutyric acid (GABA) release. Moreover, current clamp analysis revealed lower resting membrane potential, higher spike threshold, and deeper afterhyperpolarization in 1-day trained rats—while 2-days trained rats showed higher membrane potential, suggesting dynamic changes in intrinsic properties. Our present results indicate dynamic changes in glutamatergic, GABAergic, and intrinsic plasticity in M1 layer II/III neurons after the motor training. PMID:27193420

Motor Training Promotes Both Synaptic and Intrinsic Plasticity of Layer II/III Pyramidal Neurons in the Primary Motor Cortex.

PubMed

Kida, Hiroyuki; Tsuda, Yasumasa; Ito, Nana; Yamamoto, Yui; Owada, Yuji; Kamiya, Yoshinori; Mitsushima, Dai

2016-08-01

Motor skill training induces structural plasticity at dendritic spines in the primary motor cortex (M1). To further analyze both synaptic and intrinsic plasticity in the layer II/III area of M1, we subjected rats to a rotor rod test and then prepared acute brain slices. Motor skill consistently improved within 2 days of training. Voltage clamp analysis showed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate (AMPA/NMDA) ratios and miniature EPSC amplitudes in 1-day trained rats compared with untrained rats, suggesting increased postsynaptic AMPA receptors in the early phase of motor learning. Compared with untrained controls, 2-days trained rats showed significantly higher miniature EPSC amplitude and frequency. Paired-pulse analysis further demonstrated lower rates in 2-days trained rats, suggesting increased presynaptic glutamate release during the late phase of learning. One-day trained rats showed decreased miniature IPSC frequency and increased paired-pulse analysis of evoked IPSC, suggesting a transient decrease in presynaptic γ-aminobutyric acid (GABA) release. Moreover, current clamp analysis revealed lower resting membrane potential, higher spike threshold, and deeper afterhyperpolarization in 1-day trained rats-while 2-days trained rats showed higher membrane potential, suggesting dynamic changes in intrinsic properties. Our present results indicate dynamic changes in glutamatergic, GABAergic, and intrinsic plasticity in M1 layer II/III neurons after the motor training. © The Author 2016. Published by Oxford University Press.

Laminar Differences in Dendritic Structure of Pyramidal Neurons in the Juvenile Rat Somatosensory Cortex.

PubMed

Rojo, Concepción; Leguey, Ignacio; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Benavides-Piccione, Ruth

2016-06-01

Pyramidal cell structure varies between different cortical areas and species, indicating that the cortical circuits that these cells participate in are likely to be characterized by different functional capabilities. Structural differences between cortical layers have been traditionally reported using either the Golgi method or intracellular labeling, but the structure of pyramidal cells has not previously been systematically analyzed across all cortical layers at a particular age. In the present study, we investigated the dendritic architecture of complete basal arbors of pyramidal neurons in layers II, III, IV, Va, Vb, and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. We found that the characteristics of basal dendritic morphologies are statistically different in each cortical layer. The variations in size and branching pattern that exist between pyramidal cells of different cortical layers probably reflect the particular functional properties that are characteristic of the cortical circuit in which they participate. This new set of complete basal dendritic arbors of 3D-reconstructed pyramidal cell morphologies across each cortical layer will provide new insights into interlaminar information processing in the cerebral cortex. © The Author 2016. Published by Oxford University Press.

Stress during a Critical Postnatal Period Induces Region-Specific Structural Abnormalities and Dysfunction of the Prefrontal Cortex via CRF1

PubMed Central

Yang, Xiao-Dun; Liao, Xue-Mei; Uribe-Mariño, Andrés; Liu, Rui; Xie, Xiao-Meng; Jia, Jiao; Su, Yun-Ai; Li, Ji-Tao; Schmidt, Mathias V; Wang, Xiao-Dong; Si, Tian-Mei

2015-01-01

During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin administration (20 μg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF1 in modulating early-life stress-induced prefrontal abnormalities. PMID:25403725

Sonic hedgehog expression in corticofugal projection neurons directs cortical microcircuit formation.

PubMed

Harwell, Corey C; Parker, Philip R L; Gee, Steven M; Okada, Ami; McConnell, Susan K; Kreitzer, Anatol C; Kriegstein, Arnold R

2012-03-22

The precise connectivity of inputs and outputs is critical for cerebral cortex function; however, the cellular mechanisms that establish these connections are poorly understood. Here, we show that the secreted molecule Sonic Hedgehog (Shh) is involved in synapse formation of a specific cortical circuit. Shh is expressed in layer V corticofugal projection neurons and the Shh receptor, Brother of CDO (Boc), is expressed in local and callosal projection neurons of layer II/III that synapse onto the subcortical projection neurons. Layer V neurons of mice lacking functional Shh exhibit decreased synapses. Conversely, the loss of functional Boc leads to a reduction in the strength of synaptic connections onto layer Vb, but not layer II/III, pyramidal neurons. These results demonstrate that Shh is expressed in postsynaptic target cells while Boc is expressed in a complementary population of presynaptic input neurons, and they function to guide the formation of cortical microcircuitry. Copyright © 2012 Elsevier Inc. All rights reserved.

A Visual-Cue-Dependent Memory Circuit for Place Navigation.

PubMed

Qin, Han; Fu, Ling; Hu, Bo; Liao, Xiang; Lu, Jian; He, Wenjing; Liang, Shanshan; Zhang, Kuan; Li, Ruijie; Yao, Jiwei; Yan, Junan; Chen, Hao; Jia, Hongbo; Zott, Benedikt; Konnerth, Arthur; Chen, Xiaowei

2018-06-05

The ability to remember and to navigate to safe places is necessary for survival. Place navigation is known to involve medial entorhinal cortex (MEC)-hippocampal connections. However, learning-dependent changes in neuronal activity in the distinct circuits remain unknown. Here, by using optic fiber photometry in freely behaving mice, we discovered the experience-dependent induction of a persistent-task-associated (PTA) activity. This PTA activity critically depends on learned visual cues and builds up selectively in the MEC layer II-dentate gyrus, but not in the MEC layer III-CA1 pathway, and its optogenetic suppression disrupts navigation to the target location. The findings suggest that the visual system, the MEC layer II, and the dentate gyrus are essential hubs of a memory circuit for visually guided navigation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Entorhinal Cortical Ocean Cells Encode Specific Contexts and Drive Context-Specific Fear Memory

PubMed Central

Kitamura, Takashi; Sun, Chen; Martin, Jared; Kitch, Lacey J; Schnitzer, Mark J; Tonegawa, Susumu

2016-01-01

Summary Forming distinct representations and memories of multiple contexts and episodes is thought to be a crucial function of the hippocampal-entorhinal cortical network. The hippocampal dentate gyrus (DG) and CA3 are known to contribute to these functions but the role of the entorhinal cortex (EC) is poorly understood. Here, we show that Ocean cells, excitatory stellate neurons in the medial EC layer II projecting into DG and CA3, rapidly form a distinct representation of a novel context and drive context-specific activation of downstream CA3 cells as well as context-specific fear memory. In contrast, Island cells, excitatory pyramidal neurons in the medial EC layer II projecting into CA1, are indifferent to context-specific encoding or memory. On the other hand, Ocean cells are dispensable for temporal association learning, for which Island cells are crucial. Together, the two excitatory medial EC layer II inputs to the hippocampus have complementary roles in episodic memory. PMID:26402611

Interlaminar and lateral excitatory amino acid connections in the striate cortex of monkey.

PubMed

Kisvarday, Z F; Cowey, A; Smith, A D; Somogyi, P

1989-02-01

The intrinsic excitatory amino acid pathways within the striate cortex of monkeys were studied by autoradiographic detection of retrogradely labeled somata following microinjections of D-3H-aspartate (D-3H-Asp) into different layers. The labeled amino acid was selectively accumulated by subpopulations of neurons and, to a small extent, by glial cells, the latter mainly in the supragranular layers. Immunocytochemical detection of neurons containing GABA showed that, apart from a few cells exclusively in layer I, GABAergic neurons do not accumulate D-3H-Asp. Several lines of evidence suggest that D-3H-Asp uptake occurred only at nerve terminals; thus, the pattern of perikaryal labeling allowed the delineation of interlaminar and lateral projections. Neurons in layer I probably project laterally, and layer I receives wide-ranging projections from layer IVB and layer V from cells up to 1300 microns laterally. Some neurons in layer II send a focused projection to lower layer VI. Some neurons in layers II/III project up to 1 mm laterally within their own layer, but relatively few neurons can be labeled in these projections. Similarly, in layers II/III few neurons can be retrogradely labeled from layers V and upper VI, and this projection is organized such that cells closer to the pia project deeper in layer V/VI. The connections of layer IVA could not be revealed separately because of the difficulty of confining injections to this thin sublamina. Neurons in layer IVB project up to 1300 microns within IVB itself. A small number of cells from IVB also project to layers III, IVC-alpha, V, and VI with much more restricted lateral spread. Neurons in upper IVC-alpha send axons to layer IVB with at least 600-800 microns lateral spread. Neurons in lower IVC-alpha/upper IVC-beta project to layer III with at least 300-500 microns lateral spread. The bottom 50-80 microns of layer IVC-beta contains neurons with a very focused projection, apparently exclusively to the layer III/IVA border region. Both layers IVC alpha and beta have rich connections within themselves, the beta sublayer having more restricted lateral connections. Some neurons in layer IVC-beta give a laterally restricted small input to layers IVC-alpha and IVB. Both IVC-alpha and -beta project to layers V and VI, and these projections are spread at least 400 microns laterally. Neurons in layer V project to all layers, but the projection to layers I-III and within layer V itself spread much further laterally than the projections to layers IV and VI.(ABSTRACT TRUNCATED AT 400 WORDS)

The cholinergic basal forebrain in the ferret and its inputs to the auditory cortex.

PubMed

Bajo, Victoria M; Leach, Nicholas D; Cordery, Patricia M; Nodal, Fernando R; King, Andrew J

2014-09-01

Cholinergic inputs to the auditory cortex can modulate sensory processing and regulate stimulus-specific plasticity according to the behavioural state of the subject. In order to understand how acetylcholine achieves this, it is essential to elucidate the circuitry by which cholinergic inputs influence the cortex. In this study, we described the distribution of cholinergic neurons in the basal forebrain and their inputs to the auditory cortex of the ferret, a species used increasingly in studies of auditory learning and plasticity. Cholinergic neurons in the basal forebrain, visualized by choline acetyltransferase and p75 neurotrophin receptor immunocytochemistry, were distributed through the medial septum, diagonal band of Broca, and nucleus basalis magnocellularis. Epipial tracer deposits and injections of the immunotoxin ME20.4-SAP (monoclonal antibody specific for the p75 neurotrophin receptor conjugated to saporin) in the auditory cortex showed that cholinergic inputs originate almost exclusively in the ipsilateral nucleus basalis. Moreover, tracer injections in the nucleus basalis revealed a pattern of labelled fibres and terminal fields that resembled acetylcholinesterase fibre staining in the auditory cortex, with the heaviest labelling in layers II/III and in the infragranular layers. Labelled fibres with small en-passant varicosities and simple terminal swellings were observed throughout all auditory cortical regions. The widespread distribution of cholinergic inputs from the nucleus basalis to both primary and higher level areas of the auditory cortex suggests that acetylcholine is likely to be involved in modulating many aspects of auditory processing. © 2014 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

PubMed Central

Krienen, Fenna M.; Yeo, B. T. Thomas; Ge, Tian; Buckner, Randy L.; Sherwood, Chet C.

2016-01-01

The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute’s human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections. PMID:26739559

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain.

PubMed

Krienen, Fenna M; Yeo, B T Thomas; Ge, Tian; Buckner, Randy L; Sherwood, Chet C

2016-01-26

The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections.

Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.

PubMed

Bifari, Francesco; Decimo, Ilaria; Pino, Annachiara; Llorens-Bobadilla, Enric; Zhao, Sheng; Lange, Christian; Panuccio, Gabriella; Boeckx, Bram; Thienpont, Bernard; Vinckier, Stefan; Wyns, Sabine; Bouché, Ann; Lambrechts, Diether; Giugliano, Michele; Dewerchin, Mieke; Martin-Villalba, Ana; Carmeliet, Peter

2017-03-02

Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2 + neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of hindlimb unloading on stereological parameters of the motor cortex and hippocampus in male rats.

PubMed

Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad

2016-11-09

Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.

Callosal connections of dorso-lateral premotor cortex.

PubMed

Marconi, B; Genovesio, A; Giannetti, S; Molinari, M; Caminiti, R

2003-08-01

This study investigated the organization of the callosal connections of the two subdivisions of the monkey dorsal premotor cortex (PMd), dorso-rostral (F7) and dorso-caudal (F2). In one animal, Fast blue and Diamidino yellow were injected in F7 and F2, respectively; in a second animal, the pattern of injections was reversed. F7 and F2 receive a major callosal input from their homotopic counterpart. The heterotopic connections of F7 originate mainly from F2, with smaller contingent from pre-supplementary motor area (pre-SMA, F6), area 8 (frontal eye fields), and prefrontal cortex (area 46), while those of F2 originate from F7, with smaller contributions from ventral premotor areas (F5, F4), SMA-proper (F3), and primary motor cortex (M1). Callosal cells projecting homotopically are mostly located in layers II-III, those projecting heterotopically occupy layers II-III and V-VI. A spectral analysis was used to characterize the spatial fluctuations of the distribution of callosal neurons, in both F7 and F2, as well as in adjacent cortical areas. The results revealed two main periodic components. The first, in the domain of the low spatial frequencies, corresponds to periodicities of cell density with peak-to-peak distances of approximately 10 mm, and suggests an arrangement of callosal cells in the form of 5-mm wide bands. The second corresponds to periodicities of approximately 2 mm, and probably reflects a 1-mm columnar-like arrangement. Coherency and phase analyses showed that, although similar in their spatial arrangements, callosal cells projecting to dorsal premotor areas are segregated in the tangential cortical domain.

Lower layers in the motor cortex are more effective targets for penetrating microelectrodes in cortical prostheses

NASA Astrophysics Data System (ADS)

Parikh, Hirak; Marzullo, Timothy C.; Kipke, Daryl R.

2009-04-01

Improving cortical prostheses requires the development of recording neural interfaces that are efficient in terms of providing maximal control information with minimal interface complexity. While the typical approaches have targeted neurons in the motor cortex with multiple penetrating shanks, an alternative approach is to determine an efficient distribution of electrode sites within the layers of the cortex with fewer penetrating shanks. The objective of this study was to compare unit activity in the upper and lower layers of the cortex with respect to movement and direction in order to inform the design of penetrating microelectrodes. Four rats were implanted bilaterally with multi-site single-shank silicon microelectrode arrays in the neck/shoulder region of the motor cortex. We simultaneously recorded unit activity across all layers of the motor cortex while the animal was engaged in a movement direction task. Localization of the electrode array within the different layers of the cortex was determined by histology. We denoted units from layers 2 and 3 and units as upper layer units, and units from layers 5 and 6 as lower layer units. Analysis of unit spiking activity demonstrated that both the upper and lower layers encode movement and direction information. Unit responses in either cortical layer of the cortex were not preferentially associated with contralateral or ipsilateral movement. Aggregate analysis (633 neurons) and best session analysis (75 neurons) indicated that units in the lower layers (layers 5, 6) are more likely to encode direction information when compared to units in the upper layers (layers 2, 3) (p< 0.05). These results suggest that electrode sites clustered in the lower layers provide access to more salient control information for cortical neuroprostheses.

Target-Selectivity of Parvalbumin-Positive Interneurons in Layer II of Medial Entorhinal Cortex in Normal and Epileptic Animals

PubMed Central

Armstrong, Caren; Wang, Jessica; Lee, Soo Yeun; Broderick, John; Bezaire, Marianne J; Lee, Sang-Hun; Soltesz, Ivan

2015-01-01

The medial entorhinal cortex layer II (MEClayerII) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII. However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII. However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII. Taken together, these findings advance our knowledge about the organization of perisomatic inhibition both in control and in epileptic animals. PMID:26663222

Target-selectivity of parvalbumin-positive interneurons in layer II of medial entorhinal cortex in normal and epileptic animals.

PubMed

Armstrong, Caren; Wang, Jessica; Yeun Lee, Soo; Broderick, John; Bezaire, Marianne J; Lee, Sang-Hun; Soltesz, Ivan

2016-06-01

The medial entorhinal cortex layer II (MEClayerII ) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII . However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII . However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII . Taken together, these findings advance our knowledge about the organization of perisomatic inhibition both in control and in epileptic animals. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

PubMed

Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

2014-09-01

A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Layer-specific optogenetic activation of pyramidal neurons causes beta–gamma entrainment of neonatal networks

PubMed Central

Bitzenhofer, Sebastian H; Ahlbeck, Joachim; Wolff, Amy; Wiegert, J. Simon; Gee, Christine E.; Oertner, Thomas G.; Hanganu-Opatz, Ileana L.

2017-01-01

Coordinated activity patterns in the developing brain may contribute to the wiring of neuronal circuits underlying future behavioural requirements. However, causal evidence for this hypothesis has been difficult to obtain owing to the absence of tools for selective manipulation of oscillations during early development. We established a protocol that combines optogenetics with electrophysiological recordings from neonatal mice in vivo to elucidate the substrate of early network oscillations in the prefrontal cortex. We show that light-induced activation of layer II/III pyramidal neurons that are transfected by in utero electroporation with a high-efficiency channelrhodopsin drives frequency-specific spiking and boosts network oscillations within beta–gamma frequency range. By contrast, activation of layer V/VI pyramidal neurons causes nonspecific network activation. Thus, entrainment of neonatal prefrontal networks in fast rhythms relies on the activation of layer II/III pyramidal neurons. This approach used here may be useful for further interrogation of developing circuits, and their behavioural readout. PMID:28216627

Cellular and molecular basis for stress-induced depression.

PubMed

Seo, J-S; Wei, J; Qin, L; Kim, Y; Yan, Z; Greengard, P

2017-10-01

Chronic stress has a crucial role in the development of psychiatric diseases, such as anxiety and depression. Dysfunction of the medial prefrontal cortex (mPFC) has been linked to the cognitive and emotional deficits induced by stress. However, little is known about the molecular and cellular determinants in mPFC for stress-associated mental disorders. Here we show that chronic restraint stress induces the selective loss of p11 (also known as annexin II light chain, S100A10), a multifunctional protein binding to 5-HT receptors, in layer II/III neurons of the prelimbic cortex (PrL), as well as depression-like behaviors, both of which are reversed by selective serotonin reuptake inhibitors (SSRIs) and the tricyclic class of antidepressant (TCA) agents. In layer II/III of the PrL, p11 is highly concentrated in dopamine D2 receptor-expressing (D2 + ) glutamatergic neurons. Viral expression of p11 in D2 + PrL neurons alleviates the depression-like behaviors exhibited by genetically manipulated mice with D2 + neuron-specific or global deletion of p11. In stressed animals, overexpression of p11 in D2 + PrL neurons rescues depression-like behaviors by restoring glutamatergic transmission. Our results have identified p11 as a key molecule in a specific cell type that regulates stress-induced depression, which provides a framework for the development of new strategies to treat stress-associated mental illnesses.

Mapping parahippocampal systems for recognition and recency memory in the absence of the rat hippocampus

PubMed Central

Kinnavane, L; Amin, E; Horne, M; Aggleton, J P

2014-01-01

The present study examined immediate-early gene expression in the perirhinal cortex of rats with hippocampal lesions. The goal was to test those models of recognition memory which assume that the perirhinal cortex can function independently of the hippocampus. The c-fos gene was targeted, as its expression in the perirhinal cortex is strongly associated with recognition memory. Four groups of rats were examined. Rats with hippocampal lesions and their surgical controls were given either a recognition memory task (novel vs. familiar objects) or a relative recency task (objects with differing degrees of familiarity). Perirhinal Fos expression in the hippocampal-lesioned groups correlated with both recognition and recency performance. The hippocampal lesions, however, had no apparent effect on overall levels of perirhinal or entorhinal cortex c-fos expression in response to novel objects, with only restricted effects being seen in the recency condition. Network analyses showed that whereas the patterns of parahippocampal interactions were differentially affected by novel or familiar objects, these correlated networks were not altered by hippocampal lesions. Additional analyses in control rats revealed two modes of correlated medial temporal activation. Novel stimuli recruited the pathway from the lateral entorhinal cortex (cortical layer II or III) to hippocampal field CA3, and thence to CA1. Familiar stimuli recruited the direct pathway from the lateral entorhinal cortex (principally layer III) to CA1. The present findings not only reveal the independence from the hippocampus of some perirhinal systems associated with recognition memory, but also show how novel stimuli engage hippocampal subfields in qualitatively different ways from familiar stimuli. PMID:25264133

Post-Inhibitory Rebound Spikes in Rat Medial Entorhinal Layer II/III Principal Cells: In Vivo, In Vitro, and Computational Modeling Characterization

PubMed Central

Ferrante, Michele; Shay, Christopher F.; Tsuno, Yusuke; William Chapman, G.; Hasselmo, Michael E.

2017-01-01

Abstract Medial entorhinal cortex Layer-II stellate cells (mEC-LII-SCs) primarily interact via inhibitory interneurons. This suggests the presence of alternative mechanisms other than excitatory synaptic inputs for triggering action potentials (APs) in stellate cells during spatial navigation. Our intracellular recordings show that the hyperpolarization-activated cation current (Ih) allows post-inhibitory-rebound spikes (PIRS) in mEC-LII-SCs. In vivo, strong inhibitory-post-synaptic potentials immediately preceded most APs shortening their delay and enhancing excitability. In vitro experiments showed that inhibition initiated spikes more effectively than excitation and that more dorsal mEC-LII-SCs produced faster and more synchronous spikes. In contrast, PIRS in Layer-II/III pyramidal cells were harder to evoke, voltage-independent, and slower in dorsal mEC. In computational simulations, mEC-LII-SCs morphology and Ih homeostatically regulated the dorso-ventral differences in PIRS timing and most dendrites generated PIRS with a narrow range of stimulus amplitudes. These results suggest inhibitory inputs could mediate the emergence of grid cell firing in a neuronal network. PMID:26965902

Layer-specific excitation/inhibition balances during neuronal synchronization in the visual cortex.

PubMed

Adesnik, Hillel

2018-05-01

Understanding the balance between synaptic excitation and inhibition in cortical circuits in the brain, and how this contributes to cortical rhythms, is fundamental to explaining information processing in the cortex. This study used cortical layer-specific optogenetic activation in mouse cortex to show that excitatory neurons in any cortical layer can drive powerful gamma rhythms, while inhibition balances excitation. The net impact of this is to keep activity within each layer in check, but simultaneously to promote the propagation of activity to downstream layers. The data show that rhythm-generating circuits exist in all principle layers of the cortex, and provide layer-specific balances of excitation and inhibition that affect the flow of information across the layers. Rhythmic activity can synchronize neural ensembles within and across cortical layers. While gamma band rhythmicity has been observed in all layers, the laminar sources and functional impacts of neuronal synchronization in the cortex remain incompletely understood. Here, layer-specific optogenetic stimulation demonstrates that populations of excitatory neurons in any cortical layer of the mouse's primary visual cortex are sufficient to powerfully entrain neuronal oscillations in the gamma band. Within each layer, inhibition balances excitation and keeps activity in check. Across layers, translaminar output overcomes inhibition and drives downstream firing. These data establish that rhythm-generating circuits exist in all principle layers of the cortex, but provide layer-specific balances of excitation and inhibition that may dynamically shape the flow of information through cortical circuits. These data might help explain how excitation/inhibition (E/I) balances across cortical layers shape information processing, and shed light on the diverse nature and functional impacts of cortical gamma rhythms. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers.

PubMed

Lanjakornsiripan, Darin; Pior, Baek-Jun; Kawaguchi, Daichi; Furutachi, Shohei; Tahara, Tomoaki; Katsuyama, Yu; Suzuki, Yutaka; Fukazawa, Yugo; Gotoh, Yukiko

2018-04-24

Non-pial neocortical astrocytes have historically been thought to comprise largely a nondiverse population of protoplasmic astrocytes. Here we show that astrocytes of the mouse somatosensory cortex manifest layer-specific morphological and molecular differences. Two- and three-dimensional observations revealed that astrocytes in the different layers possess distinct morphologies as reflected by differences in cell orientation, territorial volume, and arborization. The extent of ensheathment of synaptic clefts by astrocytes in layer II/III was greater than that by those in layer VI. Moreover, differences in gene expression were observed between upper-layer and deep-layer astrocytes. Importantly, layer-specific differences in astrocyte properties were abrogated in reeler and Dab1 conditional knockout mice, in which neuronal layers are disturbed, suggesting that neuronal layers are a prerequisite for the observed morphological and molecular differences of neocortical astrocytes. This study thus demonstrates the existence of layer-specific interactions between neurons and astrocytes, which may underlie their layer-specific functions.

Progression of hippocampal degeneration in amyotrophic lateral sclerosis with or without memory impairment: distinction from Alzheimer disease.

PubMed

Takeda, Takahiro; Uchihara, Toshiki; Arai, Nobutaka; Mizutani, Toshio; Iwata, Makoto

2009-01-01

The hippocampal involvement in amyotrophic lateral sclerosis (ALS) patients has been known for more than a decade, however, its relationship to clinical manifestations including memory deficits and topographical differentiation from Alzheimer disease (AD) remain unclear. In order to clarify the anatomopathological features in the hippocampus and their relevance to disease-specific memory deficits in ALS patients, topography and cytopathology of the hippocampal lesions along the perforant pathway were quantitatively and semiquantitatively surveyed in 14 ALS patients with extramotor involvement. These pathological findings were compared with clinical characteristics assessed from their clinical records. Cytoplasmic inclusions initially appear in the granular cells of the dentate gyrus (DG) and superficial small neurons of the transentorhinal cortex (TEC) with mild subicular degeneration (stage I: inclusion stage). Subsequent gliosis and neuronal loss of the TEC, concomitant with presynaptic degeneration of the outer molecular layer of the DG, suggests an extension of the degeneration through the perforant pathway (stage II: early perforant stage). In a more advanced stage, the presynaptic degeneration is more evident with moderate to severe neuronal loss in the TEC (stage III: advanced perforant stage). This advanced stage was associated with episodic memory deficits mimicking AD in some ALS patients. This ALS pathology initiated by cytoplasmic inclusions and neuronal loss in layer II-III of the TEC is different from neurofibrillary tangles of AD, dominant in layer II-III of the entorhinal cortex. Because this involvement of the TEC-molecular DG projection and subiculum is specific to ALS, it will provide a basis for clinical characterization of memory deficits of ALS, which could be distinct from those of AD.

Upregulation of Neurotrophic Factors Selectively in Frontal Cortex in Response to Olfactory Discrimination Learning

PubMed Central

Naimark, Ari; Barkai, Edi; Matar, Michael A.; Kaplan, Zeev; Kozlovsky, Nitzan; Cohen, Hagit

2007-01-01

We have previously shown that olfactory discrimination learning is accompanied by several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons selectively in the piriform cortex. This study sought to examine whether the previously demonstrated olfactory-learning-task-induced modifications are preceded by suitable changes in the expression of mRNA for neurotrophic factors and in which brain areas this occurs. Rats were trained to discriminate positive cues in pair of odors for a water reward. The relationship between the learning task and local levels of mRNA for brain-derived neurotrophic factor, tyrosine kinase B, nerve growth factor, and neurotrophin-3 in the frontal cortex, hippocampal subregions, and other regions were assessed 24 hours post olfactory learning. The olfactory discrimination learning activated production of endogenous neurotrophic factors and induced their signal transduction in the frontal cortex, but not in other brain areas. These findings suggest that different brain areas may be preferentially involved in different learning/memory tasks. PMID:17710248

Hemispheric comparisons of neuron density in the planum temporale of schizophrenia and nonpsychiatric brains

PubMed Central

Smiley, John F.; Rosoklija, Gorazd; Mancevski, Branislav; Pergolizzi, Denise; Figarsky, Khadija; Bleiwas, Cynthia; Duma, Aleksej; Mann, J. John; Javitt, Daniel C.; Dwork, Andrew J.

2010-01-01

Postmortem and in vivo studies of schizophrenia frequently reveal reduced cortical volume, but the underlying cellular abnormalities are incompletely defined. One influential hypothesis, especially investigated in Brodmann’s area 9 of prefrontal cortex, is that the number of neurons is normal, and the volume change is caused by reduction of the surrounding neuropil. However, studies have differed on whether the cortex has the increased neuron density that is predicted by this hypothesis. In a recent study of bilateral planum temporale (PT), we reported smaller volume and width of the outer cortex (layers I-III), especially in the left hemisphere, among subjects with schizophrenia. In the present study, we measured neuron density and size in the same PT samples, and also in prefrontal area 9 of the same brains. In the PT, separate stereological measurements were made in layers II, IIIc, and VI, whereas area 9 was sampled in layer IIIb-c. In both cortical regions, there was no significant effect of schizophrenia on neuronal density or size. There was, nevertheless, a trend-level right>left hemispheric asymmetry of neuron density in the PT, which may partially explain the previously reported left>right asymmetry of cortical width. In schizophrenia, our findings suggest that closer packing of neurons may not always explain reduced cortical volume, and subtly decreased neuron number may be a contributing factor. PMID:21377842

Elevated GRIA1 mRNA expression in Layer II/III and V pyramidal cells of the DLPFC in schizophrenia

PubMed Central

O’Connor, J.A.; Hemby, S.E.

2012-01-01

The functional integrity of the dorsolateral prefrontal cortex (DLPFC) is altered in schizophrenia leading to profound deficits in working memory and cognition. Growing evidence indicates that dysregulation of glutamate signaling may be a significant contributor to the pathophysiology mediating these effects; however, the contribution of NMDA and AMPA receptors in the mediation of this deficit remains unclear. The equivocality of data regarding ionotropic glutamate receptor alterations of subunit expression in the DLPFC of schizophrenics is likely reflective of subtle alterations in the cellular and molecular composition of specific neuronal populations within the region. Given previous evidence of Layer II/III and V pyramidal cell alterations in schizophrenia and the significant influence of subunit composition on NMDA and AMPA receptor function, laser capture microdissection combined with quantitative PCR was used to examine the expression of AMPA (GRIA1-4) and NMDA (GRIN1, 2A and 2B) subunit mRNA levels in Layer II/III and Layer V pyramidal cells in the DLPFC. Comparisons were made between individuals diagnosed with schizophrenia, bipolar disorder, major depressive disorder and controls (n=15/group). All subunits were expressed at detectable levels in both cell populations for all diseases as well as for the control group. Interestingly, GRIA1 mRNA was significantly increased in both cell types in the schizophrenia group compare to controls, while similar trends were observed in major depressive disorder (Layers II/III and V) and bipolar disorder (Layer V). These data suggest that increased GRIA1 subunit expression may contribute to schizophrenia pathology. PMID:17942280

Cortical layers: Cyto-, myelo-, receptor- and synaptic architecture in human cortical areas.

PubMed

Palomero-Gallagher, Nicola; Zilles, Karl

2017-08-12

Cortical layers have classically been identified by their distinctive and prevailing cell types and sizes, as well as the packing densities of cell bodies or myelinated fibers. The densities of multiple receptors for classical neurotransmitters also vary across the depth of the cortical ribbon, and thus determine the neurochemical properties of cyto- and myeloarchitectonic layers. However, a systematic comparison of the correlations between these histologically definable layers and the laminar distribution of transmitter receptors is currently lacking. We here analyze the densities of 17 different receptors of various transmitter systems in the layers of eight cytoarchitectonically identified, functionally (motor, sensory, multimodal) and hierarchically (primary and secondary sensory, association) distinct areas of the human cerebral cortex. Maxima of receptor densities are found in different layers when comparing different cortical regions, i.e. laminar receptor densities demonstrate differences in receptorarchitecture between isocortical areas, notably between motor and primary sensory cortices, specifically the primary visual and somatosensory cortices, as well as between allocortical and isocortical areas. Moreover, considerable differences are found between cytoarchitectonical and receptor architectonical laminar patterns. Whereas the borders of cyto- and myeloarchitectonic layers are well comparable, the laminar profiles of receptor densities rarely coincide with the histologically defined borders of layers. Instead, highest densities of most receptors are found where the synaptic density is maximal, i.e. in the supragranular layers, particularly in layers II-III. The entorhinal cortex as an example of the allocortex shows a peculiar laminar organization, which largely deviates from that of all the other cortical areas analyzed here. Copyright © 2017. Published by Elsevier Inc.

A cytological and experimental study of the neuropil and primary olfactory afferences to the piriform cortex.

PubMed

Vargas-Barroso, Víctor; Larriva-Sahd, Jorge

2013-09-01

The microscopic organization of the piriform cortex (PC) was studied in normal and experimental material from adult albino rats. In rapid-Golgi specimens a set of collaterals from the lateral olfactory tract (i.e., sublayer Ia) to the neuropil of the Layer II (LII) was identified. Specimens from experimental animals that received electrolytic lesion of the main olfactory bulb three days before sacrificing, were further processed for pre-embedding immunocytochemistry to the enzyme glutamic acid decarboxylase 67 (GAD 67). This novel approach permitted a simultaneous visualization at electron microscopy of both synaptic degeneration and GAD67-immunoreactive (GAD-I) sites. Degenerating and GAD-I synapses were separately found in the neuropil of Layers I and II of the PC. Previously overlooked patches of neuropil were featured in sublayer Ia. These areas consisted of dendritic and axonal processes including four synaptic types. Tridimensional reconstructions from serial thin sections from LI revealed the external appearance of the varicose and tubular dendrites as well as the synaptic terminals therein. The putative source(s) of processes to the neuropil of sublayer Ia is discussed in the context of the internal circuitry of the PC and an alternative model is introduced. Copyright © 2013 Wiley Periodicals, Inc.

Modulatory Effects of Metabotropic Glutamate Receptors on Local Cortical Circuits

PubMed Central

De Pasquale, Roberto; Sherman, S. Murray

2012-01-01

Glutamatergic pathways in various thalamic and cortical circuits have been classified into two types: Class 1 and Class 2, where it has been suggested that Class 1 carries main information for processing and Class 2 is mainly modulatory. We now extend this to the local circuitry of visual cortex of the mouse by demonstrating the modulatory actions on the Class 1 pathway from layer 4 to layers 2/3 of a Class 2 input from adjacent locations in layers 2/3. We found that this Class 2 input produces a long lasting hyperpolarization and suppresses the initial responses of input from layer 4 and that this involves the postsynaptic activation of Group II metabotropic glutamate receptors. This modulation also shifts the paired pulse ratio of the layer 4 input from depression to facilitation. PMID:22623682

Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex

NASA Technical Reports Server (NTRS)

Chen, W. R.; Lee, S.; Kato, K.; Spencer, D. D.; Shepherd, G. M.; Williamson, A.

1996-01-01

The primate temporal cortex has been demonstrated to play an important role in visual memory and pattern recognition. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here we address this issue by examining the induction of synaptic plasticity in surgically resected human inferior and middle temporal cortex. The results show that synaptic strength in the human temporal cortex could undergo bidirectional modifications, depending on the pattern of conditioning stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long-term potentiation (LTP) of both intracellular excitatory postsynaptic potentials and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that N-methyl-D-aspartate receptors were responsible for its induction. Long-term depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15 min). It was reduced, but not completely blocked, by DL-2-amino-5-phosphonovaleric acid, implying that some other mechanisms in addition to N-methyl-DL-aspartate receptors were involved in LTD induction. LTD was input-specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic transmission in that pathway only. Finally, the LTP and LTD could reverse each other, suggesting that they can act cooperatively to modify the functional state of cortical network. These results suggest that LTP and LTD are possible mechanisms for the visual memory and pattern recognition functions performed in the human temporal cortex.

Columnar organization of orientation domains in V1

NASA Astrophysics Data System (ADS)

Liedtke, Joscha; Wolf, Fred

In the primary visual cortex (V1) of primates and carnivores, the functional architecture of basic stimulus selectivities appears similar across cortical layers (Hubel & Wiesel, 1962) justifying the use of two-dimensional cortical models and disregarding organization in the third dimension. Here we show theoretically that already small deviations from an exact columnar organization lead to non-trivial three-dimensional functional structures. We extend two-dimensional random field models (Schnabel et al., 2007) to a three-dimensional cortex by keeping a typical scale in each layer and introducing a correlation length in the third, columnar dimension. We examine in detail the three-dimensional functional architecture for different cortical geometries with different columnar correlation lengths. We find that (i) topological defect lines are generally curved and (ii) for large cortical curvatures closed loops and reconnecting topological defect lines appear. This theory extends the class of random field models by introducing a columnar dimension and provides a systematic statistical assessment of the three-dimensional functional architecture of V1 (see also (Tanaka et al., 2011)).

Defining the Pathophysiological Role of Tau in Experimental TBI

DTIC Science & Technology

2017-10-01

clinically a blood test for improving the diagnosis of TBI-induced chronic neurodegenerative disease in the long-term post -injury time period. The...we will complete the quantitative analysis of perforant pathway synapse integrity in all 63 long-term post -injury cases. Our results thus far support...substantiated by quantitative analysis of NeuN-positive neuronal density in lateral entorhinal cortex layer II at 4 months post -injury (Table 1). At

Visual Information Present in Infragranular Layers of Mouse Auditory Cortex.

PubMed

Morrill, Ryan J; Hasenstaub, Andrea R

2018-03-14

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

Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

PubMed Central

Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

2018-01-01

Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely to form the anatomical basis for the impaired functioning of this brain area. Indeed, impaired functioning of the prefrontal cortex, such as cognitive deficits are common in stressed individuals as well as in depressed patients. PMID:29440995

Gradients in cytoarchitectural landscapes of the isocortex: Diprotodont marsupials in comparison to eutherian mammals.

PubMed

Charvet, Christine J; Stimpson, Cheryl D; Kim, Young Do; Raghanti, Mary Ann; Lewandowski, Albert H; Hof, Patrick R; Gómez-Robles, Aida; Krienen, Fenna M; Sherwood, Chet C

2017-06-01

Although it has been claimed that marsupials possess a lower density of isocortical neurons compared with other mammals, little is known about cross-cortical variation in neuron distributions in this diverse taxonomic group. We quantified upper-layer (layers II-IV) and lower-layer (layers V-VI) neuron numbers per unit of cortical surface area in three diprotodont marsupial species (two macropodiformes, the red kangaroo and the parma wallaby, and a vombatiform, the koala) and compared these results to eutherian mammals (e.g., xenarthrans, rodents, primates). In contrast to the notion that the marsupial isocortex contains a low density of neurons, we found that neuron numbers per unit of cortical surface area in several marsupial species overlap with those found in eutherian mammals. Furthermore, neuron numbers vary systematically across the isocortex of the marsupial mammals examined. Neuron numbers under a unit of cortical surface area are low toward the frontal cortex and high toward the caudo-medial (occipital) pole. Upper-layer neurons (i.e., layers II-IV) account for most of the variation in neuron numbers across the isocortex. The variation in neuron numbers across the rostral to the caudal pole resembles primates. These findings suggest that diprotodont marsupials and eutherian mammals share a similar cortical architecture despite their distant evolutionary divergence. © 2017 Wiley Periodicals, Inc.

Laminar Module Cascade from Layer 5 to 6 Implementing Cue-to-Target Conversion for Object Memory Retrieval in the Primate Temporal Cortex.

PubMed

Koyano, Kenji W; Takeda, Masaki; Matsui, Teppei; Hirabayashi, Toshiyuki; Ohashi, Yohei; Miyashita, Yasushi

2016-10-19

The cerebral cortex computes through the canonical microcircuit that connects six stacked layers; however, how cortical processing streams operate in vivo, particularly in the higher association cortex, remains elusive. By developing a novel MRI-assisted procedure that reliably localizes recorded single neurons at resolution of six individual layers in monkey temporal cortex, we show that transformation of representations from a cued object to a to-be-recalled object occurs at the infragranular layer in a visual cued-recall task. This cue-to-target conversion started in layer 5 and was followed by layer 6. Finally, a subset of layer 6 neurons exclusively encoding the sought target became phase-locked to surrounding field potentials at theta frequency, suggesting that this coordinated cell assembly implements cortical long-distance outputs of the recalled target. Thus, this study proposes a link from local computation spanning laminar modules of the temporal cortex to the brain-wide network for memory retrieval in primates. Copyright © 2016 Elsevier Inc. All rights reserved.

Cytology of human caudomedial cingulate, retrosplenial, and caudal parahippocampal cortices.

PubMed

Vogt, B A; Vogt, L J; Perl, D P; Hof, P R

2001-09-24

Brodmann showed areas 26, 29, 30, 23, and 31 on the human posterior cingulate gyrus without marking sulcal areas. Histologic studies of retrosplenial areas 29 and 30 identify them on the ventral bank of the cingulate gyrus (CGv), whereas standardized atlases show area 30 on the surface of the caudomedial region. This study evaluates all areas on the CGv and caudomedial region with rigorous cytologic criteria in coronal and oblique sections Nissl stained or immunoreacted for neuron-specific nuclear binding protein and nonphosphorylated neurofilament proteins (NFP-ir). Ectosplenial area 26 has a granular layer with few large pyramidal neurons below. Lateral area 29 (29l) has a dense granular layer II-IV and undifferentiated layers V and VI. Medial area 29 (29m) has a layer III of medium and NFP-ir pyramids and a layer IV with some large, NFP-ir pyramidal neurons that distinguish it from areas 29l, 30, and 27. Although area 29m is primarily on the CGv, a terminal branch can extend onto the caudomedial lobule. Area 30 is dysgranular with a variable thickness layer IV that is interrupted by large NFP-ir neurons in layers IIIc and Va. Although area 30 does not appear on the surface of the caudomedial lobule, a terminal branch can form less that 1% of this gyrus. Area 23a is isocortex with a clear layer IV and large, NFP-ir neurons in layers IIIc and Va. Area 23b is similar to area 23a but with a thicker layer IV, more large neurons in layer Va, and a higher density of NFP-ir neurons in layer III. The caudomedial gyral surface is composed of areas 23a and 23b and a caudal extension of area 31. Although posterior area 27 and the parasubiculum are similar to rostral levels, posterior area 36' differs from rostral area 36. Subregional flat maps show that retrosplenial cortex is on the CGv, most of the surface of caudomedial cortex is areas 23a, 23b, and 31, and the retrosplenial/parahippocampal border is at the ventral edge of the splenium. Thus, Brodmann's map understates the rostral extent of retrosplenial cortex, overstates its caudoventral extent, and abridges the caudomedial extent of area 23. Copyright 2001 Wiley-Liss, Inc.

Wiring Economy of Pyramidal Cells in the Juvenile Rat Somatosensory Cortex

PubMed Central

Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier

2016-01-01

Ever since Cajal hypothesized that the structure of neurons is designed in such a way as to save space, time and matter, numerous researchers have analyzed wiring properties at different scales of brain organization. Here we test the hypothesis that individual pyramidal cells, the most abundant type of neuron in the cerebral cortex, optimize brain connectivity in terms of wiring length. In this study, we analyze the neuronal wiring of complete basal arborizations of pyramidal neurons in layer II, III, IV, Va, Vb and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. For each cell, we search for the optimal basal arborization and compare its length with the length of the real dendritic structure. Here the optimal arborization is defined as the arborization that has the shortest total wiring length provided that all neuron bifurcations are respected and the extent of the dendritic arborizations remain unchanged. We use graph theory and evolutionary computation techniques to search for the minimal wiring arborizations. Despite morphological differences between pyramidal neurons located in different cortical layers, we found that the neuronal wiring is near-optimal in all cases (the biggest difference between the shortest synthetic wiring found for a dendritic arborization and the length of its real wiring was less than 5%). We found, however, that the real neuronal wiring was significantly closer to the best solution found in layers II, III and IV. Our studies show that the wiring economy of cortical neurons is related not to the type of neurons or their morphological complexities but to general wiring economy principles. PMID:27832100

Wiring Economy of Pyramidal Cells in the Juvenile Rat Somatosensory Cortex.

PubMed

Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier

2016-01-01

Ever since Cajal hypothesized that the structure of neurons is designed in such a way as to save space, time and matter, numerous researchers have analyzed wiring properties at different scales of brain organization. Here we test the hypothesis that individual pyramidal cells, the most abundant type of neuron in the cerebral cortex, optimize brain connectivity in terms of wiring length. In this study, we analyze the neuronal wiring of complete basal arborizations of pyramidal neurons in layer II, III, IV, Va, Vb and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. For each cell, we search for the optimal basal arborization and compare its length with the length of the real dendritic structure. Here the optimal arborization is defined as the arborization that has the shortest total wiring length provided that all neuron bifurcations are respected and the extent of the dendritic arborizations remain unchanged. We use graph theory and evolutionary computation techniques to search for the minimal wiring arborizations. Despite morphological differences between pyramidal neurons located in different cortical layers, we found that the neuronal wiring is near-optimal in all cases (the biggest difference between the shortest synthetic wiring found for a dendritic arborization and the length of its real wiring was less than 5%). We found, however, that the real neuronal wiring was significantly closer to the best solution found in layers II, III and IV. Our studies show that the wiring economy of cortical neurons is related not to the type of neurons or their morphological complexities but to general wiring economy principles.

Circumscribed malformation and nerve cell alterations in the entorhinal cortex of schizophrenics. Pathogenetic and clinical aspects.

PubMed

Jakob, H; Beckmann, H

1994-01-01

A postmortem histological comparison of 5 selected cases of schizophrenia with 5 non-schizophrenic controls showed a circumscribed malformation of the entorhinal cortex. The cortical alterations consisted mainly of a lack or a change of the characteristic island formations in layer II pre-alpha. Further, there were atypical neurons in layers II and III showing a conspicuous decrease of volume, often a change of the shape. They lay either in clusters or in columnar formations. These cells were considered "young neurons". The changes varied considerably from case to case and sometimes extended to all entorhinal layers. In one case the extension of the changes is described by means of serial sections in steps which extend over the whole rostral entorhinal region. Here, the striking architectural changes were formed in an exactly circumscribed sector and did not extend to the rostral hippocampal formation. On the whole, the changes are regarded as local migrational disturbances that occur during the second trimester of brain development. Neuronal displacements like these could give rise to various aberrant connections within the limbic system and related structures (e.g. the central position of the entorhinal region in circuits such as the entorhino-hippocampal loop, entorhinol-insula and entorhino-orbitofrontal reciprocal connections). Whereas alterations of the genetic programming of cell migrations may be suspected, various environmental influences (e.g. viral infections during the months III-V of pregnancy) appear to play a significant role. The malformations may be a decisive vulnerability factor for the later manifestation of the illness.

Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine

PubMed Central

Elsworth, John D; Morrow, Bret A; Hajszan, Tibor; Leranth, Csaba; Roth, Robert H

2011-01-01

Enduring cognitive deficits exist in schizophrenic patients, long-term abusers of phencyclidine (PCP), as well as in animal PCP models of schizophrenia. It has been suggested that cognitive performance and memory processes are coupled with remodeling of pyramidal dendritic spine synapses in prefrontal cortex (PFC), and that reduced spine density and number of spine synapses in the medial PFC of PCP-treated rats may potentially underlie, at least partially, the cognitive dysfunction previously observed in this animal model. The present data show that the decrease in number of asymmetric (excitatory) spine synapses in layer II/III of PFC, previously noted at 1-week post PCP treatment also occurs, to a lesser degree, in layer V. The decrease in the number of spine synapses in layer II/III was sustained and persisted for at least 4 weeks, paralleling the observed cognitive deficits. Both acute and chronic treatment with the atypical antipsychotic drug, olanzapine, starting at 1 week after PCP treatment at doses that restore cognitive function, reversed the asymmetric spine synapse loss in PFC of PCP-treated rats. Olanzapine had no significant effect on spine synapse number in saline-treated controls. These studies demonstrate that the effect of PCP on asymmetric spine synapse number in PFC lasts at least 4 weeks in this model. This spine synapse loss in PFC is reversed by acute treatment with olanzapine, and this reversal is maintained by chronic oral treatment, paralleling the time course of the restoration of the dopamine deficit, and normalization of cognitive function produced by olanzapine. PMID:21677652

Physiological roles of Kv2 channels in entorhinal cortex layer II stellate cells revealed by Guangxitoxin‐1E

PubMed Central

Hönigsperger, Christoph; Nigro, Maximiliano J.

2016-01-01

Key points Kv2 channels underlie delayed‐rectifier potassium currents in various neurons, although their physiological roles often remain elusive. Almost nothing is known about Kv2 channel functions in medial entorhinal cortex (mEC) neurons, which are involved in representing space, memory formation, epilepsy and dementia.Stellate cells in layer II of the mEC project to the hippocampus and are considered to be space‐representing grid cells. We used the new Kv2 blocker Guangxitoxin‐1E (GTx) to study Kv2 functions in these neurons.Voltage clamp recordings from mEC stellate cells in rat brain slices showed that GTx inhibited delayed‐rectifier K+ current but not transient A‐type current.In current clamp, GTx had multiple effects: (i) increasing excitability and bursting at moderate spike rates but reducing firing at high rates; (ii) enhancing after‐depolarizations; (iii) reducing the fast and medium after‐hyperpolarizations; (iv) broadening action potentials; and (v) reducing spike clustering.GTx is a useful tool for studying Kv2 channels and their functions in neurons. Abstract The medial entorhinal cortex (mEC) is strongly involved in spatial navigation, memory, dementia and epilepsy. Although potassium channels shape neuronal activity, their roles in mEC are largely unknown. We used the new Kv2 blocker Guangxitoxin‐1E (GTx; 10–100 nm) in rat brain slices to investigate Kv2 channel functions in mEC layer II stellate cells (SCs). These neurons project to the hippocampus and are considered to be grid cells representing space. Voltage clamp recordings from SCs nucleated patches showed that GTx inhibited a delayed rectifier K+ current activating beyond –30 mV but not transient A‐type current. In current clamp, GTx (i) had almost no effect on the first action potential but markedly slowed repolarization of late spikes during repetitive firing; (ii) enhanced the after‐depolarization (ADP); (iii) reduced fast and medium after‐hyperpolarizations (AHPs); (iv) strongly enhanced burst firing and increased excitability at moderate spike rates but reduced spiking at high rates; and (v) reduced spike clustering and rebound potentials. The changes in bursting and excitability were related to the altered ADPs and AHPs. Kv2 channels strongly shape the activity of mEC SCs by affecting spike repolarization, after‐potentials, excitability and spike patterns. GTx is a useful tool and may serve to further clarify Kv2 channel functions in neurons. We conclude that Kv2 channels in mEC SCs are important determinants of intrinsic properties that allow these neurons to produce spatial representation. The results of the present study may also be important for the accurate modelling of grid cells. PMID:27562026

Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory

PubMed Central

Bastos, André M.; Loonis, Roman; Kornblith, Simon; Lundqvist, Mikael; Miller, Earl K.

2018-01-01

All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50–250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4–22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM. PMID:29339471

Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory.

PubMed

Bastos, André M; Loonis, Roman; Kornblith, Simon; Lundqvist, Mikael; Miller, Earl K

2018-01-30

All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50-250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4-22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM. Copyright © 2018 the Author(s). Published by PNAS.

The Microcircuit Concept Applied to Cortical Evolution: from Three-Layer to Six-Layer Cortex

PubMed Central

Shepherd, Gordon M.

2011-01-01

Understanding the principles of organization of the cerebral cortex requires insight into its evolutionary history. This has traditionally been the province of anatomists, but evidence regarding the microcircuit organization of different cortical areas is providing new approaches to this problem. Here we use the microcircuit concept to focus first on the principles of microcircuit organization of three-layer cortex in the olfactory cortex, hippocampus, and turtle general cortex, and compare it with six-layer neocortex. From this perspective it is possible to identify basic circuit elements for recurrent excitation and lateral inhibition that are common across all the cortical regions. Special properties of the apical dendrites of pyramidal cells are reviewed that reflect the specific adaptations that characterize the functional operations in the different regions. These principles of microcircuit function provide a new approach to understanding the expanded functional capabilities elaborated by the evolution of the neocortex. PMID:21647397

Frequency preference and attention effects across cortical depths in the human primary auditory cortex.

PubMed

De Martino, Federico; Moerel, Michelle; Ugurbil, Kamil; Goebel, Rainer; Yacoub, Essa; Formisano, Elia

2015-12-29

Columnar arrangements of neurons with similar preference have been suggested as the fundamental processing units of the cerebral cortex. Within these columnar arrangements, feed-forward information enters at middle cortical layers whereas feedback information arrives at superficial and deep layers. This interplay of feed-forward and feedback processing is at the core of perception and behavior. Here we provide in vivo evidence consistent with a columnar organization of the processing of sound frequency in the human auditory cortex. We measure submillimeter functional responses to sound frequency sweeps at high magnetic fields (7 tesla) and show that frequency preference is stable through cortical depth in primary auditory cortex. Furthermore, we demonstrate that-in this highly columnar cortex-task demands sharpen the frequency tuning in superficial cortical layers more than in middle or deep layers. These findings are pivotal to understanding mechanisms of neural information processing and flow during the active perception of sounds.

Mapping Cortical Laminar Structure in the 3D BigBrain.

PubMed

Wagstyl, Konrad; Lepage, Claude; Bludau, Sebastian; Zilles, Karl; Fletcher, Paul C; Amunts, Katrin; Evans, Alan C

2018-07-01

Histological sections offer high spatial resolution to examine laminar architecture of the human cerebral cortex; however, they are restricted by being 2D, hence only regions with sufficiently optimal cutting planes can be analyzed. Conversely, noninvasive neuroimaging approaches are whole brain but have relatively low resolution. Consequently, correct 3D cross-cortical patterns of laminar architecture have never been mapped in histological sections. We developed an automated technique to identify and analyze laminar structure within the high-resolution 3D histological BigBrain. We extracted white matter and pial surfaces, from which we derived histologically verified surfaces at the layer I/II boundary and within layer IV. Layer IV depth was strongly predicted by cortical curvature but varied between areas. This fully automated 3D laminar analysis is an important requirement for bridging high-resolution 2D cytoarchitecture and in vivo 3D neuroimaging. It lays the foundation for in-depth, whole-brain analyses of cortical layering.

Laminar-specific distribution of zinc: evidence for presence of layer IV in forelimb motor cortex in the rat.

PubMed

Alaverdashvili, Mariam; Hackett, Mark J; Pickering, Ingrid J; Paterson, Phyllis G

2014-12-01

The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a "Zn valley" in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding is also critical for future investigation of the biochemical mechanisms through which therapeutic interventions can enhance neural plasticity, particularly through Zn dependent pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

Laminar-specific distribution of zinc: Evidence for presence of layer IV in forelimb motor cortex in the rat

PubMed Central

Alaverdashvili, Mariam; Hackett, Mark J.; Pickering, Ingrid J.; Paterson, Phyllis G.

2015-01-01

The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a “Zn valley” in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding is also critical for future investigation of the biochemical mechanisms through which therapeutic interventions can enhance neural plasticity, particularly through Zn dependent pathways. PMID:25192655

Comparison of frailty of primary neurons, embryonic, and aging mouse cortical layers.

PubMed

Fugistier, Patrick; Vallet, Philippe G; Leuba, Geneviève; Piotton, Françoise; Marin, Pascale; Bouras, Constantin; Savioz, Armand

2014-02-01

Superficial layers I to III of the human cerebral cortex are more vulnerable toward Aβ peptides than deep layers V to VI in aging. Three models of layers were used to investigate this pattern of frailty. First, primary neurons from E14 and E17 embryonic murine cortices, corresponding respectively to future deep and superficial layers, were treated either with Aβ(1-42), okadaic acid, or kainic acid. Second, whole E14 and E17 embryonic cortices, and third, in vitro separated deep and superficial layers of young and old C57BL/6J mice, were treated identically. We observed that E14 and E17 neurons in culture were prone to death after the Aβ and particularly the kainic acid treatment. This was also the case for the superficial layers of the aged cortex, but not for the embryonic, the young cortex, and the deep layers of the aged cortex. Thus, the aged superficial layers appeared to be preferentially vulnerable against Aβ and kainic acid. This pattern of vulnerability corresponds to enhanced accumulation of senile plaques in the superficial cortical layers with aging and Alzheimer's disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Spectral Signatures of Feedforward and Recurrent Circuitry in Monkey Area MT.

PubMed

Solomon, Selina S; Morley, John W; Solomon, Samuel G

2017-05-01

Recordings of local field potential (LFP) in the visual cortex can show rhythmic activity at gamma frequencies (30-100 Hz). While the gamma rhythms in the primary visual cortex have been well studied, the structural and functional characteristics of gamma rhythms in extrastriate visual cortex are less clear. Here, we studied the spatial distribution and functional specificity of gamma rhythms in extrastriate middle temporal (MT) area of visual cortex in marmoset monkeys. We found that moving gratings induced narrowband gamma rhythms across cortical layers that were coherent across much of area MT. Moving dot fields instead induced a broadband increase in LFP in middle and upper layers, with weaker narrowband gamma rhythms in deeper layers. The stimulus dependence of LFP response in middle and upper layers of area MT appears to reflect the presence (gratings) or absence (dot fields and other textures) of strongly oriented contours. Our results suggest that gamma rhythms in these layers are propagated from earlier visual cortex, while those in the deeper layers may emerge in area MT. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Laminar and dorsoventral molecular organization of the medial entorhinal cortex revealed by large-scale anatomical analysis of gene expression.

PubMed

Ramsden, Helen L; Sürmeli, Gülşen; McDonagh, Steven G; Nolan, Matthew F

2015-01-01

Neural circuits in the medial entorhinal cortex (MEC) encode an animal's position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. We also reveal laminar organization of genes related to disease pathology and suggest that a high metabolic demand predisposes layer II to neurodegenerative pathology. In principle, our computational pipeline can be applied to high-throughput analysis of many forms of neuroanatomical data. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations.

Laminar and Dorsoventral Molecular Organization of the Medial Entorhinal Cortex Revealed by Large-scale Anatomical Analysis of Gene Expression

PubMed Central

Ramsden, Helen L.; Sürmeli, Gülşen; McDonagh, Steven G.; Nolan, Matthew F.

2015-01-01

Neural circuits in the medial entorhinal cortex (MEC) encode an animal’s position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. We also reveal laminar organization of genes related to disease pathology and suggest that a high metabolic demand predisposes layer II to neurodegenerative pathology. In principle, our computational pipeline can be applied to high-throughput analysis of many forms of neuroanatomical data. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations. PMID:25615592

Layer-specific gene expression in epileptogenic type II focal cortical dysplasia: normal-looking neurons reveal the presence of a hidden laminar organization

PubMed Central

2014-01-01

Background Type II focal cortical dysplasias (FCDs) are malformations of cortical development characterised by the disorganisation of the normal neocortical structure and the presence of dysmorphic neurons (DNs) and balloon cells (BCs). The pathogenesis of FCDs has not yet been clearly established, although a number of histopathological patterns and molecular findings suggest that they may be due to abnormal neuronal and glial proliferation and migration processes. In order to gain further insights into cortical layering disruption and investigate the origin of DNs and BCs, we used in situ RNA hybridisation of human surgical specimens with a neuropathologically definite diagnosis of Type IIa/b FCD and a panel of layer-specific genes (LSGs) whose expression covers all cortical layers. We also used anti-phospho-S6 ribosomal protein antibody to investigate mTOR pathway hyperactivation. Results LSGs were expressed in both normal and abnormal cells (BCs and DNs) but their distribution was different. Normal-looking neurons, which were visibly reduced in the core of the lesion, were apparently located in the appropriate cortical laminae thus indicating a partial laminar organisation. On the contrary, DNs and BCs, labelled with anti-phospho-S6 ribosomal protein antibody, were spread throughout the cortex without any apparent rule and showed a highly variable LSG expression pattern. Moreover, LSGs did not reveal any differences between Type IIa and IIb FCD. Conclusion These findings suggest the existence of hidden cortical lamination involving normal-looking neurons, which retain their ability to migrate correctly in the cortex, unlike DNs which, in addition to their morphological abnormalities and mTOR hyperactivation, show an altered migratory pattern. Taken together these data suggest that an external or environmental hit affecting selected precursor cells during the very early stages of cortical development may disrupt normal cortical development. PMID:24735483

Antioxidative effects of cinnamomi cortex: A potential role of iNOS and COX-II

PubMed Central

Chung, Jin-Won; Kim, Jeong-Jun; Kim, Sung-Jin

2011-01-01

Background: Cinnamomi cortex has wide varieties of pharmacological actions such as anti-inflammatory action, anti-platelet aggregation, and improving blood circulation. In this study, we tested to determine whether the Cinnamomi cortex extract has antioxidant activities. Materials and Methods: Antioxidative actions were explored by measuring free radical scavenging activity, NO levels, and reducing power. The mechanism of antioxidative action of Cinnamomi cortex was determined by measuring iNOS and COX-II expression in lipopolysaccharide (LPS) stimulated Raw cells. Results: Seventy percent methanolic extract of Cinnamomi cortex exerted significant 1,1-diphenyl--2--picrylhydrazyl (DPPH) free radicals and NO scavenging activities in a dose-dependent manner. More strikingly, the Cinnamomi cortex extract exerted dramatic reducing power activity (13-fold over control). Production of iNOS induced by LPS was significantly inhibited by the Cinnamomi cortex extract, suggesting that it inhibits NO production by suppressing iNOS expression. Additionally, COX-2 induced by LPS was dramatically inhibited by the Cinnamomi cortex extract. Conclusion: These results suggest that 70% methanolic extract of Cinnamomi cortex exerts significant antioxidant activity via inhibiting iNOS and COX-II induction. PMID:22262934

Visual deprivation alters dendritic bundle architecture in layer 4 of rat visual cortex.

PubMed

Gabbott, P L; Stewart, M G

2012-04-05

The effect of visual deprivation followed by light exposure on the tangential organisation of dendritic bundles passing through layer 4 of the rat visual cortex was studied quantitatively in the light microscope. Four groups of animals were investigated: (I) rats reared in an environment illuminated normally--group 52 dL; (II) rats reared in the dark until 21 days postnatum (DPN) and subsequently light exposed for 31 days-group 21/31; (III) rats dark reared until 52 DPN and then subsequently light exposed for 3 days--group 3 dL; and (IV) rats totally dark reared until 52 DPN--group 52 DPN. Each group contained five animals. Semithin 0.5-1-μm thick resin-embedded sections were collected from tangential sampling levels through the middle of layer 4 in area 17 and stained with Toluidine Blue. These sections were used to quantitatively analyse the composition and distribution of dendritic clusters in the tangential plane. The key result of this study indicates a significant reduction in the mean number of medium- and small-sized dendritic profiles (diameter less than 2 μm) contributing to clusters in layer 4 of groups 3 dL and 52 dD compared with group 21/31. No differences were detected in the mean number of large-sized dendritic profiles composing a bundle in these experimental groups. Moreover, the mean number of clusters and their tangential distribution in layer 4 did not vary significantly between all four groups. Finally, the clustering parameters were not significantly different between groups 21/31 and the normally reared group 52 dL. This study demonstrates, for the first time, that extended periods of dark rearing followed by light exposure can alter the morphological composition of dendritic bundles in thalamorecipient layer 4 of rat visual cortex. Because these changes occur in the primary region of thalamocortical input, they may underlie specific alterations in the processing of visual information both cortically and subcortically during periods of dark rearing and light exposure. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Three-dimensional distribution of cortical synapses: a replicated point pattern-based analysis

PubMed Central

Anton-Sanchez, Laura; Bielza, Concha; Merchán-Pérez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Larrañaga, Pedro

2014-01-01

The biggest problem when analyzing the brain is that its synaptic connections are extremely complex. Generally, the billions of neurons making up the brain exchange information through two types of highly specialized structures: chemical synapses (the vast majority) and so-called gap junctions (a substrate of one class of electrical synapse). Here we are interested in exploring the three-dimensional spatial distribution of chemical synapses in the cerebral cortex. Recent research has showed that the three-dimensional spatial distribution of synapses in layer III of the neocortex can be modeled by a random sequential adsorption (RSA) point process, i.e., synapses are distributed in space almost randomly, with the only constraint that they cannot overlap. In this study we hypothesize that RSA processes can also explain the distribution of synapses in all cortical layers. We also investigate whether there are differences in both the synaptic density and spatial distribution of synapses between layers. Using combined focused ion beam milling and scanning electron microscopy (FIB/SEM), we obtained three-dimensional samples from the six layers of the rat somatosensory cortex and identified and reconstructed the synaptic junctions. A total volume of tissue of approximately 4500μm3 and around 4000 synapses from three different animals were analyzed. Different samples, layers and/or animals were aggregated and compared using RSA replicated spatial point processes. The results showed no significant differences in the synaptic distribution across the different rats used in the study. We found that RSA processes described the spatial distribution of synapses in all samples of each layer. We also found that the synaptic distribution in layers II to VI conforms to a common underlying RSA process with different densities per layer. Interestingly, the results showed that synapses in layer I had a slightly different spatial distribution from the other layers. PMID:25206325

Three-dimensional distribution of cortical synapses: a replicated point pattern-based analysis.

PubMed

Anton-Sanchez, Laura; Bielza, Concha; Merchán-Pérez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Larrañaga, Pedro

2014-01-01

The biggest problem when analyzing the brain is that its synaptic connections are extremely complex. Generally, the billions of neurons making up the brain exchange information through two types of highly specialized structures: chemical synapses (the vast majority) and so-called gap junctions (a substrate of one class of electrical synapse). Here we are interested in exploring the three-dimensional spatial distribution of chemical synapses in the cerebral cortex. Recent research has showed that the three-dimensional spatial distribution of synapses in layer III of the neocortex can be modeled by a random sequential adsorption (RSA) point process, i.e., synapses are distributed in space almost randomly, with the only constraint that they cannot overlap. In this study we hypothesize that RSA processes can also explain the distribution of synapses in all cortical layers. We also investigate whether there are differences in both the synaptic density and spatial distribution of synapses between layers. Using combined focused ion beam milling and scanning electron microscopy (FIB/SEM), we obtained three-dimensional samples from the six layers of the rat somatosensory cortex and identified and reconstructed the synaptic junctions. A total volume of tissue of approximately 4500μm(3) and around 4000 synapses from three different animals were analyzed. Different samples, layers and/or animals were aggregated and compared using RSA replicated spatial point processes. The results showed no significant differences in the synaptic distribution across the different rats used in the study. We found that RSA processes described the spatial distribution of synapses in all samples of each layer. We also found that the synaptic distribution in layers II to VI conforms to a common underlying RSA process with different densities per layer. Interestingly, the results showed that synapses in layer I had a slightly different spatial distribution from the other layers.

Mouse auditory cortex differs from visual and somatosensory cortices in the laminar distribution of cytochrome oxidase and acetylcholinesterase.

PubMed

Anderson, L A; Christianson, G B; Linden, J F

2009-02-03

Cytochrome oxidase (CYO) and acetylcholinesterase (AChE) staining density varies across the cortical layers in many sensory areas. The laminar variations likely reflect differences between the layers in levels of metabolic activity and cholinergic modulation. The question of whether these laminar variations differ between primary sensory cortices has never been systematically addressed in the same set of animals, since most studies of sensory cortex focus on a single sensory modality. Here, we compared the laminar distribution of CYO and AChE activity in the primary auditory, visual, and somatosensory cortices of the mouse, using Nissl-stained sections to define laminar boundaries. Interestingly, for both CYO and AChE, laminar patterns of enzyme activity were similar in the visual and somatosensory cortices, but differed in the auditory cortex. In the visual and somatosensory areas, staining densities for both enzymes were highest in layers III/IV or IV and in lower layer V. In the auditory cortex, CYO activity showed a reliable peak only at the layer III/IV border, while AChE distribution was relatively homogeneous across layers. These results suggest that laminar patterns of metabolic activity and cholinergic influence are similar in the mouse visual and somatosensory cortices, but differ in the auditory cortex.

Synaptic activation patterns of the perirhinal-entorhinal inter-connections.

PubMed

de Villers-Sidani, E; Tahvildari, B; Alonso, A

2004-01-01

Ample neuropsychological evidence supports the role of rhinal cortices in memory. The perirhinal cortex (PRC) represents one of the main conduits for the bi-directional flow of information between the entorhinal-hippocampal network and the cortical mantle, a process essential in memory formation. However, despite anatomical evidence for a robust reciprocal connectivity between the perirhinal and entorhinal cortices, neurophysiological understanding of this circuitry is lacking. We now present the results of a series of electrophysiological experiments in rats that demonstrate robust synaptic activation patterns of the perirhinal-entorhinal inter-connections. First, using silicon multi-electrode arrays placed under visual guidance in vivo we performed current source density (CSD) analysis of lateral entorhinal cortex (LEC) responses to PRC stimulation, which demonstrated a current sink in layers II-III of the LEC with a latency consistent with monosynaptic activation. To further substantiate and extend this conclusion, we developed a PRC-LEC slice preparation where CSD analysis also revealed a current sink in superficial LEC layers in response to PRC stimulation. Importantly, intracellular recording of superficial LEC layer neurons confirmed that they receive a major monosynaptic excitatory input from the PRC. Finally, CSD analysis of the LEC to PRC projection in vivo also allowed us to document robust feedback synaptic activation of PRC neurons to deep LEC layer activation. We conclude that a clear bidirectional pattern of synaptic interactions exists between the PRC and LEC that would support a dynamic flow of information subserving memory function in the temporal lobe.

Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex.

PubMed

Murray, Helen C; Swanson, Molly E V; Dieriks, B Victor; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

2018-02-21

Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM + interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM + interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM + cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM + cells per mm 2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM + cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN + cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Chronic lead exposure reduces doublecortin-expressing immature neurons in young adult guinea pig cerebral cortex.

PubMed

Huang, JuFang; Huang, Kai; Shang, Lei; Wang, Hui; Zhang, Mengqi; Fan, Chun-Ling; Chen, Dan; Yan, Xiaoxin; Xiong, Kun

2012-07-19

Chronic lead (Pb) poisoning remains an environmental risk especially for the pediatric population, and it may affect brain development. Immature neurons expressing doublecortin (DCX+) exist around cortical layer II in various mammals, including adult guinea pigs and humans. Using young adult guinea pigs as an experimental model, the present study explored if chronic Pb exposure affects cortical DCX + immature neurons and those around the subventricular and subgranular zones (SVZ, SGZ). Two month-old guinea pigs were treated with 0.2% lead acetate in drinking water for 2, 4 and 6 months. Blood Pb levels in these animals reached 10.27 ± 0.62, 16.25 ± 0.78 and 19.03 ± 0.86 μg/dL at the above time points, respectively, relative to ~3 μg/dL in vehicle controls. The density of DCX + neurons was significantly reduced around cortical layer II, SVZ and SGZ in Pb-treated animals surviving 4 and 6 months relative to controls. Bromodeoxyuridine (BrdU) pulse-chasing studies failed to find cellular colocalization of this DNA synthesis indicator in DCX + cells around layer II in Pb-treated and control animals. These cortical immature neurons were not found to coexist with active caspase-3 or Fluoro-Jade C labeling. Chronic Pb exposure can lead to significant reduction in the number of the immature neurons around cortical layer II and in the conventional neurogenic sites in young adult guinea pigs. No direct evidence could be identified to link the reduced cortical DCX expression with alteration in local neurogenesis or neuronal death.

Nitric oxide synthase and the acetylcholine receptor in the prefrontal cortex: metasynaptic organization of the brain.

PubMed

Csillik, B; Nemcsók, J; Boncz, I; Knyihár-Csillik, E

1998-01-01

Nitric oxide synthase (NOS) and the nicotinic acetylcholine receptor (nAChR) immunoreactivity of the cerebral cortex was studied in adult Macaca fascicularis monkeys at light- and electron microscopic levels. NOS was located by means of the polyclonal antibodies developed by Transduction Laboratories (Lexington, KY, USA), as primary serum, in a dilution of 1:1000, and nAChR was located by means of biotinylated alpha-bungarotoxin (BTX) obtained from Molecular probes (Eugene, Oregon, USA) in a dilution of 1:2000. While endothelial eNOS outlined blood vessels in the brain, brain-derived (neural) bNOS labelled three well-defined cell types in area 46 of the prefrontal cortex, viz. (a) bipolar cells, scattered through layers III to V, equipped with long dendrites which pass over the thickness of the cortex in a right angle to the pial surface, establishing dendritic bundles closely reminiscent of a columnar organization; (b) large multipolar cells, located mainly in layers V and VI, with axons which interconnect dendritic bundles of the bipolar cells and establish synapses with dendritic shafts and spines of the former; and (c) stellate cells, located in lamina II and III, which establish an axonal network in lamina zonalis (lamina I). This arrangement is most characteristic in area 46 of the prefrontal cortex; areas 10 and 12 display similar features. In contrast, the primary visual cortex (area 17), is lacking any sign of columnar organization. Localization of bNOS immunoreactivity is at marked variance to that of NADPH-diaphorase which labels large pyramidal cells in the primate cortex. Binding of alpha-bungarotoxin (BTX) which labels the alpha 7 subunit of nAChR is located in somata, dendrites and axons of interneurons scattered over the entire width of the prefrontal cortex; on the other hand, the monoclonal antibody mAb 35 which labels subunits alpha 1, alpha 3 and alpha 5 in the main immunogenic region of the receptor, visualizes apical dendritic shafts similar to those like bNOS. Strategic localization of bNOS in the primate prefrontal cortex fulfills criteria of producing a freely diffusing retrograde messenger molecule operative in signal transduction routes subserving topography and columnar organization of the cortex, as well as long-term potentiation and long-term depression phenomena underlying mnemonic and gnostic functions. Common occurrence of bNOS and nAChR in identical or similar structures in the prefrontal cortex suggests that interactions between nitrogen oxide and presynaptically released acetylcholine might be involved in the metasynaptic organization of the cerebral cortex, operating in a non-synaptic manner in maintaining optimal performance on cognitive tasks.

Sensory-driven and spontaneous gamma oscillations engage distinct cortical circuitry

PubMed Central

2015-01-01

Gamma oscillations are a robust component of sensory responses but are also part of the background spontaneous activity of the brain. To determine whether the properties of gamma oscillations in cortex are specific to their mechanism of generation, we compared in mouse visual cortex in vivo the laminar geometry and single-neuron rhythmicity of oscillations produced during sensory representation with those occurring spontaneously in the absence of stimulation. In mouse visual cortex under anesthesia (isoflurane and xylazine), visual stimulation triggered oscillations mainly between 20 and 50 Hz, which, because of their similar functional significance to gamma oscillations in higher mammals, we define here as gamma range. Sensory representation in visual cortex specifically increased gamma oscillation amplitude in the supragranular (L2/3) and granular (L4) layers and strongly entrained putative excitatory and inhibitory neurons in infragranular layers, while spontaneous gamma oscillations were distributed evenly through the cortical depth and primarily entrained putative inhibitory neurons in the infragranular (L5/6) cortical layers. The difference in laminar distribution of gamma oscillations during the two different conditions may result from differences in the source of excitatory input to the cortex. In addition, modulation of superficial gamma oscillation amplitude did not result in a corresponding change in deep-layer oscillations, suggesting that superficial and deep layers of cortex may utilize independent but related networks for gamma generation. These results demonstrate that stimulus-driven gamma oscillations engage cortical circuitry in a manner distinct from spontaneous oscillations and suggest multiple networks for the generation of gamma oscillations in cortex. PMID:26719085

Three-dimensional visual feature representation in the primary visual cortex

PubMed Central

Tanaka, Shigeru; Moon, Chan-Hong; Fukuda, Mitsuhiro; Kim, Seong-Gi

2011-01-01

In the cat primary visual cortex, it is accepted that neurons optimally responding to similar stimulus orientations are clustered in a column extending from the superficial to deep layers. The cerebral cortex is, however, folded inside a skull, which makes gyri and fundi. The primary visual area of cats, area 17, is located on the fold of the cortex called the lateral gyrus. These facts raise the question of how to reconcile the tangential arrangement of the orientation columns with the curvature of the gyrus. In the present study, we show a possible configuration of feature representation in the visual cortex using a three-dimensional (3D) self-organization model. We took into account preferred orientation, preferred direction, ocular dominance and retinotopy, assuming isotropic interaction. We performed computer simulation only in the middle layer at the beginning and expanded the range of simulation gradually to other layers, which was found to be a unique method in the present model for obtaining orientation columns spanning all the layers in the flat cortex. Vertical columns of preferred orientations were found in the flat parts of the model cortex. On the other hand, in the curved parts, preferred orientations were represented in wedge-like columns rather than straight columns, and preferred directions were frequently reversed in the deeper layers. Singularities associated with orientation representation appeared as warped lines in the 3D model cortex. Direction reversal appeared on the sheets that were delimited by orientation-singularity lines. These structures emerged from the balance between periodic arrangements of preferred orientations and vertical alignment of same orientations. Our theoretical predictions about orientation representation were confirmed by multi-slice, high-resolution functional MRI in the cat visual cortex. We obtained a close agreement between theoretical predictions and experimental observations. The present study throws a doubt about the conventional columnar view of orientation representation, although more experimental data are needed. PMID:21724370

Three-dimensional visual feature representation in the primary visual cortex.

PubMed

Tanaka, Shigeru; Moon, Chan-Hong; Fukuda, Mitsuhiro; Kim, Seong-Gi

2011-12-01

In the cat primary visual cortex, it is accepted that neurons optimally responding to similar stimulus orientations are clustered in a column extending from the superficial to deep layers. The cerebral cortex is, however, folded inside a skull, which makes gyri and fundi. The primary visual area of cats, area 17, is located on the fold of the cortex called the lateral gyrus. These facts raise the question of how to reconcile the tangential arrangement of the orientation columns with the curvature of the gyrus. In the present study, we show a possible configuration of feature representation in the visual cortex using a three-dimensional (3D) self-organization model. We took into account preferred orientation, preferred direction, ocular dominance and retinotopy, assuming isotropic interaction. We performed computer simulation only in the middle layer at the beginning and expanded the range of simulation gradually to other layers, which was found to be a unique method in the present model for obtaining orientation columns spanning all the layers in the flat cortex. Vertical columns of preferred orientations were found in the flat parts of the model cortex. On the other hand, in the curved parts, preferred orientations were represented in wedge-like columns rather than straight columns, and preferred directions were frequently reversed in the deeper layers. Singularities associated with orientation representation appeared as warped lines in the 3D model cortex. Direction reversal appeared on the sheets that were delimited by orientation-singularity lines. These structures emerged from the balance between periodic arrangements of preferred orientations and vertical alignment of the same orientations. Our theoretical predictions about orientation representation were confirmed by multi-slice, high-resolution functional MRI in the cat visual cortex. We obtained a close agreement between theoretical predictions and experimental observations. The present study throws a doubt about the conventional columnar view of orientation representation, although more experimental data are needed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Early postnatal development of vasoactive intestinal polypeptide- and peptide histidine isoleucine-immunoreactive structures in the cat visual cortex.

PubMed

Wahle, P; Meyer, G

1989-04-08

The early postnatal development of neurons containing vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) has been analyzed in visual areas 17 and 18 of cats aged from postnatal day (P) 0 to adulthood. Neuronal types are established mainly by axonal criteria. Both peptides occur in the same neuronal types and display the same postnatal chronology of appearance. Several cell types are transient, which means that they are present in the cortex only for a limited period of development. According to their chronology of appearance the VIP/PHI-immunoreactive (ir) cell types are grouped into three neuronal populations. The first population comprises six cell types which appear early in postnatal life. The pseudohorsetail cells of layer I possess a vertically descending axon which initially gives rise to recurrent collaterals, then forms a bundle passing layers III to V, and finally, horizontal terminal fibers in layer VI. The neurons differentiate at P 4 and disappear by degeneration around P 30. The neurons with columnar dendritic fields of layers IV/V are characterized by a vertical arrangement of long dendrites ascending or descending parallel to each other, thus forming an up to 600 microns long dendritic column. Their axons always descend and terminate in broad fields in layer VI. The neurons appear at P 7 and are present until P 20. The multipolar neurons of layer VI occur in isolated positions and have broad axonal territories. The neurons differentiate at P 7 and persist into adulthood. Bitufted to multipolar neurons of layers II/III have axons descending as a single fiber to layer VI, where they terminate. The neurons appear at P 12 and persist into adulthood. The four cell types described above issue a vertically oriented fiber architecture in layers II-V and a horizontal terminal plexus in layer VI which is dense during the second, third and fourth week. Concurrent with the disappearance of the two transient types the number of descending axonal bundles and the density of the layer VI plexus is reduced, but the latter is maintained during adulthood by the two persisting cell types. Two further cell types belong to the first population: The transient bipolar cells of layers IV, V, and VI have long dendrites which extend through the entire cortical width. Their axons always descend, leave the gray matter, and apparently terminate in the upper white matter. The neurons differentiate concurrently with the pseudohorsetail cells at P 4, are very frequent during the following weeks, and eventually disappear at P 30.(ABSTRACT TRUNCATED AT 400 WORDS)

Localization of P-type calcium channels in the central nervous system.

PubMed Central

Hillman, D; Chen, S; Aung, T T; Cherksey, B; Sugimori, M; Llinás, R R

1991-01-01

The distribution of the P-type calcium channel in the mammalian central nervous system has been demonstrated immunohistochemically by using a polyclonal specific antibody. This antibody was generated after P-channel isolation via a fraction from funnel-web spider toxin (FTX) that blocks the voltage-gated P channels in cerebellar Purkinje cells. In the cerebellar cortex, immunolabeling to the antibody appeared throughout the molecular layer, while all the other regions were negative. Intensely labeled patches of reactivity were seen on Purkinje cell dendrites, especially at bifurcations; much weaker reactivity was present in the soma and stem segment. Electron microscopic localization revealed labeled patches of plasma membrane on the soma, main dendrites, spiny branchlets, and spines; portions of the smooth endoplasmic reticulum were also labeled. Strong labeling was present in the periglomerular cells of the olfactory bulb and scattered neurons in the deep layer of the entorhinal and pyriform cortices. Neurons in the brainstem, habenula, nucleus of the trapezoid body and inferior olive and along the floor of the fourth ventricle were also labeled intensely. Medium-intensity reactions were observed in layer II pyramidal cells of the frontal cortex, the CA1 cells of the hippocampus, the lateral nucleus of the substantia nigra, lateral reticular nucleus, and spinal fifth nucleus. Light labeling was seen in the neocortex, striatum, and in some brainstem neurons. Images PMID:1651493

Localization of P-type calcium channels in the central nervous system.

PubMed

Hillman, D; Chen, S; Aung, T T; Cherksey, B; Sugimori, M; Llinás, R R

1991-08-15

The distribution of the P-type calcium channel in the mammalian central nervous system has been demonstrated immunohistochemically by using a polyclonal specific antibody. This antibody was generated after P-channel isolation via a fraction from funnel-web spider toxin (FTX) that blocks the voltage-gated P channels in cerebellar Purkinje cells. In the cerebellar cortex, immunolabeling to the antibody appeared throughout the molecular layer, while all the other regions were negative. Intensely labeled patches of reactivity were seen on Purkinje cell dendrites, especially at bifurcations; much weaker reactivity was present in the soma and stem segment. Electron microscopic localization revealed labeled patches of plasma membrane on the soma, main dendrites, spiny branchlets, and spines; portions of the smooth endoplasmic reticulum were also labeled. Strong labeling was present in the periglomerular cells of the olfactory bulb and scattered neurons in the deep layer of the entorhinal and pyriform cortices. Neurons in the brainstem, habenula, nucleus of the trapezoid body and inferior olive and along the floor of the fourth ventricle were also labeled intensely. Medium-intensity reactions were observed in layer II pyramidal cells of the frontal cortex, the CA1 cells of the hippocampus, the lateral nucleus of the substantia nigra, lateral reticular nucleus, and spinal fifth nucleus. Light labeling was seen in the neocortex, striatum, and in some brainstem neurons.

Layer-specific chromatin accessibility landscapes reveal regulatory networks in adult mouse visual cortex

PubMed Central

Gray, Lucas T; Yao, Zizhen; Nguyen, Thuc Nghi; Kim, Tae Kyung; Zeng, Hongkui; Tasic, Bosiljka

2017-01-01

Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers. Integration of these data with layer-specific transcriptomic profiles and transcription factor binding motifs enabled us to construct a regulatory network revealing potential key layer-specific regulators, including Cux1/2, Foxp2, Nfia, Pou3f2, and Rorb. This dataset is a valuable resource for identifying candidate layer-specific cis-regulatory elements in adult mouse cortex. DOI: http://dx.doi.org/10.7554/eLife.21883.001 PMID:28112643

The claustrum's proposed role in consciousness is supported by the effect and target localization of Salvia divinorum.

PubMed

Stiefel, Klaus M; Merrifield, Alistair; Holcombe, Alex O

2014-01-01

THIS ARTICLE BRINGS TOGETHER THREE FINDINGS AND IDEAS RELEVANT FOR THE UNDERSTANDING OF HUMAN CONSCIOUSNESS: (I) Crick's and Koch's theory that the claustrum is a "conductor of consciousness" crucial for subjective conscious experience. (II) Subjective reports of the consciousness-altering effects the plant Salvia divinorum, whose primary active ingredient is salvinorin A, a κ-opioid receptor agonist. (III) The high density of κ-opioid receptors in the claustrum. Fact III suggests that the consciousness-altering effects of S. divinorum/salvinorin A (II) are due to a κ-opioid receptor mediated inhibition of primarily the claustrum and, additionally, the deep layers of the cortex, mainly in prefrontal areas. Consistent with Crick and Koch's theory that the claustrum plays a key role in consciousness (I), the subjective effects of S. divinorum indicate that salvia disrupts certain facets of consciousness much more than the largely serotonergic hallucinogen lysergic acid diethylamide (LSD). Based on this data and on the relevant literature, we suggest that the claustrum does indeed serve as a conductor for certain aspects of higher-order integration of brain activity, while integration of auditory and visual signals relies more on coordination by other areas including parietal cortex and the pulvinar.

Constraints on the synchronization of entorhinal cortex stellate cells

NASA Astrophysics Data System (ADS)

Crotty, Patrick; Lasker, Eric; Cheng, Sen

2012-07-01

Synchronized oscillations of large numbers of central neurons are believed to be important for a wide variety of cognitive functions, including long-term memory recall and spatial navigation. It is therefore plausible that evolution has optimized the biophysical properties of central neurons in some way for synchronized oscillations to occur. Here, we use computational models to investigate the relationships between the presumably genetically determined parameters of stellate cells in layer II of the entorhinal cortex and the ability of coupled populations of these cells to synchronize their intrinsic oscillations: in particular, we calculate the time it takes circuits of two or three cells with initially randomly distributed phases to synchronize their oscillations to within one action potential width, and the metabolic energy they consume in doing so. For recurrent circuit topologies, we find that parameters giving low intrinsic firing frequencies close to those actually observed are strongly advantageous for both synchronization time and metabolic energy consumption.

Immunolocalization of tripeptidyl peptidase II, a cholecystokinin-inactivating enzyme, in rat brain.

PubMed

Facchinetti, P; Rose, C; Rostaing, P; Triller, A; Schwartz, J C

1999-01-01

Tripeptidyl peptidase II (EC 3.4.14.10) is a serine peptidase apparently involved in the inactivation of cholecystokinin octapeptide [Rose C. et al. (1996) Nature 380, 403-409]. We have compared its distribution with that of cholecystokinin in rat brain, using a polyclonal antibody raised against a highly purified preparation for immunohistochemistry at the photon and electron microscope levels. Tripeptidyl peptidase II-like immunoreactivity was mostly detected in neurons, and also in ependymal cells and choroid plexuses, localizations consistent with a possible participation of the peptidase in the inactivation of cholecystokinin circulating in the cerebrospinal fluid. Immunoreactivity was mostly detected in cell bodies, large processes and, to a lesser extent, axons of various neuronal populations. Their localization, relative to that of cholecystokinin terminals, appears to define three distinct situations. The first corresponds to neurons with high immunoreactivity in areas containing cholecystokinin terminals, as in the cerebral cortex or hippocampal formation, where pyramidal cell bodies and processes surrounded by cholecystokinin axons were immunoreactive. A similar situation was encountered in many other areas, namely along the pathways through which cholecystokinin controls satiety, i.e. in sensory vagal neurons, the nucleus tractus solitarius and hypothalamic nuclei. The second situation corresponds to cholecystokinin neuronal populations containing tripeptidyl peptidase II-like immunoreactivity, as in neurons of the supraoptic or paraventricular nuclei, axons in the median eminence or nigral neurons. In both situations, localization of tripeptidyl peptidase II-like immunoreactivity is consistent with a role in cholecystokinin inactivation. The third situation corresponds to areas with mismatches, such as the cerebellum, a region devoid of cholecystokinin, but in which Purkinje cells displayed high tripeptidyl peptidase II-like immunoreactivity, possibly related to a role in the inactivation of neuropeptides other than cholecystokinin. Also, some areas with cholecystokinin terminals, e.g., the molecular layer of the cerebral cortex, were devoid of tripeptidyl peptidase II-like immunoreactivity, suggesting that processes other than cleavage by tripeptidyl peptidase II may be involved in cholecystokinin inactivation. Tripeptidyl peptidase II-like immunoreactivity was also detected at the ultrastructural level in the cerebral cortex and hypothalamus using either immunoperoxidase or silver-enhanced immunogold detection. It was mainly associated with the cytoplasm of neuronal somata and dendrites, often in the vicinity of reticulum cisternae, Golgi apparatus or vesicles, and with the inner side of the dendritic plasma membrane. Hence, whereas a fraction of tripeptidyl peptidase II-like immunoreactivity localization at the cellular level is consistent with its alleged function in cholecystokinin octapeptide inactivation, its association with the outside plasma membrane of neurons remains to be confirmed.

Contribution of near-threshold currents to intrinsic oscillatory activity in rat medial entorhinal cortex layer II stellate cells

PubMed Central

Boehlen, Anne; Henneberger, Christian; Erchova, Irina

2013-01-01

The temporal lobe is well known for its oscillatory activity associated with exploration, navigation, and learning. Intrinsic membrane potential oscillations (MPOs) and resonance of stellate cells (SCs) in layer II of the entorhinal cortex are thought to contribute to network oscillations and thereby to the encoding of spatial information. Generation of both MPOs and resonance relies on the expression of specific voltage-dependent ion currents such as the hyperpolarization-activated cation current (IH), the persistent sodium current (INaP), and the noninactivating muscarine-modulated potassium current (IM). However, the differential contributions of these currents remain a matter of debate. We therefore examined how they modify neuronal excitability near threshold and generation of near-threshold MPOs and resonance in vitro. We found that resonance mainly relied on IH and was reduced by IH blockers and modulated by cAMP and an IM enhancer but that neither of the currents exhibited full control over MPOs in these cells. As previously reported, IH controlled a theta-frequency component of MPOs such that blockade of IH resulted in fewer regular oscillations that retained low-frequency components and high peak amplitude. However, pharmacological inhibition and augmentation of IM also affected MPO frequencies and amplitudes. In contrast to other cell types, inhibition of INaP did not result in suppression of MPOs but only in a moderation of their properties. We reproduced the experimentally observed effects in a single-compartment stochastic model of SCs, providing further insight into the interactions between different ionic conductances. PMID:23076110

Direct demonstration of persistent Na+ channel activity in dendritic processes of mammalian cortical neurones

PubMed Central

Magistretti, Jacopo; Ragsdale, David S; Alonso, Angel

1999-01-01

Single Na+ channel activity was recorded in patch-clamp, cell-attached experiments performed on dendritic processes of acutely isolated principal neurones from rat entorhinal-cortex layer II. The distances of the recording sites from the soma ranged from ≈20 to ≈100 μm.Step depolarisations from holding potentials of −120 to −100 mV to test potentials of −60 to +10 mV elicited Na+ channel openings in all of the recorded patches (n= 16).In 10 patches, besides transient Na+ channel openings clustered within the first few milliseconds of the depolarising pulses, prolonged and/or late Na+ channel openings were also regularly observed. This ‘persistent’ Na+ channel activity produced net inward, persistent currents in ensemble-average traces, and remained stable over the entire duration of the experiments (≈9 to 30 min).Two of these patches contained <= 3 channels. In these cases, persistent Na+ channel openings could be attributed to the activity of one single channel.The voltage dependence of persistent-current amplitude in ensemble-average traces closely resembled that of whole-cell, persistent Na+ current expressed by the same neurones, and displayed the same characteristic low threshold of activation.Dendritic, persistent Na+ channel openings had relatively high single-channel conductance (≈20 pS), similar to what is observed for somatic, persistent Na+ channels.We conclude that a stable, persistent Na+ channel activity is expressed by proximal dendrites of entorhinal-cortex layer II principal neurones, and can contribute a significant low-threshold, persistent Na+ current to the dendritic processing of excitatory synaptic inputs. PMID:10601494

Perinatal Asphyxia Reduces the Number of Reelin Neurons in the Prelimbic Cortex and Deteriorates Social Interaction in Rats.

PubMed

Vázquez-Borsetti, Pablo; Peña, Elena; Rico, Catalina; Noto, Mariana; Miller, Nathalie; Cohon, Diego; Acosta, Juan Manuel; Ibarra, Mariano; Loidl, Fabián C

2016-01-01

Obstetrical complications of perinatal asphyxia (PA) can often induce lesions that, in the long-term, manifest as schizophrenia. A deterioration of the medial prefrontal cortex (mPFC) and a reduction in the number of GABAergic neurons are commonly observed in the pathophysiology of schizophrenia. In this study, we investigated the link between PA, reelin and calbindin diminution and psychiatric diseases that involve social interaction deficits. This was achieved by observing the effect of 19 min of asphyxia on both subpopulations of GABAergic neurons. PA was produced by water immersion of fetus-containing uterus horns removed by cesarean section from ready-to-deliver rats. PA generated a significant and specific decrease in the number of reelin-secreting neurons in mPFC layer VI [F(2, 6) = 8.716, p = 0.016; PA vs. vaginal controls (VC), p = 0.03, and PA vs. cesarean controls (CC), p = 0.022]. This reduction reached approximately 60% on average. Changes in the percentage of reelin neurons including all the cortex layers did not achieve a significant outcome but a trend: CC % 10.61 ± 1.34; PA % 8.64 ± 1.71 [F(2, 6) = 1.299, p = 0.33]. In the case of calbindin, there was a significant decrease in cell density in the PA group [2-way repeated-measures ANOVA, F(1, 4) = 13.03, p = 0.0226]. The multiple-comparisons test showed significant differences in the superficial aspect of layer II (Sidak test for multiple comparisons CC vs. PA at 200 µm: p = 0.003). A small, but significant difference could be seen when the distance from the pia mater to the start of layer VI was analyzed (CC mean ± SEM = 768.9 ± 8.382; PA mean ± SEM = 669.3 ± 17.75; p = 0.036). Rats exposed to PA showed deterioration in social interactions, which manifested as a decrease in play soliciting. In this model, which involved severe/moderate asphyxia, we did not find significant changes in locomotive activity or anxiety indicators in the open field task. The loss of reelin neurons could be conducive to the shrinkage of the prelimbic cortex through the reduction in neuropil and the deterioration of the function of this structure. © 2016 S. Karger AG, Basel.

Iridescence in the neck feathers of domestic pigeons

NASA Astrophysics Data System (ADS)

Yin, Haiwei; Shi, Lei; Sha, Jing; Li, Yizhou; Qin, Youhua; Dong, Biqin; Meyer, Serge; Liu, Xiaohan; Zhao, Li; Zi, Jian

2006-11-01

We conducted structural characterizations, reflection measurements, and theoretical simulations on the iridescent green and purple neck feathers of domestic pigeons (Columba livia domestica). We found that both green and purple barbules are composed of an outer keratin cortex layer surrounding a medullary layer. The thickness of the keratin cortex layer shows a distinct difference between green and purple barbules. Green barbules vary colors from green to purple with the observing angle changed from normal to oblique, while purple barbules from purple to green in an opposite way. Both the experimental and theoretical results suggest that structural colors in green and purple neck feathers should originate from the interference in the top keratin cortex layer, while the structure beyond acts as a poor mirror.

Neural responses of rat cortical layers due to infrared neural modulation and photoablation of thalamocortical brain slices

NASA Astrophysics Data System (ADS)

Jenkins, J. Logan; Kao, Chris C.; Cayce, Jonathan M.; Mahadevan-Jansen, Anita; Jansen, E. Duco

2017-02-01

Infrared neural modulation (INM) is a label-free method for eliciting neural activity with high spatial selectivity in mammalian models. While there has been an emphasis on INM research towards applications in the peripheral nervous system and the central nervous system (CNS), the biophysical mechanisms by which INM occurs remains largely unresolved. In the rat CNS, INM has been shown to elicit and inhibit neural activity, evoke calcium signals that are dependent on glutamate transients and astrocytes, and modulate inhibitory GABA currents. So far, in vivo experiments have been restricted to layers I and II of the rat cortex which consists mainly of astrocytes, inhibitory neurons, and dendrites from deeper excitatory neurons owing to strong absorption of light in these layers. Deeper cortical layers (III-VI) have vastly different cell type composition, consisting predominantly of excitatory neurons which can be targeted for therapies such as deep brain stimulation. The neural responses to infrared light of deeper cortical cells have not been well defined. Acute thalamocortical brain slices will allow us to analyze the effects of INS on various components of the cortex, including different cortical layers and cell populations. In this study, we present the use of photoablation with an erbium:YAG laser to reduce the thickness of the dead cell zone near the cutting surface of brain slices. This technique will allow for more optical energy to reach living cells, which should contribute the successful transduction of pulsed infrared light to neural activity. In the future, INM-induced neural responses will lead to a finer characterization of the parameter space for the neuromodulation of different cortical cell types and may contribute to understanding the cell populations that are important for allowing optical stimulation of neurons in the CNS.

Neural dynamics and information representation in microcircuits of motor cortex.

PubMed

Tsubo, Yasuhiro; Isomura, Yoshikazu; Fukai, Tomoki

2013-01-01

The brain has to analyze and respond to external events that can change rapidly from time to time, suggesting that information processing by the brain may be essentially dynamic rather than static. The dynamical features of neural computation are of significant importance in motor cortex that governs the process of movement generation and learning. In this paper, we discuss these features based primarily on our recent findings on neural dynamics and information coding in the microcircuit of rat motor cortex. In fact, cortical neurons show a variety of dynamical behavior from rhythmic activity in various frequency bands to highly irregular spike firing. Of particular interest are the similarity and dissimilarity of the neuronal response properties in different layers of motor cortex. By conducting electrophysiological recordings in slice preparation, we report the phase response curves (PRCs) of neurons in different cortical layers to demonstrate their layer-dependent synchronization properties. We then study how motor cortex recruits task-related neurons in different layers for voluntary arm movements by simultaneous juxtacellular and multiunit recordings from behaving rats. The results suggest an interesting difference in the spectrum of functional activity between the superficial and deep layers. Furthermore, the task-related activities recorded from various layers exhibited power law distributions of inter-spike intervals (ISIs), in contrast to a general belief that ISIs obey Poisson or Gamma distributions in cortical neurons. We present a theoretical argument that this power law of in vivo neurons may represent the maximization of the entropy of firing rate with limited energy consumption of spike generation. Though further studies are required to fully clarify the functional implications of this coding principle, it may shed new light on information representations by neurons and circuits in motor cortex.

Developmental ethanol exposure alters the morphology of mouse prefrontal neurons in a layer-specific manner.

PubMed

Louth, Emma L; Luctkar, Hanna D; Heney, Kayla A; Bailey, Craig D C

2018-01-01

Chronic developmental exposure to ethanol can lead to a wide variety of teratogenic effects, which in humans are known as fetal alcohol spectrum disorders (FASD). Individuals affected by FASD may exhibit persistent impairments to cognitive functions such as learning, memory, and attention, which are highly dependent on medial prefrontal cortex (mPFC) circuitry. The objective of this study was to determine long-term effects of chronic developmental ethanol exposure on mPFC neuron morphology, in order to better-understand potential neuronal mechanisms underlying cognitive impairments associated with FASD. C57BL/6-strain mice were exposed to ethanol or an isocaloric/isovolumetric amount of sucrose (control) via oral gavage, administered both to the dam from gestational day 10-18 and directly to pups from postnatal day 4-14. Brains from male mice were collected at postnatal day 90 and neurons were stained using a modified Golgi-Cox method. Pyramidal neurons within layers II/III, V and VI of the mPFC were imaged, traced in three dimensions, and assessed using Sholl and branch structure analyses. Developmental ethanol exposure differentially impacted adult pyramidal neuron morphology depending on mPFC cortical layer. Neurons in layer II/III exhibited increased size and diameter of dendrite trees, whereas neurons in layer V were not affected. Layer VI neurons with long apical dendrites had trees with decreased diameter that extended farther from the soma, and layer VI neurons with short apical dendrite trees exhibited decreased tree size overall. These layer-specific alterations to mPFC neuron morphology may form a novel morphological mechanism underlying long-term mPFC dysfunction and resulting cognitive impairments in FASD. Copyright © 2017 Elsevier B.V. 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

In vitro Neurons in Mammalian Cortical Layer 4 Exhibit Intrinsic Oscillatory Activity in the 10- to 50-Hz Frequency Range

NASA Astrophysics Data System (ADS)

Llinas, Rodolfo R.; Grace, Anthony A.; Yarom, Yosef

1991-02-01

We report here the presence of fast subthreshold oscillatory potentials recorded in vitro from neurons within layer 4 of the guinea pig frontal cortex. Two types of oscillatory neurons were recorded: (i) One type exhibited subthreshold oscillations whose frequency increased with membrane depolarization and encompassed a range of 10-45 Hz. Action potentials in this type of neuron demonstrated clear after-hyperpolarizations. (ii) The second type of neuron was characterized by narrow-frequency oscillations near 35-50 Hz. These oscillations often outlasted the initiating depolarizing stimulus. No calcium component could be identified in their action potential. In both types of cell the subthreshold oscillations were tetrodotoxin-sensitive, indicating that the depolarizing phase of the oscillation was generated by a voltage-dependent sodium conductance. The initial depolarizing phase was followed by a potassium conductance responsible for the falling phase of the oscillatory wave. In both types of cell, the subthreshold oscillation could trigger spikes at the oscillatory frequency, if the membrane was sufficiently depolarized. Combining intracellular recordings with Lucifer yellow staining showed that the narrow-frequency oscillatory activity was produced by a sparsely spinous interneuron located in layer 4 of the cortex. This neuron has extensive local axonal collaterals that ramify in layers 3 and 4 such that they may contribute to the columnar synchronization of activity in the 40- to 50-Hz range. Cortical activity in this frequency range has been proposed as the basis for the "conjunctive properties" of central nervous system networks.

High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

PubMed

Cosottini, M; Donatelli, G; Costagli, M; Caldarazzo Ienco, E; Frosini, D; Pesaresi, I; Biagi, L; Siciliano, G; Tosetti, M

2016-03-01

Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009). The combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of patients with amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis. © 2016 by American Journal of Neuroradiology.

The connections of layer 4 subdivisions in the primary visual cortex (V1) of the owl monkey.

PubMed

Boyd, J D; Mavity-Hudson, J A; Casagrande, V A

2000-07-01

The primary visual cortex (V1) of primates receives signals from parallel lateral geniculate nucleus (LGN) channels. These signals are utilized by the laminar and compartmental [i.e. cytochrome oxidase (CO) blob and interblob] circuitry of V1 to synthesize new output pathways appropriate for the next steps of analysis. Within this framework, this study had two objectives: (i) to analyze the con- nections between primary input and output layers and compartments of V1; and (ii) to determine differences in connection patterns that might be related to species differences in physiological properties in an effort to link specific pathways to visual functions. In this study we examined the intrinsic interlaminar connections of V1 in the owl monkey, a nocturnal New World monkey, with a special emphasis on the projections from layer 4 to layer 3. Interlaminar connections were labeled via small iontophoretic or pressure injections of tracers [horseradish peroxidase, biocytin, biotinylated dextrine amine (BDA) or cholera toxin subunit B conjugated to colloidal gold particles]. Our most significant finding was that layer 4 (4C of Brodmann) can be divided into three tiers based upon projections to the superficial layers. Specifically, we find that 4alpha (4Calpha), 4beta (4Cbeta) and 4ctr send primary projections to layers 3C (4B), 3Bbeta (4A) and 3Balpha (3B), respectively. Examination of laminar structure with Nissl staining supports a tripartite organization of layer 4. The cortical output layer above layer 3Balpha (3B) (e.g. layer 3A) does not appear to receive any direct connections from layer 4 but receives heavy input from layers 3Balpha (3B) and 3C (4B). Some connectional differences also were observed between the subdivisions of layer 3 and the infragranular layers. No consistent differences in connections were observed that distinguished CO blobs from interblobs or that could be correlated with differences in visual lifestyle (nocturnal versus diurnal) when compared with connectional data in other primates. Re-examination of data from previous studies in squirrel and macaque monkeys suggests that the tripartite organization of layer 4 and the unique projection pattern of layer 4ctr are not restricted to owl monkeys, but are common to a number of primate species.

Molecular analysis of neocortical layer structure in the ferret

PubMed Central

Rowell, Joanna J.; Mallik, Atul K.; Dugas-Ford, Jennifer; Ragsdale, Clifton W.

2010-01-01

Molecular markers that distinguish specific layers of rodent neocortex are increasingly employed to study cortical development and the physiology of cortical circuits. The extent to which these markers represent general features of neocortical cell type identity across mammals is, however, unknown. To assess the conservation of layer markers more broadly, we isolated orthologs for fifteen layer-enriched genes in the ferret, a carnivore with a large, gyrencephalic brain, and analyzed their patterns of neocortical gene expression. Our major findings are: (1) Many but not all layer markers tested show similar patterns of layer-specific gene expression between mouse and ferret cortex, supporting the view that layer-specific cell type identity is conserved at a molecular level across mammalian superorders; (2) Our panel of deep layer markers (ER81/ETV1, SULF2, PCP4, FEZF2/ZNF312, CACNA1H, KCNN2/SK2, SYT6, FOXP2, CTGF) provides molecular evidence that the specific stratifications of layer 5 and 6 into 5a, 5b, 6a and 6b are also conserved between rodents and carnivores. (3) Variations in layer-specific gene expression are more pronounced across areas of ferret cortex than between homologous areas of mouse and ferret cortex; (4) This variation of area gene expression was clearest with the superficial layer markers studied (SERPINE2, MDGA1, CUX1, UNC5D, RORB/NR1F2, EAG2/KCNH5). Most dramatically, the layer 4 markers RORB and EAG2 disclosed a molecular sublamination to ferret visual cortex and demonstrated a molecular dissociation among the so-called agranular areas of the neocortex. Our findings establish molecular markers as a powerful complement to cytoarchitecture for neocortical layer and cell-type comparisons across mammals. PMID:20575059

Molecular analysis of neocortical layer structure in the ferret.

PubMed

Rowell, Joanna J; Mallik, Atul K; Dugas-Ford, Jennifer; Ragsdale, Clifton W

2010-08-15

Molecular markers that distinguish specific layers of rodent neocortex are increasingly employed to study cortical development and the physiology of cortical circuits. The extent to which these markers represent general features of neocortical cell type identity across mammals, however, is unknown. To assess the conservation of layer markers more broadly, we isolated orthologs for 15 layer-enriched genes in the ferret, a carnivore with a large, gyrencephalic brain, and analyzed their patterns of neocortical gene expression. Our major findings are: 1) Many but not all layer markers tested show similar patterns of layer-specific gene expression between mouse and ferret cortex, supporting the view that layer-specific cell type identity is conserved at a molecular level across mammalian superorders; 2) Our panel of deep layer markers (ER81/ETV1, SULF2, PCP4, FEZF2/ZNF312, CACNA1H, KCNN2/SK2, SYT6, FOXP2, CTGF) provides molecular evidence that the specific stratifications of layers 5 and 6 into 5a, 5b, 6a, and 6b are also conserved between rodents and carnivores; 3) Variations in layer-specific gene expression are more pronounced across areas of ferret cortex than between homologous areas of mouse and ferret cortex; 4) This variation of area gene expression was clearest with the superficial layer markers studied (SERPINE2, MDGA1, CUX1, UNC5D, RORB/NR1F2, EAG2/KCNH5). Most dramatically, the layer 4 markers RORB and EAG2 disclosed a molecular sublamination to ferret visual cortex and demonstrated a molecular dissociation among the so-called agranular areas of the neocortex. Our findings establish molecular markers as a powerful complement to cytoarchitecture for neocortical layer and cell-type comparisons across mammals. (c) 2010 Wiley-Liss, Inc.

Amygdalo-cortical sprouting continues into early adulthood: implications for the development of normal and abnormal function during adolescence.

PubMed

Cunningham, Miles Gregory; Bhattacharyya, Sujoy; Benes, Francine Mary

2002-11-11

Adolescence is a critical stage for the development of emotional maturity and diverse forms of psychopathology. The posterior basolateral nucleus of the amygdala is known to mediate fear and anxiety and is important in assigning emotional valence to cognitive processes. The medial prefrontal cortex, a homologue of the human anterior cingulate cortex, mediates emotional, attentional, and motivational behaviors at the cortical level. We postulate that the development of connectivity between these two corticolimbic regions contributes to an enhanced integration of emotion and cognition during the postnatal period. In order to characterize the development of this relay, injections of the anterograde tracer biocytin were stereotaxically placed within the posterior basolateral nucleus of the amygdala of rats at successive postnatal time points (postnatal days 6-120). Labeled fibers in the medial prefrontal cortex were evaluated using a combination of brightfield, confocal, and electron microscopy. We found that the density of labeled fibers originating from the posterior basolateral nucleus shows a sharp curvilinear increase within layers II and V of the anterior cingulate cortex and the infralimbic subdivisions of medial prefrontal cortex during the late postweanling period. This increase was paralleled by a linear rise in the number of axospinous and axodendritic synapses present in the neuropil. Based on these results, we propose that late maturation of amygdalo-cortical connectivity may provide an anatomical basis for the development and integration of normal and possibly abnormal emotional behavior during adolescence and early adulthood. Copyright 2002 Wiley-Liss, Inc.

Thalamic input to auditory cortex is locally heterogeneous but globally tonotopic

PubMed Central

Vasquez-Lopez, Sebastian A; Weissenberger, Yves; Lohse, Michael; Keating, Peter; King, Andrew J

2017-01-01

Topographic representation of the receptor surface is a fundamental feature of sensory cortical organization. This is imparted by the thalamus, which relays information from the periphery to the cortex. To better understand the rules governing thalamocortical connectivity and the origin of cortical maps, we used in vivo two-photon calcium imaging to characterize the properties of thalamic axons innervating different layers of mouse auditory cortex. Although tonotopically organized at a global level, we found that the frequency selectivity of individual thalamocortical axons is surprisingly heterogeneous, even in layers 3b/4 of the primary cortical areas, where the thalamic input is dominated by the lemniscal projection. We also show that thalamocortical input to layer 1 includes collaterals from axons innervating layers 3b/4 and is largely in register with the main input targeting those layers. Such locally varied thalamocortical projections may be useful in enabling rapid contextual modulation of cortical frequency representations. PMID:28891466

A morphological basis for orientation tuning in primary visual cortex.

PubMed

Mooser, François; Bosking, William H; Fitzpatrick, David

2004-08-01

Feedforward connections are thought to be important in the generation of orientation-selective responses in visual cortex by establishing a bias in the sampling of information from regions of visual space that lie along a neuron's axis of preferred orientation. It remains unclear, however, which structural elements-dendrites or axons-are ultimately responsible for conveying this sampling bias. To explore this question, we have examined the spatial arrangement of feedforward axonal connections that link non-oriented neurons in layer 4 and orientation-selective neurons in layer 2/3 of visual cortex in the tree shrew. Target sites of labeled boutons in layer 2/3 resulting from focal injections of biocytin in layer 4 show an orientation-specific axial bias that is sufficient to confer orientation tuning to layer 2/3 neurons. We conclude that the anisotropic arrangement of axon terminals is the principal source of the orientation bias contributed by feedforward connections.

Laminar Differences in Associative Memory Signals in Monkey Perirhinal Cortex.

PubMed

Vogels, Rufin

2016-10-19

New research published in Neuron describes assignment of cortical layer to single neurons recorded in awake monkeys. Applying the procedure to perirhinal cortex, Koyano et al. (2016) found marked and unsuspected differences among layers in the coding of associative memory signals. Copyright © 2016. Published by Elsevier Inc.

Layer-specific input to distinct cell types in layer 6 of monkey primary visual cortex.

PubMed

Briggs, F; Callaway, E M

2001-05-15

Layer 6 of monkey V1 contains a physiologically and anatomically diverse population of excitatory pyramidal neurons. Distinctive arborization patterns of axons and dendrites within the functionally specialized cortical layers define eight types of layer 6 pyramidal neurons and suggest unique information processing roles for each cell type. To address how input sources contribute to cellular function, we examined the laminar sources of functional excitatory input onto individual layer 6 pyramidal neurons using scanning laser photostimulation. We find that excitatory input sources correlate with cell type. Class I neurons with axonal arbors selectively targeting magnocellular (M) recipient layer 4Calpha receive input from M-dominated layer 4B, whereas class I neurons whose axonal arbors target parvocellular (P) recipient layer 4Cbeta receive input from P-dominated layer 2/3. Surprisingly, these neuronal types do not differ significantly in the inputs they receive directly from layers 4Calpha or 4Cbeta. Class II cells, which lack dense axonal arbors within layer 4C, receive excitatory input from layers targeted by their local axons. Specifically, type IIA cells project axons to and receive input from the deep but not superficial layers. Type IIB neurons project to and receive input from the deepest and most superficial, but not middle layers. Type IIC neurons arborize throughout the cortical layers and tend to receive inputs from all cortical layers. These observations have implications for the functional roles of different layer 6 cell types in visual information processing.

Neocortical maturation during adolescence: change in neuronal soma dimension.

PubMed

Rabinowicz, Theodore; Petetot, Jean Macdonald-Comber; Khoury, Jane C; de Courten-Myers, Gabrielle M

2009-03-01

During adolescence, cognitive abilities increase robustly. To search for possible related structural alterations of the cerebral cortex, we measured neuronal soma dimension (NSD = width times height), cortical thickness and neuronal densities in different types of neocortex in post-mortem brains of five 12-16 and five 17-24 year-olds (each 2F, 3M). Using a generalized mixed model analysis, mean normalized NSD comparing the age groups shows layer-specific change for layer 2 (p < .0001) and age-related differences between categorized type of cortex: primary/primary association cortex (BA 1, 3, 4, and 44) shows a generalized increase; higher-order regions (BA 9, 21, 39, and 45) also show increase in layers 2 and 5 but decrease in layers 3, 4, and 6 while limbic/orbital cortex (BA 23, 24, and 47) undergoes minor decrease (BA 1, 3, 4, and 44 vs. BA 9, 21, 39, and 45: p = .036 and BA 1, 3, 4, and 44 vs. BA 23, 24, and 47: p = .004). These data imply the operation of cortical layer- and type-specific processes of growth and regression adding new evidence that the human brain matures during adolescence not only functionally but also structurally.

Cortical and thalamic contributions to response dynamics across layers of the primary somatosensory cortex during tactile discrimination

PubMed Central

Pais-Vieira, Miguel; Kunicki, Carolina; Tseng, Po-He; Martin, Joel; Lebedev, Mikhail

2015-01-01

Tactile information processing in the rodent primary somatosensory cortex (S1) is layer specific and involves modulations from both thalamocortical and cortico-cortical loops. However, the extent to which these loops influence the dynamics of the primary somatosensory cortex while animals execute tactile discrimination remains largely unknown. Here, we describe neural dynamics of S1 layers across the multiple epochs defining a tactile discrimination task. We observed that neuronal ensembles within different layers of the S1 cortex exhibited significantly distinct neurophysiological properties, which constantly changed across the behavioral states that defined a tactile discrimination. Neural dynamics present in supragranular and granular layers generally matched the patterns observed in the ventral posterior medial nucleus of the thalamus (VPM), whereas the neural dynamics recorded from infragranular layers generally matched the patterns from the posterior nucleus of the thalamus (POM). Selective inactivation of contralateral S1 specifically switched infragranular neural dynamics from POM-like to those resembling VPM neurons. Meanwhile, ipsilateral M1 inactivation profoundly modulated the firing suppression observed in infragranular layers. This latter effect was counterbalanced by contralateral S1 block. Tactile stimulus encoding was layer specific and selectively affected by M1 or contralateral S1 inactivation. Lastly, causal information transfer occurred between all neurons in all S1 layers but was maximal from infragranular to the granular layer. These results suggest that tactile information processing in the S1 of awake behaving rodents is layer specific and state dependent and that its dynamics depend on the asynchronous convergence of modulations originating from ipsilateral M1 and contralateral S1. PMID:26180115

Automatic detection and quantitative analysis of cells in the mouse primary motor cortex

NASA Astrophysics Data System (ADS)

Meng, Yunlong; He, Yong; Wu, Jingpeng; Chen, Shangbin; Li, Anan; Gong, Hui

2014-09-01

Neuronal cells play very important role on metabolism regulation and mechanism control, so cell number is a fundamental determinant of brain function. Combined suitable cell-labeling approaches with recently proposed three-dimensional optical imaging techniques, whole mouse brain coronal sections can be acquired with 1-μm voxel resolution. We have developed a completely automatic pipeline to perform cell centroids detection, and provided three-dimensional quantitative information of cells in the primary motor cortex of C57BL/6 mouse. It involves four principal steps: i) preprocessing; ii) image binarization; iii) cell centroids extraction and contour segmentation; iv) laminar density estimation. Investigations on the presented method reveal promising detection accuracy in terms of recall and precision, with average recall rate 92.1% and average precision rate 86.2%. We also analyze laminar density distribution of cells from pial surface to corpus callosum from the output vectorizations of detected cell centroids in mouse primary motor cortex, and find significant cellular density distribution variations in different layers. This automatic cell centroids detection approach will be beneficial for fast cell-counting and accurate density estimation, as time-consuming and error-prone manual identification is avoided.

The primary vestibular projection to the cerebellar cortex in the pigeon (Columba livia)

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

Schwarz, I.E.; Schwarz, D.W.

1983-06-01

The cerebellar cortex of the pigeon receiving direct vestibular afferents was delineated by anterograde transport of (/sup 3/H)-amino acids injected into the vestibular nerve. Labelled mossy fiber rosettes in the granular layer were concentrated in lobule X (nodulus) and to a lesser extent, in the ventral portion of lobule IXd (uvula and paraflocculus). A few solitary labelled rosettes were also found in more dorsal portions of lobule IX, as well as in the anterior lobe between lobule II and IV. The lingula remained unlabelled. Discrete injections of (/sup 3/H)-leucine into the cristae of each of the three semicircular canals ormore » the utricular macula yielded a similar distribution of fewer labelled rosettes. A few primary mossy fiber terminals labelled after cochlear injections are attributed to afferents from the lagenar macula. Since effective diffusion of label from the injection site was excluded by controls, it is concluded that projection of individual canal and macula nerves to the vestibulocerebellar cortex is not topographically separated. It is proposed that this extensive convergence of various afferents is required by the cerebellum to compute precise and directionally specific control signals during head rotation in all conceivable planes.« less

Self-organization of globally continuous and locally distributed information representation.

PubMed

Wada, Koji; Kurata, Koji; Okada, Masato

2004-01-01

A number of findings suggest that the preferences of neighboring neurons in the inferior temporal (IT) cortex of macaque monkeys tend to be similar. However, a recent study reports convincingly that the preferences of neighboring neurons actually differ. These findings seem contradictory. To explain this conflict, we propose a new view of information representation in the IT cortex. This view takes into account sparse and local neuronal excitation. Since the excitation is sparse, information regarding visual objects seems to be encoded in a distributed manner. The local excitation of neurons coincides with the classical notion of a column structure. Our model consists of input layer and output layer. The main difference from conventional models is that the output layer has local and random intra-layer connections. In this paper, we adopt two rings embedded in three-dimensional space as an input signal space, and examine how resultant information representation depends on the distance between two rings that is denoted as D. We show that there exists critical value for the distance Dc. When D > Dc the output layer becomes able to form the column structure, this model can obtain the distributed representation within the column. While the output layer acquires the conventional information representation observed in the V1 cortex when D < Dc. Moreover, we consider the origin of the difference between information representation of the V1 cortex and that of the IT cortex. Our finding suggests that the difference in the information representations between the V1 and the IT cortices could be caused by difference between the input space structures.

No differences in calcium-binding protein immunoreactivity in the posterior cingulate and visual cortex: schizophrenia and controls.

PubMed

Wheeler, David G; Dixon, Gavin; Harper, Clive G

2006-06-01

Schizophrenia-specific alterations in the densities of interneurons immunoreactive (ir) to the calcium binding proteins are reported for several cortical regions. However, no reported studies have searched for such differences within the posterior cingulate cortex using antibodies to a specific calcium binding protein, calbindin (Cb). Compare the (a) relative density of Cb-ir neurons (ratio of labeled neurons to total neurons), (b) relative width of cortical layers II/III and (c) somal areas of Cb-ir neurons in people with schizophrenia and non-psychiatric age-, gender- and postmortem index-matched controls (9 per group). Tissue from Brodmann's area (BA) 30 and 23 and an internal control region, the visual cortex (BA 18) were labeled with polyclonal Cb antibodies then Nissl counter-stained. Cb-ir neurons as well as counter-stained neurons with clearly visible nucleoli were plotted and counted within their area 1 and laminar boundaries. No qualitative or statistical differences in the relative density of Cb-ir neurons were observed. A trend towards a significant effect was detected in BA 30, the relative density of Cb-ir neurons for controls was greater than for schizophrenics (P=0.0518). There were no significant differences in the relative cortical widths or somal areas. The data from this study suggest that the posterior cingulate cortex may not be involved in schizophrenia, at least not as far as Cb-ir neurons are concerned.

Spectral integration in primary auditory cortex attributable to temporally precise convergence of thalamocortical and intracortical input.

PubMed

Happel, Max F K; Jeschke, Marcus; Ohl, Frank W

2010-08-18

Primary sensory cortex integrates sensory information from afferent feedforward thalamocortical projection systems and convergent intracortical microcircuits. Both input systems have been demonstrated to provide different aspects of sensory information. Here we have used high-density recordings of laminar current source density (CSD) distributions in primary auditory cortex of Mongolian gerbils in combination with pharmacological silencing of cortical activity and analysis of the residual CSD, to dissociate the feedforward thalamocortical contribution and the intracortical contribution to spectral integration. We found a temporally highly precise integration of both types of inputs when the stimulation frequency was in close spectral neighborhood of the best frequency of the measurement site, in which the overlap between both inputs is maximal. Local intracortical connections provide both directly feedforward excitatory and modulatory input from adjacent cortical sites, which determine how concurrent afferent inputs are integrated. Through separate excitatory horizontal projections, terminating in cortical layers II/III, information about stimulus energy in greater spectral distance is provided even over long cortical distances. These projections effectively broaden spectral tuning width. Based on these data, we suggest a mechanism of spectral integration in primary auditory cortex that is based on temporally precise interactions of afferent thalamocortical inputs and different short- and long-range intracortical networks. The proposed conceptual framework allows integration of different and partly controversial anatomical and physiological models of spectral integration in the literature.

Continuous Attractor Network Model for Conjunctive Position-by-Velocity Tuning of Grid Cells

PubMed Central

Si, Bailu; Romani, Sandro; Tsodyks, Misha

2014-01-01

The spatial responses of many of the cells recorded in layer II of rodent medial entorhinal cortex (MEC) show a triangular grid pattern, which appears to provide an accurate population code for animal spatial position. In layer III, V and VI of the rat MEC, grid cells are also selective to head-direction and are modulated by the speed of the animal. Several putative mechanisms of grid-like maps were proposed, including attractor network dynamics, interactions with theta oscillations or single-unit mechanisms such as firing rate adaptation. In this paper, we present a new attractor network model that accounts for the conjunctive position-by-velocity selectivity of grid cells. Our network model is able to perform robust path integration even when the recurrent connections are subject to random perturbations. PMID:24743341

Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

PubMed

Rompala, Gregory R; Zsiros, Veronika; Zhang, Shuqin; Kolata, Stefan M; Nakazawa, Kazu

2013-01-01

Pharmacological and genetic studies support a role for NMDA receptor (NMDAR) hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1) deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice), in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior). Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

Cell Class-Dependent Intracortical Connectivity and Output Dynamics of Layer 6 Projection Neurons of the Rat Primary Visual Cortex.

PubMed

Cotel, Florence; Fletcher, Lee N; Kalita-de Croft, Simon; Apergis-Schoute, John; Williams, Stephen R

2018-07-01

Neocortical information processing is powerfully influenced by the activity of layer 6 projection neurons through control of local intracortical and subcortical circuitry. Morphologically distinct classes of layer 6 projection neuron have been identified in the mammalian visual cortex, which exhibit contrasting receptive field properties, but little information is available on their functional specificity. To address this we combined anatomical tracing techniques with high-resolution patch-clamp recording to identify morphological and functional distinct classes of layer 6 projection neurons in the rat primary visual cortex, which innervated separable subcortical territories. Multisite whole-cell recordings in brain slices revealed that corticoclaustral and corticothalamic layer 6 projection neurons exhibited similar somatically recorded electrophysiological properties. These classes of layer 6 projection neurons were sparsely and reciprocally synaptically interconnected, but could be differentiated by cell-class, but not target-cell-dependent rules of use-dependent depression and facilitation of unitary excitatory synaptic output. Corticoclaustral and corticothalamic layer 6 projection neurons were differentially innervated by columnar excitatory circuitry, with corticoclaustral, but not corticothalamic, neurons powerfully driven by layer 4 pyramidal neurons, and long-range pathways conveyed in neocortical layer 1. Our results therefore reveal projection target-specific, functionally distinct, streams of layer 6 output in the rodent neocortex.

The claustrum’s proposed role in consciousness is supported by the effect and target localization of Salvia divinorum

PubMed Central

Stiefel, Klaus M.; Merrifield, Alistair; Holcombe, Alex O.

2014-01-01

This article brings together three findings and ideas relevant for the understanding of human consciousness: (I) Crick’s and Koch’s theory that the claustrum is a “conductor of consciousness” crucial for subjective conscious experience. (II) Subjective reports of the consciousness-altering effects the plant Salvia divinorum, whose primary active ingredient is salvinorin A, a κ-opioid receptor agonist. (III) The high density of κ-opioid receptors in the claustrum. Fact III suggests that the consciousness-altering effects of S. divinorum/salvinorin A (II) are due to a κ-opioid receptor mediated inhibition of primarily the claustrum and, additionally, the deep layers of the cortex, mainly in prefrontal areas. Consistent with Crick and Koch’s theory that the claustrum plays a key role in consciousness (I), the subjective effects of S. divinorum indicate that salvia disrupts certain facets of consciousness much more than the largely serotonergic hallucinogen lysergic acid diethylamide (LSD). Based on this data and on the relevant literature, we suggest that the claustrum does indeed serve as a conductor for certain aspects of higher-order integration of brain activity, while integration of auditory and visual signals relies more on coordination by other areas including parietal cortex and the pulvinar. PMID:24624064

Detecting and discriminating novel objects: The impact of perirhinal cortex disconnection on hippocampal activity patterns

PubMed Central

Amin, Eman; Olarte‐Sánchez, Cristian M.; Aggleton, John P.

2016-01-01

ABSTRACT Perirhinal cortex provides object‐based information and novelty/familiarity information for the hippocampus. The necessity of these inputs was tested by comparing hippocampal c‐fos expression in rats with or without perirhinal lesions. These rats either discriminated novel from familiar objects (Novel‐Familiar) or explored pairs of novel objects (Novel‐Novel). Despite impairing Novel‐Familiar discriminations, the perirhinal lesions did not affect novelty detection, as measured by overall object exploration levels (Novel‐Novel condition). The perirhinal lesions also largely spared a characteristic network of linked c‐fos expression associated with novel stimuli (entorhinal cortex→CA3→distal CA1→proximal subiculum). The findings show: I) that perirhinal lesions preserve behavioral sensitivity to novelty, whilst still impairing the spontaneous ability to discriminate novel from familiar objects, II) that the distinctive patterns of hippocampal c‐fos activity promoted by novel stimuli do not require perirhinal inputs, III) that entorhinal Fos counts (layers II and III) increase for novelty discriminations, IV) that hippocampal c‐fos networks reflect proximal‐distal connectivity differences, and V) that discriminating novelty creates different pathway interactions from merely detecting novelty, pointing to top‐down effects that help guide object selection. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27398938

Congenital deafness affects deep layers in primary and secondary auditory cortex

PubMed Central

Berger, Christoph; Kühne, Daniela; Scheper, Verena

2017-01-01

Abstract Congenital deafness leads to functional deficits in the auditory cortex for which early cochlear implantation can effectively compensate. Most of these deficits have been demonstrated functionally. Furthermore, the majority of previous studies on deafness have involved the primary auditory cortex; knowledge of higher‐order areas is limited to effects of cross‐modal reorganization. In this study, we compared the cortical cytoarchitecture of four cortical areas in adult hearing and congenitally deaf cats (CDCs): the primary auditory field A1, two secondary auditory fields, namely the dorsal zone and second auditory field (A2); and a reference visual association field (area 7) in the same section stained either using Nissl or SMI‐32 antibodies. The general cytoarchitectonic pattern and the area‐specific characteristics in the auditory cortex remained unchanged in animals with congenital deafness. Whereas area 7 did not differ between the groups investigated, all auditory fields were slightly thinner in CDCs, this being caused by reduced thickness of layers IV–VI. The study documents that, while the cytoarchitectonic patterns are in general independent of sensory experience, reduced layer thickness is observed in both primary and higher‐order auditory fields in layer IV and infragranular layers. The study demonstrates differences in effects of congenital deafness between supragranular and other cortical layers, but similar dystrophic effects in all investigated auditory fields. PMID:28643417

Neurofilament protein defines regional patterns of cortical organization in the macaque monkey visual system: a quantitative immunohistochemical analysis

NASA Technical Reports Server (NTRS)

Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1995-01-01

Visual function in monkeys is subserved at the cortical level by a large number of areas defined by their specific physiological properties and connectivity patterns. For most of these cortical fields, a precise index of their degree of anatomical specialization has not yet been defined, although many regional patterns have been described using Nissl or myelin stains. In the present study, an attempt has been made to elucidate the regional characteristics, and to varying degrees boundaries, of several visual cortical areas in the macaque monkey using an antibody to neurofilament protein (SMI32). This antibody labels a subset of pyramidal neurons with highly specific regional and laminar distribution patterns in the cerebral cortex. Based on the staining patterns and regional quantitative analysis, as many as 28 cortical fields were reliably identified. Each field had a homogeneous distribution of labeled neurons, except area V1, where increases in layer IVB cell and in Meynert cell counts paralleled the increase in the degree of eccentricity in the visual field representation. Within the occipitotemporal pathway, areas V3 and V4 and fields in the inferior temporal cortex were characterized by a distinct population of neurofilament-rich neurons in layers II-IIIa, whereas areas located in the parietal cortex and part of the occipitoparietal pathway had a consistent population of large labeled neurons in layer Va. The mediotemporal areas MT and MST displayed a distinct population of densely labeled neurons in layer VI. Quantitative analysis of the laminar distribution of the labeled neurons demonstrated that the visual cortical areas could be grouped in four hierarchical levels based on the ratio of neuron counts between infragranular and supragranular layers, with the first (areas V1, V2, V3, and V3A) and third (temporal and parietal regions) levels characterized by low ratios and the second (areas MT, MST, and V4) and fourth (frontal regions) levels characterized by high to very high ratios. Such density trends may correspond to differential representation of corticocortically (and corticosubcortically) projecting neurons at several functional steps in the integration of the visual stimuli. In this context, it is possible that neurofilament protein is crucial for the unique capacity of certain subsets of neurons to perform the highly precise mapping functions of the monkey visual system.

Cytidine-5-diphosphocholine supplement in early life induces stable increase in dendritic complexity of neurons in the somatosensory cortex of adult rats

PubMed Central

Rema, V.; Bali, K.K.; Ramachandra, R.; Chugh, M.; Darokhan, Z.; Chaudhary, R.

2008-01-01

Cytidine-5-diphosphocholine (CDP-choline or citicholine) is an essential molecule that is required for biosynthesis of cell membranes. In adult humans it is used as a memory-enhancing drug for treatment of age-related dementia and cerebrovascular conditions. However the effect of CDP-choline on perinatal brain is not known. We administered CDP-choline to Long Evans rats each day from conception (maternal ingestion) to postnatal day 60 (P60). Pyramidal neurons from supragranular layers 2/3, granular layer 4 and infragranular layer 5 of somatosensory cortex were examined with Golgi–Cox staining at P240. CDP-choline treatment significantly increased length and branch points of apical and basal dendrites. Sholl analysis shows that the complexity of apical and basal dendrites of neurons is maximal in layers 2/3 and layer 5. In layer 4 significant increases were seen in basilar dendritic arborization. CDP-choline did not increase the number of primary basal dendrites on neurons in the somatosensory cortex. Primary cultures from somatosensory cortex were treated with CDP-choline to test its effect on neuronal survival. CDP-choline treatment neither enhanced the survival of neurons in culture nor increased the number of neurites. However significant increases in neurite length, branch points and total area occupied by the neurons were observed. We conclude that exogenous supplementation of CDP-choline during development causes stable changes in neuronal morphology. Significant increase in dendritic growth and branching of pyramidal neurons from the somatosensory cortex resulted in enlarging the surface area occupied by the neurons which we speculate will augment processing of sensory information. PMID:18619738

Cell Type-Specific Structural Organization of the Six Layers in Rat Barrel Cortex

PubMed Central

Narayanan, Rajeevan T.; Udvary, Daniel; Oberlaender, Marcel

2017-01-01

The cytoarchitectonic subdivision of the neocortex into six layers is often used to describe the organization of the cortical circuitry, sensory-evoked signal flow or cortical functions. However, each layer comprises neuronal cell types that have different genetic, functional and/or structural properties. Here, we reanalyze structural data from some of our recent work in the posterior-medial barrel-subfield of the vibrissal part of rat primary somatosensory cortex (vS1). We quantify the degree to which somata, dendrites and axons of the 10 major excitatory cell types of the cortex are distributed with respect to the cytoarchitectonic organization of vS1. We show that within each layer, somata of multiple cell types intermingle, but that each cell type displays dendrite and axon distributions that are aligned to specific cytoarchitectonic landmarks. The resultant quantification of the structural composition of each layer in terms of the cell type-specific number of somata, dendritic and axonal path lengths will aid future studies to bridge between layer- and cell type-specific analyses. PMID:29081739

Pain Relief in CRPS-II after Spinal Cord and Motor Cortex Simultaneous Dual Stimulation.

PubMed

Lopez, William Oc; Barbosa, Danilo C; Teixera, Manoel J; Paiz, Martin; Moura, Leonardo; Monaco, Bernardo A; Fonoff, Erich T

2016-05-01

We describe a case of a 30-year-old woman who suffered a traumatic injury of the right brachial plexus, developing severe complex regional pain syndrome type II (CRPS-II). After clinical treatment failure, spinal cord stimulation (SCS) was indicated with initial positive pain control. However, after 2 years her pain progressively returned to almost baseline intensity before SCS. Additional motor cortex electrode implant was then proposed as a rescue therapy and connected to the same pulse generator. This method allowed simultaneous stimulation of the motor cortex and SCS in cycling mode with independent stimulation parameters in each site. At 2 years follow-up, the patient reported sustained improvement in pain with dual stimulation, reduction of painful crises, and improvement in quality of life. The encouraging results in this case suggests that this can be an option as add-on therapy over SCS as a possible rescue therapy in the management of CRPS-II. However, comparative studies must be performed in order to determine the effectiveness of this therapy. Chronic neuropathic pain, Complex regional pain syndrome Type II, brachial plexus injury, motor cortex stimulation, spinal cord stimulation.

Excitatory neuronal connectivity in the barrel cortex

PubMed Central

Feldmeyer, Dirk

2012-01-01

Neocortical areas are believed to be organized into vertical modules, the cortical columns, and the horizontal layers 1–6. In the somatosensory barrel cortex these columns are defined by the readily discernible barrel structure in layer 4. Information processing in the neocortex occurs along vertical and horizontal axes, thereby linking individual barrel-related columns via axons running through the different cortical layers of the barrel cortex. Long-range signaling occurs within the neocortical layers but also through axons projecting through the white matter to other neocortical areas and subcortical brain regions. Because of the ease of identification of barrel-related columns, the rodent barrel cortex has become a prototypical system to study the interactions between different neuronal connections within a sensory cortical area and between this area and other cortical as well subcortical regions. Such interactions will be discussed specifically for the feed-forward and feedback loops between the somatosensory and the somatomotor cortices as well as the different thalamic nuclei. In addition, recent advances concerning the morphological characteristics of excitatory neurons and their impact on the synaptic connectivity patterns and signaling properties of neuronal microcircuits in the whisker-related somatosensory cortex will be reviewed. In this context, their relationship between the structural properties of barrel-related columns and their function as a module in vertical synaptic signaling in the whisker-related cortical areas will be discussed. PMID:22798946

Laminar distribution of cholinergic- and serotonergic-dependent plasticity within kitten visual cortex.

PubMed

Kojic, L; Gu, Q; Douglas, R M; Cynader, M S

2001-02-28

Both cholinergic and serotonergic modulatory projections to mammalian striate cortex have been demonstrated to be involved in the regulation of postnatal plasticity, and a striking alteration in the number and intracortical distribution of cholinergic and serotonergic receptors takes place during the critical period for cortical plasticity. As well, agonists of cholinergic and serotonergic receptors have been demonstrated to facilitate induction of long-term synaptic plasticity in visual cortical slices supporting their involvement in the control of activity-dependent plasticity. We recorded field potentials from layers 4 and 2/3 in visual cortex slices of 60--80 day old kittens after white matter stimulation, before and after a period of high frequency stimulation (HFS), in the absence or presence of either cholinergic or serotonergic agonists. At these ages, the HFS protocol alone almost never induced long-term changes of synaptic plasticity in either layers 2/3 or 4. In layer 2/3, agonist stimulation of m1 receptors facilitated induction of long-term potentiation (LTP) with HFS stimulation, while the activation of serotonergic receptors had only a modest effect. By contrast, a strong serotonin-dependent LTP facilitation and insignificant muscarinic effects were observed after HFS within layer 4. The results show that receptor-dependent laminar stratification of synaptic modifiability occurs in the cortex at these ages. This plasticity may underly a control system gating the experience-dependent changes of synaptic organization within developing visual cortex.

[Macro- and microscopic systematization of cerebral cortex malformations in children].

PubMed

Milovanov, A P; Milovanova, O A

2011-01-01

For the first time in pediatric pathologicoanatomic practice the complete systematization of cerebral cortex malformations is represented. Organ, macroscopic forms: microencephaly, macroencephaly, micropolygyria, pachygyria, schizencephaly, porencephaly, lissencephaly. Histic microdysgenesis of cortex: type I includes isolated abnormalities such as radial (IA) and tangential (I B) subtypes of cortical dislamination; type II includes sublocal cortical dislamination with immature dysmorphic neurons (II A) and balloon cells (II B); type III are the combination focal cortical dysplasia with tuberous sclerosis of the hippocampus (III A), tumors (III B) and malformations of vessels, traumatic and hypoxic disorders (III C). Band heterotopias. Subependimal nodular heterotopias. Tuberous sclerosis. Cellular typification of cortical dysplasia: immature neurons and balloon cells.

Intracortical Microstimulation (ICMS) Activates Motor Cortex Layer 5 Pyramidal Neurons Mainly Transsynaptically.

PubMed

Hussin, Ahmed T; Boychuk, Jeffery A; Brown, Andrew R; Pittman, Quentin J; Teskey, G Campbell

2015-01-01

Intracortical microstimulation (ICMS) is a technique used for a number of purposes including the derivation of cortical movement representations (motor maps). Its application can activate the output layer 5 of motor cortex and can result in the elicitation of body movements depending upon the stimulus parameters used. The extent to which pyramidal tract projection neurons of the motor cortex are activated transsynaptically or directly by ICMS remains an open question. Given this uncertainty in the mode of activation, we used a preparation that combined patch clamp whole-cell recordings from single layer 5 pyramidal neurons and extracellular ICMS in slices of motor cortex as well as a standard in vivo mapping technique to ask how ICMS activated motor cortex pyramidal neurons. We measured changes in synaptic spike threshold and spiking rate to ICMS in vitro and movement threshold in vivo in the presence or absence of specific pharmacological blockers of glutamatergic (AMPA, NMDA and Kainate) receptors and GABAA receptors. With major excitatory and inhibitory synaptic transmission blocked (with DNQX, APV and bicuculline methiodide), we observed a significant increase in the ICMS current intensity required to elicit a movement in vivo as well as to the first spike and an 85% reduction in spiking responses in vitro. Subsets of neurons were still responsive after the synaptic block, especially at higher current intensities, suggesting a modest direct activation. Taken together our data indicate a mainly synaptic mode of activation to ICMS in layer 5 of rat motor cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

Activity-dependent regulation of NMDAR1 immunoreactivity in the developing visual cortex.

PubMed

Catalano, S M; Chang, C K; Shatz, C J

1997-11-01

NMDA receptors have been implicated in activity-dependent synaptic plasticity in the developing visual cortex. We examined the distribution of immunocytochemically detectable NMDAR1 in visual cortex of cats and ferrets from late embryonic ages to adulthood. Cortical neurons are initially highly immunostained. This level declines gradually over development, with the notable exception of cortical layers 2/3, where levels of NMDAR1 immunostaining remain high into adulthood. Within layer 4, the decline in NMDAR1 immunostaining to adult levels coincides with the completion of ocular dominance column formation and the end of the critical period for layer 4. To determine whether NMDAR1 immunoreactivity is regulated by retinal activity, animals were dark-reared or retinal activity was completely blocked in one eye with tetrodotoxin (TTX). Dark-rearing does not cause detectable changes in NMDAR1 immunoreactivity. However, 2 weeks of monocular TTX administration decreases NMDAR1 immunoreactivity in layer 4 of the columns of the blocked eye. Thus, high levels of NMDAR1 immunostaining within the visual cortex are temporally correlated with ocular dominance column formation and developmental plasticity; the persistence of staining in layers 2/3 also correlates with the physiological plasticity present in these layers in the adult. In addition, visual experience is not required for the developmental changes in the laminar pattern of NMDAR1 levels, but the presence of high levels of NMDAR1 in layer 4 during the critical period does require retinal activity. These observations are consistent with a central role for NMDA receptors in promoting and ultimately limiting synaptic rearrangements in the developing neocortex.

Neuron density is decreased in the prefrontal cortex in Williams syndrome.

PubMed

Lew, Caroline Horton; Brown, Chelsea; Bellugi, Ursula; Semendeferi, Katerina

2017-01-01

Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with a hemideletion in chromosome 7, which manifests a distinct behavioral phenotype characterized by a hyperaffiliative social drive, in striking contrast to the social avoidance behaviors that are common in Autism Spectrum Disorder (ASD). MRI studies have observed structural and functional abnormalities in WS cortex, including the prefrontal cortex (PFC), a region implicated in social cognition. This study utilizes the Bellugi Williams Syndrome Brain Collection, a unique resource that comprises the largest WS postmortem brain collection in existence, and is the first to quantitatively examine WS PFC cytoarchitecture. We measured neuron density in layers II/III and V/VI of five cortical areas: PFC areas BA 10 and BA 11, primary motor BA 4, primary somatosensory BA 3, and visual area BA 18 in six matched pairs of WS and typically developing (TD) controls. Neuron density in PFC was lower in WS relative to TD, with layers V/VI demonstrating the largest decrease in density, reaching statistical significance in BA 10. In contrast, BA 3 and BA 18 demonstrated a higher density in WS compared to TD, although this difference was not statistically significant. Neuron density in BA 4 was similar in WS and TD. While other cortical areas were altered in WS, prefrontal areas appeared to be most affected. Neuron density is also altered in the PFC of individuals with ASD. Together these findings suggest that the PFC is targeted in neurodevelopmental disorders associated with sociobehavioral alterations. Autism Res 2017, 10: 99-112. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Estrogen and Hydroxysteroid Sulfotransterases in Guinea Pig Adrenal Cortex: Cellular and Subcellular Distributions

DTIC Science & Technology

1993-06-01

hydroxysteroid substrate specificities (32 and 33 kilodaltons, respectively) were previously purified from guinea pig adrenal cortex and characterized. Western...labeling with these antisera revealed that the sulfortransferases were expressed only within the ACTH- responsive layers of the guinea pig adrenal cortex

Computational model for perception of objects and motions.

PubMed

Yang, WenLu; Zhang, LiQing; Ma, LiBo

2008-06-01

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

Correlations Decrease with Propagation of Spiking Activity in the Mouse Barrel Cortex

PubMed Central

Ranganathan, Gayathri Nattar; Koester, Helmut Joachim

2011-01-01

Propagation of suprathreshold spiking activity through neuronal populations is important for the function of the central nervous system. Neural correlations have an impact on cortical function particularly on the signaling of information and propagation of spiking activity. Therefore we measured the change in correlations as suprathreshold spiking activity propagated between recurrent neuronal networks of the mammalian cerebral cortex. Using optical methods we recorded spiking activity from large samples of neurons from two neural populations simultaneously. The results indicate that correlations decreased as spiking activity propagated from layer 4 to layer 2/3 in the rodent barrel cortex. PMID:21629764

Parvalbumin interneurons and calretinin fibers arising from the thalamic nucleus reuniens degenerate in the subiculum after kainic acid-induced seizures

PubMed Central

Drexel, M.; Preidt, A.P.; Kirchmair, E.; Sperk, G.

2011-01-01

The subiculum is the major output area of the hippocampus. It is closely interconnected with the entorhinal cortex and other parahippocampal areas. In animal models of temporal lobe epilepsy (TLE) and in TLE patients it exerts increased network excitability and may crucially contribute to the propagation of limbic seizures. Using immunohistochemistry and in situ-hybridization we now investigated neuropathological changes affecting parvalbumin and calretinin containing neurons in the subiculum and other parahippocampal areas after kainic acid-induced status epilepticus. We observed prominent losses in parvalbumin containing interneurons in the subiculum and entorhinal cortex, and in the principal cell layers of the pre- and parasubiculum. Degeneration of parvalbumin-positive neurons was associated with significant precipitation of parvalbumin-immunoreactive debris 24 h after kainic acid injection. In the subiculum the superficial portion of the pyramidal cell layer was more severely affected than its deep part. In the entorhinal cortex, the deep layers were more severely affected than the superficial ones. The decrease in number of parvalbumin-positive neurons in the subiculum and entorhinal cortex correlated with the number of spontaneous seizures subsequently experienced by the rats. The loss of parvalbumin neurons thus may contribute to the development of spontaneous seizures. On the other hand, surviving parvalbumin neurons revealed markedly increased expression of parvalbumin mRNA notably in the pyramidal cell layer of the subiculum and in all layers of the entorhinal cortex. This indicates increased activity of these neurons aiming to compensate for the partial loss of this functionally important neuron population. Furthermore, calretinin-positive fibers terminating in the molecular layer of the subiculum, in sector CA1 of the hippocampus proper and in the entorhinal cortex degenerated together with their presumed perikarya in the thalamic nucleus reuniens. In addition, a significant loss of calretinin containing interneurons was observed in the subiculum. Notably, the loss in parvalbumin positive neurons in the subiculum equaled that in human TLE. It may result in marked impairment of feed-forward inhibition of the temporo-ammonic pathway and may significantly contribute to epileptogenesis. Similarly, the loss of calretinin-positive fiber tracts originating from the nucleus reuniens thalami significantly contributes to the rearrangement of neuronal circuitries in the subiculum and entorhinal cortex during epileptogenesis. PMID:21616128

Functional Connectivity and Genetic Profile of a “Double-Cortex”-Like Malformation

PubMed Central

Sprugnoli, Giulia; Vatti, Giampaolo; Rossi, Simone; Cerase, Alfonso; Renieri, Alessandra; Mencarelli, Maria A.; Zara, Federico; Rossi, Alessandro; Santarnecchi, Emiliano

2018-01-01

Laminar heterotopia is a rare condition consisting in an extra layer of gray matter under properly migrated cortex; it configures an atypical presentation of periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy patient with “double-cortex”-like malformation to reveal her functional connectivity (FC) as well as a wide genetic analysis to identify possible genetic substrates. Heterotopias were segmented into region of interests (ROIs), whose voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii) its contralateral homologous, and (iii) those of 30 age-matched healthy controls. Extensive genetic analysis was conducted to screen cortical malformations-associated genes. Compared to healthy controls, both laminar heterotopias and the overlying cortex showed significant reduction of FC with the contralateral hemisphere. Two heterozygous variants of uncertain clinical significance were found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1. This first FC analysis of a unique case of “double-cortex”-like malformation revealed a hemispheric connectivity segregation both in the laminar cortex as in the correctly migrated one, with a new pattern of genes’ mutations. Our study suggests the altered FC could have an electrophysiological and functional impact on large-scale brain networks, and the involvement of not yet identified genes in “double-cortex”-like malformation with a possible role of rare variants in recessive genes as pathogenic cofactors. PMID:29946244

Local and Global Spatial Organization of Interaural Level Difference and Frequency Preferences in Auditory Cortex

PubMed Central

Panniello, Mariangela; King, Andrew J; Dahmen, Johannes C; Walker, Kerry M M

2018-01-01

Abstract Despite decades of microelectrode recordings, fundamental questions remain about how auditory cortex represents sound-source location. Here, we used in vivo 2-photon calcium imaging to measure the sensitivity of layer II/III neurons in mouse primary auditory cortex (A1) to interaural level differences (ILDs), the principal spatial cue in this species. Although most ILD-sensitive neurons preferred ILDs favoring the contralateral ear, neurons with either midline or ipsilateral preferences were also present. An opponent-channel decoder accurately classified ILDs using the difference in responses between populations of neurons that preferred contralateral-ear-greater and ipsilateral-ear-greater stimuli. We also examined the spatial organization of binaural tuning properties across the imaged neurons with unprecedented resolution. Neurons driven exclusively by contralateral ear stimuli or by binaural stimulation occasionally formed local clusters, but their binaural categories and ILD preferences were not spatially organized on a more global scale. In contrast, the sound frequency preferences of most neurons within local cortical regions fell within a restricted frequency range, and a tonotopic gradient was observed across the cortical surface of individual mice. These results indicate that the representation of ILDs in mouse A1 is comparable to that of most other mammalian species, and appears to lack systematic or consistent spatial order. PMID:29136122

Estimation of electrode location in a rat motor cortex by laminar analysis of electrophysiology and intracortical electrical stimulation

NASA Astrophysics Data System (ADS)

Yazdan-Shahmorad, A.; Lehmkuhle, M. J.; Gage, G. J.; Marzullo, T. C.; Parikh, H.; Miriani, R. M.; Kipke, D. R.

2011-08-01

While the development of microelectrode arrays has enabled access to disparate regions of a cortex for neurorehabilitation, neuroprosthetic and basic neuroscience research, accurate interpretation of the signals and manipulation of the cortical neurons depend upon the anatomical placement of the electrode arrays in a layered cortex. Toward this end, this report compares two in vivo methods for identifying the placement of electrodes in a linear array spaced 100 µm apart based on in situ laminar analysis of (1) ketamine-xylazine-induced field potential oscillations in a rat motor cortex and (2) an intracortical electrical stimulation-induced movement threshold. The first method is based on finding the polarity reversal in laminar oscillations which is reported to appear at the transition between layers IV and V in laminar 'high voltage spindles' of the rat cortical column. Analysis of histological images in our dataset indicates that polarity reversal is detected 150.1 ± 104.2 µm below the start of layer V. The second method compares the intracortical microstimulation currents that elicit a physical movement for anodic versus cathodic stimulation. It is based on the hypothesis that neural elements perpendicular to the electrode surface are preferentially excited by anodic stimulation while cathodic stimulation excites those with a direction component parallel to its surface. With this method, we expect to see a change in the stimulation currents that elicits a movement at the beginning of layer V when comparing anodic versus cathodic stimulation as the upper cortical layers contain neuronal structures that are primarily parallel to the cortical surface and lower layers contain structures that are primarily perpendicular. Using this method, there was a 78.7 ± 68 µm offset in the estimate of the depth of the start of layer V. The polarity reversal method estimates the beginning of layer V within ±90 µm with 95% confidence and the intracortical stimulation method estimates it within ±69.3 µm. We propose that these methods can be used to estimate the in situ location of laminar electrodes implanted in the rat motor cortex.

Evolution of the cerebellar cortex: the selective expansion of prefrontal-projecting cerebellar lobules.

PubMed

Balsters, J H; Cussans, E; Diedrichsen, J; Phillips, K A; Preuss, T M; Rilling, J K; Ramnani, N

2010-02-01

It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Morphology and kainate-receptor immunoreactivity of identified neurons within the entorhinal cortex projecting to superior temporal sulcus in the cynomolgus monkey

NASA Technical Reports Server (NTRS)

Good, P. F.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1995-01-01

Projections of the entorhinal cortex to the hippocampus are well known from the classical studies of Cajal (Ramon y Cajal, 1904) and Lorente de No (1933). Projections from the entorhinal cortex to neocortical areas are less well understood. Such connectivity is likely to underlie the consolidation of long-term declarative memory in neocortical sites. In the present study, a projection arising in layer V of the entorhinal cortex and terminating in a polymodal association area of the superior temporal gyrus has been identified with the use of retrograde tracing. The dendritic arbors of neurons giving rise to this projection were further investigated by cell filling and confocal microscopy with computer reconstruction. This analysis demonstrated that the dendritic arbor of identified projection neurons was largely confined to layer V, with the exception of a solitary, simple apical dendrite occasionally ascending to superficial laminae but often confined to the lamina dissecans (layer IV). Finally, immunoreactivity for glutamate-receptor subunit proteins GluR 5/6/7 of the dendritic arbor of identified entorhinal projection neurons was examined. The solitary apical dendrite of identified entorhinal projection neurons was prominently immunolabeled for GluR 5/6/7, as was the dendritic arbor of basilar dendrites of these neurons. The restriction of the large bulk of the dendritic arbor of identified entorhinal projection neurons to layer V implies that these neurons are likely to be heavily influenced by hippocampal output arriving in the deep layers of the entorhinal cortex. Immunoreactivity for GluR 5/6/7 throughout the dendritic arbor of such neurons indicates that this class of glutamate receptor is in a position to play a prominent role in mediating excitatory neurotransmission within hippocampal-entorhinal circuits.

Asymmetric temporal integration of layer 4 and layer 2/3 inputs in visual cortex.

PubMed

Hang, Giao B; Dan, Yang

2011-01-01

Neocortical neurons in vivo receive concurrent synaptic inputs from multiple sources, including feedforward, horizontal, and feedback pathways. Layer 2/3 of the visual cortex receives feedforward input from layer 4 and horizontal input from layer 2/3. Firing of the pyramidal neurons, which carries the output to higher cortical areas, depends critically on the interaction of these pathways. Here we examined synaptic integration of inputs from layer 4 and layer 2/3 in rat visual cortical slices. We found that the integration is sublinear and temporally asymmetric, with larger responses if layer 2/3 input preceded layer 4 input. The sublinearity depended on inhibition, and the asymmetry was largely attributable to the difference between the two inhibitory inputs. Interestingly, the asymmetric integration was specific to pyramidal neurons, and it strongly affected their spiking output. Thus via cortical inhibition, the temporal order of activation of layer 2/3 and layer 4 pathways can exert powerful control of cortical output during visual processing.

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

Patterns of cytochrome oxidase activity in the visual cortex of a South American opossum (Didelphis marsupialis aurita).

PubMed

Martinich, S; Rosa, M G; Rocha-Miranda, C E

1990-01-01

The normal pattern of cytochrome oxidase (CO) activity in the posterior cortical areas of the South American opossum (Didelphis marsupialis aurita) was assessed both in horizontal sections of flattened cortices and in transversal cortical sections. The tangential distribution of CO activity was uniformly high in the striate cortex. In the peristriate region alternating bands of dense and weak staining occupied all the cortical layers with the exception of layer I. This observation suggests the existence of a functional segregation of visual processing in the peristriate cortex of the opossum similar to that present in phylogenetically more recent groups.

A repetitive intracortical microstimulation pattern induces long-lasting synaptic depression in brain slices of the rat primary somatosensory cortex.

PubMed

Heusler, P; Cebulla, B; Boehmer, G; Dinse, H R

2000-12-01

Repetitive intracortical microstimulation (ICMS) applied to the rat primary somatosensory cortex (SI) in vivo was reported to induce reorganization of receptive fields and cortical maps. The present study was designed to examine the effect of such an ICMS pattern applied to layer IV of brain slices containing SI on the efficacy of synaptic input to layer II/III. Effects of ICMS on the synaptic strength was quantified for the first synaptic component (s1) of cortical field potentials (FPs) recorded from layer II/III of SI. FPs were evoked by stimulation in layer IV. The pattern of ICMS was identical to that used in vivo. However, stimulation intensity had to be raised to induce an alteration of synaptic strength. In brain slices superfused with standard ACSF, repetitive ICMS induced a short-lasting (60 min) reduction of the amplitude (-37%) and the slope (-61%) of s1 evoked from the ICMS site, while the amplitude and the slope of s1 evoked from a control stimulation site in cortical layer IV underwent a slow onset increase (13% and 50%, respectively). In brain slices superfused with ACSF containing 1.25 microM bicuculline, ICMS induced an initial strong reduction of the amplitude (-50%) and the slope (-79%) of s1 evoked from the ICMS site. These effects decayed to a sustained level of depression by -30% (amplitude) and -60% (slope). In contrast to experiments using standard ACSF, s1 evoked from the control site was not affected by ICMS. The presynaptic volley was not affected in either of the two groups of experiments. A conventional high frequency stimulation (HFS) protocol induced input-specific long-term potentiation (LTP) of the amplitude and slope of s1 (25% and 76%, respectively). Low frequency stimulation (LFS) induced input-specific long-term depression (LTD) of the amplitude and slope of s1 (24% and 30%, respectively). Application of common forms of conditioning stimulation (HFS and LFS) resulted in LTP or LTD of s1, indicating normal susceptibility of the brain slices studied to the induction of common forms of synaptic plasticity. Therefore, the effects of repetitive ICMS on synaptic FP components were considered ICMS-specific forms of short-lasting (standard ACSF) or long-lasting synaptic depression (ACSF containing bicuculline), the latter resembling neocortical LTD. Results of this study suggest that synaptic depression of excitatory mechanisms are involved in the cortical reorganization induced by repetitive ICMS in vivo. An additional contribution of an ICMS-induced modification of inhibitory mechanisms to cortical reorganization is discussed.

Alpha and gamma oscillations characterize feedback and feedforward processing in monkey visual cortex

PubMed Central

van Kerkoerle, Timo; Self, Matthew W.; Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Poort, Jasper; van der Togt, Chris; Roelfsema, Pieter R.

2014-01-01

Cognitive functions rely on the coordinated activity of neurons in many brain regions, but the interactions between cortical areas are not yet well understood. Here we investigated whether low-frequency (α) and high-frequency (γ) oscillations characterize different directions of information flow in monkey visual cortex. We recorded from all layers of the primary visual cortex (V1) and found that γ-waves are initiated in input layer 4 and propagate to the deep and superficial layers of cortex, whereas α-waves propagate in the opposite direction. Simultaneous recordings from V1 and downstream area V4 confirmed that γ- and α-waves propagate in the feedforward and feedback direction, respectively. Microstimulation in V1 elicited γ-oscillations in V4, whereas microstimulation in V4 elicited α-oscillations in V1, thus providing causal evidence for the opposite propagation of these rhythms. Furthermore, blocking NMDA receptors, thought to be involved in feedback processing, suppressed α while boosting γ. These results provide new insights into the relation between brain rhythms and cognition. PMID:25205811

Alpha and gamma oscillations characterize feedback and feedforward processing in monkey visual cortex.

PubMed

van Kerkoerle, Timo; Self, Matthew W; Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Poort, Jasper; van der Togt, Chris; Roelfsema, Pieter R

2014-10-07

Cognitive functions rely on the coordinated activity of neurons in many brain regions, but the interactions between cortical areas are not yet well understood. Here we investigated whether low-frequency (α) and high-frequency (γ) oscillations characterize different directions of information flow in monkey visual cortex. We recorded from all layers of the primary visual cortex (V1) and found that γ-waves are initiated in input layer 4 and propagate to the deep and superficial layers of cortex, whereas α-waves propagate in the opposite direction. Simultaneous recordings from V1 and downstream area V4 confirmed that γ- and α-waves propagate in the feedforward and feedback direction, respectively. Microstimulation in V1 elicited γ-oscillations in V4, whereas microstimulation in V4 elicited α-oscillations in V1, thus providing causal evidence for the opposite propagation of these rhythms. Furthermore, blocking NMDA receptors, thought to be involved in feedback processing, suppressed α while boosting γ. These results provide new insights into the relation between brain rhythms and cognition.

Ultrasound-guided near-infrared spectroscopy for brain functional study: feasibility analysis and preliminary work

NASA Astrophysics Data System (ADS)

Xu, Ronald; Qiang, Bo; Liu, Jun

2005-04-01

Recent advances in diffuse optical imaging and spectroscopy (DOIS) allow the noninvasive measurement of local changes in cerebral oxygenation and hemodynamics. Available DOIS devices fall into three categories: time domain (TD), frequency domain (FD) and continuous wave (CW). The TD and FD devices have potential for high spatial resolution, high temporal resolution and high accuracy measurement, but the instrument cost and the hardware size prevent their wide clinical application. Furthermore, the presence of the low scattering cerebrospinal fluid layer (CSF) and its thickness variation during motion challenges quantitative, continuous monitoring of the cortex layer oxygenation and blood content. MRI has been used to provide a priori knowledge of the head anatomy that helps the NIR image reconstruction. However, the technology is expensive and lacks portability. This paper proposes a method that combines the accuracy of a TD/FD system and the portability of a CW device. With the optical baseline measured by a TD or FD device and the layer thickness characterized by an ultrasound transducer, a conventional CW system may be able to quantify the cortex layer optical absorption with high accuracy. In this paper, the feasibility of using ultrasound guided CW spectroscopy to monitor brain activities was studied on a multi layer head model using Monte Carlo simulation and order of magnitude analysis. A forward algorithm based on diffuse approximation and 2D Fourier Transform was used to optimize the source detector separation. Both analytical and neuron network approaches were developed for inverse calculation of the cortex layer absorption in real time. An ultrasound transducer was used to monitor the thickness of different layers surrounding the cerebral cortex. The concept of ultrasound guided CW spectroscopy was demonstrated by numerical simulation on a 2 layer head model and the use of the ultrasound transducer for layer thickness characterization was verified by animal and bench top results.

Thalamocortical Connections Drive Intracortical Activation of Functional Columns in the Mislaminated Reeler Somatosensory Cortex

PubMed Central

Wagener, Robin J.; Witte, Mirko; Guy, Julien; Mingo-Moreno, Nieves; Kügler, Sebastian; Staiger, Jochen F.

2016-01-01

Neuronal wiring is key to proper neural information processing. Tactile information from the rodent's whiskers reaches the cortex via distinct anatomical pathways. The lemniscal pathway relays whisking and touch information from the ventral posteromedial thalamic nucleus to layer IV of the primary somatosensory “barrel” cortex. The disorganized neocortex of the reeler mouse is a model system that should severely compromise the ingrowth of thalamocortical axons (TCAs) into the cortex. Moreover, it could disrupt intracortical wiring. We found that neuronal intermingling within the reeler barrel cortex substantially exceeded previous descriptions, leading to the loss of layers. However, viral tracing revealed that TCAs still specifically targeted transgenically labeled spiny layer IV neurons. Slice electrophysiology and optogenetics proved that these connections represent functional synapses. In addition, we assessed intracortical activation via immediate-early-gene expression resulting from a behavioral exploration task. The cellular composition of activated neuronal ensembles suggests extensive similarities in intracolumnar information processing in the wild-type and reeler brains. We conclude that extensive ectopic positioning of neuronal partners can be compensated for by cell-autonomous mechanisms that allow for the establishment of proper connectivity. Thus, genetic neuronal fate seems to be of greater importance for correct cortical wiring than radial neuronal position. PMID:26564256

Interlaminar differences in the pyramidal cell phenotype in parietal cortex of an Indian bat, cynopterus sphinx.

PubMed

Srivastava, U C; Pathak, S V

2010-10-30

To study interlaminar phenotypic variations in the pyramidal neurons of parietal isocortex in bat (Cynopterus sphinx), Golgi and Nissl methods have been employed. The parietal isocortex is relatively thin in the bat as compared to prototheria with layer III, V and VI accounting for more than two—thirds of total cortical thickness. Thick cell free layer I and thinnest accentuated layer II are quite in connotation with other chiropterids. Poor demarcation of layer III/IV in the present study is also in connotation with primitive eutherian mammal (i.e. prototherian) and other chiropterids. Most of the pyramidal cells in the different layers of the parietal isocortex are of typical type as seen in other eutherians but differ significantly in terms of soma shape and size, extent of dendritic arbor, diameter of dendrites and spine density. Percentage of pyramidal neurons, diameter of apical dendrite and spine density on apical dendrite appear to follow an increasing trend from primitive to advanced mammals; but extent of dendrites are probably governed by the specific life patterns of these mammals. It is thus concluded that 'typical' pyramidal neurons in parietal isocortex are similar in therians but different from those in prototherians. It is possible that these cells might have arisen among early eutherians after divergence from prototherian stock.

SHR overexpression induces the formation of supernumerary cell layers with cortex cell identity in rice.

PubMed

Henry, S; Dievart, A; Divol, F; Pauluzzi, G; Meynard, D; Swarup, R; Wu, S; Gallagher, K L; Périn, C

2017-05-01

The number of root cortex cell layers varies among plants, and many species have several cortical cell layers. We recently demonstrated that the two rice orthologs of the Arabidopsis SHR gene, OsSHR1 and OsSHR2, could complement the A. thaliana shr mutant. Moreover, OsSHR1 and OsSHR2 expression in A. thaliana roots induced the formation of extra root cortical cell layers. In this article, we demonstrate that the overexpression of AtSHR and OsSHR2 in rice roots leads to plants with wide and short roots that contain a high number of extra cortical cell layers. We hypothesize that SHR genes share a conserved function in the control of cortical cell layer division and the number of ground tissue cell layers in land plants. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential Mechanisms Underlying Intercortical Signal Regulation via Cholinergic Neuromodulators

PubMed Central

Whittington, Miles A.; Kopell, Nancy J.

2015-01-01

The dynamical behavior of the cortex is extremely complex, with different areas and even different layers of a cortical column displaying different temporal patterns. A major open question is how the signals from different layers and different brain regions are coordinated in a flexible manner to support function. Here, we considered interactions between primary auditory cortex and adjacent association cortex. Using a biophysically based model, we show how top-down signals in the beta and gamma regimes can interact with a bottom-up gamma rhythm to provide regulation of signals between the cortical areas and among layers. The flow of signals depends on cholinergic modulation: with only glutamatergic drive, we show that top-down gamma rhythms may block sensory signals. In the presence of cholinergic drive, top-down beta rhythms can lift this blockade and allow signals to flow reciprocally between primary sensory and parietal cortex. SIGNIFICANCE STATEMENT Flexible coordination of multiple cortical areas is critical for complex cognitive functions, but how this is accomplished is not understood. Using computational models, we studied the interactions between primary auditory cortex (A1) and association cortex (Par2). Our model is capable of replicating interaction patterns observed in vitro and the simulations predict that the coordination between top-down gamma and beta rhythms is central to the gating process regulating bottom-up sensory signaling projected from A1 to Par2 and that cholinergic modulation allows this coordination to occur. PMID:26558772

Cortical Isolation from Xenopus laevis Oocytes and Eggs.

PubMed

Sive, Hazel L; Grainger, Robert M; Harland, Richard M

2007-06-01

INTRODUCTIONIn Xenopus laevis, the cortex is the layer of gelatinous cytoplasm that lies just below the plasma membrane of the egg. Rotation of the cortex relative to the deeper cytoplasm soon after fertilization is intimately linked to normal dorsal axis specification. The cortex can be dissected from the egg to analyze its composition and activity or to clone associated RNAs. This protocol describes a procedure for isolating the vegetal cortex of the fertilized egg.

Gain control by layer six in cortical circuits of vision.

PubMed

Olsen, Shawn R; Bortone, Dante S; Adesnik, Hillel; Scanziani, Massimo

2012-02-22

After entering the cerebral cortex, sensory information spreads through six different horizontal neuronal layers that are interconnected by vertical axonal projections. It is believed that through these projections layers can influence each other's response to sensory stimuli, but the specific role that each layer has in cortical processing is still poorly understood. Here we show that layer six in the primary visual cortex of the mouse has a crucial role in controlling the gain of visually evoked activity in neurons of the upper layers without changing their tuning to orientation. This gain modulation results from the coordinated action of layer six intracortical projections to superficial layers and deep projections to the thalamus, with a substantial role of the intracortical circuit. This study establishes layer six as a major mediator of cortical gain modulation and suggests that it could be a node through which convergent inputs from several brain areas can regulate the earliest steps of cortical visual processing.

Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly

PubMed Central

de Juan Romero, Camino; Bruder, Carl; Tomasello, Ugo; Sanz-Anquela, José Miguel; Borrell, Víctor

2015-01-01

Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ∼80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices. PMID:25916825

Electron microscope study of the vitelline body of some spider oocytes.

PubMed

SOTELO, J R; TRUJILLO-CENOZ, O

1957-03-25

THE STRUCTURE OF THE VITELLINE NUCLEI OF LYCOSIDAE AND THOMISIDAE WAS DESCRIBED AS FOLLOWS: Vitelline nuclei are constituted of two parts: (a) a peripheral layer (vitelline body cortex), and (b) a central core. The vitelline body cortex is demonstrated to be formed by many cisternae of the endoplasmic reticulum among which mitochondria and Golgi elements are intermingled. The central core is made up mainly of a special type of body described under the name of "capsulated body." Capsulated bodies comprise a capsular layer, limited by a membrane, and two central masses called "geminated masses," each one limited by a double membrane. Irregular masses of closely packed vesicles are found in some cases among the capsulated bodies and free vesicles are present in large numbers. The optical properties of the vitelline body cortex compared with the electron microscope findings lead us to the concept that this layer is a "composite body" according to Weiner's theory.

Dopamine-Modulated Recurrent Corticoefferent Feedback in Primary Sensory Cortex Promotes Detection of Behaviorally Relevant Stimuli

PubMed Central

Handschuh, Juliane

2014-01-01

Dopaminergic neurotransmission in primary auditory cortex (AI) has been shown to be involved in learning and memory functions. Moreover, dopaminergic projections and D1/D5 receptor distributions display a layer-dependent organization, suggesting specific functions in the cortical circuitry. However, the circuit effects of dopaminergic neurotransmission in sensory cortex and their possible roles in perception, learning, and memory are largely unknown. Here, we investigated layer-specific circuit effects of dopaminergic neuromodulation using current source density (CSD) analysis in AI of Mongolian gerbils. Pharmacological stimulation of D1/D5 receptors increased auditory-evoked synaptic currents in infragranular layers, prolonging local thalamocortical input via positive feedback between infragranular output and granular input. Subsequently, dopamine promoted sustained cortical activation by prolonged recruitment of long-range corticocortical networks. A detailed circuit analysis combining layer-specific intracortical microstimulation (ICMS), CSD analysis, and pharmacological cortical silencing revealed that cross-laminar feedback enhanced by dopamine relied on a positive, fast-acting recurrent corticoefferent loop, most likely relayed via local thalamic circuits. Behavioral signal detection analysis further showed that activation of corticoefferent output by infragranular ICMS, which mimicked auditory activation under dopaminergic influence, was most effective in eliciting a behaviorally detectable signal. Our results show that D1/D5-mediated dopaminergic modulation in sensory cortex regulates positive recurrent corticoefferent feedback, which enhances states of high, persistent activity in sensory cortex evoked by behaviorally relevant stimuli. In boosting horizontal network interactions, this potentially promotes the readout of task-related information from cortical synapses and improves behavioral stimulus detection. PMID:24453315

Despite similar reduction of blood pressure and renal ANG II and ET-1 levels aliskiren but not losartan normalizes albuminuria in hypertensive Ren-2 rats.

PubMed

Vanourková, Z; Kramer, H J; Husková, Z; Cervenka, L; Vanecková, I

2010-01-01

The relationship between angiotensin II (ANG II) and endothelin-1 (ET-1) is known to be complex; both peptides can initiate and potentiate the gene expression of each other. This pilot study investigated the effects of the AT(1) receptor blocker losartan or the direct renin inhibitor aliskiren on mean arterial pressure (MAP) and albuminuria and the renal ANG II and ET-1 levels. 3-month-old male Ren-2 transgenic rats (TGR) were treated either with losartan (5 mg kg(-1) day(-1)) or aliskiren (10 mg kg(-1) day(-1)) for 10 weeks. At the end of the experiment, rats were decapitated and cortical and papillary parts of kidneys were separated. Plasma and tissue ANG II levels were measured by RIA and tissue ET-1 concentrations by ELISA. In all four groups of animals ET-1 levels were lowest in renal cortex and more than 100-fold higher in the papilla. Cortical and papillary ET-1 concentrations in untreated TGR significantly exceeded those of control HanSD rats and were significantly depressed by both drugs. In both strains, papillary ANG II concentrations were moderately but significantly higher than cortical ANG II, TGR exhibited higher ANG II levels both in cortex and papilla as compared to control HanSD rats. Aliskiren and losartan at the doses used depressed similarly the levels of ANG II in cortex and papilla and reduced ET-1 significantly in the renal cortex and papilla below control levels in HanSD rats. Albuminuria, which was more than twice as high in TGR as in HanSD rats, was normalized with aliskiren and reduced by 28% with losartan, although MAP was reduced to a similar degree by both drugs. Despite similar reductions of MAP and renal ET-1 and ANG II levels aliskiren appears to be more effective than losartan, at the doses used, in reducing albuminuria in heterozygous hypertensive Ren-2 rats.

Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II.

PubMed

Carvalho-Silva, Milena; Gomes, Lara M; Scaini, Giselli; Rebelo, Joyce; Damiani, Adriani P; Pereira, Maiara; Andrade, Vanessa M; Gava, Fernanda F; Valvassori, Samira S; Schuck, Patricia F; Ferreira, Gustavo C; Streck, Emilio L

2017-08-01

Tyrosinemia type II is an inborn error of metabolism caused by a mutation in a gene encoding the enzyme tyrosine aminotransferase leading to an accumulation of tyrosine in the body, and is associated with neurologic and development difficulties in numerous patients. Because the accumulation of tyrosine promotes oxidative stress and DNA damage, the main aim of this study was to investigate the possible antioxidant and neuroprotective effects of omega-3 treatment in a chemically-induced model of Tyrosinemia type II in hippocampus, striatum and cerebral cortex of rats. Our results showed chronic administration of L-tyrosine increased the frequency and the index of DNA damage, as well as the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the hippocampus, striatum and cerebral cortex. Moreover, omega-3 fatty acid treatment totally prevented increased DNA damage in the striatum and hippocampus, and partially prevented in the cerebral cortex, whereas the increase in 8-OHdG levels was totally prevented by omega-3 fatty acid treatment in hippocampus, striatum and cerebral cortex. In conclusion, the present study demonstrated that the main accumulating metabolite in Tyrosinemia type II induce DNA damage in hippocampus, striatum and cerebral cortex, possibly mediated by free radical production, and the supplementation with omega-3 fatty acids was able to prevent this damage, suggesting that could be involved in the prevention of oxidative damage to DNA in this disease. Thus, omega-3 fatty acids supplementation to Tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the curren t treatment of this disease.

Polarity of cortical electrical stimulation differentially affects neuronal activity of deep and superficial layers of rat motor cortex.

PubMed

Yazdan-Shahmorad, Azadeh; Kipke, Daryl R; Lehmkuhle, Mark J

2011-10-01

Cortical electrical stimulation (CES) techniques are practical tools in neurorehabilitation that are currently being used to test models of functional recovery after neurologic injury. However, the mechanisms by which CES has therapeutic effects, are not fully understood. In this study, we investigated the effects of CES on unit activity of different neuronal elements in layers of rat primary motor cortex after the offset of stimulation. We evaluated the effects of monopolar CES pulse polarity (anodic-first versus cathodic-first) using various stimulation frequencies and amplitudes on unit activity after stimulation. A penetrating single shank silicon microelectrode array enabled us to span the entirety of six layer motor cortex allowing simultaneous electrophysiologic recordings from different depths after monopolar CES. Neural spiking activity before the onset and after the offset of CES was modeled using point processes fit to capture neural spiking dynamics as a function of extrinsic stimuli based on generalized linear model methods. We found that neurons in lower layers have a higher probability of being excited after anodic CES. Conversely, neurons located in upper cortical layers have a higher probability of being excited after cathodic stimulation. The opposing effects observed following anodic versus cathodic stimulation in upper and lower layers were frequency- and amplitude-dependent. The data demonstrates that the poststimulus changes in neural activity after manipulation of CES parameters changes according to the location (depth) of the recorded units in rat primary motor cortex. The most effective pulse polarity for eliciting action potentials after stimulation in lower layers was not as effective in upper layers. Likewise, lower amplitudes and frequencies of CES were more effective than higher amplitudes and frequencies for eliciting action potentials. These results have important implications in the context of maximizing efficacy of CES for neurorehabilitation and neuroprosthetic applications. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

A Corticocortical Circuit Directly Links Retrosplenial Cortex to M2 in the Mouse

PubMed Central

Radulovic, Jelena

2016-01-01

Retrosplenial cortex (RSC) is a dorsomedial parietal area involved in a range of cognitive functions, including episodic memory, navigation, and spatial memory. Anatomically, the RSC receives inputs from dorsal hippocampal networks and in turn projects to medial neocortical areas. A particularly prominent projection extends rostrally to the posterior secondary motor cortex (M2), suggesting a functional corticocortical link from the RSC to M2 and thus a bridge between hippocampal and neocortical networks involved in mnemonic and sensorimotor aspects of navigation. We investigated the cellular connectivity in this RSC→M2 projection in the mouse using optogenetic photostimulation, retrograde labeling, and electrophysiology. Axons from RSC formed monosynaptic excitatory connections onto M2 pyramidal neurons across layers and projection classes, including corticocortical/intratelencephalic neurons (reciprocally and callosally projecting) in layers 2–6, pyramidal tract neurons (corticocollicular, corticopontine) in layer 5B, and, to a lesser extent, corticothalamic neurons in layer 6. In addition to these direct connections, disynaptic connections were made via posterior parietal cortex (RSC→PPC→M2) and anteromedial thalamus (RSC→AM→M2). In the reverse direction, axons from M2 monosynaptically excited M2-projecting corticocortical neurons in the RSC, especially in the superficial layers of the dysgranular region. These findings establish an excitatory RSC→M2 corticocortical circuit that engages diverse types of excitatory projection neurons in the downstream area, suggesting a basis for direct communication from dorsal hippocampal networks involved in spatial memory and navigation to neocortical networks involved in diverse aspects of sensorimotor integration and motor control. SIGNIFICANCE STATEMENT Corticocortical pathways interconnect cortical areas extensively, but the cellular connectivity in these pathways remains largely uncharacterized. Here, we show that a posterior part of secondary motor cortex receives corticocortical axons from the rostral retrosplenial cortex (RSC) and these form monosynaptic excitatory connections onto a wide spectrum of excitatory projection neurons in this area. Our results define a cellular basis for direct communication from RSC to this medial frontal area, suggesting a direct link from dorsal hippocampal networks involved in spatial cognition and navigation (the “map”) to sensorimotor networks involved the control of movement (the “motor”). PMID:27605612

Dual Gamma Rhythm Generators Control Interlaminar Synchrony in Auditory Cortex

PubMed Central

Ainsworth, Matthew; Lee, Shane; Cunningham, Mark O.; Roopun, Anita K.; Traub, Roger D.; Kopell, Nancy J.; Whittington, Miles A.

2013-01-01

Rhythmic activity in populations of cortical neurons accompanies, and may underlie, many aspects of primary sensory processing and short-term memory. Activity in the gamma band (30 Hz up to > 100 Hz) is associated with such cognitive tasks and is thought to provide a substrate for temporal coupling of spatially separate regions of the brain. However, such coupling requires close matching of frequencies in co-active areas, and because the nominal gamma band is so spectrally broad, it may not constitute a single underlying process. Here we show that, for inhibition-based gamma rhythms in vitro in rat neocortical slices, mechanistically distinct local circuit generators exist in different laminae of rat primary auditory cortex. A persistent, 30 – 45 Hz, gap-junction-dependent gamma rhythm dominates rhythmic activity in supragranular layers 2/3, whereas a tonic depolarization-dependent, 50 – 80 Hz, pyramidal/interneuron gamma rhythm is expressed in granular layer 4 with strong glutamatergic excitation. As a consequence, altering the degree of excitation of the auditory cortex causes bifurcation in the gamma frequency spectrum and can effectively switch temporal control of layer 5 from supragranular to granular layers. Computational modeling predicts the pattern of interlaminar connections may help to stabilize this bifurcation. The data suggest that different strategies are used by primary auditory cortex to represent weak and strong inputs, with principal cell firing rate becoming increasingly important as excitation strength increases. PMID:22114273

Basal ganglia—thalamus and the “crowning enigma”

PubMed Central

Garcia-Munoz, Marianela; Arbuthnott, Gordon W.

2015-01-01

When Hubel (1982) referred to layer 1 of primary visual cortex as “… a ‘crowning mystery’ to keep area-17 physiologists busy for years to come …” he could have been talking about any cortical area. In the 80’s and 90’s there were no methods to examine this neuropile on the surface of the cortex: a tangled web of axons and dendrites from a variety of different places with unknown specificities and doubtful connections to the cortical output neurons some hundreds of microns below. Recently, three changes have made the crowning enigma less of an impossible mission: the clear presence of neurons in layer 1 (L1), the active conduction of voltage along apical dendrites and optogenetic methods that might allow us to look at one source of input at a time. For all of those reasons alone, it seems it is time to take seriously the function of L1. The functional properties of this layer will need to wait for more experiments but already L1 cells are GAD67 positive, i.e., inhibitory! They could reverse the sign of the thalamic glutamate (GLU) input for the entire cortex. It is at least possible that in the near future normal activity of individual sources of L1 could be detected using genetic tools. We are at the outset of important times in the exploration of thalamic functions and perhaps the solution to the crowning enigma is within sight. Our review looks forward to that solution from the solid basis of the anatomy of the basal ganglia output to motor thalamus. We will focus on L1, its afferents, intrinsic neurons and its influence on responses of pyramidal neurons in layers 2/3 and 5. Since L1 is present in the whole cortex we will provide a general overview considering evidence mainly from the somatosensory (S1) cortex before focusing on motor cortex. PMID:26582979

The Impact of Development and Sensory Deprivation on Dendritic Protrusions in the Mouse Barrel Cortex

PubMed Central

Chen, Chia-Chien; Bajnath, Adesh; Brumberg, Joshua C.

2015-01-01

Dendritic protrusions (spines and filopodia) are structural indicators of synapses that have been linked to neuronal learning and memory through their morphological alterations induced by development and experienced-dependent activities. Although previous studies have demonstrated that depriving sensory experience leads to structural changes in neocortical organization, the more subtle effects on dendritic protrusions remain unclear, mostly due to focus on only one specific cell type and/or age of manipulation. Here, we show that sensory deprivation induced by whisker trimming influences the dendritic protrusions of basilar dendrites located in thalamocortical recipient lamina (IV and VI) of the mouse barrel cortex in a layer-specific manner. Following 1 month of whisker trimming after birth, the density of dendritic protrusions increased in layer IV, but decreased in layer VI. Whisker regrowth for 1 month returned protrusion densities to comparable level of age-matched controls in layer VI, but not in layer IV. In adults, chronic sensory deprivation led to an increase in protrusion densities in layer IV, but not in layer VI. In addition, chronic pharmacological blockade of N-methyl-d-aspartate receptors (NMDARs) increased protrusion density in both layers IV and VI, which returned to the control level after 1 month of drug withdrawal. Our data reveal that different cortical layers respond to chronic sensory deprivation in different ways, with more pronounced effects during developmental critical periods than adulthood. We also show that chronically blocking NMDARs activity during developmental critical period also influences the protrusion density and morphology in the cerebral cortex. PMID:24408954

Architectonic subdivisions of neocortex in the tree shrew (Tupaia belangeri)

PubMed Central

Wong, Peiyan; Kaas, Jon H.

2010-01-01

Tree shrews are small mammals that bear some semblance to squirrels, but are actually close relatives of primates. Thus, they have been extensively studied as a model for the early stages of primate evolution. In the present study, subdivisions of cortex were reconstructed from brain sections cut in the coronal, sagittal or horizontal planes, and processed for parvalbumin (PV), SMI-32 immunopositive neurofilament protein epitopes, vesicle glutamate transporter 2 (VGluT2), free ionic zinc, myelin, cytochrome oxidase (CO) and Nissl substance. These different procedures revealed similar boundaries between areas, suggesting the detection of functionally relevant borders and allowed a more precise demarcation of cortical areal boundaries. Primary cortical areas were most clearly revealed by the zinc stain, due to the poor staining of layer 4, as thalamocortical terminations lack free ionic zinc. Area 17 (V1) was especially prominent, as the broad layer 4 was nearly free of zinc stain. However, this feature was less pronounced in primary auditory and somatosensory, cortex. In primary sensory areas, thalamocortical terminations in layer 4 densely express VGluT2. Auditory cortex consists of two architectonically distinct subdivisions, a primary core region (Ac), surrounded by a belt region (Ab) that had a slightly less developed koniocellular appearance. Primary motor cortex (M1) was identified by the absence of VGluT2 staining in the poorly developed granular layer 4 and the presence of SMI-32 labeled pyramidal cells in layers 3 and 5. The presence of well-differentiated cortical areas in tree shrews indicates their usefulness in studies of cortical organization and function. PMID:19462403

Stream-related preferences of inputs to the superior colliculus from areas of dorsal and ventral streams of mouse visual cortex.

PubMed

Wang, Quanxin; Burkhalter, Andreas

2013-01-23

Previous studies of intracortical connections in mouse visual cortex have revealed two subnetworks that resemble the dorsal and ventral streams in primates. Although calcium imaging studies have shown that many areas of the ventral stream have high spatial acuity whereas areas of the dorsal stream are highly sensitive for transient visual stimuli, there are some functional inconsistencies that challenge a simple grouping into "what/perception" and "where/action" streams known in primates. The superior colliculus (SC) is a major center for processing of multimodal sensory information and the motor control of orienting the eyes, head, and body. Visual processing is performed in superficial layers, whereas premotor activity is generated in deep layers of the SC. Because the SC is known to receive input from visual cortex, we asked whether the projections from 10 visual areas of the dorsal and ventral streams terminate in differential depth profiles within the SC. We found that inputs from primary visual cortex are by far the strongest. Projections from the ventral stream were substantially weaker, whereas the sparsest input originated from areas of the dorsal stream. Importantly, we found that ventral stream inputs terminated in superficial layers, whereas dorsal stream inputs tended to be patchy and either projected equally to superficial and deep layers or strongly preferred deep layers. The results suggest that the anatomically defined ventral and dorsal streams contain areas that belong to distinct functional systems, specialized for the processing of visual information and visually guided action, respectively.

An analysis of current source density profiles activated by local stimulation in the mouse auditory cortex in vitro.

PubMed

Yamamura, Daiki; Sano, Ayaka; Tateno, Takashi

2017-03-15

To examine local network properties of the mouse auditory cortex in vitro, we recorded extracellular spatiotemporal laminar profiles driven by short electric local stimulation on a planar multielectrode array substrate. The recorded local field potentials were subsequently evaluated using current source density (CSD) analysis to identify sources and sinks. Current sinks are thought to be an indicator of net synaptic current in the small volume of cortex surrounding the recording site. Thus, CSD analysis combined with multielectrode arrays enabled us to compare mean synaptic activity in response to small current stimuli on a layer-by-layer basis. We also used senescence-accelerated mice (SAM), some strains of which show earlier onset of age-related hearing loss, to examine the characteristic spatiotemporal CSD profiles stimulated by electrodes in specific cortical layers. Thus, the CSD patterns were classified into several clusters based on stimulation sites in the cortical layers. We also found some differences in CSD patterns between the two SAM strains in terms of aging according to principle component analysis with dimension reduction. For simultaneous two-site stimulation, we modeled the obtained CSD profiles as a linear superposition of the CSD profiles to individual single-site stimulation. The model analysis indicated the nonlinearity of spatiotemporal integration over stimulus-driven activity in a layer-specific manner. Finally, on the basis of these results, we discuss the auditory cortex local network properties and the effects of aging on these mouse strains. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular and Electrophysiological Characterization of GABAergic Interneurons Expressing the Transcription Factor COUP-TFII in the Adult Human Temporal Cortex

PubMed Central

Varga, Csaba; Tamas, Gabor; Barzo, Pal; Olah, Szabolcs; Somogyi, Peter

2015-01-01

Transcription factors contribute to the differentiation of cortical neurons, orchestrate specific interneuronal circuits, and define synaptic relationships. We have investigated neurons expressing chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), which plays a role in the migration of GABAergic neurons. Whole-cell, patch-clamp recording in vitro combined with colocalization of molecular cell markers in the adult cortex differentiates distinct interneurons. The majority of strongly COUP-TFII-expressing neurons were in layers I–III. Most calretinin (CR) and/or cholecystokinin- (CCK) and/or reelin-positive interneurons were also COUP-TFII-positive. CR-, CCK-, or reelin-positive neurons formed 80%, 20%, or 17% of COUP-TFII-positive interneurons, respectively. About half of COUP-TFII-/CCK-positive interneurons were CR-positive, a quarter of them reelin-positive, but none expressed both. Interneurons positive for COUP-TFII fired irregular, accommodating and adapting trains of action potentials (APs) and innervated mostly small dendritic shafts and rarely spines or somata. Paired recording showed that a calretinin-/COUP-TFII-positive interneuron elicited inhibitory postsynaptic potentials (IPSPs) in a reciprocally connected pyramidal cell. Calbindin, somatostatin, or parvalbumin-immunoreactive interneurons and most pyramidal cells express no immunohistochemically detectable COUP-TFII. In layers V and VI, some pyramidal cells expressed a low level of COUP-TFII in the nucleus. In conclusion, COUP-TFII is expressed in a diverse subset of GABAergic interneurons predominantly innervating small dendritic shafts originating from both interneurons and pyramidal cells. PMID:25787832

An evaluation of the conductivity profile in the somatosensory barrel cortex of Wistar rats.

PubMed

Goto, Takakuni; Hatanaka, Rieko; Ogawa, Takeshi; Sumiyoshi, Akira; Riera, Jorge; Kawashima, Ryuta

2010-12-01

Microelectrode arrays used to record local field potentials from the brain are being built with increasingly more spatial resolution, ranging from the initially developed laminar arrays to those with planar and three-dimensional (3D) formats. In parallel with such development in recording techniques, current source density (CSD) analyses have recently been expanded up to the continuous-3D form. Unfortunately, the effect of the conductivity profile on the CSD analysis performed with contemporary microelectrode arrays has not yet been evaluated and most of the studies assumed it was homogeneous and isotropic. In this study, we measured the conductivity profile in the somatosensory barrel cortex of Wistar rats. To that end, we combined multisite electrophysiological data recorded with a homemade assembly of silicon-based probes and a nonlinear least-squares algorithm that implicitly assumed that the cerebral cortex of rodents could be locally approximated as a layered anisotropic spherical volume conductor. The eccentricity of the six cortical layers in the somatosensory barrel cortex was evaluated from postmortem histological images. We provided evidence for the local spherical character of the entire barrels field, with concentric cortical layers. We found significant laminar dependencies in the conductivity values with radial/tangential anisotropies. These results were in agreement with the layer-dependent orientations of myelinated axons, but hardly related to densities of cells. Finally, we demonstrated through simulations that ignoring the real conductivity profile in the somatosensory barrel cortex of rats caused considerable errors in the CSD reconstruction, with pronounced effects on the continuous-3D form and charge-unbalanced CSD. We concluded that the conductivity profile must be included in future developments of CSD analysis, especially for rodents.

The Cytoarchitecture of the Inferior Colliculus Revisited

PubMed Central

Loftus, William C.; Malmierca, Manuel S.; Bishop, Deborah C.; Oliver, Douglas L.

2008-01-01

The inferior colliculus (IC) is the major component of the auditory midbrain and contains three major subdivisions: a central nucleus, a dorsal cortex, and a lateral cortex (LC). Discrepancies in the nomenclature and parcellation of the LC in the rat and cat seem to imply different, species-specific functions for this region. To establish a comparable parcellation of the LC for both rat and cat, we investigated the histochemistry and inputs of the LC. In both species, the deep lateral cortex is marked by a transition between the NADPH-d rich superficial cortex and a cytochrome oxidase rich central nucleus. In both species, focal injections of anterograde tracers in the cochlear nucleus at sites of known best frequency produced bands of labeled inputs in two different subdivisions of the IC. A medial band of axons terminated in the central nucleus, while shorter bands were located laterally and oriented nearly perpendicularly to the medial bands. In the rat, these lateral bands were located in the third, deepest layer of the lateral (external) cortex. In the cat, the bands were located in a region that was previously ascribed to the central nucleus, but now considered to belong to the third, deepest layer of the LC, the ventrolateral nucleus. In both species, the LC inputs had a tonotopic organization. In view of this parallel organization, we propose a common parcellation of the IC for rat and cat with a new nomenclature. The deep layer of the LC, previously referred to as layer 3 in the rat, is designated as the ‘ventrolateral nucleus’ of the LC, making it clear that this region is thought to be homologous with the ventrolateral nucleus in the cat. The similar organization of the LC implies that this subdivision of the IC has similar functions in cats and rats. PMID:18313229

Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex

PubMed Central

Naumann, Robert K.; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L.

2016-01-01

ABSTRACT To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin‐positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin‐negative and calbindin‐positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin‐positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin‐positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10‐fold over a 20,000‐fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. J. Comp. Neurol. 524:783–806, 2016. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26223342

Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex.

PubMed

Naumann, Robert K; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L; Brecht, Michael

2016-03-01

To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin-positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin-negative and calbindin-positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin-positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin-positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10-fold over a 20,000-fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

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.

Structured networks support sparse traveling waves in rodent somatosensory cortex.

PubMed

Moldakarimov, Samat; Bazhenov, Maxim; Feldman, Daniel E; Sejnowski, Terrence J

2018-05-15

Neurons responding to different whiskers are spatially intermixed in the superficial layer 2/3 (L2/3) of the rodent barrel cortex, where a single whisker deflection activates a sparse, distributed neuronal population that spans multiple cortical columns. How the superficial layer of the rodent barrel cortex is organized to support such distributed sensory representations is not clear. In a computer model, we tested the hypothesis that sensory representations in L2/3 of the rodent barrel cortex are formed by activity propagation horizontally within L2/3 from a site of initial activation. The model explained the observed properties of L2/3 neurons, including the low average response probability in the majority of responding L2/3 neurons, and the existence of a small subset of reliably responding L2/3 neurons. Sparsely propagating traveling waves similar to those observed in L2/3 of the rodent barrel cortex occurred in the model only when a subnetwork of strongly connected neurons was immersed in a much larger network of weakly connected neurons.

The Generation of Superficial Cortical Layers Is Regulated by Levels of the Transcription Factor Pax6

PubMed Central

Manuel, Martine; Price, David J.

2011-01-01

The ventricular zone (VZ) of the embryonic dorsal telencephalon is a major site for generating cortical projection neurons. The transcription factor Pax6 is highly expressed in apical progenitors (APs) residing in the VZ from the earliest stages of corticogenesis. Previous studies mainly focused on Pax6−/− mice have implicated Pax6 in regulating cortical progenitor proliferation, neurogenesis, and formation of superficial cortical layers. We analyzed the developing cortex of PAX77 transgenic mice that overexpress Pax6 in its normal domains of expression. We show that Pax6 overexpression increases cell cycle length of APs and drives the system toward neurogenesis. These effects are specific to late stages of corticogenesis, when superficial layer neurons are normally generated, in cortical regions that express Pax6 at the highest levels. The number of superficial layer neurons is reduced in postnatal PAX77 mice, whereas radial migration and lamina specification of cortical neurons are not affected by Pax6 overexpression. Conditional deletion of Pax6 in cortical progenitors at midstages of corticogenesis, by using a tamoxifen-inducible Emx1-CreER line, affected both numbers and specification of late-born neurons in superficial layers of the mutant cortex. Our analyses suggest that correct levels of Pax6 are essential for normal production of superficial layers of the cortex. PMID:20413449

Layer 5 Pyramidal Neurons' Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

PubMed Central

Urrego, Diana; Troncoso, Julieta; Múnera, Alejandro

2015-01-01

This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans. PMID:26064916

A periodic network of neurochemical modules in the inferior colliculus.

PubMed

Chernock, Michelle L; Larue, David T; Winer, Jeffery A

2004-02-01

A new organization has been found in shell nuclei of rat inferior colliculus. Chemically specific modules with a periodic distribution fill about half of layer 2 of external cortex and dorsal cortex. Modules contain clusters of small glutamic acid decarboxylase-positive neurons and large boutons at higher density than in other inferior colliculus subdivisions. The modules are also present in tissue stained for parvalbumin, cytochrome oxidase, nicotinamide adenine dinucleotide phosphate-diaphorase, and acetylcholinesterase. Six to seven bilaterally symmetrical modules extend from the caudal extremity of the external cortex of the inferior colliculus to its rostral pole. Modules are from approximately 800 to 2200 microm long and have areas between 5000 and 40,000 microm2. Modules alternate with immunonegative regions. Similar modules are found in inbred and outbred strains of rat, and in both males and females. They are absent in mouse, squirrel, cat, bat, macaque monkey, and barn owl. Modules are immunonegative for glycine, calbindin, serotonin, and choline acetyltransferase. The auditory cortex and ipsi- and contralateral inferior colliculi project to the external cortex. Somatic sensory influences from the dorsal column nuclei and spinal trigeminal nucleus are the primary ascending sensory input to the external cortex; ascending auditory input to layer 2 is sparse. If the immunopositive modular neurons receive this input, the external cortex could participate in spatial orientation and somatic motor control through its intrinsic and extrinsic projections.

Distinct GABAergic targets of feedforward and feedback connections between lower and higher areas of rat visual cortex.

PubMed

Gonchar, Yuri; Burkhalter, Andreas

2003-11-26

Processing of visual information is performed in different cortical areas that are interconnected by feedforward (FF) and feedback (FB) pathways. Although FF and FB inputs are excitatory, their influences on pyramidal neurons also depend on the outputs of GABAergic neurons, which receive FF and FB inputs. Rat visual cortex contains at least three different families of GABAergic neurons that express parvalbumin (PV), calretinin (CR), and somatostatin (SOM) (Gonchar and Burkhalter, 1997). To examine whether pathway-specific inhibition (Shao and Burkhalter, 1996) is attributable to distinct connections with GABAergic neurons, we traced FF and FB inputs to PV, CR, and SOM neurons in layers 1-2/3 of area 17 and the secondary lateromedial area in rat visual cortex. We found that in layer 2/3 maximally 2% of FF and FB inputs go to CR and SOM neurons. This contrasts with 12-13% of FF and FB inputs onto layer 2/3 PV neurons. Unlike inputs to layer 2/3, connections to layer 1, which contains CR but lacks SOM and PV somata, are pathway-specific: 21% of FB inputs go to CR neurons, whereas FF inputs to layer 1 and its CR neurons are absent. These findings suggest that FF and FB influences on layer 2/3 pyramidal neurons mainly involve disynaptic connections via PV neurons that control the spike outputs to axons and proximal dendrites. Unlike FF input, FB input in addition makes a disynaptic link via CR neurons, which may influence the excitability of distal pyramidal cell dendrites in layer 1.

Fast voltage-sensitive dye imaging of excitatory and inhibitory synaptic transmission in the rat granular retrosplenial cortex.

PubMed

Nixima, Ken'ichi; Okanoya, Kazuo; Ichinohe, Noritaka; Kurotani, Tohru

2017-09-01

Rodent granular retrosplenial cortex (GRS) has dense connections between the anterior thalamic nuclei (ATN) and hippocampal formation. GRS superficial pyramidal neurons exhibit distinctive late spiking (LS) firing property and form patchy clusters with prominent apical dendritic bundles. The aim of this study was to investigate spatiotemporal dynamics of signal transduction in the GRS induced by ATN afferent stimulation by using fast voltage-sensitive dye imaging in rat brain slices. In coronal slices, layer 1a stimulation, which presumably activated thalamic fibers, evoked propagation of excitatory synaptic signals from layers 2-4 to layers 5-6 in a direction perpendicular to the layer axis, followed by transverse signal propagation within each layer. In the presence of ionotropic glutamate receptor antagonists, inhibitory responses were observed in superficial layers, induced by direct activation of inhibitory interneurons in layer 1. In horizontal slices, excitatory signals in deep layers propagated transversely mainly from posterior to anterior via superficial layers. Cortical inhibitory responses upon layer 1a stimulation in horizontal slices were weaker than those in the coronal slices. Observed differences between coronal and horizontal planes suggest anisotropy of the intracortical circuitry. In conclusion, ATN inputs are processed differently in coronal and horizontal planes of the GRS and then conveyed to other cortical areas. In both planes, GRS superficial layers play an important role in signal propagation, which suggests that superficial neuronal cascade is crucial in the integration of multiple information sources. NEW & NOTEWORTHY Superficial neurons in the rat granular retrosplenial cortex (GRS) show distinctive late-spiking (LS) firing property. However, little is known about spatiotemporal dynamics of signal transduction in the GRS. We demonstrated LS neuron network relaying thalamic inputs to deep layers and anisotropic distribution of inhibition between coronal and horizontal planes. Since deep layers of the GRS receive inputs from the subiculum, GRS circuits may work as an integrator of multiple sources such as sensory and memory information. Copyright © 2017 the American Physiological Society.

[Morphological and laminar distribution of cholecystokinin-immunoreactive neurons in cortex of human inferior parietal lobe and their clinical significance].

PubMed

Puskas, Laslo; Draganić-Gajić, Saveta; Malobabić, Slobodan; Puskas, Nela; Krivokuća, Dragan; Stanković, Gordana

2008-01-01

Cholecystocinine is a neuropeptide whose function in the cortex has not yet been clarified, although its relation with some psychic disorders has been noticed. Previous studies have not provided detailed data about types, or arrangement of neurons that contain those neuropeptide in the cortex of human inferior parietal lobe. The aim of this study was to examine precisely the morphology and typography of neurons containing cholecytocinine in the human cortex of inferior parietal lobule. There were five human brains on which we did the immunocystochemical research of the shape and laminar distribution of cholecystocinine immunoreactive neurons on serial sections of supramarginal gyrus and angular gyrus. The morphological analysis of cholecystocinine-immunoreactive neurons was done on frozen sections using avidin-biotin technique, by antibody to cholecystocinine diluted in the proportion 1:6000 using diamine-benzedine. Cholecystocinine immunoreactive neurons were found in the first three layers of the cortex of inferior parietal lobule, and their densest concentration was in the 2nd and 3rd layer. The following types of neurons were found: bipolar neurons, then its fusiform subtype, Cajal-Retzius neurons (in the 1st layer), reverse pyramidal (triangular) and unipolar neurons. The diameters of some types of neurons were from 15 to 35 microm, and the diameters of dendritic arborization were from 85-207 microm. A special emphasis is put on the finding of Cajal-Retzius neurons that are immunoreactive to cholecystocinine, which demands further research. Bearing in mind numerous clinical studies pointing out the role of cholecystokinine in the pathogenesis of schizophrenia, the presence of a great number of cholecystokinine immunoreactive neurons in the cortex of inferior parietal lobule suggests their role in the pathogenesis of schizophrenia.

Investigation of Implantable Multi-Channel Electrode Array in Rat Cerebral Cortex Used for Recording

NASA Astrophysics Data System (ADS)

Taniguchi, Noriyuki; Fukayama, Osamu; Suzuki, Takafumi; Mabuchi, Kunihiko

There have recently been many studies concerning the control of robot movements using neural signals recorded from the brain (usually called the Brain-Machine interface (BMI)). We fabricated implantable multi-electrode arrays to obtain neural signals from the rat cerebral cortex. As any multi-electrode array should have electrode alignment that minimizes invasion, it is necessary to customize the recording site. We designed three types of 22-channel multi-electrode arrays, i.e., 1) wide, 2) three-layered, and 3) separate. The first extensively covers the cerebral cortex. The second has a length of 2 mm, which can cover the area of the primary motor cortex. The third array has a separate structure, which corresponds to the position of the forelimb and hindlimb areas of the primary motor cortex. These arrays were implanted into the cerebral cortex of a rat. We estimated the walking speed from neural signals using our fabricated three-layered array to investigate its feasibility for BMI research. The neural signal of the rat and its walking speed were simultaneously recorded. The results revealed that evaluation using either the anterior electrode group or posterior group provided accurate estimates. However, two electrode groups around the center yielded poor estimates although it was possible to record neural signals.

Cortex content of asporogenous mutants of Bacillus subtilis.

PubMed Central

Imae, Y; Strominger, J L

1976-01-01

A method for the measurement of muramic lactam, which is specifically located in the cortical peptidoglycan of bacterial spores, was developed as a quantitative assay method for spore cortex content. During sporulation of Bacillus subtilis 168, muramic lactam (i.e., spore cortex) began to appear at state IV of sporulation and continued to increase over most of the late stages of sporulation. Spore cortex contents of various spo mutants of B. subitils were surveyed. Cortex was not detected in mutants in which sporulation was blocked earlier than stage II sporulation. Spores of spo IV mutant had about 40% of the cortex content of the wild-type spores. One spo III mutant had a low amount of cortex, but four others had none. PMID:1262319

Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas

PubMed Central

Sellers, Kristin K.; Bennett, Davis V.; Hutt, Axel; Williams, James H.

2015-01-01

During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers. PMID:25833839

Pyramid image codes

NASA Technical Reports Server (NTRS)

Watson, Andrew B.

1990-01-01

All vision systems, both human and machine, transform the spatial image into a coded representation. Particular codes may be optimized for efficiency or to extract useful image features. Researchers explored image codes based on primary visual cortex in man and other primates. Understanding these codes will advance the art in image coding, autonomous vision, and computational human factors. In cortex, imagery is coded by features that vary in size, orientation, and position. Researchers have devised a mathematical model of this transformation, called the Hexagonal oriented Orthogonal quadrature Pyramid (HOP). In a pyramid code, features are segregated by size into layers, with fewer features in the layers devoted to large features. Pyramid schemes provide scale invariance, and are useful for coarse-to-fine searching and for progressive transmission of images. The HOP Pyramid is novel in three respects: (1) it uses a hexagonal pixel lattice, (2) it uses oriented features, and (3) it accurately models most of the prominent aspects of primary visual cortex. The transform uses seven basic features (kernels), which may be regarded as three oriented edges, three oriented bars, and one non-oriented blob. Application of these kernels to non-overlapping seven-pixel neighborhoods yields six oriented, high-pass pyramid layers, and one low-pass (blob) layer.

Nicotinic α5 Subunits Drive Developmental Changes in the Activation and Morphology of Prefrontal Cortex Layer VI Neurons

PubMed Central

Bailey, Craig D.C.; Alves, Nyresa C.; Nashmi, Raad; De Biasi, Mariella; Lambe, Evelyn K.

2013-01-01

Background Nicotinic signaling in prefrontal layer VI pyramidal neurons is important to the function of mature attention systems. The normal incorporation of α5 subunits into α4β2* nicotinic acetylcholine receptors augments nicotinic signaling in these neurons and is required for normal attention performance in adult mice. However, the role of α5 subunits in the development of the prefrontal cortex is not known. Methods We sought to answer this question by examining nicotinic currents and neuronal morphology in layer VI neurons of medial prefrontal cortex of wild-type and α5 subunit knockout (α5−/−) mice during postnatal development and in adulthood. Results In wild-type but not in α5−/− mice, there is a developmental peak in nicotinic acetylcholine currents in the third postnatal week. At this juvenile time period, the majority of neurons in all mice have long apical dendrites extending into cortical layer I. Yet, by early adulthood, wild-type but not α5−/− mice show a pronounced shift toward shorter apical dendrites. This cellular difference occurs in the absence of genotype differences in overall cortical morphology. Conclusions Normal developmental changes in nicotinic signaling and dendritic morphology in prefrontal cortex depend on α5-comprising nicotinic acetylcholine receptors. It appears that these receptors mediate a specific developmental retraction of apical dendrites in layer VI neurons. This finding provides novel insight into the cellular mechanisms underlying the known attention deficits in α5−/− mice and potentially also into the pathophysiology of developmental neuropsychiatric disorders such as attention-deficit disorder and autism. PMID:22030359

Enhanced HMAX model with feedforward feature learning for multiclass categorization.

PubMed

Li, Yinlin; Wu, Wei; Zhang, Bo; Li, Fengfu

2015-01-01

In recent years, the interdisciplinary research between neuroscience and computer vision has promoted the development in both fields. Many biologically inspired visual models are proposed, and among them, the Hierarchical Max-pooling model (HMAX) is a feedforward model mimicking the structures and functions of V1 to posterior inferotemporal (PIT) layer of the primate visual cortex, which could generate a series of position- and scale- invariant features. However, it could be improved with attention modulation and memory processing, which are two important properties of the primate visual cortex. Thus, in this paper, based on recent biological research on the primate visual cortex, we still mimic the first 100-150 ms of visual cognition to enhance the HMAX model, which mainly focuses on the unsupervised feedforward feature learning process. The main modifications are as follows: (1) To mimic the attention modulation mechanism of V1 layer, a bottom-up saliency map is computed in the S1 layer of the HMAX model, which can support the initial feature extraction for memory processing; (2) To mimic the learning, clustering and short-term memory to long-term memory conversion abilities of V2 and IT, an unsupervised iterative clustering method is used to learn clusters with multiscale middle level patches, which are taken as long-term memory; (3) Inspired by the multiple feature encoding mode of the primate visual cortex, information including color, orientation, and spatial position are encoded in different layers of the HMAX model progressively. By adding a softmax layer at the top of the model, multiclass categorization experiments can be conducted, and the results on Caltech101 show that the enhanced model with a smaller memory size exhibits higher accuracy than the original HMAX model, and could also achieve better accuracy than other unsupervised feature learning methods in multiclass categorization task.

Callosal responses in a retrosplenial column.

PubMed

Sempere-Ferràndez, Alejandro; Andrés-Bayón, Belén; Geijo-Barrientos, Emilio

2018-04-01

The axons forming the corpus callosum sustain the interhemispheric communication across homotopic cortical areas. We have studied how neurons throughout the columnar extension of the retrosplenial cortex integrate the contralateral input from callosal projecting neurons in cortical slices. Our results show that pyramidal neurons in layers 2/3 and the large, thick-tufted pyramidal neurons in layer 5B showed larger excitatory callosal responses than layer 5A and layer 5B thin-tufted pyramidal neurons, while layer 6 remained silent to this input. Feed-forward inhibitory currents generated by fast spiking, parvalbumin expressing  interneurons recruited by callosal axons mimicked the response size distribution of excitatory responses across pyramidal subtypes, being larger in those of superficial layers and in the layer 5B thick-tufted pyramidal cells. Overall, the combination of the excitatory and inhibitory currents evoked by callosal input had a strong and opposed effect in different layers of the cortex; while layer 2/3 pyramidal neurons were powerfully inhibited, the thick-tufted but not thin-tufted pyramidal neurons in layer 5 were strongly recruited. We believe that these results will help to understand the functional role of callosal connections in physiology and disease.

Cholinergic Neuromodulation Controls Directed Temporal Communication in Neocortex in Vitro

PubMed Central

Roopun, Anita K.; LeBeau, Fiona E.N.; Rammell, James; Cunningham, Mark O.; Traub, Roger D.; Whittington, Miles A.

2010-01-01

Acetylcholine is the primary neuromodulator involved in cortical arousal in mammals. Cholinergic modulation is involved in conscious awareness, memory formation and attention – processes that involve intercommunication between different cortical regions. Such communication is achieved in part through temporal structuring of neuronal activity by population rhythms, particularly in the beta and gamma frequency ranges (12–80 Hz). Here we demonstrate, using in vitro and in silico models, that spectrally identical patterns of beta2 and gamma rhythms are generated in primary sensory areas and polymodal association areas by fundamentally different local circuit mechanisms: Glutamatergic excitation induced beta2 frequency population rhythms only in layer 5 association cortex whereas cholinergic neuromodulation induced this rhythm only in layer 5 primary sensory cortex. This region-specific sensitivity of local circuits to cholinergic modulation allowed for control of the extent of cortical temporal interactions. Furthermore, the contrasting mechanisms underlying these beta2 rhythms produced a high degree of directionality, favouring an influence of association cortex over primary auditory cortex. PMID:20407636

[An autopsied case of senile onset frontotemporal lobar degeneration].

PubMed

Iwasaki, Yasushi; Mori, Keiko; Ito, Masumi; Deguchi, Akira; Yoshida, Mari

2011-06-01

A Japanese male with no family history of neurological disease or dementia showed behavioral abnormalities including egocentric and antisocial behavior at the age of 80. Over the next few years, other psychiatric symptoms such as allotriophagy and stereotypical behavior were also observed and his abnormal behavior became a social problem. Neurological examination revealed no apparent motor abnormalities, pyramidal and extrapyramidal signs, or ataxia. Aphasia, including semantic dementia was not apparent. The severity of memory disturbance was relatively milder than his psychiatric symptoms. Daily living activities and conversational ability were relatively maintained until shortly before his death at the age of 86. The clinical diagnosis was Alzheimer disease. Autopsy revealed that the brain weighed 950 g; frontotemporal atrophy with lateral ventricular dilatation was apparent. Neuron loss, gliosis, and tissue rarefaction were recognized in the frontotemporal cortex, subiculum, transentorhinal cortex, amygdala, and insular cortex and were particularly noticeable in the superficial layer of the cortex. Many ubiquitin-positive/TDP-43 positive but tau-negative dystrophic neurites with a few neuronal cytoplasmic inclusions were widely observed. Neuronal cytoplasmic inclusions were also observed in the dentate gyrus of the hippocampus. Although the spinal cord was not investigated, there was no apparent involvement of the motor neuron system. Small numbers of neurofibrillary tangles and senile plaques were observed, corresponding to Braak stage II and CERAD stage B, respectively. Argyrophilic grains, Lewy bodies and Pick bodies were not observed. The patient was pathologically diagnosed with frontotemporal lobar degeneration with ubiquitin-positive/TDP-43-positive inclusions (FTLD-TDP) and without motor neuron disease. No mutation was found in the TDP-43 gene. We considered the psychiatric symptoms and head CT findings of the present patient to be important observations for helping to discriminate between Alzheimer disease or other neurodegenerative diseases with dementia, and FTLD-TDP.

Transcriptional Dysregulation of γ-Aminobutyric Acid Transporter in Parvalbumin-Containing Inhibitory Neurons in the Prefrontal Cortex in Schizophrenia

PubMed Central

Bitanihirwe, Byron K. Y.; Woo, Tsung-Ung W.

2015-01-01

Parvalbumin (PV)-containing neurons are functionally compromised in schizophrenia. Using double in situ hybridization in postmortem human prefrontal cortex, we found that the messenger RNA (mRNA) for the γ-aminobutyric acid transporter GAT-1 was undetectable in 22-41% of PV neurons in layers 3-4 in schizophrenia. In the remaining PV neurons with detectable GAT-1 mRNA, transcript expression was decreased by 26% in layer 3. Hence, the dysfunction of PV neurons involves the molecular dysregulation of presynaptic GABA reuptake. PMID:25312391

Neural discriminability in rat lateral extrastriate cortex and deep but not superficial primary visual cortex correlates with shape discriminability.

PubMed

Vermaercke, Ben; Van den Bergh, Gert; Gerich, Florian; Op de Beeck, Hans

2015-01-01

Recent studies have revealed a surprising degree of functional specialization in rodent visual cortex. It is unknown to what degree this functional organization is related to the well-known hierarchical organization of the visual system in primates. We designed a study in rats that targets one of the hallmarks of the hierarchical object vision pathway in primates: selectivity for behaviorally relevant dimensions. We compared behavioral performance in a visual water maze with neural discriminability in five visual cortical areas. We tested behavioral discrimination in two independent batches of six rats using six pairs of shapes used previously to probe shape selectivity in monkey cortex (Lehky and Sereno, 2007). The relative difficulty (error rate) of shape pairs was strongly correlated between the two batches, indicating that some shape pairs were more difficult to discriminate than others. Then, we recorded in naive rats from five visual areas from primary visual cortex (V1) over areas LM, LI, LL, up to lateral occipito-temporal cortex (TO). Shape selectivity in the upper layers of V1, where the information enters cortex, correlated mostly with physical stimulus dissimilarity and not with behavioral performance. In contrast, neural discriminability in lower layers of all areas was strongly correlated with behavioral performance. These findings, in combination with the results from Vermaercke et al. (2014b), suggest that the functional specialization in rodent lateral visual cortex reflects a processing hierarchy resulting in the emergence of complex selectivity that is related to behaviorally relevant stimulus differences.

Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala.

PubMed

Ghashghaei, H T; Hilgetag, C C; Barbas, H

2007-02-01

The prefrontal cortex and the amygdala have synergistic roles in regulating purposive behavior, effected through bidirectional pathways. Here we investigated the largely unknown extent and laminar relationship of prefrontal input-output zones linked with the amygdala using neural tracers injected in the amygdala in rhesus monkeys. Prefrontal areas varied vastly in their connections with the amygdala, with the densest connections found in posterior orbitofrontal and posterior medial cortices, and the sparsest in anterior lateral prefrontal areas, especially area 10. Prefrontal projection neurons directed to the amygdala originated in layer 5, but significant numbers were also found in layers 2 and 3 in posterior medial and orbitofrontal cortices. Amygdalar axonal terminations in prefrontal cortex were most frequently distributed in bilaminar bands in the superficial and deep layers, by columns spanning the entire cortical depth, and less frequently as small patches centered in the superficial or deep layers. Heavy terminations in layers 1-2 overlapped with calbindin-positive inhibitory neurons. A comparison of the relationship of input to output projections revealed that among the most heavily connected cortices, cingulate areas 25 and 24 issued comparatively more projections to the amygdala than they received, whereas caudal orbitofrontal areas were more receivers than senders. Further, there was a significant relationship between the proportion of 'feedforward' cortical projections from layers 2-3 to 'feedback' terminations innervating the superficial layers of prefrontal cortices. These findings indicate that the connections between prefrontal cortices and the amygdala follow similar patterns as corticocortical connections, and by analogy suggest pathways underlying the sequence of information processing for emotions.

Postnatal Changes in the Distribution of Acetylcholinesterase in Kitten Visual Cortex.

DTIC Science & Technology

1985-02-18

in cat striate cortex. However, a subpopulation of stained neurons appers in layer V by one year of age that persists into adulthood. The possible...next two months until, at three months of age, ! ’ there are no AChE-positive cells in cat striate cortex. However, a subpopulation of stained...undertake a systematic investigation of cholinergic inputs to area 17 in the cat . 4 4: • ." "k

Effects of oxotremorine on local glucose utilization in the rat cerebral cortex

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

Dam, M.; Wamsley, J.K.; Rapoport, S.I.

The (/sup 14/C)2-deoxy-D-glucose technique was used to examine the effects of central muscarinic stimulation on local cerebral glucose utilization (LCGU) in the cerebral cortex of the unanesthetized rat. Systemic administration of the muscarinic agonist oxotremorine (OXO, 0.1 to 1.0 mg/kg, i.p.) increased LCGU in the neocortex, mesocortex, and paleocortex. In the neocortex, OXO was more potent in elevating LCGU of the auditory, frontal, and sensorimotor regions compared with the visual cortex. Within these neocortical regions, OXO effects were greatest in cortical layers IV and V. OXO effects were more dramatic in the neocortex than in the meso- or paleocortex, andmore » no significant effect occurred in the perirhinal and pyriform cortices. OXO-induced LCGU increases were not influenced by methylatropine (1 mg/kg, s.c.) but were antagonized completely by scopolamine (2.5 mg/kg, i.p.). Scopolamine reduced LCGU in layer IV of the auditory cortex and in the retrosplenial cortex. The distribution and magnitude of the cortical LCGU response to OXO apparently were related to the distributions of cholinergic neurochemical markers, especially high affinity muscarinic binding sites.« less

Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways

NASA Technical Reports Server (NTRS)

Hof, P. R.; Ungerleider, L. G.; Webster, M. J.; Gattass, R.; Adams, M. M.; Sailstad, C. A.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1996-01-01

Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57-100%), than to area V4 (25-36%). In contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70-80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and VI in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II-III and V-VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of corticocortically projecting neurons with distinct regional and laminar distribution in the monkey visual system. It is possible that the preferential distribution of neurofilament protein within feedforward connections to area MT and all feedback projections is related to other distinctive properties of these corticocortical projection neurons.

Ocular dominance in layer IV of the cat's visual cortex and the effects of monocular deprivation.

PubMed Central

Shatz, C J; Stryker, M P

1978-01-01

1. The relation between the physiological pattern of ocular dominance and the anatomical distribution of geniculocortical afferents serving each eye was studied in layer IV of the primary visual cortex of normal and monocularly deprived cats. 2. One eye was injected with radioactive label. After allowing sufficient time for transeuronal transport, micro-electrode recordings were made, and the geniculocoritcal afferents serving the injected eye were located autoradiographically. 3. In layer IV of normal cats, cell were clustered according to eye preference, and fewer cells were binocularly driven than in other layers. Points of transition between groups of cells dominated by one eye and those dominated by the other were marked with electrolytic lesions. A good correspondence was found between the location of cells dominated by the injected eye and the patches of radioactively labelled geniculocortical afferents. 4. Following prolonged early monocular deprivation, the patches of geniculocortical afferents in layer IV serving the deprived eye were smaller, and those serving the non-deprived eye larger, than normal. Again there was a coincidence between the patches of radioactively labelled afferents and the location of cells dominated by the injected eye. 5. The deprived eye was found to dominate a substantial fraction (22%) of cortical cells in the fourth layer. In other cortical layers, only 7% of the cells were dominated by the deprived eye. 6. These findings suggest that the thalamocortical projection is physically rearranged as a consequence of monocular deprivation, as has been demonstrated for layer IVc of the monkey's visual cortex (Hubel, Wiesel & Le Vay, 1977). Images Plate 1 Plate 2 Plate 3 Plate 4 Plate 5 Plate 6 PMID:702379

Induction of superficial cortical layer neurons from mouse embryonic stem cells by valproic acid.

PubMed

Juliandi, Berry; Abematsu, Masahiko; Sanosaka, Tsukasa; Tsujimura, Keita; Smith, Austin; Nakashima, Kinichi

2012-01-01

Within the developing mammalian cortex, neural progenitors first generate deep-layer neurons and subsequently more superficial-layer neurons, in an inside-out manner. It has been reported recently that mouse embryonic stem cells (mESCs) can, to some extent, recapitulate cortical development in vitro, with the sequential appearance of neurogenesis markers resembling that in the developing cortex. However, mESCs can only recapitulate early corticogenesis; superficial-layer neurons, which are normally produced in later developmental periods in vivo, are under-represented. This failure of mESCs to reproduce later corticogenesis in vitro implies the existence of crucial factor(s) that are absent or uninduced in existing culture systems. Here we show that mESCs can give rise to superficial-layer neurons efficiently when treated with valproic acid (VPA), a histone deacetylase inhibitor. VPA treatment increased the production of Cux1-positive superficial-layer neurons, and decreased that of Ctip2-positive deep-layer neurons. These results shed new light on the mechanisms of later corticogenesis. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Parvalbumin interneuron mediated feedforward inhibition controls signal output in the deep layers of the perirhinal‐entorhinal cortex

PubMed Central

Willems, Janske G. P.; Wadman, Wytse J.

2018-01-01

Abstract The perirhinal (PER) and lateral entorhinal (LEC) cortex form an anatomical link between the neocortex and the hippocampus. However, neocortical activity is transmitted through the PER and LEC to the hippocampus with a low probability, suggesting the involvement of the inhibitory network. This study explored the role of interneuron mediated inhibition, activated by electrical stimulation in the agranular insular cortex (AiP), in the deep layers of the PER and LEC. Activated synaptic input by AiP stimulation rarely evoked action potentials in the PER‐LEC deep layer excitatory principal neurons, most probably because the evoked synaptic response consisted of a small excitatory and large inhibitory conductance. Furthermore, parvalbumin positive (PV) interneurons—a subset of interneurons projecting onto the axo‐somatic region of principal neurons—received synaptic input earlier than principal neurons, suggesting recruitment of feedforward inhibition. This synaptic input in PV interneurons evoked varying trains of action potentials, explaining the fast rising, long lasting synaptic inhibition received by deep layer principal neurons. Altogether, the excitatory input from the AiP onto deep layer principal neurons is overruled by strong feedforward inhibition. PV interneurons, with their fast, extensive stimulus‐evoked firing, are able to deliver this fast evoked inhibition in principal neurons. This indicates an essential role for PV interneurons in the gating mechanism of the PER‐LEC network. PMID:29341361

Systematic, cross-cortex variation in neuron numbers in rodents and primates.

PubMed

Charvet, Christine J; Cahalane, Diarmuid J; Finlay, Barbara L

2015-01-01

Uniformity, local variability, and systematic variation in neuron numbers per unit of cortical surface area across species and cortical areas have been claimed to characterize the isocortex. Resolving these claims has been difficult, because species, techniques, and cortical areas vary across studies. We present a stereological assessment of neuron numbers in layers II-IV and V-VI per unit of cortical surface area across the isocortex in rodents (hamster, Mesocricetus auratus; agouti, Dasyprocta azarae; paca, Cuniculus paca) and primates (owl monkey, Aotus trivigratus; tamarin, Saguinus midas; capuchin, Cebus apella); these chosen to vary systematically in cortical size. The contributions of species, cortical areas, and techniques (stereology, "isotropic fractionator") to neuron estimates were assessed. Neurons per unit of cortical surface area increase across the rostro-caudal (RC) axis in primates (varying by a factor of 1.64-2.13 across the rostral and caudal poles) but less in rodents (varying by a factor of 1.15-1.54). Layer II-IV neurons account for most of this variation. When integrated into the context of species variation, and this RC gradient in neuron numbers, conflicts between studies can be accounted for. The RC variation in isocortical neurons in adulthood mirrors the gradients in neurogenesis duration in development. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Excitatory and inhibitory synaptic connectivity to layer V fast-spiking interneurons in the freeze lesion model of cortical microgyria

PubMed Central

Jin, Xiaoming; Jiang, Kewen

2014-01-01

A variety of major developmental cortical malformations are closely associated with clinically intractable epilepsy. Pathophysiological aspects of one such disorder, human polymicrogyria, can be modeled by making neocortical freeze lesions (FL) in neonatal rodents, resulting in the formation of microgyri. Previous studies showed enhanced excitatory and inhibitory synaptic transmission and connectivity in cortical layer V pyramidal neurons in the paramicrogyral cortex. In young adult transgenic mice that express green fluorescent protein (GFP) specifically in parvalbumin positive fast-spiking (FS) interneurons, we used laser scanning photostimulation (LSPS) of caged glutamate to map excitatory and inhibitory synaptic connectivity onto FS interneurons in layer V of paramicrogyral cortex in control and FL groups. The proportion of uncaging sites from which excitatory postsynaptic currents (EPSCs) could be evoked (hotspot ratio) increased slightly but significantly in FS cells of the FL vs. control cortex, while the mean amplitude of LSPS-evoked EPSCs at hotspots did not change. In contrast, the hotspot ratio of inhibitory postsynaptic currents (IPSCs) was significantly decreased in FS neurons of the FL cortex. These alterations in synaptic inputs onto FS interneurons may result in an enhanced inhibitory output. We conclude that alterations in synaptic connectivity to cortical layer V FS interneurons do not contribute to hyperexcitability of the FL model. Instead, the enhanced inhibitory output from these neurons may partially offset an earlier demonstrated increase in synaptic excitation of pyramidal cells and thereby maintain a relative balance between excitation and inhibition in the affected cortical circuitry. PMID:24990567

Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type

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

Chalmers, D.T.; Dewar, D.; Graham, D.I.

1990-02-01

Involvement of cortical glutamatergic mechanisms in senile dementia of the Alzheimer type (SDAT) has been investigated with quantitative ligand-binding autoradiography. The distribution and density of Na(+)-dependent glutamate uptake sites and glutamate receptor subtypes--kainate, quisqualate, and N-methyl-D-aspartate--were measured in adjacent sections of frontal cortex obtained postmortem from six patients with SDAT and six age-matched controls. The number of senile plaques was determined in the same brain region. Binding of D-(3H)aspartate to Na(+)-dependent uptake sites was reduced by approximately 40% throughout SDAT frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. (3H)Kainate receptor binding was significantly increased bymore » approximately 70% in deep layers of SDAT frontal cortex compared with controls, whereas this binding was unaltered in superficial laminae. There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers. Quisqualate receptors, as assessed by 2-amino-3-hydroxy-5-(3H)methylisoxazole-4-propionic acid binding, were unaltered in SDAT frontal cortex compared with controls. There was a small reduction (25%) in N-methyl-D-aspartate-sensitive (3H)glutamate binding only in superficial cortical layers of SDAT brains relative to control subjects. (3H)Glutamate binding in SDAT subjects was unrelated to senile plaque number in superficial cortical layers (r = 0.104). These results indicate that in the presence of cortical glutamatergic terminal loss in SDAT plastic alterations occur in some glutamate receptor subtypes but not in others.« less

Effect of the environment on the dendritic morphology of the rat auditory cortex

PubMed Central

Bose, Mitali; Muñoz-Llancao, Pablo; Roychowdhury, Swagata; Nichols, Justin A.; Jakkamsetti, Vikram; Porter, Benjamin; Byrapureddy, Rajasekhar; Salgado, Humberto; Kilgard, Michael P.; Aboitiz, Francisco; Dagnino-Subiabre, Alexies; Atzori, Marco

2010-01-01

The present study aimed to identify morphological correlates of environment-induced changes at excitatory synapses of the primary auditory cortex (A1). We used the Golgi-Cox stain technique to compare pyramidal cells dendritic properties of Sprague-Dawley rats exposed to different environmental manipulations. Sholl analysis, dendritic length measures, and spine density counts were used to monitor the effects of sensory deafness and an auditory version of environmental enrichment (EE). We found that deafness decreased apical dendritic length leaving basal dendritic length unchanged, whereas EE selectively increased basal dendritic length without changing apical dendritic length. On the contrary, deafness decreased while EE increased spine density in both basal and apical dendrites of A1 layer 2/3 (LII/III) neurons. To determine whether stress contributed to the observed morphological changes in A1, we studied neural morphology in a restraint-induced model that lacked behaviorally relevant acoustic cues. We found that stress selectively decreased apical dendritic length in the auditory but not in the visual primary cortex. Similar to the acoustic manipulation, stress-induced changes in dendritic length possessed a layer specific pattern displaying LII/III neurons from stressed animals with normal apical dendrites but shorter basal dendrites, while infragranular neurons (layers V and VI) displayed shorter apical dendrites but normal basal dendrites. The same treatment did not induce similar changes in the visual cortex, demonstrating that the auditory cortex is an exquisitely sensitive target of neocortical plasticity, and that prolonged exposure to different acoustic as well as emotional environmental manipulation may produce specific changes in dendritic shape and spine density. PMID:19771593

Serotype-dependent transduction efficiencies of recombinant adeno-associated viral vectors in monkey neocortex

PubMed Central

Gerits, Annelies; Vancraeyenest, Pascaline; Vreysen, Samme; Laramée, Marie-Eve; Michiels, Annelies; Gijsbers, Rik; Van den Haute, Chris; Moons, Lieve; Debyser, Zeger; Baekelandt, Veerle; Arckens, Lutgarde; Vanduffel, Wim

2015-01-01

Abstract. Viral vector-mediated expression of genes (e.g., coding for opsins and designer receptors) has grown increasingly popular. Cell-type specific expression is achieved by altering viral vector tropism through crosspackaging or by cell-specific promoters driving gene expression. Detailed information about transduction properties of most recombinant adeno-associated viral vector (rAAV) serotypes in macaque cortex is gradually becoming available. Here, we compare transduction efficiencies and expression patterns of reporter genes in two macaque neocortical areas employing different rAAV serotypes and promoters. A short version of the calmodulin-kinase-II (CaMKIIα0.4) promoter resulted in reporter gene expression in cortical neurons for all tested rAAVs, albeit with different efficiencies for spread: rAAV2/5>>rAAV2/7>rAAV2/8>rAAV2/9>>rAAV2/1 and proportion of transduced cells: rAAV2/1>rAAV2/5>rAAV2/7=rAAV2/9>rAAV2/8. In contrast to rodent studies, the cytomegalovirus (CMV) promoter appeared least efficient in macaque cortex. The human synapsin-1 promoter preceded by the CMV enhancer (enhSyn1) produced homogeneous reporter gene expression across all layers, while two variants of the CaMKIIα promoter resulted in different laminar transduction patterns and cell specificities. Finally, differences in expression patterns were observed when the same viral vector was injected in two neocortical areas. Our results corroborate previous findings that reporter-gene expression patterns and efficiency of rAAV transduction depend on serotype, promoter, cortical layer, and area. PMID:26839901

Projections from the pontine nuclei proper and reticular tegmental nucleus onto the cerebellar cortex in the cat. An autoradiographic study

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

Kawamura, K.; Hashikawa, T.

1981-09-20

After injections of 0.5 microliter of tritiated leucine and/or proline into various parts of the pontine nuclei proper or the pontine tegmental reticular nucleus (N.r.t.) of 34 cats, labeled terminals of pontocerebellar fibers were found in the cerebellar cortex. Fibers from the pontine nuclei and N.r.t. terminate as mossy fibers in the granular layer of the cerebellum, and no evidence is obtained of labeled fibers in the molecular layer. The pontocerebellar projection is, in general, bilateral with a contralateral preponderance, and a complex organization has been shown to exist in the cat. Clear evidence of divergence of this projection frommore » a small pontine area has been demonstrated. Thus, the dorsolateral nucleus has a heavy projection to lobule VII, besides modest projections to lobules VI, VIII, and IX, crus I and II, paraflocculus, and paramedian lobule. On the other hand, a particular cerebellar region receives afferent fibers from several pontine regions, confirming previous HRP studies. This is a convergent feature of the pontocerebellar projections. In addition, small adjoining areas within a pontine subdivision have different patterns of cerebellar projections, showing preferential sites of terminations. The cerebellar projection from the N.r.t. shows an essentially similar organization as the projection from the pontine nuclei proper, an apparent difference being only that the former is more extensive in the fields of termination than the latter. Some evidence for a parasagittal termination of pontocerebellar projections to the paramedian lobule has been found in this study.« less

FGF-2 induces behavioral recovery after early adolescent injury to the motor cortex of rats.

PubMed

Nemati, Farshad; Kolb, Bryan

2011-11-20

Motor cortex injuries in adulthood lead to poor performance in behavioral tasks sensitive to limb movements in the rat. We have shown previously that motor cortex injury on day 10 or day 55 allow significant spontaneous recovery but not injury in early adolescence (postnatal day 35 "P35"). Previous studies have indicated that injection of basic fibroblast growth factor (FGF-2) enhances behavioral recovery after neonatal cortical injury but such effect has not been studied following motor cortex lesions in early adolescence. The present study undertook to investigate the possibility of such behavioral recovery. Rats with unilateral motor cortex lesions were assigned to two groups in which they received FGF-2 or bovine serum albumin (BSA) and were tested in a number of behavioral tests (postural asymmetry, skilled reaching, sunflower seed manipulation, forepaw inhibition in swimming). Golgi-Cox analysis was used to examine the dendritic structure of pyramidal cells in the animals' parietal (layer III) and forelimb (layer V) area of the cortex. The results indicated that rats injected with FGF-2 (but not BSA) showed significant behavioral recovery that was associated with increased dendritic length and spine density. The present study suggests a role for FGF-2 in the recovery of function following injury during early adolescence. Copyright © 2011 Elsevier B.V. All rights reserved.

Chronic In Vivo Imaging Shows No Evidence of Dendritic Plasticity or Functional Remapping in the Contralesional Cortex after Stroke

PubMed Central

Johnston, David G.; Denizet, Marie; Mostany, Ricardo

2013-01-01

Most stroke survivors exhibit a partial recovery from their deficits. This presumably occurs because of remapping of lost capabilities to functionally related brain areas. Functional brain imaging studies suggest that remapping in the contralateral uninjured cortex might represent a transient stage of compensatory plasticity. Some postmortem studies have also shown that cortical lesions, including stroke, can trigger dendritic plasticity in the contralateral hemisphere, but the data are controversial. We used longitudinal in vivo two-photon microscopy in the contralateral homotopic cortex to record changes in dendritic spines of layer 5 pyramidal neurons in green fluorescent protein mice. We could not detect de novo growth of dendrites or changes in the density or turnover of spines for up to 4 weeks after stroke. We also used intrinsic optical signal imaging to investigate whether the forepaw (FP) sensory representation is remapped to the spared homotopic cortex after stroke. Stimulation of the contralateral FP reliably produced strong intrinsic signals in the spared hemisphere, but we could never detect a signal with ipsilateral FP stimulation after stroke. This lack of contralateral plasticity at the level of apical dendrites of layer 5 pyramidal neurons and FP sensory maps suggests that the contralesional cortex may not contribute to functional recovery after stroke and that, at least in mice, the peri-infarct cortex plays the dominant role in postischemic plasticity. PMID:22499800

Chronic in vivo imaging shows no evidence of dendritic plasticity or functional remapping in the contralesional cortex after stroke.

PubMed

Johnston, David G; Denizet, Marie; Mostany, Ricardo; Portera-Cailliau, Carlos

2013-04-01

Most stroke survivors exhibit a partial recovery from their deficits. This presumably occurs because of remapping of lost capabilities to functionally related brain areas. Functional brain imaging studies suggest that remapping in the contralateral uninjured cortex might represent a transient stage of compensatory plasticity. Some postmortem studies have also shown that cortical lesions, including stroke, can trigger dendritic plasticity in the contralateral hemisphere, but the data are controversial. We used longitudinal in vivo two-photon microscopy in the contralateral homotopic cortex to record changes in dendritic spines of layer 5 pyramidal neurons in green fluorescent protein mice. We could not detect de novo growth of dendrites or changes in the density or turnover of spines for up to 4 weeks after stroke. We also used intrinsic optical signal imaging to investigate whether the forepaw (FP) sensory representation is remapped to the spared homotopic cortex after stroke. Stimulation of the contralateral FP reliably produced strong intrinsic signals in the spared hemisphere, but we could never detect a signal with ipsilateral FP stimulation after stroke. This lack of contralateral plasticity at the level of apical dendrites of layer 5 pyramidal neurons and FP sensory maps suggests that the contralesional cortex may not contribute to functional recovery after stroke and that, at least in mice, the peri-infarct cortex plays the dominant role in postischemic plasticity.

Quantitative changes of GABA-immunoreactive cells in the hindlimb representation of the rat somatosensory cortex after 14-day hindlimb unloading by tail suspension

NASA Technical Reports Server (NTRS)

D'Amelio, F.; Fox, R. A.; Wu, L. C.; Daunton, N. G.

1996-01-01

The present study was aimed at evaluating quantitatively gamma-aminobutyric acid (GABA) immunoreactivity in the hindlimb representation of the rat somatosensory cortex after 14 days of hindlimb unloading by tail suspension. A reduction in the number of GABA-immunoreactive cells with respect to the control animals was observed in layer Va and Vb. GABA-containing terminals were also reduced in the same layers, particularly those terminals surrounding the soma and apical dendrites of pyramidal cells in layer Vb. On the basis of previous morphological and behavioral studies of the neuromuscular system of hindlimb-suspended animals, it is suggested that the unloading due to hindlimb suspension alters afferent signaling and feedback information from intramuscular receptors to the cerebral cortex due to modifications in the reflex organization of hindlimb muscle groups. We propose that the reduction in immunoreactivity of local circuit GABAergic neurons and terminals is an expression of changes in their modulatory activity to compensate for the alterations in the afferent information.

[Osseontegration of trial implants of carbon fiber reinforced plastics].

PubMed

Schreiner, U; Schwarz, M; Scheller, G; Schroeder-Boersch, H; Jani, L

2000-01-01

To what extent are carbon fibre-reinforced plastics (CFRP) suitable as an osseous integration surface for implants? CFRP test implants having a plexus-structured, rhombus-structured, and plexus-structured, hydroxyapatite surface were implanted in the femura of mini-plgs. Exposure time lasted 12 weeks. The implants were subjected to a macroradiological, a histological-histomorphometrical, and a fluorescence-microscopical evaluation. One half of the uncoated, plexus-structured implants were not osteointegrated, the other half displayed an osteointegration rate of 11.8% in the spongy area and 29.8% in the cortex layer. The HA-coated test implants showed an osteointegration of 29.5% in the spongiosa and 56.8% in the cortex layer. The rhombus-structured test implants had an osteointegration of 29.2% (spongiosa) and 46.2% (cortex layer). Compared to the osteointegration of metallic, especially titanium surfaces the CFRP surfaces tested by us fared worse, especially the uncoated, plexus-structured surfaces. For this reason we view very critically the use of carbon-fibre reinforced plastics together with the surfaces tested by us as osteointegrating surfaces.

Two-photon voltage imaging using a genetically encoded voltage indicator

PubMed Central

Akemann, Walther; Sasaki, Mari; Mutoh, Hiroki; Imamura, Takeshi; Honkura, Naoki; Knöpfel, Thomas

2013-01-01

Voltage-sensitive fluorescent proteins (VSFPs) are a family of genetically-encoded voltage indicators (GEVIs) reporting membrane voltage fluctuation from genetically-targeted cells in cell cultures to whole brains in awake mice as demonstrated earlier using 1-photon (1P) fluorescence excitation imaging. However, in-vivo 1P imaging captures optical signals only from superficial layers and does not optically resolve single neurons. Two-photon excitation (2P) imaging, on the other hand, has not yet been convincingly applied to GEVI experiments. Here we show that 2P imaging of VSFP Butterfly 1.2 expresssing pyramidal neurons in layer 2/3 reports optical membrane voltage in brain slices consistent with 1P imaging but with a 2–3 larger ΔR/R value. 2P imaging of mouse cortex in-vivo achieved cellular resolution throughout layer 2/3. In somatosensory cortex we recorded sensory responses to single whisker deflections in anesthetized mice at full frame video rate. Our results demonstrate the feasibility of GEVI-based functional 2P imaging in mouse cortex. PMID:23868559

Multiple Transmitter Receptors in Regions and Layers of the Human Cerebral Cortex

PubMed Central

Zilles, Karl; Palomero-Gallagher, Nicola

2017-01-01

We measured the densities (fmol/mg protein) of 15 different receptors of various transmitter systems in the supragranular, granular and infragranular strata of 44 areas of visual, somatosensory, auditory and multimodal association systems of the human cerebral cortex. Receptor densities were obtained after labeling of the receptors using quantitative in vitro receptor autoradiography in human postmortem brains. The mean density of each receptor type over all cortical layers and of each of the three major strata varies between cortical regions. In a single cortical area, the multi-receptor fingerprints of its strata (i.e., polar plots, each visualizing the densities of multiple different receptor types in supragranular, granular or infragranular layers of the same cortical area) differ in shape and size indicating regional and laminar specific balances between the receptors. Furthermore, the three strata are clearly segregated into well definable clusters by their receptor fingerprints. Fingerprints of different cortical areas systematically vary between functional networks, and with the hierarchical levels within sensory systems. Primary sensory areas are clearly separated from all other cortical areas particularly by their very high muscarinic M2 and nicotinic α4β2 receptor densities, and to a lesser degree also by noradrenergic α2 and serotonergic 5-HT2 receptors. Early visual areas of the dorsal and ventral streams are segregated by their multi-receptor fingerprints. The results are discussed on the background of functional segregation, cortical hierarchies, microstructural types, and the horizontal (layers) and vertical (columns) organization in the cerebral cortex. We conclude that a cortical column is composed of segments, which can be assigned to the cortical strata. The segments differ by their patterns of multi-receptor balances, indicating different layer-specific signal processing mechanisms. Additionally, the differences between the strata-and area-specific fingerprints of the 44 areas reflect the segregation of the cerebral cortex into functionally and topographically definable groups of cortical areas (visual, auditory, somatosensory, limbic, motor), and reveals their hierarchical position (primary and unimodal (early) sensory to higher sensory and finally to multimodal association areas). Highlights Densities of transmitter receptors vary between areas of human cerebral cortex.Multi-receptor fingerprints segregate cortical layers.The densities of all examined receptor types together reach highest values in the supragranular stratum of all areas.The lowest values are found in the infragranular stratum.Multi-receptor fingerprints of entire areas and their layers segregate functional systemsCortical types (primary sensory, motor, multimodal association) differ in their receptor fingerprints. PMID:28970785

Reduced Mitochondrial Activity is Early and Steady in the Entorhinal Cortex but it is Mainly Unmodified in the Frontal Cortex in Alzheimer's Disease.

PubMed

Armand-Ugon, Mercedes; Ansoleaga, Belen; Berjaoui, Sara; Ferrer, Isidro

2017-01-01

It is well established that mitochondrial damage plays a role in the pathophysiology of Alzheimer's disease (AD). However, studies carried out in humans barely contemplate regional differences with disease progression. To study the expression of selected nuclear genes encoding subunits of the mitochondrial complexes and the activity of mitochondrial complexes in AD, in two regions: the entorhinal cortex (EC) and frontal cortex area 8 (FC). Frozen samples from 148 cases processed for gene expression by qRT-PCR and determination of individual activities of mitochondrial complexes I, II, IV and V using commercial kits and home-made assays. Decreased expression of NDUFA2, NDUFB3, UQCR11, COX7C, ATPD, ATP5L and ATP50, covering subunits of complex I, II, IV and V, occurs in total homogenates of the EC in AD stages V-VI when compared with stages I-II. However reduced activity of complexes I, II and V of isolated mitochondria occurs as early as stages I-II when compared with middle-aged individuals in the EC. In contrast, no alterations in the expression of the same genes and no alterations in the activity of mitochondrial complexes are found in the FC in the same series. Different mechanisms of impaired energy metabolism may occur in AD, one of them, represented by the EC, is the result of primary and early alteration of mitochondria; the other one is probably the result, at least in part, of decreased functional input and is represented by hypometabolism in the FC in AD patients aged 86 or younger. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Studies on ethyl acetate soluble constituents of Huanglian Jiedutang].

PubMed

Ma, Zhao-Tang; Yang, Xiu-Wei

2008-09-01

To study the ethyl acetate soluble constituents from the water extractive of Huanglian Jiedutang decoction, which are composed of Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri and Fructus Gardeniae, and provide substances foundation for its pharmacokinetic and pharmacodynamic investigation. The chemical constituents were isolated by various column chromatographic methods and structurally elucidated by NMR and MS techniques. Thirty-five compounds were isolated, among which twenty compounds have been identified as beta-sitosterol (1), oroxylin A (2), wogonin (3), ursolic acid (4), skullcapflavone I (5), tenaxin I (6), skullcapflavone II (7), limonin (8), 5, 2'-dihydroxy-6, 7, 8, 3'-tetramethoxyflavone (9), chrysin (12), baicalein (17), tenaxin II (19), 5, 7, 2'-trihydroxy-6, 8-dimethoxyflavone (21), shihulimonin A (22), 6, 2'-dihydroxy-5, 7, 8, 6'-tetramethoxyflavone (26), viscidulin II (28), 5, 7, 4'-trihydroxy-8-methoxyflavone (29), 5, 7, 2', 6'-tetrahydroxyflavone (30), wogonin-7-O-beta-D-glucuronide methyl ester (31) and daucosterol (34). On the basis of reported results of the chemical constituents of Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri and Fructus Gardeniae, it was estimated that all flavonoid compounds rised from the Radix Scutellariae, and compounds 8 and 22 rised from Cortex Phellodendri. Compound 22 was identified in the Cortex Phellodendri for the first time.

Laminar activity in the hippocampus and entorhinal cortex related to novelty and episodic encoding

PubMed Central

Maass, Anne; Schütze, Hartmut; Speck, Oliver; Yonelinas, Andrew; Tempelmann, Claus; Heinze, Hans-Jochen; Berron, David; Cardenas-Blanco, Arturo; Brodersen, Kay H.; Enno Stephan, Klaas; Düzel, Emrah

2014-01-01

The ability to form long-term memories for novel events depends on information processing within the hippocampus (HC) and entorhinal cortex (EC). The HC–EC circuitry shows a quantitative segregation of anatomical directionality into different neuronal layers. Whereas superficial EC layers mainly project to dentate gyrus (DG), CA3 and apical CA1 layers, HC output is primarily sent from pyramidal CA1 layers and subiculum to deep EC layers. Here we utilize this directionality information by measuring encoding activity within HC/EC subregions with 7 T high resolution functional magnetic resonance imaging (fMRI). Multivariate Bayes decoding within HC/EC subregions shows that processing of novel information most strongly engages the input structures (superficial EC and DG/CA2–3), whereas subsequent memory is more dependent on activation of output regions (deep EC and pyramidal CA1). This suggests that while novelty processing is strongly related to HC–EC input pathways, the memory fate of a novel stimulus depends more on HC–EC output. PMID:25424131

Pilocarpine-Induced Status Epilepticus in Rats Involves Ischemic and Excitotoxic Mechanisms

PubMed Central

Fabene, Paolo Francesco; Merigo, Flavia; Galiè, Mirco; Benati, Donatella; Bernardi, Paolo; Farace, Paolo; Nicolato, Elena; Marzola, Pasquina; Sbarbati, Andrea

2007-01-01

The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE). Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE) degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology. PMID:17971868

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.

Transcriptional dysregulation of γ-aminobutyric acid transporter in parvalbumin-containing inhibitory neurons in the prefrontal cortex in schizophrenia.

PubMed

Bitanihirwe, Byron K Y; Woo, Tsung-Ung W

2014-12-30

Parvalbumin (PV)-containing neurons are functionally compromised in schizophrenia. Using double in situ hybridization in postmortem human prefrontal cortex, we found that the messenger RNA (mRNA) for the γ-aminobutyric acid (GABA) transporter GAT-1 was undetectable in 22-41% of PV neurons in layers 3-4 in schizophrenia. In the remaining PV neurons with detectable GAT-1 mRNA, transcript expression was decreased by 26% in layer 3. Hence, the dysfunction of PV neurons involves the molecular dysregulation of presynaptic GABA reuptake. Copyright © 2014 Elsevier Ireland Ltd. 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

Structural investigations of human hairs by spectrally resolved ellipsometry

NASA Astrophysics Data System (ADS)

Schulz, Benjamin; Chan, D.; Ruebhausen, M.; Wessel, S.; Wepf, R.

2006-03-01

Human hair is a biological layered system composed of two major layers, the cortex and the cuticle. We show spectrally resolved ellipsometry measurements of the ellipsometric parameters ψ and δ of single human hairs. The spectra reflect the layered nature of hair and the optical anisotropy of the hair’s structure. In addition, measurements on strands of human hair show a high reproducibility of the ellipsometric parameters for different hair fiber bundles from the same person. Based on the measurements, we develop a model of the dielectric function of hair that explains the spectra. This model includes the dielectric properties of the cuticle and cortex as well as their associated layer thicknesses. In addition, surface roughness effects modelled by a roughness layer with an complex refractive index given by an effective medium approach can have a significant effect on the measurements. We derive values for the parameters of the cuticle surface roughness layer of the thickness dACu= 273-360 nm and the air inclusion fA= 0.6 -5.7%. [1] accepted for publication in J. Biomed Opt., 2005

Selective Activation of the Deep Layers of the Human Primary Visual Cortex by Top-Down Feedback.

PubMed

Kok, Peter; Bains, Lauren J; van Mourik, Tim; Norris, David G; de Lange, Floris P

2016-02-08

In addition to bottom-up input, the visual cortex receives large amounts of feedback from other cortical areas [1-3]. One compelling example of feedback activation of early visual neurons in the absence of bottom-up input occurs during the famous Kanizsa illusion, where a triangular shape is perceived, even in regions of the image where there is no bottom-up visual evidence for it. This illusion increases the firing activity of neurons in the primary visual cortex with a receptive field on the illusory contour [4]. Feedback signals are largely segregated from feedforward signals within each cortical area, with feedforward signals arriving in the middle layer, while top-down feedback avoids the middle layers and predominantly targets deep and superficial layers [1, 2, 5, 6]. Therefore, the feedback-mediated activity increase in V1 during the perception of illusory shapes should lead to a specific laminar activity profile that is distinct from the activity elicited by bottom-up stimulation. Here, we used fMRI at high field (7 T) to empirically test this hypothesis, by probing the cortical response to illusory figures in human V1 at different cortical depths [7-14]. We found that, whereas bottom-up stimulation activated all cortical layers, feedback activity induced by illusory figures led to a selective activation of the deep layers of V1. These results demonstrate the potential for non-invasive recordings of neural activity with laminar specificity in humans and elucidate the role of top-down signals during perceptual processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons.

PubMed

Khateb, Mohamed; Schiller, Jackie; Schiller, Yitzhak

2017-01-06

The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat. To dissociate the vibrissae sensory-motor loop, we optogenetically activated vM1 and independently passively stimulated principal vibrissae. Optogenetic activation of vM1 supra-linearly amplified the response of vS1 neurons to passive vibrissa stimulation in all cortical layers measured. Maximal amplification occurred when onset of vM1 optogenetic activation preceded vibrissa stimulation by 20 ms. In addition to amplification, vM1 activation also sharpened angular tuning of vS1 neurons in all cortical layers measured. Our findings indicated that in addition to output motor signals, vM1 also sends preparatory signals to vS1 that serve to amplify and sharpen the response of neurons in the barrel cortex to incoming sensory input signals.

A new model for diffuse brain injury by rotational acceleration: I model, gross appearance, and astrocytosis.

PubMed

Gutierrez, E; Huang, Y; Haglid, K; Bao, F; Hansson, H A; Hamberger, A; Viano, D

2001-03-01

Rapid head rotation is a major cause of brain damage in automobile crashes and falls. This report details a new model for rotational acceleration about the center of mass of the rabbit head. This allows the study of brain injury without translational acceleration of the head. Impact from a pneumatic cylinder was transferred to the skull surface to cause a half-sine peak acceleration of 2.1 x 10(5) rad/s2 and 0.96-ms pulse duration. Extensive subarachnoid hemorrhages and small focal bleedings were observed in the brain tissue. A pronounced reactive astrogliosis was found 8-14 days after trauma, both as networks around the focal hemorrhages and more diffusely in several brain regions. Astrocytosis was prominent in the gray matter of the cerebral cortex, layers II-V, and in the granule cell layer and around the axons of the pyramidal neurons in the hippocampus. The nuclei of cranial nerves, such as the hypoglossal and facial nerves, also showed intense astrocytosis. The new model allows study of brain injuries from head rotation in the absence of translational influences.

Electron microscopic examination of uncultured soil-dwelling bacteria.

PubMed

Amako, Kazunobu; Takade, Akemi; Taniai, Hiroaki; Yoshida, Shin-ichi

2008-05-01

Bacteria living in soil collected from a rice paddy in Fukuoka, Japan, were examined by electron microscopy using a freeze-substitution fixation method. Most of the observed bacteria could be categorized, based on the structure of the cell envelope and overall morphology, into one of five groups: (i) bacterial spore; (ii) Gram-positive type; (iii) Gram-negative type; (iv) Mycobacterium like; and (v) Archaea like. However, a few of the bacteria could not be readily categorized into one of these groups because they had unique cell wall structures, basically resembling those of Gram-negative bacteria, but with the layer corresponding to the peptidoglycan layer in Gram-negative bacteria being extremely thick, like that of the cortex of a bacterial spore. The characteristic morphological features found in many of these uncultured, soil-dwelling cells were the nucleoid being in a condensed state and the cytoplasm being shrunken. We were able to produce similar morphologies in vitro using a Salmonella sp. by culturing under low-temperature, low-nutrient conditions, similar to those found in some natural environments. These unusual morphologies are therefore hypothesized to be characteristic of bacteria in resting or dormant stages.

CX-516 Cortex pharmaceuticals.

PubMed

Danysz, Wojciech

2002-07-01

CX-516 is one of a series of AMPA modulators under development by Cortex, in collaboration with Shire and Servier, for the potential treatment of Alzheimer's disease (AD), schizophrenia and mild cognitive impairment (MCI) [234221]. By June 2001, CX-516 was in phase II trials for both schizophrenia and attention deficit hyperactivity disorder (ADHD) [412513]. A phase II trial in fragile X syndrome and autism was expected to start in May 2002 [449861]. In October 2001, Cortex was awarded a Phase II SBIR grant of $769,818 from the National Institutes of Mental Health to investigate the therapeutic potential of AMPAkines in schizophrenia. This award was to support a phase IIb study of CX-516 as a combination therapy in schizophrenia patients concomitantly treated with olanzapine. The trial was to enroll 80 patients and employ a randomized, double-blind, placebo-controlled design in which the placebo group was to receive olanzapine plus placebo and the active group was to receive olanzapine plus CX-516 [425982]. In April 2000, Shire and Cortex signed an option agreement in which Shire was to evaluate CX-516for the treatment of ADHD. Under the terms of the agreement, Shire would undertake a double-blind, placebo-controlled evaluation of CX-516 involving ADHD patients. If the study proved effective, Shire would have the right to convert its option into an exclusive worldwide license for the AMPAkines for ADHD under a development and licensing agreement. Should Shire elect to execute this agreement, Shire would bear all future developmental costs [363618]. By February 2002, Cortex and Servier had revealed their intention to begin enrolment for an international study of an AMPAkine compound as a potential treatment for MCI in the near future. Assuming enrollment proceeded as anticipated, results were expected during the second quarter of 2003 [439301]. By May 2002, phase II trials were underway [450134]. In March 2002, Cortex was awarded extended funding under the University of California BioSTAR projectfor the research project: 'Ampakine modulation of brain neurotrophin expression: a novel therapeutic strategy'. This funding was expected to amount to $193,000 over a two-year period [444872].

Comparative analysis of cortical layering and supragranular layer enlargement in rodent carnivore and primate species.

PubMed

Hutsler, Jeffrey J; Lee, Dong-Geun; Porter, Kristin K

2005-08-02

The mammalian cerebral cortex is composed of individual layers characterized by the cell types they contain and their afferent and efferent connections. The current study examined the raw, and size-normalized, laminar thicknesses in three cortical regions (somatosensory, motor, and premotor) of fourteen species from three orders of mammals: primates, carnivores, and rodents. The proportional size of the pyramidal cell layers (supra- and infragranular) varied between orders but was similar within orders despite wide variance in absolute cortical thickness. Further, supragranular layer thickness was largest in primates (46 +/- 3 percent), followed by carnivores (36 +/- 3 percent), and then rodents (19 +/- 4 percent), suggesting a distinct difference in the proportion of cortex devoted to corticocortical connectivity across these orders. Although measures of supragranular layer thickness are highly correlated with measures of overall brain size, such associations are not present when independent contrasts are used to control for phylogenetic inertia. Interestingly, neurogenesis time span remains strongly associated with supragranular layer thickness despite size normalization and controlling for phylogenetic inertia. Such layering differences between orders, and similarities amongst species within an order, suggest that supragranular layer expansion may have occurred early in mammalian evolution and may be related to ontogenetic variables such as neurogenesis time span rather than measures of overall size.

Document Image Parsing and Understanding using Neuromorphic Architecture

DTIC Science & Technology

2015-03-01

processing speed at different layers. In the pattern matching layer, the computing power of multicore processors is explored to reduce the processing...developed to reduce the processing speed at different layers. In the pattern matching layer, the computing power of multicore processors is explored... cortex where the complex data is reduced to abstract representations. The abstract representation is compared to stored patterns in massively parallel

Low levels of muscarinic M1 receptor-positive neurons in cortical layers III and V in Brodmann areas 9 and 17 from individuals with schizophrenia.

PubMed

Scarr, Elizabeth; Hopper, Shaun; Vos, Valentina; Seo, Myoung Suk; Everall, Ian Paul; Aumann, Timothy Douglas; Chunam, Gursharan; Dean, Brian

2018-05-30

Results of neuroimaging and postmortem studies suggest that people with schizophrenia may have lower levels of muscarinic M1 receptors (CHRM1) in the cortex, but not in the hippocampus or thalamus. Here, we use a novel immunohistochemical approach to better understand the likely cause of these low receptor levels. We determined the distribution and number of CHRM1-positive (CHRM1+) neurons in the cortex, medial dorsal nucleus of the thalamus and regions of the hippocampus from controls ( n = 12, 12 and 5, respectively) and people with schizophrenia ( n = 24, 24 and 13, respectively). Compared with controls, levels of CHRM1+ neurons in people with schizophrenia were lower on pyramidal cells in layer III of Brodmann areas 9 (-44%) and 17 (-45%), and in layer V in Brodmann areas 9 (-45%) and 17 (-62%). We found no significant differences in the number of CHRM1+ neurons in the medial dorsal nucleus of the thalamus or in the hippocampus. Although diagnostic cohort sizes were typical for this type of study, they were relatively small. As well, people with schizophrenia were treated with antipsychotic drugs before death. The loss of CHRM1+ pyramidal cells in the cortex of people with schizophrenia may underpin derangements in the cholinergic regulation of GABAergic activity in cortical layer III and in cortical/subcortical communication via pyramidal cells in layer V.

Imaging laminar structures in the gray matter with diffusion MRI.

PubMed

Assaf, Yaniv

2018-01-05

The cortical layers define the architecture of the gray matter and its neuroanatomical regions and are essential for brain function. Abnormalities in cortical layer development, growth patterns, organization, or size can affect brain physiology and cognition. Unfortunately, while large population studies are underway that will greatly increase our knowledge about these processes, current non-invasive techniques for characterizing the cortical layers remain inadequate. For decades, high-resolution T1 and T2 Weighted Magnetic Resonance Imaging (MRI) have been the method-of-choice for gray matter and layer characterization. In the past few years, however, diffusion MRI has shown increasing promise for its unique insights into the fine structure of the cortex. Several different methods, including surface analysis, connectivity exploration, and sub-voxel component modeling, are now capable of exploring the diffusion characteristics of the cortex. In this review, we will discuss current advances in the application of diffusion imaging for cortical characterization and its unique features, with a particular emphasis on its spatial resolution, arguably its greatest limitation. In addition, we will explore the relationship between the diffusion MRI signal and the cellular components of the cortex, as visualized by histology. While the obstacles facing the widespread application of cortical diffusion imaging remain daunting, the information it can reveal may prove invaluable. Within the next few years, we predict a surge in the application of this technique and a concomitant expansion of our knowledge of cortical layers. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuroanatomical distribution of oxytocin and vasopressin 1a receptors in the socially monogamous coppery titi monkey (Callicebus cupreus)

PubMed Central

Freeman, Sara M.; Walum, Hasse; Inoue, Kiyoshi; Smith, Aaron L.; Goodman, Mark M.; Bales, Karen L.; Young, Larry J.

2014-01-01

The coppery titi monkey (Callicebus cupreus) is a socially monogamous New World primate that has been studied in the field and the laboratory to investigate the behavioral neuroendocrinology of primate pair bonding and parental care. Arginine vasopressin has been shown to influence male titi monkey pair-bonding behavior, and studies are currently underway to examine the effects of oxytocin on titi monkey behavior and physiology. Here, we use receptor autoradiography to identify the distribution of arginine vasopressin 1a (AVPR1a) and oxytocin receptors (OXTR) in hemispheres of titi monkey brain (n=5). AVPR1a are diffuse and widespread throughout the brain, but the OXTR distribution is much more limited, with the densest binding being in the hippocampal formation (dentate gyrus, CA1 field) and the presubiculum (layers I and III). Moderate OXTR binding was detected in the nucleus basalis of Meynert, pulvinar, superior colliculus, layer 4C of primary visual cortex, periaqueductal gray, pontine gray, nucleus prepositus, and spinal trigeminal nucleus. OXTR mRNA overlapped with OXTR radioligand binding, confirming that the radioligand was detecting OXTR protein. AVPR1a binding is present throughout the cortex, especially in cingulate, insular, and occipital cortices, as well as in the caudate, putamen, nucleus accumbens, central amygdala, endopiriform nucleus, hippocampus (CA4 field), globus pallidus, lateral geniculate nucleus, infundibulum, habenula, periaqueductal gray, substantia nigra, olivary nucleus, hypoglossal nucleus, and cerebellum. Furthermore, we show that, in titi monkey brain, the OXTR antagonist ALS-II-69 is highly selective for OXTR and that the AVPR1a antagonist SR49059 is highly selective for AVPR1a. Based on these results and the fact that both ALS-II-69 and SR49059 are non-peptide, small-molecule antagonists that should be capable of crossing the blood brain barrier, these two compounds emerge as excellent candidates for the pharmacological manipulation of OXTR and AVPR1a in future behavioral experiments in titi monkeys and other primate species. PMID:24814726

Spiking in auditory cortex following thalamic stimulation is dominated by cortical network activity

PubMed Central

Krause, Bryan M.; Raz, Aeyal; Uhlrich, Daniel J.; Smith, Philip H.; Banks, Matthew I.

2014-01-01

The state of the sensory cortical network can have a profound impact on neural responses and perception. In rodent auditory cortex, sensory responses are reported to occur in the context of network events, similar to brief UP states, that produce “packets” of spikes and are associated with synchronized synaptic input (Bathellier et al., 2012; Hromadka et al., 2013; Luczak et al., 2013). However, traditional models based on data from visual and somatosensory cortex predict that ascending sensory thalamocortical (TC) pathways sequentially activate cells in layers 4 (L4), L2/3, and L5. The relationship between these two spatio-temporal activity patterns is unclear. Here, we used calcium imaging and electrophysiological recordings in murine auditory TC brain slices to investigate the laminar response pattern to stimulation of TC afferents. We show that although monosynaptically driven spiking in response to TC afferents occurs, the vast majority of spikes fired following TC stimulation occurs during brief UP states and outside the context of the L4>L2/3>L5 activation sequence. Specifically, monosynaptic subthreshold TC responses with similar latencies were observed throughout layers 2–6, presumably via synapses onto dendritic processes located in L3 and L4. However, monosynaptic spiking was rare, and occurred primarily in L4 and L5 non-pyramidal cells. By contrast, during brief, TC-induced UP states, spiking was dense and occurred primarily in pyramidal cells. These network events always involved infragranular layers, whereas involvement of supragranular layers was variable. During UP states, spike latencies were comparable between infragranular and supragranular cells. These data are consistent with a model in which activation of auditory cortex, especially supragranular layers, depends on internally generated network events that represent a non-linear amplification process, are initiated by infragranular cells and tightly regulated by feed-forward inhibitory cells. PMID:25285071

Tracking blue cone signals in the primate brain.

PubMed

Jayakumar, Jaikishan; Dreher, Bogdan; Vidyasagar, Trichur R

2013-05-01

In this paper, we review the path taken by signals originating from the short wavelength sensitive cones (S-cones) in Old World and New World primates. Two types of retinal ganglion cells (RGCs) carrying S-cone signals (blue-On and blue-Off cells) project to the dorsal lateral geniculate nucleus (dLGN) in the thalamus. In all primates, these S-cone signals are relayed through the 'dust-like' (konis in classical Greek) dLGN cells. In New World primates such as common marmoset, these very small cells are known to form distinct and spatially extensive, koniocellular layers. Although in Old World primates, such as macaques, koniocellular layers tend to be very thin, the adjacent parvocellular layers contain distinct koniocellular extensions. It appears that all S-cone signals are relayed through such konio cells, whether they are in the main koniocellular layers or in their colonies within the parvocellular layers of the dLGN. In the primary visual cortex, these signals begin to merge with the signals carried by the other two principal parallel channels, namely the magnocellular and parvocellular channels. This article will also review the possible routes taken by the S-cone signals to reach one of the topographically organised extrastriate visual cortical areas, the middle temporal area (area MT). This area is the major conduit for signals reaching the parietal cortex. Alternative visual inputs to area MT not relayed via the primary visual cortex area (V1) may provide the neurological basis for the phenomenon of 'blindsight' observed in human and non-human primates, who have partial or complete damage to the primary visual cortex. Short wavelength sensitive cone (S-cone) signals to area MT may also play a role in directing visual attention with possible implications for understanding the pathology in dyslexia and some of its treatment options. © 2012 The Authors. Clinical and Experimental Optometry © 2012 Optometrists Association Australia.

Area 4 has layer IV in adult primates

PubMed Central

García-Cabezas, Miguel Ángel; Barbas, Helen

2014-01-01

There are opposing views about the status of layer IV in primary motor cortex (area 4). Cajal described a layer IV in area 4 of adult humans. In contrast, Brodmann found layer IV in development but not in adult primates and called area 4 ‘agranular’. We addressed this issue in rhesus monkeys using the neural marker SMI-32, which labels neurons in lower layer III and upper V, but not in layer IV. SMI-32 delineated a central unlabeled cortical stripe in area 4 that corresponds to layer IV, which was populated with small interneurons also found in layer IV in ‘granular’ areas (such as area 46). We distinguished layer IV interneurons from projection neurons in the layers above and below using cellular criteria. The commonly used term ‘agranular’ for area 4 is also used for the phylogenetically ancient limbic cortices, confusing areas that differ markedly in laminar structure. This issue pertains to the systematic variation in the architecture across cortices, traced from limbic cortices through areas with increasingly more elaborate laminar structure. The principle of systematic variation can be used to predict laminar patterns of connections across cortical systems. This principle places area 4 and agranular anterior cingulate cortices at opposite poles of the graded laminar differentiation of motor cortices. The status of layer IV in area 4 thus pertains to core organizational features of the cortex, its connections and evolution. PMID:24735460

Anatomical evidence for brainstem circuits mediating feeding motor programs in the leopard frog, Rana pipiens.

PubMed

Anderson, C W

2001-09-01

Using injections of small molecular weight fluorescein dextran amines, combined with activity-dependent uptake of sulforhodamine 101 (SR101), brainstem circuits presumed to be involved in feeding motor output were investigated. As has been shown previously in other studies, projections to the cerebellar nuclei were identified from the cerebellar cortex, the trigeminal motor nucleus, and the vestibular nuclei. Results presented here suggest an additional pathway from the hypoglossal motor nuclei to the cerebellar nucleus as well as an afferent projection from the peripheral hypoglossal nerve to the Purkinje cell layer of the cerebellar cortex. Injections in the cerebellar cortex combined with retrograde labeling of the peripheral hypoglossal nerve demonstrate anatomical convergence at the level of the medial reticular formation. This suggests a possible integrative region for afferent feedback from the hypoglossal nerve and information through the Purkinje cell layer of the cerebellar cortex. The activity-dependent uptake of SR101 additionally suggests a reciprocal, polysynaptic pathway between this same area of the medial reticular formation and the trigeminal motor nuclei. The trigeminal motor neurons innervate the m adductor mandibulae, the primary mouth-closing muscle. The SR101 uptake clearly labeled the ventrolateral hypoglossal nuclei, the medial reticular formation, and the Purkinje cell layer of the cerebellar cortex. Unlike retrograde labeling of the peripheral hypoglossal nerve, stimulating the hypoglossal nerve while SR101 was bath-applied labeled trigeminal motor neurons. This, combined with the dextran labeling, suggests a reciprocal connection between the trigeminal motor nuclei and the cerebellar nuclei, as well as the medulla. Taken together, these data are important for understanding the neurophysiological pathways used to coordinate the proper timing of an extremely rapid, goal-directed movement and may prove useful for elucidating some of the first principles of sensorimotor integration.

Training-Dependent Associative Learning Induced Neocortical Structural Plasticity: A Trace Eyeblink Conditioning Analysis

PubMed Central

Chau, Lily S.; Prakapenka, Alesia V.; Zendeli, Liridon; Davis, Ashley S.; Galvez, Roberto

2014-01-01

Studies utilizing general learning and memory tasks have suggested the importance of neocortical structural plasticity for memory consolidation. However, these learning tasks typically result in learning of multiple different tasks over several days of training, making it difficult to determine the synaptic time course mediating each learning event. The current study used trace-eyeblink conditioning to determine the time course for neocortical spine modification during learning. With eyeblink conditioning, subjects are presented with a neutral, conditioned stimulus (CS) paired with a salient, unconditioned stimulus (US) to elicit an unconditioned response (UR). With multiple CS-US pairings, subjects learn to associate the CS with the US and exhibit a conditioned response (CR) when presented with the CS. Trace conditioning is when there is a stimulus free interval between the CS and the US. Utilizing trace-eyeblink conditioning with whisker stimulation as the CS (whisker-trace-eyeblink: WTEB), previous findings have shown that primary somatosensory (barrel) cortex is required for both acquisition and retention of the trace-association. Additionally, prior findings demonstrated that WTEB acquisition results in an expansion of the cytochrome oxidase whisker representation and synaptic modification in layer IV of barrel cortex. To further explore these findings and determine the time course for neocortical learning-induced spine modification, the present study utilized WTEB conditioning to examine Golgi-Cox stained neurons in layer IV of barrel cortex. Findings from this study demonstrated a training-dependent spine proliferation in layer IV of barrel cortex during trace associative learning. Furthermore, findings from this study showing that filopodia-like spines exhibited a similar pattern to the overall spine density further suggests that reorganization of synaptic contacts set the foundation for learning-induced neocortical modifications through the different neocortical layers. PMID:24760074

Competitive (AP7) and non-competitive (MK-801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex

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

Clow, D.W.; Lee, S.J.; Hammer, R.P. Jr.

1991-04-01

The effects of D,L-2-amino-7-phosphonoheptanoic acid (AP7), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801, a non-competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative {sup 14}C2-deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose-dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK-801 (0.1 or 1.0 mg/kg) resulted in a dose-dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK-801 also produced amore » biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK-801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK-801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK-801 administration also decreased metabolic activity in granular SI relative to dysgranular SI, and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non-competitive NMDA receptor antagonist suppressed activity from extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions, while the competitive NMDA antagonist depressed metabolic activity in all cortical regions.« less

Locomotion Enhances Neural Encoding of Visual Stimuli in Mouse V1

PubMed Central

2017-01-01

Neurons in mouse primary visual cortex (V1) are selective for particular properties of visual stimuli. Locomotion causes a change in cortical state that leaves their selectivity unchanged but strengthens their responses. Both locomotion and the change in cortical state are thought to be initiated by projections from the mesencephalic locomotor region, the latter through a disinhibitory circuit in V1. By recording simultaneously from a large number of single neurons in alert mice viewing moving gratings, we investigated the relationship between locomotion and the information contained within the neural population. We found that locomotion improved encoding of visual stimuli in V1 by two mechanisms. First, locomotion-induced increases in firing rates enhanced the mutual information between visual stimuli and single neuron responses over a fixed window of time. Second, stimulus discriminability was improved, even for fixed population firing rates, because of a decrease in noise correlations across the population. These two mechanisms contributed differently to improvements in discriminability across cortical layers, with changes in firing rates most important in the upper layers and changes in noise correlations most important in layer V. Together, these changes resulted in a threefold to fivefold reduction in the time needed to precisely encode grating direction and orientation. These results support the hypothesis that cortical state shifts during locomotion to accommodate an increased load on the visual system when mice are moving. SIGNIFICANCE STATEMENT This paper contains three novel findings about the representation of information in neurons within the primary visual cortex of the mouse. First, we show that locomotion reduces by at least a factor of 3 the time needed for information to accumulate in the visual cortex that allows the distinction of different visual stimuli. Second, we show that the effect of locomotion is to increase information in cells of all layers of the visual cortex. Third, we show that the means by which information is enhanced by locomotion differs between the upper layers, where the major effect is the increasing of firing rates, and in layer V, where the major effect is the reduction in noise correlations. PMID:28264980

Volume electron microscopy of the distribution of synapses in the neuropil of the juvenile rat somatosensory cortex.

PubMed

Santuy, A; Rodriguez, J R; DeFelipe, J; Merchan-Perez, A

2018-01-01

Knowing the proportions of asymmetric (excitatory) and symmetric (inhibitory) synapses in the neuropil is critical for understanding the design of cortical circuits. We used focused ion beam milling and scanning electron microscopy (FIB/SEM) to obtain stacks of serial sections from the six layers of the juvenile rat (postnatal day 14) somatosensory cortex (hindlimb representation). We segmented in three-dimensions 6184 synaptic junctions and determined whether they were established on dendritic spines or dendritic shafts. Of all these synapses, 87-94% were asymmetric and 6-13% were symmetric. Asymmetric synapses were preferentially located on dendritic spines in all layers (80-91%) while symmetric synapses were mainly located on dendritic shafts (62-86%). Furthermore, we found that less than 6% of the dendritic spines establish more than one synapse. The vast majority of axospinous synapses were established on the spine head. Synapses on the spine neck were scarce, although they were more common when the dendritic spine established multiple synapses. This study provides a new large quantitative dataset that may contribute not only to the knowledge of the ultrastructure of the cortex, but also towards defining the connectivity patterns through all cortical layers.

On the growth and form of cortical convolutions

NASA Astrophysics Data System (ADS)

Tallinen, Tuomas; Chung, Jun Young; Rousseau, François; Girard, Nadine; Lefèvre, Julien; Mahadevan, L.

2016-06-01

The rapid growth of the human cortex during development is accompanied by the folding of the brain into a highly convoluted structure. Recent studies have focused on the genetic and cellular regulation of cortical growth, but understanding the formation of the gyral and sulcal convolutions also requires consideration of the geometry and physical shaping of the growing brain. To study this, we use magnetic resonance images to build a 3D-printed layered gel mimic of the developing smooth fetal brain; when immersed in a solvent, the outer layer swells relative to the core, mimicking cortical growth. This relative growth puts the outer layer into mechanical compression and leads to sulci and gyri similar to those in fetal brains. Starting with the same initial geometry, we also build numerical simulations of the brain modelled as a soft tissue with a growing cortex, and show that this also produces the characteristic patterns of convolutions over a realistic developmental course. All together, our results show that although many molecular determinants control the tangential expansion of the cortex, the size, shape, placement and orientation of the folds arise through iterations and variations of an elementary mechanical instability modulated by early fetal brain geometry.

Kindling alters entorhinal cortex-hippocampal interaction by increased efficacy of presynaptic GABA(B) autoreceptors in layer III of the entorhinal cortex.

PubMed

Gloveli, Tengis; Behr, Joachim; Dugladze, Tamar; Kokaia, Zaal; Kokaia, Merab; Heinemann, Uwe

2003-08-01

We studied the effect of kindling, a model of temporal lobe epilepsy, on the frequency-dependent information transfer from the entorhinal cortex to the hippocampus in vitro. In control rats repetitive synaptic activation of layer III projection cells resulted in a frequency dependent depression of the synaptic transfer of action potentials to the hippocampus. One-to-two-days after kindling this effect was strongly reduced. Although no substantial change in synaptic inhibition upon single electrical stimulation was detected in kindled rats, there was a significant depression in the prolonged inhibition following high frequency stimulation. In kindled animals, paired-pulse depression (PPD) of stimulus-evoked IPSCs in layer III neurons was significantly stronger than in control rats. The increase of PPD is most likely caused by an increased presynaptic GABA(B) receptor-mediated autoinhibition. In kindled animals activation of presynaptic GABA(B) receptors by baclofen (10 microM) suppressed monosynaptic IPSCs significantly more than in control rats. In contrast, activation of postsynaptic GABA(B) receptors by baclofen was accompanied by comparable changes of the membrane conductance in both animal groups. Thus, in kindled animals activation of the layer III-CA1 pathway is facilitated by an increased GABA(B) receptor-mediated autoinhibition leading to an enhanced activation of the monosynaptic EC-CA1 pathway.

Visual Receptive Field Structure of Cortical Inhibitory Neurons Revealed by Two-Photon Imaging Guided Recording

PubMed Central

Liu, Bao-hua; Li, Pingyang; Li, Ya-tang; Sun, Yujiao J.; Yanagawa, Yuchio; Obata, Kunihiko; Zhang, Li I.; Tao, Huizhong W.

2009-01-01

Synaptic inhibition plays an important role in shaping receptive field (RF) properties in the visual cortex. However, the underlying mechanisms remain not well understood, partly due to difficulties in systematically studying functional properties of cortical inhibitory neurons in vivo. Here, we established two-photon imaging guided cell-attached recordings from genetically labelled inhibitory neurons and nearby “shadowed” excitatory neurons in the primary visual cortex of adult mice. Our results revealed that in layer 2/3, the majority of excitatory neurons exhibited both On and Off spike subfields, with their spatial arrangement varying from being completely segregated to overlapped. On the other hand, most layer 4 excitatory neurons exhibited only one discernable subfield. Interestingly, no RF structure with significantly segregated On and Off subfields was observed for layer 2/3 inhibitory neurons of either the fast-spike or regular-spike type. They predominantly possessed overlapped On and Off subfields with a significantly larger size than the excitatory neurons, and exhibited much weaker orientation tuning. These results from the mouse visual cortex suggest that different from the push-pull model proposed for simple cells, layer 2/3 simple-type neurons with segregated spike On and Off subfields likely receive spatially overlapped inhibitory On and Off inputs. We propose that the phase-insensitive inhibition can enhance the spatial distinctiveness of On and Off subfields through a gain control mechanism. PMID:19710305

Ipsilateral corticotectal projections from the primary, premotor and supplementary motor cortical areas in adult macaque monkeys: a quantitative anterograde tracing study

PubMed Central

Fregosi, Michela; Rouiller, Eric M.

2018-01-01

The corticotectal projection from cortical motor areas is one of several descending pathways involved in the indirect control of spinal motoneurons. In non-human primates, previous studies reported that cortical projections to the superior colliculus originated from the premotor cortex and the primary motor cortex, whereas no projection originated from the supplementary motor area. The aim of the present study was to investigate and compare the properties of corticotectal projections originating from these three cortical motor areas in intact adult macaques (n=9). The anterograde tracer BDA was injected into one of these cortical areas in each animal. Individual axonal boutons, both en passant and terminaux, were charted and counted in the different layers of the ipsilateral superior colliculus. The data confirmed the presence of strong corticotectal projections from the premotor cortex. A new observation was that strong corticotectal projections were also found to originate from the supplementary motor area (its proper division). The corticotectal projection from the primary motor cortex was quantitatively less strong than that from either the premotor or supplementary motor areas. The corticotectal projection from each motor area was directed mainly to the deep layer of the superior colliculus, although its intermediate layer was also a consistent target of fairly dense terminations. The strong corticotectal projections from non-primary motor areas are in position to influence the preparation and planning of voluntary movements. PMID:28921678

Distinct speed dependence of entorhinal island and ocean cells, including respective grid cells

PubMed Central

Sun, Chen; Kitamura, Takashi; Yamamoto, Jun; Martin, Jared; Pignatelli, Michele; Kitch, Lacey J.; Schnitzer, Mark J.; Tonegawa, Susumu

2015-01-01

Entorhinal–hippocampal circuits in the mammalian brain are crucial for an animal’s spatial and episodic experience, but the neural basis for different spatial computations remain unknown. Medial entorhinal cortex layer II contains pyramidal island and stellate ocean cells. Here, we performed cell type-specific Ca2+ imaging in freely exploring mice using cellular markers and a miniature head-mounted fluorescence microscope. We found that both oceans and islands contain grid cells in similar proportions, but island cell activity, including activity in a proportion of grid cells, is significantly more speed modulated than ocean cell activity. We speculate that this differential property reflects island cells’ and ocean cells’ contribution to different downstream functions: island cells may contribute more to spatial path integration, whereas ocean cells may facilitate contextual representation in downstream circuits. PMID:26170279

Progesterone Sharpens Temporal Response Profiles of Sensory Cortical Neurons in Animals Exposed to Traumatic Brain Injury

PubMed Central

Allitt, Benjamin J.; Johnstone, Victoria P. A.; Richards, Katrina L.; Yan, Edwin B.

2017-01-01

Traumatic brain injury (TBI) initiates a cascade of pathophysiological changes that are both complex and difficult to treat. Progesterone (P4) is a neuroprotective treatment option that has shown excellent preclinical benefits in the treatment of TBI, but these benefits have not translated well in the clinic. We have previously shown that P4 exacerbates the already hypoactive upper cortical responses in the short-term post-TBI and does not reduce upper cortical hyperactivity in the long term, and we concluded that there is no tangible benefit to sensory cortex firing strength. Here we examined the effects of P4 treatment on temporal coding resolution in the rodent sensory cortex in both the short term (4 d) and long term (8 wk) following impact-acceleration–induced TBI. We show that in the short-term postinjury, TBI has no effect on sensory cortex temporal resolution and that P4 also sharpens the response profile in all cortical layers in the uninjured brain and all layers other than layer 2 (L2) in the injured brain. In the long term, TBI broadens the response profile in all cortical layers despite firing rate hyperactivity being localized to upper cortical layers and P4 sharpens the response profile in TBI animals in all layers other than L2 and has no long-term effect in the sham brain. These results indicate that P4 has long-term effects on sensory coding that may translate to beneficial perceptual outcomes. The effects seen here, combined with previous beneficial preclinical data, emphasize that P4 is still a potential treatment option in ameliorating TBI-induced disorders. PMID:28933224

Distribution of Vesicular Glutamate Transporter 2 (VGluT2) in the Primary Visual Cortex of the Macaque and Human

PubMed Central

Garcia-Marin, Virginia; Ahmed, Tunazzina H.; Afzal, Yasmeen C.; Hawken, Michael J.

2014-01-01

The majority of thalamic terminals in V1 arise from lateral geniculate nucleus (LGN) afferents. Thalamic afferent terminals are preferentially labeled by an isoform of the vesicular glutamate transporter, VGluT2. The goal of our study was to determine the distribution of VGluT2-ir puncta in macaque and human visual cortex. First, we investigated the distribution of VGluT2-ir puncta in all layers of macaque monkey primary visual cortex (V1), and found a very close correspondence between the known distribution of LGN afferents from previous studies and the distribution of VGluT2-immunoreactive (-ir) puncta. There was also a close correspondence between cytochrome oxidase density and VGluT2-ir puncta distribution. After validating the correspondence in macaque, we made a comparative study in human V1. In many aspects, the distribution of VGluT2-ir puncta in human was qualitatively similar to that of the macaque: high densities in layer 4C, patches of VGluT2-ir puncta in the supragranular layer (2/3), lower but clear distribution in layers 1 and 6, and very few puncta in layers 5 and 4B. However, there were also important differences between macaques and humans. In layer 4A of human, there was a sparse distribution of VGluT2-ir puncta, whereas in macaque, there was a dense distribution with the characteristic honeycomb organization. The results suggest important changes in the pattern of cortical VGluT2 immunostaining that may be related to evolutionary differences in the cortical organization of LGN afferents between Old World monkeys and humans. PMID:22684983

Intra- and Interhemispheric Propagation of Electrophysiological Synchronous Activity and Its Modulation by Serotonin in the Cingulate Cortex of Juvenile Mice

PubMed Central

Rovira, Víctor; Geijo-Barrientos, Emilio

2016-01-01

Disinhibition of the cortex (e.g., by GABA -receptor blockade) generates synchronous and oscillatory electrophysiological activity that propagates along the cortex. We have studied, in brain slices of the cingulate cortex of mice (postnatal age 14–20 days), the propagation along layer 2/3 as well as the interhemispheric propagation through the corpus callosum of synchronous discharges recorded extracellularly and evoked in the presence of 10 μM bicuculline by electrical stimulation of layer 1. The latency of the responses obtained at the same distance from the stimulus electrode was longer in anterior cingulate cortex (ACC: 39.53 ± 2.83 ms, n = 7) than in retrosplenial cortex slices (RSC: 21.99 ± 2.75 ms, n = 5; p<0.05), which is equivalent to a lower propagation velocity in the dorso-ventral direction in ACC than in RSC slices (43.0 mm/s vs 72.9 mm/s). We studied the modulation of this propagation by serotonin. Serotonin significantly increased the latency of the intracortical synchronous discharges (18.9% in the ipsilateral hemisphere and 40.2% in the contralateral hemisphere), and also increased the interhemispheric propagation time by 86.4%. These actions of serotonin were mimicked by the activation of either 5-HT1B or 5-HT2A receptors, but not by the activation of the 5-HT1A subtype. These findings provide further knowledge about the propagation of synchronic electrical activity in the cerebral cortex, including its modulation by serotonin, and suggest the presence of deep differences between the ACC and RSC in the structure of the local cortical microcircuits underlying the propagation of synchronous discharges. PMID:26930051

Increased GABA-A receptor binding and reduced connectivity at the motor cortex in children with hemiplegic cerebral palsy: a multimodal investigation using 18F-fluoroflumazenil PET, immunohistochemistry, and MR imaging.

PubMed

Park, Hae-Jeong; Kim, Chul Hoon; Park, Eun Sook; Park, Bumhee; Oh, So Ra; Oh, Maeng-Keun; Park, Chang Il; Lee, Jong Doo

2013-08-01

γ-aminobutyric acid (GABA)-A receptor-mediated neural transmission is important to promote practice-dependent plasticity after brain injury. This study investigated alterations in GABA-A receptor binding and functional and anatomic connectivity within the motor cortex in children with cerebral palsy (CP). We conducted (18)F-fluoroflumazenil PET on children with hemiplegic CP to investigate whether in vivo GABA-A receptor binding is altered in the ipsilateral or contralateral hemisphere of the lesion site. To evaluate changes in the GABA-A receptor subunit after prenatal brain injury, we performed GABA-A receptor immunohistochemistry using rat pups with a diffuse hypoxic ischemic insult. We also performed diffusion tensor MR imaging and resting-state functional MR imaging on the same children with hemiplegic CP to investigate alterations in anatomic and functional connectivity at the motor cortex with increased GABA-A receptor binding. In children with hemiplegic CP, the (18)F-fluoroflumazenil binding potential was increased within the ipsilateral motor cortex. GABA-A receptors with the α1 subunit were highly expressed exclusively within cortical layers III, IV, and VI of the motor cortex in rat pups. The motor cortex with increased GABA-A receptor binding in children with hemiplegic CP had reduced thalamocortical and corticocortical connectivity, which might be linked to increased GABA-A receptor distribution in cortical layers in rats. Increased expression of the GABA-A receptor α1 subunit within the ipsilateral motor cortex may be an important adaptive mechanism after prenatal brain injury in children with CP but may be associated with improper functional connectivity after birth and have adverse effects on the development of motor plasticity.

Spike phase synchronization in multiplex cortical neural networks

NASA Astrophysics Data System (ADS)

Jalili, Mahdi

2017-01-01

In this paper we study synchronizability of two multiplex cortical networks: whole-cortex of hermaphrodite C. elegans and posterior cortex in male C. elegans. These networks are composed of two connection layers: network of chemical synapses and the one formed by gap junctions. This work studies the contribution of each layer on the phase synchronization of non-identical spiking Hindmarsh-Rose neurons. The network of male C. elegans shows higher phase synchronization than its randomized version, while it is not the case for hermaphrodite type. The random networks in each layer are constructed such that the nodes have the same degree as the original network, thus providing an unbiased comparison. In male C. elegans, although the gap junction network is sparser than the chemical network, it shows higher contribution in the synchronization phenomenon. This is not the case in hermaphrodite type, which is mainly due to significant less density of gap junction layer (0.013) as compared to chemical layer (0.028). Also, the gap junction network in this type has stronger community structure than the chemical network, and this is another driving factor for its weaker synchronizability.

Contribution of Ih to the relative facilitation of synaptic responses induced by carbachol in the entorhinal cortex during repetitive stimulation of the parasubiculum.

PubMed

Sparks, D W; Chapman, C A

2014-10-10

Neurons in the superficial layers of the entorhinal cortex provide the hippocampus with the majority of its cortical sensory input, and also receive the major output projection from the parasubiculum. This puts the parasubiculum in a position to modulate the activity of entorhinal neurons that project to the hippocampus. These brain areas receive cholinergic projections that are active during periods of theta- and gamma-frequency electroencephalographic (EEG) activity. The purpose of this study was to investigate how cholinergic receptor activation affects the strength of repetitive synaptic responses at these frequencies in the parasubiculo-entorhinal pathway and the cellular mechanisms involved. Whole-cell patch-clamp recordings of rat layer II medial entorhinal neurons were conducted using an acute slice preparation, and responses to 5-pulse trains of stimulation at theta- and gamma-frequency delivered to the parasubiculum were recorded. The cholinergic agonist carbachol (CCh) suppressed the amplitude of single synaptic responses, but also produced a relative facilitation of synaptic responses evoked during stimulation trains. The N-methyl-d-aspartate (NMDA) glutamate receptor blocker APV did not significantly reduce the relative facilitation effect. However, the hyperpolarization-activated cationic current (Ih) channel blocker ZD7288 mimicked the relative facilitation induced by CCh, suggesting that CCh-induced inhibition of Ih could produce the effect by increasing dendritic input resistance (Rin). Inward-rectifying and leak K(+) currents are known to interact with Ih to affect synaptic excitability. Application of the K(+) channel antagonist Ba(2+) depolarized neurons and enhanced temporal summation, but did not block further facilitation of train-evoked responses by ZD7288. The Ih-dependent facilitation of synaptic responses can therefore occur during reductions in inward-rectifying potassium current (IKir) associated with dendritic depolarization. Thus, in addition to cholinergic reductions in transmitter release that are known to facilitate train-evoked responses, these findings emphasize the role of inhibition of Ih in the integration of synaptic inputs within the entorhinal cortex during cholinergically-induced oscillatory states, likely due to enhanced summation of excitatory postsynaptic potentials (EPSPs) induced by increases in dendritic Rin. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Ketamine-induced apoptosis in the mouse cerebral cortex follows similar characteristic of physiological apoptosis and can be regulated by neuronal activity.

PubMed

Wang, Qi; Shen, Feng-Yan; Zou, Rong; Zheng, Jing-Jing; Yu, Xiang; Wang, Ying-Wei

2017-06-17

The effects of general anesthetics on inducing neuronal apoptosis during early brain development are well-documented. However, since physiological apoptosis also occurs during this developmental window, it is important to determine whether anesthesia-induced apoptosis targets the same cell population as physiological apoptosis or different cell types altogether. To provide an adequate plane of surgery, ketamine was co-administered with dexmedetomidine. The apoptotic neurons in the mouse primary somatosensory cortex (S1) were quantitated by immunohistochemistry. To explore the effect of neural activity on ketamine-induced apoptosis, the approaches of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and an environmental enrichment (EE) were performed. Ketamine-induced apoptosis in S1 is most prominent at postnatal days 5 and 7 (P5 - P7), and becomes insignificant by P12. Physiological and ketamine-induced apoptosis follow similar developmental patterns, mostly comprised of layer V pyramidal neurons at P5 and shifting to mostly layer II to IV GABAergic neurons by P9. Changes in neuronal activity induced by the DREADD system bidirectionally regulated the pattern of ketamine-induced apoptosis, with reduced activity inducing increased apoptosis and shifting the lamination pattern to a more immature form. Importantly, rearing mice in an EE significantly reduced the magnitude of ketamine-induced apoptosis and shifted its developmental pattern to a more mature form. Together, these results demonstrate that lamination pattern and cell-type dependent vulnerability to ketamine-induced apoptosis follow the physiological apoptosis pattern and are age- and activity-dependent. Naturally elevating neuronal activity is a possible method for reducing the adverse effects of general anesthesia.

A radial map of multi-whisker correlation selectivity in the rat barrel cortex

PubMed Central

Estebanez, Luc; Bertherat, Julien; Shulz, Daniel E.; Bourdieu, Laurent; Léger, Jean- François

2016-01-01

In the barrel cortex, several features of single-whisker stimuli are organized in functional maps. The barrel cortex also encodes spatio-temporal correlation patterns of multi-whisker inputs, but so far the cortical mapping of neurons tuned to such input statistics is unknown. Here we report that layer 2/3 of the rat barrel cortex contains an additional functional map based on neuronal tuning to correlated versus uncorrelated multi-whisker stimuli: neuron responses to uncorrelated multi-whisker stimulation are strongest above barrel centres, whereas neuron responses to correlated and anti-correlated multi-whisker stimulation peak above the barrel–septal borders, forming rings of multi-whisker synchrony-preferring cells. PMID:27869114

A radial map of multi-whisker correlation selectivity in the rat barrel cortex.

PubMed

Estebanez, Luc; Bertherat, Julien; Shulz, Daniel E; Bourdieu, Laurent; Léger, Jean-François

2016-11-21

In the barrel cortex, several features of single-whisker stimuli are organized in functional maps. The barrel cortex also encodes spatio-temporal correlation patterns of multi-whisker inputs, but so far the cortical mapping of neurons tuned to such input statistics is unknown. Here we report that layer 2/3 of the rat barrel cortex contains an additional functional map based on neuronal tuning to correlated versus uncorrelated multi-whisker stimuli: neuron responses to uncorrelated multi-whisker stimulation are strongest above barrel centres, whereas neuron responses to correlated and anti-correlated multi-whisker stimulation peak above the barrel-septal borders, forming rings of multi-whisker synchrony-preferring cells.

Thioredoxin, thioredoxin reductase, and alpha-crystallin revive inactivated glyceraldehyde 3-phosphate dehydrogenase in human aged and cataract lens extracts.

PubMed

Yan, Hong; Lou, Marjorie F; Fernando, M Rohan; Harding, John J

2006-10-02

To investigate whether mammalian thioredoxin (Trx) and thioredoxin reductase (TrxR), with or without alpha-crystallin can revive inactivated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in both the cortex and nucleus of human aged clear and cataract lenses. The lens cortex (including capsule-epithelium) and the nucleus were separated from human aged clear and cataract lenses (grade II and grade IV) with similar average age. The activity of GAPDH in the water-soluble fraction after incubation with or without Trx or/and TrxR for 60 min at 30 degrees C was measured spectrophotometrically. In addition, the effect of a combination of Trx/TrxR and bovine lens alpha-crystallin was investigated. GAPDH activity was lower in the nucleus of clear lenses than in the cortex, and considerably diminished in the cataractous lenses, particularly in the nucleus of cataract lenses grade IV. Trx and TrxR were able to revive the activity of GAPDH markedly in both the cortex and nucleus of the clear and cataract lenses. The percentage increase of activity in the cortex of the clear lenses was less than that of the nucleus in the presence of Trx and TrxR, whereas it was opposite in the cataract lenses. The revival of activity in both the cortex and nucleus from the cataract lenses grade II was higher than that of the grade IV. Moreover, Trx alone, but not TrxR, efficiently enhanced GAPDH activity. The combination of Trx and TrxR had greater effect than that of either alone. In addition, alpha(L)-crystallin enhanced the activity in the cortex of cataract grade II with Trx and TrxR present. However, it failed to provide a statistically significant increase of activity in the nucleus. This is the first evidence to show that mammalian Trx and TrxR are able to revive inactivated GAPDH in human aged clear and cataract lenses, and alpha-crystallin helped this effect. The inactivation of GAPDH during aging and cataract development must be caused in part by disulphide formation and in part by unfolding, and can be recovered by reducing agents and a molecular chaperone.

Pericellular innervation of neurons expressing abnormally hyperphosphorylated tau in the hippocampal formation of Alzheimer's disease patients.

PubMed

Blazquez-Llorca, Lidia; Garcia-Marin, Virginia; Defelipe, Javier

2010-01-01

Neurofibrillary tangles (NFT) represent one of the main neuropathological features in the cerebral cortex associated with Alzheimer's disease (AD). This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons. We have used immunocytochemical techniques and confocal microscopy reconstructions to examine the distribution of PHF-tau-immunoreactive (ir) cells, and their perisomatic GABAergic and glutamatergic innervations in the hippocampal formation and adjacent cortex of AD patients. Furthermore, correlative light and electron microscopy was employed to examine these neurons and the perisomatic synapses. We observed two patterns of staining in PHF-tau-ir neurons, pattern I (without NFT) and pattern II (with NFT), the distribution of which varies according to the cortical layer and area. Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau. At the electron microscope level, a normal looking neuropil with typical symmetric and asymmetric synapses was observed around PHF-tau-ir neurons. These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered.

Optical coherence tomography visualizes neurons in human entorhinal cortex

PubMed Central

Magnain, Caroline; Augustinack, Jean C.; Konukoglu, Ender; Frosch, Matthew P.; Sakadžić, Sava; Varjabedian, Ani; Garcia, Nathalie; Wedeen, Van J.; Boas, David A.; Fischl, Bruce

2015-01-01

Abstract. The cytoarchitecture of the human brain is of great interest in diverse fields: neuroanatomy, neurology, neuroscience, and neuropathology. Traditional histology is a method that has been historically used to assess cell and fiber content in the ex vivo human brain. However, this technique suffers from significant distortions. We used a previously demonstrated optical coherence microscopy technique to image individual neurons in several square millimeters of en-face tissue blocks from layer II of the human entorhinal cortex, over 50  μm in depth. The same slices were then sectioned and stained for Nissl substance. We registered the optical coherence tomography (OCT) images with the corresponding Nissl stained slices using a nonlinear transformation. The neurons were then segmented in both images and we quantified the overlap. We show that OCT images contain information about neurons that is comparable to what can be obtained from Nissl staining, and thus can be used to assess the cytoarchitecture of the ex vivo human brain with minimal distortion. With the future integration of a vibratome into the OCT imaging rig, this technique can be scaled up to obtain undistorted volumetric data of centimeter cube tissue blocks in the near term, and entire human hemispheres in the future. PMID:25741528

Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer's and Parkinson's diseases.

PubMed

Cheng, A V; Ferrier, I N; Morris, C M; Jabeen, S; Sahgal, A; McKeith, I G; Edwardson, J A; Perry, R H; Perry, E K

1991-11-01

The binding of the selective 5-HT2 antagonist [3H]ketanserin has been investigated in the temporal cortex of patients with Alzheimer's disease (SDAT), Parkinson's disease (PD), senile dementia of Lewy body type (SDLT) and neuropathologically normal subjects (control). 5-HT2 binding was reduced in SDAT, PD with dementia and SDLT. SDAT showed a 5-HT2 receptor deficit across most of the cortical layers. A significant decrease in 5-HT2 binding in the deep cortical layers was found in those SDLT cases without hallucinations. SDLT cases with hallucinations only showed a deficit in one upper layer. There was a significant difference in cortical layers III and V between SDLT without hallucinations and SDLT with hallucinations. The results confirm an abnormality of serotonin binding in various forms of dementia and suggest that preservation of 5-HT2 receptor in the temporal cortex may differentiate hallucinating from non-hallucinating cases of SDLT.

Modular Representation of Luminance Polarity In the Superficial Layers Of Primary Visual Cortex

PubMed Central

Smith, Gordon B.; Whitney, David E.; Fitzpatrick, David

2016-01-01

Summary The spatial arrangement of luminance increments (ON) and decrements (OFF) falling on the retina provides a wealth of information used by central visual pathways to construct coherent representations of visual scenes. But how the polarity of luminance change is represented in the activity of cortical circuits remains unclear. Using wide-field epifluorescence and two-photon imaging we demonstrate a robust modular representation of luminance polarity (ON or OFF) in the superficial layers of ferret primary visual cortex. Polarity-specific domains are found with both uniform changes in luminance and single light/dark edges, and include neurons selective for orientation and direction of motion. The integration of orientation and polarity preference is evident in the selectivity and discrimination capabilities of most layer 2/3 neurons. We conclude that polarity selectivity is an integral feature of layer 2/3 neurons, ensuring that the distinction between light and dark stimuli is available for further processing in downstream extrastriate areas. PMID:26590348

Deficient plasticity in the primary visual cortex of alpha-calcium/calmodulin-dependent protein kinase II mutant mice.

PubMed

Gordon, J A; Cioffi, D; Silva, A J; Stryker, M P

1996-09-01

The recent characterization of plasticity in the mouse visual cortex permits the use of mutant mice to investigate the cellular mechanisms underlying activity-dependent development. As calcium-dependent signaling pathways have been implicated in neuronal plasticity, we examined visual cortical plasticity in mice lacking the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha CaMKII). In wild-type mice, brief occlusion of vision in one eye during a critical period reduces responses in the visual cortex. In half of the alpha CaMKII-deficient mice, visual cortical responses developed normally, but visual cortical plasticity was greatly diminished. After intensive training, spatial learning in the Morris water maze was severely impaired in a similar fraction of mutant animals. These data indicate that loss of alpha CaMKII results in a severe but variable defect in neuronal plasticity.

Parvalbumin and calbindin immunoreactivity in the cerebral cortex of the hedgehog (Erinaceus europaeus).

PubMed Central

Ferrer, I; Zujar, M J; Admella, C; Alcantara, S

1992-01-01

To investigate the morphology and distribution of nonpyramidal neurons in the brain of insectivores, parvalbumin and calbindin 28 kDa immunoreactivity was examined in the cerebral cortex of the hedgehog (Erinaceus europaeus). Parvalbumin-immunoreactive cells were found in all layers of the isocortex, but in contrast to other mammals, a laminar organisation or specific regional distribution was not seen. Characteristic parvalbumin-immunoreactive neurons were multipolar cells with large ascending and descending dendrites extending throughout several layers. Calbindin-immunoreactive neurons were similar to those found in other species, although appearing in smaller numbers than in the cerebral cortex of more advanced mammals. The morphology and distribution of parvalbumin- and calbindin-immunoreactive cells in the piriform and entorhinal cortices were similar in hedgehogs and rodents. Parvalbumin-immunoreactive cells in the hippocampal complex were pyramidal-like and bitufted neurons, which were mainly found in the stratum oriens and stratum pyramidale of the hippocampus, and in the stratum moleculare and hilus of the fascia dentata. Heavily stained cells were found in the deep part of the stratum granulare. Intense calbindin immunoreactivity occurred mainly in the granule cell and molecular layers of the dentate gyrus and in the mossy fibre layer. The most outstanding feature in the hippocampal complex of the hedgehog was the extension of calbindin immunoreactivity to CA1 field of the hippocampus, suggesting, in agreement with other reports, that mossy fibres can establish synaptic contacts throughout the pyramidal cell layer. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1452472

The Functioning of a Cortex without Layers.

PubMed

Guy, Julien; Staiger, Jochen F

2017-01-01

A major hallmark of cortical organization is the existence of a variable number of layers, i.e., sheets of neurons stacked on top of each other, in which neurons have certain commonalities. However, even for the neocortex, variable numbers of layers have been described and it is just a convention to distinguish six layers from each other. Whether cortical layers are a structural epiphenomenon caused by developmental dynamics or represent a functionally important modularization of cortical computation is still unknown. Here we present our insights from the reeler mutant mouse, a model for a developmental, "molecular lesion"-induced loss of cortical layering that could serve as ground truth of what an intact layering adds to the cortex in terms of functionality. We could demonstrate that the reeler neocortex shows no inversion of cortical layers but rather a severe disorganization that in the primary somatosensory cortex leads to the complete loss of layers. Nevertheless, the somatosensory system is well organized. When exploring an enriched environment with specific sets of whiskers, activity-dependent gene expression takes place in the corresponding modules. Precise whisker stimuli lead to the functional activation of somatotopically organized barrel columns as visualized by intrinsic signal optical imaging. Similar results were obtained in the reeler visual system. When analyzing pathways that could be responsible for preservation of tactile perception, lemniscal thalamic projections were found to be largely intact, despite the smearing of target neurons across the cortical mantle. However, with optogenetic experiments we found evidence for a mild dispersion of thalamic synapse targeting on layer IV-spiny stellate cells, together with a general weakening in thalamocortical input strength. This weakening of thalamic inputs was compensated by intracortical mechanisms involving increased recurrent excitation and/or reduced feedforward inhibition. In conclusion, a layer loss so far only led to the detection of subtle defects in sensory processing by reeler mice. This argues in favor of a view in which cortical layers are not an essential component for basic perception and cognition. A view also supported by recent studies in birds, which can have remarkable cognitive capacities despite the lack of a neocortex with multiple cortical layers. In conclusion, we suggest that future studies directed toward understanding cortical functions should rather focus on circuits specified by functional cell type composition than mere laminar location.

Does the visual system of the flying fox resemble that of primates? The distribution of calcium-binding proteins in the primary visual pathway of Pteropus poliocephalus.

PubMed

Ichida, J M; Rosa, M G; Casagrande, V A

2000-01-31

It has been proposed that flying foxes and echolocating bats evolved independently from early mammalian ancestors in such a way that flying foxes form one of the suborders most closely related to primates. A major piece of evidence offered in support of a flying fox-primate link is the highly developed visual system of flying foxes, which is theorized to be primate-like in several different ways. Because the calcium-binding proteins parvalbumin (PV) and calbindin (CB) show distinct and consistent distributions in the primate visual system, the distribution of these same proteins was examined in the flying fox (Pteropus poliocephalus) visual system. Standard immunocytochemical techniques reveal that PV labeling within the lateral geniculate nucleus (LGN) of the flying fox is sparse, with clearly labeled cells located only within layer 1, adjacent to the optic tract. CB labeling in the LGN is profuse, with cells labeled in all layers throughout the nucleus. Double labeling reveals that all PV+ cells also contain CB, and that these cells are among the largest in the LGN. In primary visual cortex (V1) PV and CB label different classes of non-pyramidal neurons. PV+ cells are found in all cortical layers, although labeled cells are found only rarely in layer I. CB+ cells are found primarily in layers II and III. The density of PV+ neuropil correlates with the density of cytochrome oxidase staining; however, no CO+ or PV+ or CB+ patches or blobs are found in V1. These results show that the distribution of calcium-binding proteins in the flying fox LGN is unlike that found in primates, in which antibodies for PV and CB label specific separate populations of relay cells that exist in different layers. Indeed, the pattern of calcium-binding protein distribution in the flying fox LGN is different from that reported in any other terrestrial mammal. Within V1 no PV+ patches, CO blobs, or patchy distribution of CB+ neuropil that might reveal interblobs characteristic of primate V1 are found; however, PV and CB are found in separate populations of non-pyramidal neurons. The types of V1 cells labeled with antibodies to PV and CB in all mammals examined including the flying fox suggest that the similarities in the cellular distribution of these proteins in cortex reflect the fact that this feature is common to all mammals.

Memory and Learning Dysfunction Following Copper Toxicity: Biochemical and Immunohistochemical Basis.

PubMed

Kalita, Jayantee; Kumar, Vijay; Misra, Usha K; Bora, Himangsu K

2018-05-01

The prototype disease of Cu toxicity in human is Wilson disease, and cognitive impairment is the presenting symptom of it. There is no study correlating Cu-induced excitotoxicity, apoptosis, and astrocytic reaction with memory dysfunction. We report excitotoxicity, apoptosis, and astrocytic reaction of the hippocampus and frontal cortex with memory dysfunction in rat model of Cu toxicity. Thirty-six rats were divided into group I (control) and group II (100 mg/kgBwt/day CuSO 4 orally). Y-maze was performed for memory and learning at 0, 30, 60, and 90 days. Frontal and hippocampal free Cu concentration, oxidative stress markers [glutathione (GSH), total antioxidant toxicity (TAC), and malondialdehyde (MDA)], and glutamate were measured by atomic absorption spectroscopy, spectrophotometry, and ELISA, respectively. N-methyl-D-aspartate receptors (NMDARs) NR1, NR2A, and NR2B were done by real-time polymerase chain reaction. Immunohistochemistry for caspase-3 and glial fibrillary acidic protein (GFAP) were done and quantified using the ImageJ software. The glutamate level in hippocampus was increased, and NMDAR expression was decreased at 30, 60, and 90 days in group II compared to group I. In the frontal cortex, glutamate was increased at 90 days, but NMDARs were not significantly different in group II compared to group I. Caspase-3 and GFAP expressions were also higher in group II compared to group I, and these changes were more marked in hippocampus than frontal cortex. These changes correlated with respective free tissue Cu, oxidative stress, and Y-maze attention score. Cu toxicity induces apoptosis and astrocytosis of the hippocampus and frontal cortex through direct or glutamate and oxidative stress pathways, and results in impaired memory and learning.

Optical responses evoked by white matter stimulation in rat visual cortical slices and their relation to neural activities.

PubMed

Tanifuji, M; Yamanaka, A; Sunaba, R; Terakawa, S; Toyama, K

1996-10-28

To characterize optical responses (ORs) evoked by white matter (WM) stimulation in slices of rat visual cortex (VC) stained with voltage sensitive dyes, time course of ORs in each layer was investigated by recording ORs with a linearly aligned photodiode array, and the spatial patterns of the ORs at specified time after stimulation were investigated by a CCD camera in combination with stroboscopic illumination. The ORs recorded by the photodiode array were an increase in absorption at 700 nm and a decrease in the wavelength below 650 nm, suggesting that the ORs were dye related. The ORs were compared with field potentials (FPs) to clarify that neural events were represented by the ORs, and in support of this view, we found that the first order spatial differentials of ORs and that of FPs were in good agreement. We further compared ORs with intracellular responses, and found that the ORs mainly represent postsynaptic potentials (PSPs) of VC neurons except for the deeper part of layer VI, where a component representing action potentials in fibers stimulated directly was observed. The time-lapse imaging of ORs showed that excitation first propagated vertically up to layer I and subsequently in the horizontal direction along layers II-III and V-VI as in previous investigations. Spatio-temporal patterns of ORs under blockade of synaptic transmission were also investigated to reveal activity of fibers evoked by WM stimulation which produced such patterns of propagation.

Sub- and suprathreshold receptive field properties of pyramidal neurones in layers 5A and 5B of rat somatosensory barrel cortex

PubMed Central

Manns, Ian D; Sakmann, Bert; Brecht, Michael

2004-01-01

Layer 5 (L5) pyramidal neurones constitute a major sub- and intracortical output of the somatosensory cortex. This layer 5 is segregated into layers 5A and 5B which receive and distribute relatively independent afferent and efferent pathways. We performed in vivo whole-cell recordings from L5 neurones of the somatosensory (barrel) cortex of urethane-anaesthetized rats (aged 27–31 days). By delivering 6 deg single whisker deflections, whisker pad receptive fields were mapped for 16 L5A and 11 L5B neurones located below the layer 4 whisker-barrels. Average resting membrane potentials were −75.6±1.1 mV, and spontaneous action potential (AP) rates were 0.54± 0.14 APs s−1. Principal whisker (PW) evoked responses were similar in L5A and L5B neurones, with an average 5.0 ± 0.6 mV postsynaptic potential (PSP) and 0.12 ± 0.03 APs per stimulus. The layer 5A sub- and suprathreshold receptive fields (RFs) were more confined to the principle whisker than those of layer 5B. The basal dendritic arbors of layer 5A and 5B cells were located below both layer 4 barrels and septa, and the cell bodies were biased towards the barrel walls. Responses in both L5A and L5B developed slowly, with onset latencies of 10.1 ± 0.5 ms and peak latencies of 33.9 ± 3.3 ms. Contralateral multi-whisker stimulation evoked PSPs similar in amplitude to those of PW deflections; whereas, ipsilateral stimulation evoked smaller and longer latency PSPs. We conclude that in L5 a whisker deflection is represented in two ways: focally by L5A pyramids and more diffusely by L5B pyramids as a result of combining different inputs from lemniscal and paralemniscal pathways. The relevant output evoked by a whisker deflection could be the ensemble activity in the anatomically defined cortical modules associated with a single or a few barrel-columns. PMID:14724202

A θ-γ oscillation code for neuronal coordination during motor behavior.

PubMed

Igarashi, Jun; Isomura, Yoshikazu; Arai, Kensuke; Harukuni, Rie; Fukai, Tomoki

2013-11-20

Sequential motor behavior requires a progression of discrete preparation and execution states. However, the organization of state-dependent activity in neuronal ensembles of motor cortex is poorly understood. Here, we recorded neuronal spiking and local field potential activity from rat motor cortex during reward-motivated movement and observed robust behavioral state-dependent coordination between neuronal spiking, γ oscillations, and θ oscillations. Slow and fast γ oscillations appeared during distinct movement states and entrained neuronal firing. γ oscillations, in turn, were coupled to θ oscillations, and neurons encoding different behavioral states fired at distinct phases of θ in a highly layer-dependent manner. These findings indicate that θ and nested dual band γ oscillations serve as the temporal structure for the selection of a conserved set of functional channels in motor cortical layer activity during animal movement. Furthermore, these results also suggest that cross-frequency couplings between oscillatory neuronal ensemble activities are part of the general coding mechanism in cortex.

Functional emergence of a column-like architecture in layer 5 of mouse somatosensory cortex in vivo.

PubMed

Koizumi, Kyo; Inoue, Masatoshi; Chowdhury, Srikanta; Bito, Haruhiko; Yamanaka, Akihiro; Ishizuka, Toru; Yawo, Hiromu

2018-05-14

To investigate how the functional architecture is organized in layer 5 (L5) of the somatosensory cortex of a mouse in vivo, the input-output relationship was investigated using an all-optical approach. The neural activity in L5 was optically recorded using a Ca 2+ sensor, R-CaMP2, through a microprism inserted in the cortex under two-photon microscopy, while the L5 was regionally excited using optogenetics. The excitability was spread around the blue-light irradiated region, but the horizontal propagation was limited to within a certain distance (λ < 130 μm from the center of the illumination spot). When two regions were photostimulated with a short interval, the excitability of each cluster was reduced. Therefore, a column-like architecture had functionally emerged with reciprocal inhibition through a minimal number of synaptic relays. This could generate a synchronous output from a region of L5 with simultaneous enhancement of the signal-to-noise ratio by silencing of the neighboring regions.

HO-1 induction in motor cortex and intestinal dysfunction in TDP-43 A315T transgenic mice.

PubMed

Guo, Yansu; Wang, Qian; Zhang, Kunxi; An, Ting; Shi, Pengxiao; Li, Zhongyao; Duan, Weisong; Li, Chunyan

2012-06-15

TAR DNA-binding protein 43 (TDP-43) has been found to be related to the pathogenesis of amyotrophic lateral sclerosis (ALS). TDP-43 A315T transgenic mice develop degeneration of specific motor neurons, and accumulation of ubiquitinated proteins has been observed in the pyramidal cells of motor cortex of these mice. In this study, we found stress-responsive HO-1 induction and no autophagic alteration in motor cortex of TDP-43 A315T transgenic mice. Glial activation, especially astrocytic proliferation, occurred in cortical layer 5 and sub-meningeal region. Interestingly, we noticed that progressively thinned colon, swollen small intestine and reduced food intake, rather than severe muscle weakness, contributed to the death of TDP-43 A315T transgenic mice. Increased TDP-43 accumulation in the myenteric nerve plexus and increased thickness of muscular layer of colon were related to the intestinal dysfunction. Copyright © 2012 Elsevier B.V. All rights reserved.

Low-noise encoding of active touch by layer 4 in the somatosensory cortex.

PubMed

Hires, Samuel Andrew; Gutnisky, Diego A; Yu, Jianing; O'Connor, Daniel H; Svoboda, Karel

2015-08-06

Cortical spike trains often appear noisy, with the timing and number of spikes varying across repetitions of stimuli. Spiking variability can arise from internal (behavioral state, unreliable neurons, or chaotic dynamics in neural circuits) and external (uncontrolled behavior or sensory stimuli) sources. The amount of irreducible internal noise in spike trains, an important constraint on models of cortical networks, has been difficult to estimate, since behavior and brain state must be precisely controlled or tracked. We recorded from excitatory barrel cortex neurons in layer 4 during active behavior, where mice control tactile input through learned whisker movements. Touch was the dominant sensorimotor feature, with >70% spikes occurring in millisecond timescale epochs after touch onset. The variance of touch responses was smaller than expected from Poisson processes, often reaching the theoretical minimum. Layer 4 spike trains thus reflect the millisecond-timescale structure of tactile input with little noise.

[Response of sensorimotor cortex neurons to weak disturbances of the magnetic field in Wistar rats. Cytochemical study].

PubMed

Shpin'kova, V N; Nikol'skaia, K A; Gershteĭn, L M

2000-01-01

The influence of weak disturbances (up to 300 microT) of natural magnetic field on the protein metabolism in neurons of sensomotor cortex (layers III and V) in Wistar rats upon learning in a complex maze was studied. It was found that sensomotor neurons were very sensitive to weak disturbances of magnetic field. The protein content increased, while the nucleus-cytoplasm ratio and osmotic state of neurons remained unchanged. The specificity of neuron's reaction manifested itself in a sharp increase of nucleus and cytoplasm dimensions. In associative neurons (layer III), both the nucleus and cytoplasm were involved in the response; in efferent neurons (layer V), only nuclear parameters changed. The variance coefficients of all parameters of protein metabolism in sensomotor neurons, independently of their functional properties, were much higher than in control, which resulted in a wide diversity of cytochemical response.

Tooele Army Depot - South Area Suspected Releases Units RCRA Facility Investigation - Phase II for SWMUs 1, 25, and 37. Appendices: D-M

DTIC Science & Technology

1995-11-01

VI) or to the acidity of the aerosol. Many cases of nasal mucosal injury (inflamed mucosa, ulcerated or perforated septum) in workers exposed to Cr0 3...degeneration in the cerebral cortex, marked chromatoloysis, nuclear changes in neurons, neuronal degenera- tion in the cerebral cortex accompanied by...by degeneration and death of nerves in the focal areas of the cerebral cortex (i.e. the largest part of the brain), loss of vision, speech impairment

Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

PubMed

Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

2017-07-01

Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na + and K + channel function could reliably reproduce the observed increase in action potential firing and altered action potential waveform. These results, in conjunction with our prior findings on L5 neurons, suggest that principal neurons in the circuitry of the medial prefrontal cortex are altered in distinct ways in the fmr1 -/y mouse and may contribute to dysfunctional prefrontal cortex processing in fragile X syndrome. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Graviresponsiveness of surgically altered primary roots of Zea mays

NASA Technical Reports Server (NTRS)

Maimon, E.; Moore, R.

1991-01-01

We examined the gravitropic responses of surgically altered primary roots of Zea mays to determine the route by which gravitropic inhibitors move from the root tip to the elongating zone. Horizontally oriented roots, from which a 1-mm-wide girdle of epidermis plus 2-10 layers of cortex were removed from the apex of the elongating zone, curve downward. However, curvature occurred only apical to the girdle. Filling the girdle with mucilage-like material transmits curvature beyond the girdle. Vertically oriented roots with a half-girdle' (i.e. the epidermis and 2-10 layers of the cortex removed from half of the circumference of the apex of the elongating zone) curve away from the girdle. Inserting the half-girdle at the base of the elongating zone induces curvature towards the girdle. Filling the half-circumference girdles with mucilage-like material reduced curvature significantly. Stripping the epidermis and outer 2-5 layers of cortex from the terminal 1.5 cm of one side of a primary root induces curvature towards the cut, irrespective of the root's orientation to gravity. This effect is not due to desiccation since treated roots submerged in water also curved towards their cut surface. Coating a root's cut surface with a mucilage-like substance minimizes curvature. These results suggest that the outer cell-layers of the root, especially the epidermis, play an important role in root gravicurvature, and the gravitropic signals emanating from the root tip can move apoplastically through mucilage.

Parenchymatous cell division characterizes the fungal cortex of some common foliose lichens.

PubMed

Sanders, William B; de Los Ríos, Asunción

2017-02-01

Lichen-forming fungi produce diverse vegetative tissues, some closely resembling those of plants. Yet it has been repeatedly affirmed that none is a true parenchyma, in which cellular compartments are subdivided from all adjacent neighbors by cross walls adjoining older cross walls. Using transmission electron microscopy (TEM), we tested this assumption by examining patterns of septum formation in the parenchyma-like cortex of three lichens of different phylogenetic affinities: Sticta canariensis , Leptogium cyanescens , and Endocarpon pusillum . In the cortex of all three lichens, new septa adjoined perpendicularly or obliquely to previous septa. Septal walls possessed an electron-transparent core (median) layer covered on both sides by layers of intermediate electron density. At septal junctures, the core layer of the newer septum was not continuous with that of the older septum. Amorphous, electron-dense material often became deposited in the core region of older septal walls, and the septum gradually delaminated along its median into what could then be recognized as the distinct walls of neighboring cells. However, cells maintained continuity at pores, where adjacent remnants of the electron-transparent core layer suggested septal partition rather than secondary establishment of a lateral wall connection via anastomosis. Although fungal tissues first arise by the coalescence of filaments early in lichen ontogeny, the mature cortical tissues of some lichens are comparable to true parenchyma in the unrestricted orientation of their septal cross walls and the resulting ontogenetic relationship among neighboring cell compartments. © 2017 Botanical Society of America.

Effects of early overnutrition on the renal response to Ang II and expression of RAAS components in rat renal tissue.

PubMed

Granado, M; Amor, S; Fernández, N; Carreño-Tarragona, G; Iglesias-Cruz, M C; Martín-Carro, B; Monge, L; García-Villalón, A L

2017-10-01

The aim of this study was to analyze the effects of early overnutrition (EON) on the expression of the renin angiotensin aldosterone system (RAAS) components in renal cortex, renal arteries and renal perivascular adipose tissue (PVAT), as well as the vascular response of renal arteries to Angiotensin II (Ang II). On birth day litters were adjusted to twelve (L12-control) or three (L3-overfed) pups per mother. Half of the animals were sacrificed at weaning (21 days old) and the other half at 5 months of age. Ang II-induced vasoconstriction of renal artery segments increased in young overfed rats and decreased in adult overfed rats. EON decreased the gene expression of angiotensinogen (Agt), Ang II receptors AT1 and AT2 and eNOS in renal arteries of young rats, while it increased the mRNA levels of AT-2 and ET-1 in adult rats. In renal PVAT EON up-regulated the gene expression of COX-2 and TNF-α in young rats and the mRNA levels of renin receptor both in young and in adult rats. On the contrary, Ang II receptors mRNA levels were downregulated at both ages. Renal cortex of overfed rats showed increased gene expression of Agt in adult rats and of AT1 in young rats. However the mRNA levels of AT1 were decreased in the renal cortex of overfed adult rats. EON is associated with alterations in the vascular response of renal arteries to Ang II and changes in the gene expression of RAAS components in renal tissue. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Fine-Tuning of Neurogenesis is Essential for the Evolutionary Expansion of the Cerebral Cortex

PubMed Central

Poluch, Sylvie; Juliano, Sharon L.

2015-01-01

We used several animal models to study global and regional cortical surface expansion: The lissencephalic mouse, gyrencephalic normal ferrets, in which the parietal cortex expands more than the temporal cortex, and moderately lissencephalic ferrets, showing a similar degree of temporal and parietal expansion. We found that overall cortical surface expansion is achieved when specific events occur prior to surpragranular layer formation. (1) The subventricular zone (SVZ) shows substantial growth, (2) the inner SVZ contains an increased number of outer radial glia and intermediate progenitor cells expressing Pax6, and (3) the outer SVZ contains a progenitor cell composition similar to the combined VZ and inner SVZ. A greater parietal expansion is also achieved by eliminating the latero-dorsal neurogenic gradient, so that neurogenesis displays a similar developmental degree between parietal and temporal regions. In contrast, mice or lissencephalic ferrets show more advanced neurogenesis in the temporal region. In conclusion, we propose that global and regional cortical surface expansion rely on similar strategies consisting in altering the timing of neurogenic events prior to the surpragranular layer formation, so that more progenitor cells, and ultimately more neurons, are produced. This hypothesis is supported by findings from a ferret model of lissencephaly obtained by transiently blocking neurogenesis during the formation of layer IV. PMID:23968831

The laminar organization of the motor cortex in monodactylous mammals: a comparative assessment based on horse, chimpanzee, and macaque.

PubMed

Cozzi, Bruno; De Giorgio, Andrea; Peruffo, A; Montelli, S; Panin, M; Bombardi, C; Grandis, A; Pirone, A; Zambenedetti, P; Corain, L; Granato, Alberto

2017-08-01

The architecture of the neocortex classically consists of six layers, based on cytological criteria and on the layout of intra/interlaminar connections. Yet, the comparison of cortical cytoarchitectonic features across different species proves overwhelmingly difficult, due to the lack of a reliable model to analyze the connection patterns of neuronal ensembles forming the different layers. We first defined a set of suitable morphometric cell features, obtained in digitized Nissl-stained sections of the motor cortex of the horse, chimpanzee, and crab-eating macaque. We then modeled them using a quite general non-parametric data representation model, showing that the assessment of neuronal cell complexity (i.e., how a given cell differs from its neighbors) can be performed using a suitable measure of statistical dispersion such as the mean absolute deviation-mean absolute deviation (MAD). Along with the non-parametric combination and permutation methodology, application of MAD allowed not only to estimate, but also to compare and rank the motor cortical complexity across different species. As to the instances presented in this paper, we show that the pyramidal layers of the motor cortex of the horse are far more irregular than those of primates. This feature could be related to the different organizations of the motor system in monodactylous mammals.

Cortex proliferation in the root is a protective mechanism against abiotic stress.

PubMed

Cui, Hongchang

2015-01-01

Although as an organ the root plays a pivotal role in nutrient and water uptake as well anchorage, individual cell types function distinctly. Cortex is regarded as the least differentiated cell type in the root, but little is known about its role in plant growth and physiology. In recent studies, we found that cortex proliferation can be induced by oxidative stress. Since all types of abiotic stress lead to oxidative stress, this finding suggests a role for cortex in coping with abiotic stress. This hypothesis was tested in this study using the spy mutant, which has an extra layer of cortex in the root. Interestingly, the spy mutant was shown to be hypersensitive to salt and oxidizing reagent applied to the leaves, but it was as tolerant as the wild type to these compounds in the soil. This result lends support to the notion that cortex has a protective role against abiotic stress arising from the soil.

A Temporally Distinct Role for Group I and Group II Metabotropic Glutamate Receptors in Object Recognition Memory

ERIC Educational Resources Information Center

Brown, Malcolm Watson; Warburton, Elizabeth Clea; Barker, Gareth Robert Isaac; Bashir, Zafar Iqbal

2006-01-01

Recognition memory, involving the ability to discriminate between a novel and familiar object, depends on the integrity of the perirhinal cortex (PRH). Glutamate, the main excitatory neurotransmitter in the cortex, is essential for many types of memory processes. Of the subtypes of glutamate receptor, metabotropic receptors (mGluRs) have received…

Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice.

PubMed

Arime, Yosefu; Akiyama, Kazufumi

2017-01-01

Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC) and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP) mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days) of either saline or PCP (10 mg/kg): (1) a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2) brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s) in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2-3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells) in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2-3 of the prelimbic cortex of the PFC.

Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice

PubMed Central

Akiyama, Kazufumi

2017-01-01

Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC) and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP) mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days) of either saline or PCP (10 mg/kg): (1) a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2) brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s) in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2–3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells) in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2–3 of the prelimbic cortex of the PFC. PMID:29253020

Selective alterations of neurons and circuits related to early memory loss in Alzheimer’s disease

PubMed Central

Llorens-Martín, Maria; Blazquez-Llorca, Lidia; Benavides-Piccione, Ruth; Rabano, Alberto; Hernandez, Felix; Avila, Jesus; DeFelipe, Javier

2014-01-01

A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer’s disease (AD). The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC). Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII → dentate gyrus → CA3 → CA1) and monosynaptic (ECIII → CA1) circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits. PMID:24904307

Selective alterations of neurons and circuits related to early memory loss in Alzheimer's disease.

PubMed

Llorens-Martín, Maria; Blazquez-Llorca, Lidia; Benavides-Piccione, Ruth; Rabano, Alberto; Hernandez, Felix; Avila, Jesus; DeFelipe, Javier

2014-01-01

A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer's disease (AD). The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC). Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII → dentate gyrus → CA3 → CA1) and monosynaptic (ECIII → CA1) circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits.

Recruitment and Consolidation of Cell Assemblies for Words by Way of Hebbian Learning and Competition in a Multi-Layer Neural Network

PubMed Central

Garagnani, Max; Wennekers, Thomas; Pulvermüller, Friedemann

2009-01-01

Current cognitive theories postulate either localist representations of knowledge or fully overlapping, distributed ones. We use a connectionist model that closely replicates known anatomical properties of the cerebral cortex and neurophysiological principles to show that Hebbian learning in a multi-layer neural network leads to memory traces (cell assemblies) that are both distributed and anatomically distinct. Taking the example of word learning based on action-perception correlation, we document mechanisms underlying the emergence of these assemblies, especially (i) the recruitment of neurons and consolidation of connections defining the kernel of the assembly along with (ii) the pruning of the cell assembly’s halo (consisting of very weakly connected cells). We found that, whereas a learning rule mapping covariance led to significant overlap and merging of assemblies, a neurobiologically grounded synaptic plasticity rule with fixed LTP/LTD thresholds produced minimal overlap and prevented merging, exhibiting competitive learning behaviour. Our results are discussed in light of current theories of language and memory. As simulations with neurobiologically realistic neural networks demonstrate here spontaneous emergence of lexical representations that are both cortically dispersed and anatomically distinct, both localist and distributed cognitive accounts receive partial support. PMID:20396612

Recruitment and Consolidation of Cell Assemblies for Words by Way of Hebbian Learning and Competition in a Multi-Layer Neural Network.

PubMed

Garagnani, Max; Wennekers, Thomas; Pulvermüller, Friedemann

2009-06-01

Current cognitive theories postulate either localist representations of knowledge or fully overlapping, distributed ones. We use a connectionist model that closely replicates known anatomical properties of the cerebral cortex and neurophysiological principles to show that Hebbian learning in a multi-layer neural network leads to memory traces (cell assemblies) that are both distributed and anatomically distinct. Taking the example of word learning based on action-perception correlation, we document mechanisms underlying the emergence of these assemblies, especially (i) the recruitment of neurons and consolidation of connections defining the kernel of the assembly along with (ii) the pruning of the cell assembly's halo (consisting of very weakly connected cells). We found that, whereas a learning rule mapping covariance led to significant overlap and merging of assemblies, a neurobiologically grounded synaptic plasticity rule with fixed LTP/LTD thresholds produced minimal overlap and prevented merging, exhibiting competitive learning behaviour. Our results are discussed in light of current theories of language and memory. As simulations with neurobiologically realistic neural networks demonstrate here spontaneous emergence of lexical representations that are both cortically dispersed and anatomically distinct, both localist and distributed cognitive accounts receive partial support.

Activity-dependent self-regulation of viscous length scales in biological systems

NASA Astrophysics Data System (ADS)

Nandi, Saroj Kumar

2018-05-01

The cellular cortex, which is a highly viscous thin cytoplasmic layer just below the cell membrane, controls the cell's mechanical properties, which can be characterized by a hydrodynamic length scale ℓ . Cells actively regulate ℓ via the activity of force-generating molecules, such as myosin II. Here we develop a general theory for such systems through a coarse-grained hydrodynamic approach including activity in the static description of the system providing an experimentally accessible parameter and elucidate the detailed mechanism of how a living system can actively self-regulate its hydrodynamic length scale, controlling the rigidity of the system. Remarkably, we find that ℓ , as a function of activity, behaves universally and roughly inversely proportional to the activity of the system. Our theory rationalizes a number of experimental findings on diverse systems, and comparison of our theory with existing experimental data shows good agreement.

Peripheral facial nerve lesions induce changes in the firing properties of primary motor cortex layer 5 pyramidal cells.

PubMed

Múnera, A; Cuestas, D M; Troncoso, J

2012-10-25

Facial nerve lesions elicit long-lasting changes in vibrissal primary motor cortex (M1) muscular representation in rodents. Reorganization of cortical representation has been attributed to potentiation of preexisting horizontal connections coming from neighboring muscle representation. However, changes in layer 5 pyramidal neuron activity induced by facial nerve lesion have not yet been explored. To do so, the effect of irreversible facial nerve injury on electrophysiological properties of layer 5 pyramidal neurons was characterized. Twenty-four adult male Wistar rats were randomly subjected to two experimental treatments: either surgical transection of mandibular and buccal branches of the facial nerve (n=18) or sham surgery (n=6). Unitary and population activity of vibrissal M1 layer 5 pyramidal neurons recorded in vivo under general anesthesia was compared between sham-operated and facial nerve-injured animals. Injured animals were allowed either one (n=6), three (n=6), or five (n=6) weeks recovery before recording in order to characterize the evolution of changes in electrophysiological activity. As compared to control, facial nerve-injured animals displayed the following sustained and significant changes in spontaneous activity: increased basal firing frequency, decreased spike-associated local field oscillation amplitude, and decreased spontaneous theta burst firing frequency. Significant changes in evoked-activity with whisker pad stimulation included: increased short latency population spike amplitude, decreased long latency population oscillations amplitude and frequency, and decreased peak frequency during evoked single-unit burst firing. Taken together, such changes demonstrate that peripheral facial nerve lesions induce robust and sustained changes of layer 5 pyramidal neurons in vibrissal motor cortex. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

[Morphological changes of neurons and neuroglial cells in the brain of senescence-accelerated prone 1 (SAMP1) mice].

PubMed

Khudoerkov, R M; Sal'kov, V N; Sal'nikova, O V; Sobolev, V B

2014-01-01

Computerized morphometry was used to examine the sizes of neuronal bodies and the compactness of arrangement of neurons and neuroglial cells in layers III and V of the sensorimotor cortex in senescence-accelerated prone 1 (SAMP1) mice (an experimental group) and senescence-accelerated-resistant strain 1 (SAMR1) ones (a control group). In the SAMP1 mice as compared to the SAMR1 ones, the neuronal body sizes were significantly unchanged; the compactness of their arrangement decreased by 17 and 20% in layers III and V, respectively; that of neuroglial cells significantly increased by 14% in layer III only. In the SAMP1 mice versus the SAMR1 ones, the glial index rose by 36% in layer III and by 24% in layer V. During simulation of physiological aging, the sizes of neuronal bodies were shown to be virtually unchanged in the cerebral cortex; the compactness of their arrangement (cell counts) moderately reduced and that of neuroglial cells increased, which caused a rise in the glioneuronal index that was indicative of the enhanced supporting function of neuroglial cells during the physiological aging of brain structures.

NADPH-diaphorase activity and neurovascular coupling in the rat cerebral cortex.

PubMed

Vlasenko, O V; Maisky, V A; Maznychenko, A V; Pilyavskii, A I

2008-01-01

The distribution of NADPH-diaphorase-reactive (NADPH-dr) neurons and neuronal processes in the cerebral cortex and basal forebrain and their association with parenchymal vessels were studied in normal adult rats using NADPH-d histochemical protocol. The intensely stained cortical interneurons and reactive subcortically originating afferents, and stained microvessels were examined through a light microscope at law (x250) and high (x630) magnifications. NADPH-dr interneurons were concentrated in layers 2-6 of the M1 and M2 areas. However, clear predominance in their concentration (14 +/- 0.8 P < 0.05 per section) was found in layer 6. A mean number of labeled neurons in auditory (AuV), granular and agranular (GI, AIP) areas of the insular cortex was calculated to reach 12.3 +/- 0.7, 18.5 +/- 1.0 and 23.3 +/- 1.7 units per section, respectively (P < 0.05). The distinct apposition of labelled neurons to intracortical vessels was found in the M1, M2. The order of frequency of neurovascular coupling in different zones of the cerebral cortex was as following sequence: AuV (31.2%, n = 1040) > GI (18.0%, n = 640) > S1 (13.3%, n = 720) > M1 (6.3%, n = 1360). A large number of structural associations between labeled cells and vessels in the temporal and insular cortex indicate that NADPH-d-reactive interneurons can contribute to regulation of the cerebral regional blood flow in these areas.

Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells.

PubMed

Tait, Luke; Wedgwood, Kyle; Tsaneva-Atanasova, Krasimira; Brown, Jon T; Goodfellow, Marc

2018-07-14

The entorhinal cortex is a crucial component of our memory and spatial navigation systems and is one of the first areas to be affected in dementias featuring tau pathology, such as Alzheimer's disease and frontotemporal dementia. Electrophysiological recordings from principle cells of medial entorhinal cortex (layer II stellate cells, mEC-SCs) demonstrate a number of key identifying properties including subthreshold oscillations in the theta (4-12 Hz) range and clustered action potential firing. These single cell properties are correlated with network activity such as grid firing and coupling between theta and gamma rhythms, suggesting they are important for spatial memory. As such, experimental models of dementia have revealed disruption of organised dorsoventral gradients in clustered action potential firing. To better understand the mechanisms underpinning these different dynamics, we study a conductance based model of mEC-SCs. We demonstrate that the model, driven by extrinsic noise, can capture quantitative differences in clustered action potential firing patterns recorded from experimental models of tau pathology and healthy animals. The differential equation formulation of our model allows us to perform numerical bifurcation analyses in order to uncover the dynamic mechanisms underlying these patterns. We show that clustered dynamics can be understood as subcritical Hopf/homoclinic bursting in a fast-slow system where the slow sub-system is governed by activation of the persistent sodium current and inactivation of the slow A-type potassium current. In the full system, we demonstrate that clustered firing arises via flip bifurcations as conductance parameters are varied. Our model analyses confirm the experimentally suggested hypothesis that the breakdown of clustered dynamics in disease occurs via increases in AHP conductance. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acetogenic and Sulfate-Reducing Bacteria Inhabiting the Rhizoplane and Deep Cortex Cells of the Sea Grass Halodule wrightii†

PubMed Central

Küsel, Kirsten; Pinkart, Holly C.; Drake, Harold L.; Devereux, Richard

1999-01-01

Recent declines in sea grass distribution underscore the importance of understanding microbial community structure-function relationships in sea grass rhizospheres that might affect the viability of these plants. Phospholipid fatty acid analyses showed that sulfate-reducing bacteria and clostridia were enriched in sediments colonized by the sea grasses Halodule wrightii and Thalassia testudinum compared to an adjacent unvegetated sediment. Most-probable-number analyses found that in contrast to butyrate-producing clostridia, acetogens and acetate-utilizing sulfate reducers were enriched by an order of magnitude in rhizosphere sediments. Although sea grass roots are oxygenated in the daytime, colorimetric root incubation studies demonstrated that acetogenic O-demethylation and sulfidogenic iron precipitation activities were tightly associated with washed, sediment-free H. wrightii roots. This suggests that the associated anaerobes are able to tolerate exposure to oxygen. To localize and quantify the anaerobic microbial colonization, root thin sections were hybridized with newly developed 33P-labeled probes that targeted (i) low-G+C-content gram-positive bacteria, (ii) cluster I species of clostridia, (iii) species of Acetobacterium, and (iv) species of Desulfovibrio. Microautoradiography revealed intercellular colonization of the roots by Acetobacterium and Desulfovibrio species. Acetogenic bacteria occurred mostly in the rhizoplane and outermost cortex cell layers, and high numbers of sulfate reducers were detected on all epidermal cells and inward, colonizing some 60% of the deepest cortex cells. Approximately 30% of epidermal cells were colonized by bacteria that hybridized with an archaeal probe, strongly suggesting the presence of methanogens. Obligate anaerobes within the roots might contribute to the vitality of sea grasses and other aquatic plants and to the biogeochemistry of the surrounding sediment. PMID:10543830

Hemodynamic monitoring in different cortical layers with a single fiber optical system

NASA Astrophysics Data System (ADS)

Yu, Linhui; Noor, M. Sohail; Kiss, Zelma H. T.; Murari, Kartikeya

2018-02-01

Functional monitoring of highly-localized deep brain structures is of great interest. However, due to light scattering, optical methods have limited depth penetration or can only measure from a large volume. In this research, we demonstrate continuous measurement of hemodynamics in different cortical layers in response to thalamic deep brain stimulation (DBS) using a single fiber optical system. A 200-μm-core-diameter multimode fiber is used to deliver and collect light from tissue. The fiber probe can be stereotaxically implanted into the brain region of interest at any depth to measure the di use reflectance spectra from a tissue volume of 0.02-0.03 mm3 near the fiber tip. Oxygenation is then extracted from the reflectance spectra using an algorithm based on Monte Carlo simulations. Measurements were performed on the surface (cortical layer I) and at 1.5 mm depth (cortical layer VI) of the motor cortex in anesthetized rats with thalamic DBS. Preliminary results revealed the oxygenation changes in response to DBS. Moreover, the baseline as well as the stimulus-evoked change in oxygenation were different at the two depths of cortex.

Top-Down Regulation of Laminar Circuit via Inter-Area Signal for Successful Object Memory Recall in Monkey Temporal Cortex.

PubMed

Takeda, Masaki; Koyano, Kenji W; Hirabayashi, Toshiyuki; Adachi, Yusuke; Miyashita, Yasushi

2015-05-06

Memory retrieval in primates is orchestrated by a brain-wide neuronal circuit. To elucidate the operation of this circuit, it is imperative to comprehend neuronal mechanisms of coordination between area-to-area interaction and information processing within individual areas. By simultaneous recording from area 36 (A36) and area TE (TE) of the temporal cortex while monkeys performed a pair-association memory task, we found two distinct inter-area signal flows during memory retrieval: A36 spiking activity exhibited coherence with low-frequency field activity in either the supragranular or infragranular layer of TE. Of these two flows, only signal flow targeting the infragranular layer of TE was further translaminarly coupled with gamma activity in the supragranular layer of TE. Moreover, this coupling was observed when monkeys succeeded in the retrieval of the sought object but not when they failed. The results suggest that local translaminar processing can be recruited via a layer-specific inter-area network for memory retrieval. Copyright © 2015 Elsevier Inc. All rights reserved.

A Layer-specific Corticofugal Input to the Mouse Superior Colliculus.

PubMed

Zurita, Hector; Rock, Crystal; Perkins, Jessica; Apicella, Alfonso Junior

2017-07-05

In the auditory cortex (AC), corticofugal projections arise from each level of the auditory system and are considered to provide feedback "loops" important to modulate the flow of ascending information. It is well established that the cortex can influence the response of neurons in the superior colliculus (SC) via descending corticofugal projections. However, little is known about the relative contribution of different pyramidal neurons to these projections in the SC. We addressed this question by taking advantage of anterograde and retrograde neuronal tracing to directly examine the laminar distribution, long-range projections, and electrophysiological properties of pyramidal neurons projecting from the AC to the SC of the mouse brain. Here we show that layer 5 cortico-superior-collicular pyramidal neurons act as bandpass filters, resonating with a broad peak at ∼3 Hz, whereas layer 6 neurons act as low-pass filters. The dissimilar subthreshold properties of layer 5 and layer 6 cortico-superior-collicular pyramidal neurons can be described by differences in the hyperpolarization-activated cyclic nucleotide-gated cation h-current (Ih). Ih also reduced the summation of short trains of artificial excitatory postsynaptic potentials injected at the soma of layer 5, but not layer 6, cortico-superior-collicular pyramidal neurons, indicating a differential dampening effect of Ih on these neurons. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Recruitment of local inhibitory networks by horizontal connections in layer 2/3 of ferret visual cortex.

PubMed

Tucker, Thomas R; Katz, Lawrence C

2003-01-01

To investigate how neurons in cortical layer 2/3 integrate horizontal inputs arising from widely distributed sites, we combined intracellular recording and voltage-sensitive dye imaging to visualize the spatiotemporal dynamics of neuronal activity evoked by electrical stimulation of multiple sites in visual cortex. Individual stimuli evoked characteristic patterns of optical activity, while delivering stimuli at multiple sites generated interacting patterns in the regions of overlap. We observed that neurons in overlapping regions received convergent horizontal activation that generated nonlinear responses due to the emergence of large inhibitory potentials. The results indicate that co-activation of multiple sets of horizontal connections recruit strong inhibition from local inhibitory networks, causing marked deviations from simple linear integration.

Distinct roles of the cortical layers of area V1 in figure-ground segregation.

PubMed

Self, Matthew W; van Kerkoerle, Timo; Supèr, Hans; Roelfsema, Pieter R

2013-11-04

What roles do the different cortical layers play in visual processing? We recorded simultaneously from all layers of the primary visual cortex while monkeys performed a figure-ground segregation task. This task can be divided into different subprocesses that are thought to engage feedforward, horizontal, and feedback processes at different time points. These different connection types have different patterns of laminar terminations in V1 and can therefore be distinguished with laminar recordings. We found that the visual response started 40 ms after stimulus presentation in layers 4 and 6, which are targets of feedforward connections from the lateral geniculate nucleus and distribute activity to the other layers. Boundary detection started shortly after the visual response. In this phase, boundaries of the figure induced synaptic currents and stronger neuronal responses in upper layer 4 and the superficial layers ~70 ms after stimulus onset, consistent with the hypothesis that they are detected by horizontal connections. In the next phase, ~30 ms later, synaptic inputs arrived in layers 1, 2, and 5 that receive feedback from higher visual areas, which caused the filling in of the representation of the entire figure with enhanced neuronal activity. The present results reveal unique contributions of the different cortical layers to the formation of a visual percept. This new blueprint of laminar processing may generalize to other tasks and to other areas of the cerebral cortex, where the layers are likely to have roles similar to those in area V1. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study.

PubMed

Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Helaly, Ahmed N

2014-01-01

This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse.

Dynamical organization of the cytoskeletal cortex probed by micropipette aspiration

PubMed Central

Brugués, Jan; Maugis, Benoit; Casademunt, Jaume; Nassoy, Pierre; Amblard, François; Sens, Pierre

2010-01-01

Bleb-based cell motility proceeds by the successive inflation and retraction of large spherical membrane protrusions (“blebs”) coupled with substrate adhesion. In addition to their role in motility, cellular blebs constitute a remarkable illustration of the dynamical interactions between the cytoskeletal cortex and the plasma membrane. Here we study the bleb-based motions of Entamoeba histolytica in the constrained geometry of a micropipette. We construct a generic theoretical model that combines the polymerization of an actin cortex underneath the plasma membrane with the myosin-generated contractile stress in the cortex and the stress-induced failure of membrane-cortex adhesion. One major parameter dictating the cell response to micropipette suction is the stationary cortex thickness, controlled by actin polymerization and depolymerization. The other relevant physical parameters can be combined into two characteristic cortex thicknesses for which the myosin stress (i) balances the suction pressure and (ii) provokes membrane-cortex unbinding. We propose a general phase diagram for cell motions inside a micropipette by comparing these three thicknesses. In particular, we theoretically predict and experimentally verify the existence of saltatory and oscillatory motions for a well-defined range of micropipette suction pressures. PMID:20713731

[CHANGES IN THE NUMBER OF NEURONS IN THE MOTOR CORTEX OF RATS AND THEIR LOCOMOTOR ACTIVITY IN THE AGE ASPECT].

PubMed

Piavchenko, G A; Shmarkova, L I; Nozdrin, V I

2015-01-01

Using Laboras hardware-software complex, which is a system of automatic registration of behavioral reactions, the locomotor activity 1-, 8- and 16-month-old male rats (12 animals in each group) was recorded followed by counting the number of neuron cell bodies of in the layer V of the motor cortex in Nissl stained slides. It was found that the number of neurons in the motor cortex varied in different age groups. Maximal number of neurons was observed in 8-month-old animals. Motor activity was found to correlate with the number of neurons.

Pyramidal tract stimulation restores normal corticospinal tract connections and visuomotor skill after early postnatal motor cortex activity blockade

PubMed Central

Salimi, I; Friel, KM; Martin, JH

2008-01-01

Motor development depends on forming specific connections between the corticospinal tract (CST) and the spinal cord. Blocking CST activity in kittens during the critical period for establishing connections with spinal motor circuits results in permanent impairments in connectivity and function. The changes in connections are consistent with the hypothesis that the inactive tract is less competitive in developing spinal connections than the active tract. In this study we tested the competition hypothesis by determining if activating CST axons, after prior silencing during the critical period, abrogated development of aberrant corticospinal connections and motor impairments. In kittens, we inactivated motor cortex by muscimol infusion between postnatal weeks 5-7. We next electrically stimulated CST axons in the medullary pyramid 2.5 hours daily, between weeks 7-10. In controls (n=3), CST terminations were densest within the contralateral deeper, premotor, spinal layers. After prior inactivation (n=3), CST terminations were densest within the dorsal, somatic sensory, layers. There were more ipsilateral terminations from the active tract. During visually guided locomotion, there was a movement endpoint impairment. Stimulation after inactivation (n=6) resulted in significantly fewer terminations in the sensory layers and more in the premotor layers, and fewer ipsilateral connections from active cortex. Chronic stimulation reduced the current threshold for evoking contralateral movements by pyramidal stimulation, suggesting strengthening of connections. Importantly, stimulation significantly improved stepping accuracy. These findings show the importance of activity-dependent processes in specifying CST connections. They also provide a strategy for harnessing activity to rescue CST axons at risk of developing aberrant connections after CNS injury. PMID:18632946

Effect of 2,450 MHz microwave radiation on the development of the rat brain

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

Inouye, M.; Galvin, M.J.; McRee, D.I.

1983-12-01

Male Sprague-Dawley rats were exposed to 2,450 MHz microwave radiation at an incident power density of 10 mW/cm2 daily for 3 hours from day 4 of pregnancy (in utero exposure) through day 40 postpartum, except for 2 days at the perinatal period. The animals were killed, and the brains removed, weighed, measured, and histologically examined at 15, 20, 30, and 40 days of age. The histologic parameters examined included the cortical architecture of the cerebral cortex, the decline of the germinal layer along the lateral ventricles, the myelination of the corpus callosum, and the decline of the external germinal layermore » of the cerebellar cortex. In 40-day-old rats, quantitative measurements of neurons were also made. The spine density of the pyramidal cells in layer III of the somatosensory cortex, and the density of basal dendritic trees of the pyramidal cells in layer V were measured in Golgi-Cox impregnated specimens. In addition, the density of Purkinje cells and the extent of the Purkinje cell layer in each lobule were measured in midsagittal sections of the cerebellum stained with thionin. There were no remarkable differences between microwave-exposed and control (sham-irradiated) groups for any of the histologic or quantitative parameters examined; however, the findings provide important information on quantitative measurements of the brain. The data from this study failed to demonstrate that there is a significant effect on rat brain development due to microwave exposure (10 mW/cm2) during the embryonic, fetal, and postnatal periods.« less

Sensitivity of complex cells in cat striate cortex to relative motion.

PubMed

Hammond, P; Smith, A T

1984-06-03

Sensitivity of 95 complex cells to relative motion between oriented bars and textured backgrounds was investigated monocularly in the striate cortex of lightly anesthetized, paralyzed cats. Cells were classified conventionally. Those in deep layers were either direction-selective, or strongly preferred one direction of motion, and responded well to background texture motion alone: backgrounds potentiated the response to the bar in the cell's preferred direction when moved in phase, or in the opposite direction when moved in antiphase; other combinations depressed the level of response compared with that for the bar alone. The majority of direction-selective or strongly direction-biased cells in superficial layers behaved similarly. The most interesting superficial-layer cells were bidirectional or weakly direction-biased, and recorded closer to the cortical surface than the direction-selective neurons. A majority showed preference for relative motion, some for antiphase, others for in-phase motion, regardless of the absolute direction of motion across the receptive field, which could not be accounted for on the basis of separate responses to bars and backgrounds alone. Three of the superficial-layer direction-selective cells also showed preference for antiphase relative motion. In a few complex cells from superficial laminae, backgrounds were either without influence on responses to oriented stimuli, or purely suppressive. Visual backgrounds against which objects are perceived are usually neither featureless nor motionless: the results suggest that most complex cells in striate cortex are sensitive to the context in which objects are seen and susceptible to relationships between objects and their backgrounds in relative motion.

Dopaminergic Modulation of Excitatory Transmission in the Anterior Cingulate Cortex of Adult Mice

PubMed Central

Darvish-Ghane, Soroush; Yamanaka, Manabu

2016-01-01

Dopamine (DA) possesses potent neuromodulatory properties in the central nervous system. In the anterior cingulate cortex, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) are key ion channels in mediating nerve injury induced long-term potentiation (LTP) and chronic pain phenotype. In the present study, we reported the effects of DA on glutamate mediated excitatory post-synaptic currents (EPSCs) in pyramidal neurons of layer II/III of the ACC in adult mice. Bath application of DA (50 μM) caused a significant, rapid and reversible inhibition of evoked EPSCs (eEPSC). This inhibitory effect is dose-related and was absent in lower concentration of DA (5 μM). Furthermore, selective postsynaptic application of GDP-β-S (1.6 mM) in the internal solution completely abolished the inhibitory effects of DA (50 μM). We also investigated modulation of spontaneous EPSCs (sEPSCs) and TTX sensitive, miniature EPSCs (mEPSCs) by DA. Our results indicated mixed effects of potentiation and inhibition of frequency and amplitude for sEPSCs and mEPSCs. Furthermore, high doses of SCH23390 (100 μM) and sulpiride (100 μM) revealed that, inhibition of eEPSCs is mediated by postsynaptic D2-receptors (D2R). Our finding posits a pre- and postsynaptic mode of pyramidal neuron EPSC modulation in mice ACC by DA. PMID:27317578

When BOLD is thicker than water: processing social information about kin and friends at different levels of the social network.

PubMed

Wlodarski, Rafael; Dunbar, Robin I M

2016-12-01

The aim of this study was to examine differences in the neural processing of social information about kin and friends at different levels of closeness and social network level. Twenty-five female participants engaged in a cognitive social task involving different individuals in their social network while undergoing functional magnetic resonance imaging scanning to detect BOLD (Blood Oxygen Level Dependent) signals changes. Greater levels of activation occurred in several regions of the brain previously associated with social cognition when thinking about friends than when thinking about kin, including the posterior cingulate cortex (PCC) and the ventral medial prefrontal cortex (vMPFC). Linear parametric analyses across network layers further showed that, when it came to thinking about friends, activation increased in the vMPFC, lingual gyrus, and sensorimotor cortex as individuals thought about friends at closer layers of the network. These findings suggest that maintaining friendships may be more cognitively exacting than maintaining kin relationships. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

The Development and Activity-Dependent Expression of Aggrecan in the Cat Visual Cortex

PubMed Central

Sengpiel, F.; Beaver, C. J.; Crocker-Buque, A.; Kelly, G. M.; Matthews, R. T.; Mitchell, D. E.

2013-01-01

The Cat-301 monoclonal antibody identifies aggrecan, a chondroitin sulfate proteoglycan in the cat visual cortex and dorsal lateral geniculate nucleus (dLGN). During development, aggrecan expression increases in the dLGN with a time course that matches the decline in plasticity. Moreover, examination of tissue from selectively visually deprived cats shows that expression is activity dependent, suggesting a role for aggrecan in the termination of the sensitive period. Here, we demonstrate for the first time that the onset of aggrecan expression in area 17 also correlates with the decline in experience-dependent plasticity in visual cortex and that this expression is experience dependent. Dark rearing until 15 weeks of age dramatically reduced the density of aggrecan-positive neurons in the extragranular layers, but not in layer IV. This effect was reversible as dark-reared animals that were subsequently exposed to light showed normal numbers of Cat-301-positive cells. The reduction in aggrecan following certain early deprivation regimens is the first biochemical correlate of the functional changes to the γ-aminobutyric acidergic system that have been reported following early deprivation in cats. PMID:22368089

Refinement of learned skilled movement representation in motor cortex deep output layer

PubMed Central

Li, Qian; Ko, Ho; Qian, Zhong-Ming; Yan, Leo Y. C.; Chan, Danny C. W.; Arbuthnott, Gordon; Ke, Ya; Yung, Wing-Ho

2017-01-01

The mechanisms underlying the emergence of learned motor skill representation in primary motor cortex (M1) are not well understood. Specifically, how motor representation in the deep output layer 5b (L5b) is shaped by motor learning remains virtually unknown. In rats undergoing motor skill training, we detect a subpopulation of task-recruited L5b neurons that not only become more movement-encoding, but their activities are also more structured and temporally aligned to motor execution with a timescale of refinement in tens-of-milliseconds. Field potentials evoked at L5b in vivo exhibit persistent long-term potentiation (LTP) that parallels motor performance. Intracortical dopamine denervation impairs motor learning, and disrupts the LTP profile as well as the emergent neurodynamical properties of task-recruited L5b neurons. Thus, dopamine-dependent recruitment of L5b neuronal ensembles via synaptic reorganization may allow the motor cortex to generate more temporally structured, movement-encoding output signal from M1 to downstream circuitry that drives increased uniformity and precision of movement during motor learning. PMID:28598433

Postnatal Development of CB1 Receptor Expression in Rodent Somatosensory Cortex

PubMed Central

Deshmukh, Suvarna; Onozuka, Kaori; Bender, Kevin J.; Bender, Vanessa A.; Lutz, Beat; Mackie, Ken; Feldman, Daniel E.

2007-01-01

Endocannabinoids are powerful modulators of synaptic transmission that act on presynaptic cannabinoid receptors. Cannabinoid receptor type 1 (CB1) is the dominant receptor in the CNS, and is present in many brain regions, including sensory cortex. To investigate the potential role of CB1 receptors in cortical development, we examined the developmental expression of CB1 in rodent primary somatosensory (barrel) cortex, using immunohistochemistry with a CB1-specific antibody. We found that before postnatal day (P) 6, CB1 receptor staining was present exclusively in the cortical white matter, and that CB1 staining appeared in the grey matter between P6 and P20 in a specific laminar pattern. CB1 staining was confined to axons, and was most prominent in cortical layers 2/3, 5a, and 6. CB1 null (−/−) mice showed altered anatomical barrel maps in layer 4, with enlarged inter-barrel septa, but normal barrel size. These results indicate that CB1 receptors are present in early postnatal development and influence development of sensory maps. PMID:17210229

Comparison of functional and morphological deficits in the rat after gestational exposure to ionizing radiation

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

Norton, S.; Kimler, B.F.

1988-07-01

Ionizing radiation is a precise tool for altering formation of the developing cerebral cortex of the fetal rat. Whole body exposure of the pregnant rat on gestational day 13, 15 or 17 to 1.0 Gy of gamma radiation resulted in maximum thinning of the cortex on days 15 and 17. In the preweaning period, functional tests (negative geotaxis, reflex suspension, continuous corridor and gait) were most affected by irradiation gestational day 15, as was body weight. When a lower dose of radiation (0.75 Gy) was used on gestational day 15, the damage to the cortex was much less but behavioralmore » changes were still present. Frontal, parietal and occipital areas of the cortex were approximately equally affected. Using stepwise multiple regression analysis, the linkage of functional tests and cortical thickness was examined. Functional variables which were most commonly included as predictors of frontal and parietal cortex were negative geotaxis and continuous corridor. Occipital cortical layers were not predicted by behavioral variables. In predicting function using cortical variables, frontal cortex was better than parietal and occipital cortex was the poorest predictor.« less

Gap Junction Modulation of Low-Frequency Oscillations in the Cerebellar Granule Cell Layer.

PubMed

Robinson, Jennifer Claire; Chapman, C Andrew; Courtemanche, Richard

2017-08-01

Local field potential (LFP) oscillations in the granule cell layer (GCL) of the cerebellar cortex have been identified previously in the awake rat and monkey during immobility. These low-frequency oscillations are thought to be generated through local circuit interactions between Golgi cells and granule cells within the GCL. Golgi cells display rhythmic firing and pacemaking properties, and also are electrically coupled through gap junctions within the GCL. Here, we tested if gap junctions in the rat cerebellar cortex contribute to the generation of LFP oscillations in the GCL. We recorded LFP oscillations under urethane anesthesia, and examined the effects of local infusion of gap junction blockers on 5-15 Hz oscillations. Local infusion of the gap junction blockers carbenoxolone and mefloquine resulted in significant decreases in the power of oscillations over a 30-min period, but the power of oscillations was unchanged in control experiments following vehicle injections. In addition, infusion of gap junction blockers had no significant effect on multi-unit activity, suggesting that the attenuation of low-frequency oscillations was likely due to reductions in electrical coupling rather than a decreased excitability within the granule cell layer. Our results indicate that electrical coupling among the Golgi cell networks in the cerebellar cortex contributes to the local circuit mechanisms that promote the occurrence of GCL LFP slow oscillations in the anesthetized rat.

A Novel Population of Inner Cortical Cells in the Adrenal Gland That Displays Sexually Dimorphic Expression of Thyroid Hormone Receptor-β1

PubMed Central

Huang, Chen-Che Jeff; Kraft, Cary; Moy, Nicole; Ng, Lily

2015-01-01

The development of the adrenal cortex involves the formation and then subsequent regression of immature or fetal inner cell layers as the mature steroidogenic outer layers expand. However, controls over this remodeling, especially in the immature inner layer, are incompletely understood. Here we identify an inner cortical cell population that expresses thyroid hormone receptor-β1 (TRβ1), one of two receptor isoforms encoded by the Thrb gene. Using mice with a Thrbb1 reporter allele that expresses lacZ instead of TRβ1, β-galactosidase was detected in the inner cortex from early stages. Expression peaked at juvenile ages in an inner zone that included cells expressing 20-α-hydroxysteroid dehydrogenase, a marker of the transient, so-called X-zone in mice. The β-galactosidase-positive zone displayed sexually dimorphic regression in males after approximately 4 weeks of age but persisted in females into adulthood in either nulliparous or parous states. T3 treatment promoted hypertrophy of inner cortical cells, induced some markers of mature cortical cells, and, in males, delayed the regression of the TRβ1-positive zone, suggesting that TRβ1 could partly divert the differentiation fate and counteract male-specific regression of inner zone cells. TRβ1-deficient mice were resistant to these actions of T3, supporting a functional role for TRβ1 in the inner cortex. PMID:25774556

Robustness effect of gap junctions between Golgi cells on cerebellar cortex oscillations

PubMed Central

2011-01-01

Background Previous one-dimensional network modeling of the cerebellar granular layer has been successfully linked with a range of cerebellar cortex oscillations observed in vivo. However, the recent discovery of gap junctions between Golgi cells (GoCs), which may cause oscillations by themselves, has raised the question of how gap-junction coupling affects GoC and granular-layer oscillations. To investigate this question, we developed a novel two-dimensional computational model of the GoC-granule cell (GC) circuit with and without gap junctions between GoCs. Results Isolated GoCs coupled by gap junctions had a strong tendency to generate spontaneous oscillations without affecting their mean firing frequencies in response to distributed mossy fiber input. Conversely, when GoCs were synaptically connected in the granular layer, gap junctions increased the power of the oscillations, but the oscillations were primarily driven by the synaptic feedback loop between GoCs and GCs, and the gap junctions did not change oscillation frequency or the mean firing rate of either GoCs or GCs. Conclusion Our modeling results suggest that gap junctions between GoCs increase the robustness of cerebellar cortex oscillations that are primarily driven by the feedback loop between GoCs and GCs. The robustness effect of gap junctions on synaptically driven oscillations observed in our model may be a general mechanism, also present in other regions of the brain. PMID:22330240

Optogenetic Stimulation Shifts the Excitability of Cerebral Cortex from Type I to Type II: Oscillation Onset and Wave Propagation.

PubMed

Heitmann, Stewart; Rule, Michael; Truccolo, Wilson; Ermentrout, Bard

2017-01-01

Constant optogenetic stimulation targeting both pyramidal cells and inhibitory interneurons has recently been shown to elicit propagating waves of gamma-band (40-80 Hz) oscillations in the local field potential of non-human primate motor cortex. The oscillations emerge with non-zero frequency and small amplitude-the hallmark of a type II excitable medium-yet they also propagate far beyond the stimulation site in the manner of a type I excitable medium. How can neural tissue exhibit both type I and type II excitability? We investigated the apparent contradiction by modeling the cortex as a Wilson-Cowan neural field in which optogenetic stimulation was represented by an external current source. In the absence of any external current, the model operated as a type I excitable medium that supported propagating waves of gamma oscillations similar to those observed in vivo. Applying an external current to the population of inhibitory neurons transformed the model into a type II excitable medium. The findings suggest that cortical tissue normally operates as a type I excitable medium but it is locally transformed into a type II medium by optogenetic stimulation which predominantly targets inhibitory neurons. The proposed mechanism accounts for the graded emergence of gamma oscillations at the stimulation site while retaining propagating waves of gamma oscillations in the non-stimulated tissue. It also predicts that gamma waves can be emitted on every second cycle of a 100 Hz oscillation. That prediction was subsequently confirmed by re-analysis of the neurophysiological data. The model thus offers a theoretical account of how optogenetic stimulation alters the excitability of cortical neural fields.

The effect of trichlorfon and methylazoxymethanol on the development of guinea pig cerebellum.

PubMed

Mehl, Anna; Schanke, Tore M; Torvik, Ansgar; Fonnum, Frode

2007-03-01

The pesticide trichlorfon (125 mg/kg on days 42-44 in gestation) gives hypoplasia of the brain of the offspring without any significant reduction in their body weights. The hypoplasia may be caused by trichlorfon itself or by its metabolite dichlorvos. This period of development coincides with the growth spurt period of guinea pig brain. The largest changes occurred in the cerebellum. Electron microscopic examination of the cerebellar cortex showed increased apoptotic death of cells in the granule cell layer after trichlorfon treatment. A reduction in thickness of the external germinal layer of the cerebellar cortex and an elevated amount of pyknotic and karyorrhexic cells in the granule cell layer was found. There was a significant reduction in choline esterase, choline acetyltransferase and glutamate decarboxylase activities in the cerebellum. Methylazoxymethanol (15 mg/kg body weight, day 43) was examined for comparison and caused similar hypoplasia of the guinea pig cerebellum, but did also induce a reduction in body weight. Trichloroethanol, the main metabolite of trichlorfon, did not give brain hypoplasia.

Study of the Size and Shape of Synapses in the Juvenile Rat Somatosensory Cortex with 3D Electron Microscopy

PubMed Central

Rodríguez, José-Rodrigo; DeFelipe, Javier

2018-01-01

Abstract Changes in the size of the synaptic junction are thought to have significant functional consequences. We used focused ion beam milling and scanning electron microscopy (FIB/SEM) to obtain stacks of serial sections from the six layers of the rat somatosensory cortex. We have segmented in 3D a large number of synapses (n = 6891) to analyze the size and shape of excitatory (asymmetric) and inhibitory (symmetric) synapses, using dedicated software. This study provided three main findings. Firstly, the mean synaptic sizes were smaller for asymmetric than for symmetric synapses in all cortical layers. In all cases, synaptic junction sizes followed a log-normal distribution. Secondly, most cortical synapses had disc-shaped postsynaptic densities (PSDs; 93%). A few were perforated (4.5%), while a smaller proportion (2.5%) showed a tortuous horseshoe-shaped perimeter. Thirdly, the curvature was larger for symmetric than for asymmetric synapses in all layers. However, there was no correlation between synaptic area and curvature. PMID:29387782

Study of the Size and Shape of Synapses in the Juvenile Rat Somatosensory Cortex with 3D Electron Microscopy.

PubMed

Santuy, Andrea; Rodríguez, José-Rodrigo; DeFelipe, Javier; Merchán-Pérez, Angel

2018-01-01

Changes in the size of the synaptic junction are thought to have significant functional consequences. We used focused ion beam milling and scanning electron microscopy (FIB/SEM) to obtain stacks of serial sections from the six layers of the rat somatosensory cortex. We have segmented in 3D a large number of synapses ( n = 6891) to analyze the size and shape of excitatory (asymmetric) and inhibitory (symmetric) synapses, using dedicated software. This study provided three main findings. Firstly, the mean synaptic sizes were smaller for asymmetric than for symmetric synapses in all cortical layers. In all cases, synaptic junction sizes followed a log-normal distribution. Secondly, most cortical synapses had disc-shaped postsynaptic densities (PSDs; 93%). A few were perforated (4.5%), while a smaller proportion (2.5%) showed a tortuous horseshoe-shaped perimeter. Thirdly, the curvature was larger for symmetric than for asymmetric synapses in all layers. However, there was no correlation between synaptic area and curvature.

Distinct Translaminar Glutamatergic Circuits to GABAergic Interneurons in the Neonatal Auditory Cortex.

PubMed

Deng, Rongkang; Kao, Joseph P Y; Kanold, Patrick O

2017-05-09

GABAergic activity is important in neocortical development and plasticity. Because the maturation of GABAergic interneurons is regulated by neural activity, the source of excitatory inputs to GABAergic interneurons plays a key role in development. We show, by laser-scanning photostimulation, that layer 4 and layer 5 GABAergic interneurons in the auditory cortex in neonatal mice (

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

Mehl, Anna; Schanke, Tore M.; Torvik, Ansgar

The pesticide trichlorfon (125 mg/kg on days 42-44 in gestation) gives hypoplasia of Brain of the offspring without any significant reduction in their body weights. The hypoplasia may be caused by trichlorfon itself or by its metabolite dichlorvos. This period of development coincides with the growth spurt period of guinea pig brain. The largest changes occurred in the cerebellum. Electron microscopic examination of the cerebellar cortex showed increased apoptotic death of cells in the granule cell layer after trichlorfon treatment. A reduction in thickness of the external germinal layer of the cerebellar cortex and an elevated amount of pyknotic andmore » karyorrhexic cells in the granule cell layer was found. There was a significant reduction in choline esterase, choline acetyltransferase and glutamate decarboxylase activities in the cerebellum. Methylazoxymethanol (15 mg/kg body weight, day 43) was examined for comparison and caused similar hypoplasia of the guinea pig cerebellum, but did also induce a reduction in body weight. Trichloroethanol, the main metabolite of trichlorfon, did not give brain hypoplasia.« less

A Circuit for Motor Cortical Modulation of Auditory Cortical Activity

PubMed Central

Nelson, Anders; Schneider, David M.; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan

2013-01-01

Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity. PMID:24005287

"Subpial Fan Cell" - A Class of Calretinin Neuron in Layer 1 of Adult Monkey Prefrontal Cortex.

PubMed

Gabbott, Paul L A

2016-01-01

Layer 1 of the cortex contains populations of neurochemically distinct neurons and afferent fibers which markedly affect neural activity in the apical dendritic tufts of pyramidal cells. Understanding the causal mechanisms requires knowledge of the cellular architecture and synaptic organization of layer 1. This study has identified eight morphological classes of calretinin immunopositive (CRet+) neurons (including Cajal-Retzius cells) in layer 1 of the prefrontal cortex (PFC) in adult monkey (Macaca fasicularis), with a distinct class - termed "subpial fan (SPF) cell" - described in detail. SPF cells were rare horizontal unipolar CRet+ cells located directly beneath the pia with a single thick primary dendrite that branched into a characteristic fan-like dendritic tree tangential to the pial surface. Dendrites had spines, filamentous processes and thorny branchlets. SPF cells lay millimeters apart with intralaminar axons that ramified widely in upper layer 1. Such cells were GABA immunonegative (-) and occurred in areas beyond PFC. Interspersed amidst SPF cells displaying normal structural integrity were degenerating CRet+ neurons (including SPF cells) and clumps of lipofuscin-rich cellular debris. The number of degenerating SPF cells increased during adulthood. Ultrastructural analyses indicated SPF cell somata received asymmetric (A - presumed excitatory) and symmetric (S - presumed inhibitory) synaptic contacts. Proximal dendritic shafts received mainly S-type and distal shafts mostly A-type input. All dendritic thorns and most dendritic spines received both synapse types. The tangential areal density of SPF cell axonal varicosities varied radially from parent somata - with dense clusters in more distal zones. All boutons formed A-type contacts with CRet- structures. The main post-synaptic targets were dendritic shafts (67%; mostly spine-bearing) and dendritic spines (24%). SPF-SPF cell innervation was not observed. Morphometry of SPF cells indicated a unique class of CRet+/GABA- neuron in adult monkey PFC - possibly a subtype of persisting Cajal-Retzius cell. The distribution and connectivity of SPF cells suggest they act as integrative hubs in upper layer 1 during postnatal maturation. The main synaptic output of SPF cells likely provides a transminicolumnar excitatory influence across swathes of apical dendritic tufts - thus affecting information processing in discrete patches of layer 1 in adult monkey PFC.

The cerebellum: a neuronal learning machine?

NASA Technical Reports Server (NTRS)

Raymond, J. L.; Lisberger, S. G.; Mauk, M. D.

1996-01-01

Comparison of two seemingly quite different behaviors yields a surprisingly consistent picture of the role of the cerebellum in motor learning. Behavioral and physiological data about classical conditioning of the eyelid response and motor learning in the vestibulo-ocular reflex suggests that (i) plasticity is distributed between the cerebellar cortex and the deep cerebellar nuclei; (ii) the cerebellar cortex plays a special role in learning the timing of movement; and (iii) the cerebellar cortex guides learning in the deep nuclei, which may allow learning to be transferred from the cortex to the deep nuclei. Because many of the similarities in the data from the two systems typify general features of cerebellar organization, the cerebellar mechanisms of learning in these two systems may represent principles that apply to many motor systems.

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

Switching modes in corticogenesis: mechanisms of neuronal subtype transitions and integration in the cerebral cortex

PubMed Central

Toma, Kenichi; Hanashima, Carina

2015-01-01

Information processing in the cerebral cortex requires the activation of diverse neurons across layers and columns, which are established through the coordinated production of distinct neuronal subtypes and their placement along the three-dimensional axis. Over recent years, our knowledge of the regulatory mechanisms of the specification and integration of neuronal subtypes in the cerebral cortex has progressed rapidly. In this review, we address how the unique cytoarchitecture of the neocortex is established from a limited number of progenitors featuring neuronal identity transitions during development. We further illuminate the molecular mechanisms of the subtype-specific integration of these neurons into the cerebral cortex along the radial and tangential axis, and we discuss these key features to exemplify how neocortical circuit formation accomplishes economical connectivity while maintaining plasticity and evolvability to adapt to environmental changes. PMID:26321900

Axonal synapse sorting in medial entorhinal cortex

NASA Astrophysics Data System (ADS)

Schmidt, Helene; Gour, Anjali; Straehle, Jakob; Boergens, Kevin M.; Brecht, Michael; Helmstaedter, Moritz

2017-09-01

Research on neuronal connectivity in the cerebral cortex has focused on the existence and strength of synapses between neurons, and their location on the cell bodies and dendrites of postsynaptic neurons. The synaptic architecture of individual presynaptic axonal trees, however, remains largely unknown. Here we used dense reconstructions from three-dimensional electron microscopy in rats to study the synaptic organization of local presynaptic axons in layer 2 of the medial entorhinal cortex, the site of grid-like spatial representations. We observe path-length-dependent axonal synapse sorting, such that axons of excitatory neurons sequentially target inhibitory neurons followed by excitatory neurons. Connectivity analysis revealed a cellular feedforward inhibition circuit involving wide, myelinated inhibitory axons and dendritic synapse clustering. Simulations show that this high-precision circuit can control the propagation of synchronized activity in the medial entorhinal cortex, which is known for temporally precise discharges.

New metal phthalocyanines/metal simple hydroxide multilayers: experimental evidence of dipolar field-driven magnetic behavior.

PubMed

Bourzami, Riadh; Eyele-Mezui, Séraphin; Delahaye, Emilie; Drillon, Marc; Rabu, Pierre; Parizel, Nathalie; Choua, Sylvie; Turek, Philippe; Rogez, Guillaume

2014-01-21

A series of new hybrid multilayers has been synthesized by insertion-grafting of transition metal (Cu(II), Co(II), Ni(II), and Zn(II)) tetrasulfonato phthalocyanines between layers of Cu(II) and Co(II) simple hydroxides. The structural and spectroscopic investigations confirm the formation of new layered hybrid materials in which the phthalocyanines act as pillars between the inorganic layers. The magnetic investigations show that all copper hydroxide-based compounds behave similarly, presenting an overall antiferromagnetic behavior with no ordering down to 1.8 K. On the contrary, the cobalt hydroxide-based compounds present a ferrimagnetic ordering around 6 K, regardless of the nature of the metal phthalocyanine between the inorganic layers. The latter observation points to strictly dipolar interactions between the inorganic layers. The amplitude of the dipolar field has been evaluated from X-band and Q-band EPR spectroscopy investigation (Bdipolar ≈ 30 mT).

Depression of neuronal excitability and epileptic activities by group II metabotropic glutamate receptors in the medial entorhinal cortex.

PubMed

Zhang, Haopeng; Cilz, Nicholas I; Yang, Chuanxiu; Hu, Binqi; Dong, Hailong; Lei, Saobo

2015-11-01

Whereas the ionotropic glutamate receptors are the major mediator in glutamatergic transmission, the metabotropic glutamate receptors (mGluRs) usually play a modulatory role. Whereas the entorhinal cortex (EC) is an essential structure involved in the generation and propagation of epilepsy, the roles and mechanisms of mGluRs in epilepsy in the EC have not been determined. Here, we studied the effects of activation of group II metabotropic glutamate receptors (mGluRs II) on epileptiform activity induced by picrotoxin or deprivation of extracellular Mg2+ and neuronal excitability in the medial EC. We found that activation of mGluRs II by application of the selective agonist, LY354740, exerted robust inhibition on epileptiform activity. LY354740 hyperpolarized entorhinal neurons via activation of a K+ conductance and inhibition of a Na+ -permeable channel. LY354740-induced hyperpolarization was G protein-dependent, but independent of adenylyl cyclase and protein kinase A. However, the function of Gβγ was involved in mGluRs II-mediated depression of both neuronal excitability and epileptiform activity. Our results provide a novel cellular mechanism to explain the antiepileptic effects of mGluRs II in the treatment of epilepsy. © 2015 Wiley Periodicals, Inc.

Texture Segregation Causes Early Figure Enhancement and Later Ground Suppression in Areas V1 and V4 of Visual Cortex

PubMed Central

Poort, Jasper; Self, Matthew W.; van Vugt, Bram; Malkki, Hemi; Roelfsema, Pieter R.

2016-01-01

Segregation of images into figures and background is fundamental for visual perception. Cortical neurons respond more strongly to figural image elements than to background elements, but the mechanisms of figure–ground modulation (FGM) are only partially understood. It is unclear whether FGM in early and mid-level visual cortex is caused by an enhanced response to the figure, a suppressed response to the background, or both. We studied neuronal activity in areas V1 and V4 in monkeys performing a texture segregation task. We compared texture-defined figures with homogeneous textures and found an early enhancement of the figure representation, and a later suppression of the background. Across neurons, the strength of figure enhancement was independent of the strength of background suppression. We also examined activity in the different V1 layers. Both figure enhancement and ground suppression were strongest in superficial and deep layers and weaker in layer 4. The current–source density profiles suggested that figure enhancement was caused by stronger synaptic inputs in feedback-recipient layers 1, 2, and 5 and ground suppression by weaker inputs in these layers, suggesting an important role for feedback connections from higher level areas. These results provide new insights into the mechanisms for figure–ground organization. PMID:27522074

Cortical actin nanodynamics determines nitric oxide release in vascular endothelium.

PubMed

Fels, Johannes; Jeggle, Pia; Kusche-Vihrog, Kristina; Oberleithner, Hans

2012-01-01

The release of the main vasodilator nitric oxide (NO) by the endothelial NO synthase (eNOS) is a hallmark of endothelial function. We aim at elucidating the underlying mechanism how eNOS activity depends on cortical stiffness (К(cortex)) of living endothelial cells. It is hypothesized that cortical actin dynamics determines К(cortex) and directly influences eNOS activity. By combined atomic force microscopy and fluorescence imaging we generated mechanical and optical sections of single living cells. This approach allows the discrimination between К(cortex) and bulk cell stiffness (К(bulk)) and, additionally, the simultaneous analysis of submembranous actin web dynamics. We show that К(cortex) softens when cortical F-actin depolymerizes and that this shift from a gel-like stiff cortex to a soft G-actin rich layer, triggers the stiffness-sensitive eNOS activity. The results implicate that stiffness changes in the ∼100 nm phase of the submembranous actin web, without affecting К(bulk), regulate NO release and thus determines endothelial function.

The Piriform Cortex and Human Focal Epilepsy

PubMed Central

Vaughan, David N.; Jackson, Graeme D.

2014-01-01

It is surprising that the piriform cortex, when compared to the hippocampus, has been given relatively little significance in human epilepsy. Like the hippocampus, it has a phylogenetically preserved three-layered cortex that is vulnerable to excitotoxic injury, has broad connections to both limbic and cortical areas, and is highly epileptogenic – being critical to the kindling process. The well-known phenomenon of early olfactory auras in temporal lobe epilepsy highlights its clinical relevance in human beings. Perhaps because it is anatomically indistinct and difficult to approach surgically, as it clasps the middle cerebral artery, it has, until now, been understandably neglected. In this review, we emphasize how its unique anatomical and functional properties, as primary olfactory cortex, predispose it to involvement in focal epilepsy. From recent convergent findings in human neuroimaging, clinical epileptology, and experimental animal models, we make the case that the piriform cortex is likely to play a facilitating and amplifying role in human focal epileptogenesis, and may influence progression to epileptic intractability. PMID:25538678

The motor cortex: a network tuned to 7-14 Hz

PubMed Central

Castro-Alamancos, Manuel A.

2013-01-01

The neocortex or six layer cortex consists of at least 52 cytoarchitectonically distinct areas in humans, and similar areas can be distinguished in rodents. Each of these areas has a defining set of extrinsic connections, identifiable functional roles, a distinct laminar arrangement, etc. Thus, neocortex is extensively subdivided into areas of anatomical and functional specialization, but less is known about the specialization of cellular and network physiology across areas. The motor cortex appears to have a distinct propensity to oscillate in the 7–14 Hz frequency range. Augmenting responses, normal mu and beta oscillations, and abnormal oscillations or after discharges caused by enhancing excitation or suppressing inhibition are all expressed around this frequency range. The substrate for this activity may be an excitatory network that is unique to the motor cortex or that is more strongly suppressed in other areas, such as somatosensory cortex. Interestingly, augmenting responses are dependent on behavioral state. They are abolished during behavioral arousal. Here, I briefly review this evidence. PMID:23439785

Mechanisms and Treatment of OP-Induced Seizures and Neuropathology

DTIC Science & Technology

1993-08-18

Millan, M. H., Patel, S., Mello, L. M. and Meldrum , B. S., Focal injection of 2-amino-7- phosphonoheptanoic acid into prepiriform cortex protects against...LIST OF FIGURES Figure 1. Rapid, selective induction of c-fos and glial fibrillary acidic protein (GFAP) in piriform cortex (PC) by a single...specific to astrocytes, glial fibrillary acidic protein (GFAP). We found that there was a robust increase in GFAP staining in layers Il-III of PC that

Factors Controlling the Formation of Oxidized Root Channels: A Review and Annotated Bibliography

DTIC Science & Technology

1993-08-01

professor at the Wetland Bio - geochemistry Institute and the Department of Oceanography and Coastal Science at LoLisiana State University. The work was...accumulated in the cells of the epidermis, exodermis, endodermis, and marginal layers of the stele . Zinc and phosphorus appeared to be associated possibly...intercellular spaces. Iron was also found on the tissue diaphragms that traverse the cortex of the root, connecting its outer cortex with the stele . Electron

[Ultrastructural changes of myelinated fibers in the brain in continuous and attack-like paranoid schizophrenia].

PubMed

Uranova, N A; Kolomeets, N S; Vikhreva, O V; Zimina, I S; Rakhmanova, V I; Orlovskaya, D D

Previously the authors have reported the ultrastructural pathology of myelinated fibers (MF) in the brain in schizophrenia. The aim of the present study was to compare the effect of disease course on ultrastructural changes of MF. Postmortem electron microscopic morphometric study of MF was performed in the prefrontal cortex, caudate nucleus and hippocampus in 19 cases of paranoid schizophrenia. Fourteen cases of continuous schizophrenia, 5 cases of attack-like schizophrenia and 25 normal matched control cases were studied. The proportion (percentage) of pathological MF was estimated in the prefrontal cortex, layer 5, CA3 area of hippocampus, pyramidal layer, and in the head of the caudate nucleus. The percentage of MF having axonal atrophy and swelling of periaxonal oligodendrocyte process was significantly higher in both continuous and attack-like schizophrenia in all brain structures studied as compared to the control group. In the hippocampus and caudate nucleus, this parameter was increased significantly in attack-like schizophrenia as compared to continuous schizophrenia. In the prefrontal cortex. The percentage of the pathological MF having signs of deformation and destruction of myelin sheaths increased significantly only in continuous schizophrenia as compared to the control group. MF pathology is similar in attack-like and continuous paranoid schizophrenia but differ by the degree of severity of pathological MF. Abnormalities in MF contribute to the disconnectivity between the prefrontal cortex, caudate nucleus and hippocampus.

Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission.

PubMed

Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J

2016-07-01

Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood. © The Author 2016. Published by Oxford University Press.

Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission

PubMed Central

Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J.

2016-01-01

Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood. PMID:26980613

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

PubMed Central

Zhao, Fang; Tsien, Joe Z.

2017-01-01

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

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

PubMed

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

2017-01-01

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

Depressed mitochondrial function and electron transport Complex II-mediated H2O2 production in the cortex of type 1 diabetic rodents.

PubMed

Chowdhury, Subir Roy; Djordjevic, Jelena; Thomson, Ella; Smith, Darrell R; Albensi, Benedict C; Fernyhough, Paul

2018-05-23

Abnormalities in mitochondrial function under diabetic conditions can lead to deficits in function of cortical neurons and their support cells exhibiting a pivotal role in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. We aimed to assess simultaneously mitochondrial respiration rates and membrane potential or H 2 O 2 generation and proteins involved in mitochondrial dynamics, antioxidants and AMPK/SIRT/PGC-1α pathway activity in cortex under diabetic conditions. Cortical mitochondria from streptozotocin (STZ)-induced type 1 diabetic rats or mice, and aged-match controls were used for simultaneous measurements of mitochondrial respiration rates and mitochondrial membrane potential (mtMP) or H 2 O 2 using OROBOROS oxygraph and measurements of enzymatic activities by a spectrophotometer. Protein levels in cortical mitochondria and homogenates were determined by Western blotting. Mitochondrial coupled respiration rates and FCCP-induced uncoupled respiration rates were significantly decreased in mitochondria of STZ-diabetic cortical rats compared to controls. The mtMP in the presence of ADP was significantly depolarized and succinate-dependent respiration rates and H 2 O 2 were significantly diminished in mitochondria of diabetic animals compared to controls, accompanied with reduced expression of CuZn- and Mn-superoxide dismutase. The enzymatic activities of Complex I, II, and IV and protein levels of certain components of Complex I and II, mitofusin 2 (Mfn2), dynamin-related protein 1 (DRP1), P-AMPK, SIRT2 and PGC-1α were significantly diminished in diabetic cortex. Deficits in mitochondrial function, dynamics, and antioxidant capabilities putatively mediated through sub-optimal AMPK/SIRT/PGC-1α signaling, are involved in the development of early sub-clinical neurodegeneration in the cortex under diabetic conditions. Copyright © 2017. Published by Elsevier Inc.

The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a.

PubMed

Cánovas, José; Berndt, F Andrés; Sepúlveda, Hugo; Aguilar, Rodrigo; Veloso, Felipe A; Montecino, Martín; Oliva, Carlos; Maass, Juan C; Sierralta, Jimena; Kukuljan, Manuel

2015-05-13

The acquisition of distinct neuronal fates is fundamental for the function of the cerebral cortex. We find that the development of subcerebral projections from layer 5 neurons in the mouse neocortex depends on the high levels of expression of the transcription factor CTIP1; CTIP1 is coexpressed with CTIP2 in neurons that project to subcerebral targets and with SATB2 in those that project to the contralateral cortex. CTIP1 directly represses Tbr1 in layer 5, which appears as a critical step for the acquisition of the subcerebral fate. In contrast, lower levels of CTIP1 in layer 6 are required for TBR1 expression, which directs the corticothalamic fate. CTIP1 does not appear to play a critical role in the acquisition of the callosal projection fate in layer 5. These findings unravel a key step in the acquisition of cell fate for closely related corticofugal neurons and indicate that differential dosages of transcriptions factors are critical to specify different neuronal identities. Copyright © 2015 the authors 0270-6474/15/357552-13$15.00/0.

High gamma power in ECoG reflects cortical electrical stimulation effects on unit activity in layers V/VI

NASA Astrophysics Data System (ADS)

Yazdan-Shahmorad, Azadeh; Kipke, Daryl R.; Lehmkuhle, Mark J.

2013-12-01

Objective. Cortical electrical stimulation (CES) has been used extensively in experimental neuroscience to modulate neuronal or behavioral activity, which has led this technique to be considered in neurorehabilitation. Because the cortex and the surrounding anatomy have irregular geometries as well as inhomogeneous and anisotropic electrical properties, the mechanism by which CES has therapeutic effects is poorly understood. Therapeutic effects of CES can be improved by optimizing the stimulation parameters based on the effects of various stimulation parameters on target brain regions. Approach. In this study we have compared the effects of CES pulse polarity, frequency, and amplitude on unit activity recorded from rat primary motor cortex with the effects on the corresponding local field potentials (LFP), and electrocorticograms (ECoG). CES was applied at the surface of the cortex and the unit activity and LFPs were recorded using a penetrating electrode array, which was implanted below the stimulation site. ECoGs were recorded from the vicinity of the stimulation site. Main results. Time-frequency analysis of LFPs following CES showed correlation of gamma frequencies with unit activity response in all layers. More importantly, high gamma power of ECoG signals only correlated with the unit activity in lower layers (V-VI) following CES. Time-frequency correlations, which were found between LFPs, ECoGs and unit activity, were frequency- and amplitude-dependent. Significance. The signature of the neural activity observed in LFP and ECoG signals provides a better understanding of the effects of stimulation on network activity, representative of large numbers of neurons responding to stimulation. These results demonstrate that the neurorehabilitation and neuroprosthetic applications of CES targeting layered cortex can be further improved by using field potential recordings as surrogates to unit activity aimed at optimizing stimulation efficacy. Likewise, the signatures of unit activity observed as changes in high gamma power in ECoGs suggest that future cortical stimulation studies could rely on less invasive feedback schemes that incorporate surface stimulation with ECoG reporting of stimulation efficacy.

A quantitative analysis of the local connectivity between pyramidal neurons in layers 2/3 of the rat visual cortex.

PubMed

Hellwig, B

2000-02-01

This study provides a detailed quantitative estimate for local synaptic connectivity between neocortical pyramidal neurons. A new way of obtaining such an estimate is presented. In acute slices of the rat visual cortex, four layer 2 and four layer 3 pyramidal neurons were intracellularly injected with biocytin. Axonal and dendritic arborizations were three-dimensionally reconstructed with the aid of a computer-based camera lucida system. In a computer experiment, pairs of pre- and postsynaptic neurons were formed and potential synaptic contacts were calculated. For each pair, the calculations were carried out for a whole range of distances (0 to 500 microm) between the presynaptic and the postsynaptic neuron, in order to estimate cortical connectivity as a function of the spatial separation of neurons. It was also differentiated whether neurons were situated in the same or in different cortical layers. The data thus obtained was used to compute connection probabilities, the average number of contacts between neurons, the frequency of specific numbers of contacts and the total number of contacts a dendritic tree receives from the surrounding cortical volume. Connection probabilities ranged from 50% to 80% for directly adjacent neurons and from 0% to 15% for neurons 500 microm apart. In many cases, connections were mediated by one contact only. However, close neighbors made on average up to 3 contacts with each other. The question as to whether the method employed in this study yields a realistic estimate of synaptic connectivity is discussed. It is argued that the results can be used as a detailed blueprint for building artificial neural networks with a cortex-like architecture.

Neurons immunoreactive for vasoactive intestinal polypeptide in the rat primary somatosensory cortex: morphology and spatial relationship to barrel-related columns.

PubMed

Bayraktar, T; Welker, E; Freund, T F; Zilles, K; Staiger, J F

2000-05-08

Vasoactive intestinal polypeptide (VIP) in neocortex affects neuronal excitability as well as cortical blood flow and metabolism. Interneurons immunoreactive for VIP (VIP-IR neurons) are characterized by their predominantly bipolar appearance and the radial orientation of their main dendrites. In order to determine whether the morphology of VIP-IR neurons is related to the functional organization of the cortex into vertical columns, we combined both immunostaining of neurons containing VIP and cytochrome oxidase histochemistry for visualizing barrels, morphological layer IV correlates of functional columns, in the primary somatosensory (barrel) cortex of rats. VIP-IR neurons were localized in supragranular (48%), granular (16%), and infragranular layers (36%) as well as in the white matter. In the granular layer, a clear trend that more neurons were located in interbarrel septa rather than in barrels could be observed, resulting in a neuronal density which was about one-third higher in the septal area. VIP-IR neurons from the different cortical layers were three-dimensionally reconstructed from serial sections by using a computer microscope system. The neurons were mostly bipolar. Striking morphological differences in both axonal and dendritic trees were found between neurons whose cell bodies were located in supragranular, granular, and the upper part of infragranular layers, and those whose cell bodies were located in the area below. The former had dendrites which often reached layer I, where they bifurcated several times, and axonal trees which were particularly oriented vertically, with a tangential extent smaller than the width of barrels. Therefore, these neurons were mostly confined to either a barrel- or septum-related column. By contrast, the dendrites of neurons of the latter group did not reach the granular layer. Furthermore, these neurons had axons with sometimes very long horizontal collaterals, which often spanned two, in one case three, barrel columns. It is proposed that the differential morphology of neurons with different locations as stated above parallels to some extent the divergence of input streaming into the corresponding layer-defined areas. As a possible consequence of this, VIP-IR neurons may be capable of adapting the excitability and metabolism of cortical compartments either in a spatially limited or more extensive way. Copyright 2000 Wiley-Liss, Inc.

Tunicamycin-induced unfolded protein response in the developing mouse brain

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

Wang, Haiping; Wang, Xin; Ke, Zun-Ji

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident bymore » the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific.« less

Method of removing oxidized contaminants from water

DOEpatents

Amonette, James E.; Fruchter, Jonathan S.; Gorby, Yuri A.; Cole, Charles R.; Cantrell, Kirk J.; Kaplan, Daniel I.

1998-01-01

The present invention is a method for removing oxidized contaminant(s) from water. More specifically, the invention has the steps of contacting water containing the oxidized contaminant(s) with a layered aluminosilicate having Fe(II). The aluminosilicate may contain naturally occurring Fe(II), or the Fe(II) may be produced by reducing Fe(III) that is initially present. Reduction may be either by exposure to a chemical or biological reductant. Contacting the water containing oxidized contaminant(s) may be by (1) injection of Fe(II)-containing layered aluminosilicate, via a well, into a saturated zone where it is likely to intercept the contaminated water; (2) injection of contaminated water into a vessel containing the Fe(II)-bearing layered aluminosilicate; and (3) first reducing Fe(III) in the layered aluminosilicate to Fe(II) by injection of a biological or chemical reductant, into an aquifer or vessel having sufficient Fe(III)-bearing aluminosilicate to produce the necessary Fe(II).

Method of removing oxidized contaminants from water

DOEpatents

Amonette, J.E.; Fruchter, J.S.; Gorby, Y.A.; Cole, C.R.; Cantrell, K.J.; Kaplan, D.I.

1998-07-21

The present invention is a method for removing oxidized contaminant(s) from water. More specifically, the invention has the steps of contacting water containing the oxidized contaminant(s) with a layered aluminosilicate having Fe(II). The aluminosilicate may contain naturally occurring Fe(II), or the Fe(II) may be produced by reducing Fe(III) that is initially present. Reduction may be either by exposure to a chemical or biological reductant. Contacting the water containing oxidized contaminant(s) may be by (1) injection of Fe(II)-containing layered aluminosilicate, via a well, into a saturated zone where it is likely to intercept the contaminated water; (2) injection of contaminated water into a vessel containing the Fe(II)-bearing layered aluminosilicate; and (3) first reducing Fe(III) in the layered aluminosilicate to Fe(II) by injection of a biological or chemical reductant, into an aquifer or vessel having sufficient Fe(III)-bearing aluminosilicate to produce the necessary Fe(II). 8 figs.

Cortical lamina-dependent blood volume changes in human brain at 7 T.

PubMed

Huber, Laurentius; Goense, Jozien; Kennerley, Aneurin J; Trampel, Robert; Guidi, Maria; Reimer, Enrico; Ivanov, Dimo; Neef, Nicole; Gauthier, Claudine J; Turner, Robert; Möller, Harald E

2015-02-15

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8-1.6mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Axon topography of layer 6 spiny cells to orientation map in the primary visual cortex of the cat (area 18).

PubMed

Karube, Fuyuki; Sári, Katalin; Kisvárday, Zoltán F

2017-04-01

To uncover the functional topography of layer 6 neurons, optical imaging was combined with three-dimensional neuronal reconstruction. Apical dendrite morphology of 23 neurons revealed three distinct types. Type Aa possessed a short apical dendrite with many oblique branches, Type Ab was characterized by a short and less branched apical dendrite, whereas Type B had a long apical dendrite with tufts in layer 2. Each type had a similar number of boutons, yet their spatial distribution differed from each other in both radial and horizontal extent. Boutons of Type Aa and Ab were almost restricted to the column of the parent soma with a laminar preference to layer 4 and 5/6, respectively. Only Type B contributed to long horizontal connections (up to 1.5 mm) mostly in deep layers. For all types, bouton distribution on orientation map showed an almost equal occurrence at iso- (52.6 ± 18.8 %) and non-iso-orientation (oblique, 27.7 ± 14.9 % and cross-orientation 19.7 ± 10.9 %) sites. Spatial convergence of axons of nearby layer 6 spiny neurons depended on soma separation of the parent cells, but only weakly on orientation preference, contrary to orientation dependence of converging axons of layer 4 spiny cells. The results show that layer 6 connections have only a weak dependence on orientation preference compared with those of layers 2/3 (Buzás et al., J Comp Neurol 499:861-881, 2006) and 4 (Karube and Kisvárday, Cereb Cortex 21:1443-1458, 2011).

Contrasting effects of strabismic amblyopia on metabolic activity in superficial and deep layers of striate cortex

PubMed Central

Adams, Daniel L.; Economides, John R.

2015-01-01

To probe the mechanism of visual suppression, we have raised macaques with strabismus by disinserting the medial rectus muscle in each eye at 1 mo of age. Typically, this operation produces a comitant, alternating exotropia with normal acuity in each eye. Here we describe an unusual occurrence: the development of severe amblyopia in one eye of a monkey after induction of exotropia. Shortly after surgery, the animal demonstrated a strong fixation preference for the left eye, with apparent suppression of the right eye. Later, behavioral testing showed inability to track or to saccade to targets with the right eye. With the left eye occluded, the animal demonstrated no visually guided behavior. Optokinetic nystagmus was absent in the right eye. Metabolic activity in striate cortex was assessed by processing the tissue for cytochrome oxidase (CO). Amblyopia caused loss of CO in one eye's rows of patches, presumably those serving the blind eye. Layers 4A and 4B showed columns of reduced CO, in register with pale rows of patches in layer 2/3. Layers 4C, 5, and 6 also showed columns of CO activity, but remarkably, comparison with more superficial layers showed a reversal in contrast. In other words, pale CO staining in layers 2/3, 4A, and 4B was aligned with dark CO staining in layers 4C, 5, and 6. No experimental intervention or deprivation paradigm has been reported previously to produce opposite effects on metabolic activity in layers 2/3, 4A, and 4B vs. layers 4C, 5, and 6 within a given eye's columns. PMID:25810480

Contrasting effects of strabismic amblyopia on metabolic activity in superficial and deep layers of striate cortex.

PubMed

Adams, Daniel L; Economides, John R; Horton, Jonathan C

2015-05-01

To probe the mechanism of visual suppression, we have raised macaques with strabismus by disinserting the medial rectus muscle in each eye at 1 mo of age. Typically, this operation produces a comitant, alternating exotropia with normal acuity in each eye. Here we describe an unusual occurrence: the development of severe amblyopia in one eye of a monkey after induction of exotropia. Shortly after surgery, the animal demonstrated a strong fixation preference for the left eye, with apparent suppression of the right eye. Later, behavioral testing showed inability to track or to saccade to targets with the right eye. With the left eye occluded, the animal demonstrated no visually guided behavior. Optokinetic nystagmus was absent in the right eye. Metabolic activity in striate cortex was assessed by processing the tissue for cytochrome oxidase (CO). Amblyopia caused loss of CO in one eye's rows of patches, presumably those serving the blind eye. Layers 4A and 4B showed columns of reduced CO, in register with pale rows of patches in layer 2/3. Layers 4C, 5, and 6 also showed columns of CO activity, but remarkably, comparison with more superficial layers showed a reversal in contrast. In other words, pale CO staining in layers 2/3, 4A, and 4B was aligned with dark CO staining in layers 4C, 5, and 6. No experimental intervention or deprivation paradigm has been reported previously to produce opposite effects on metabolic activity in layers 2/3, 4A, and 4B vs. layers 4C, 5, and 6 within a given eye's columns. Copyright © 2015 the American Physiological Society.

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

PubMed Central

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

2017-01-01

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

Altered fatty acid concentrations in prefrontal cortex of schizophrenic patients

PubMed Central

Taha, Ameer Y.; Cheon, Yewon; Ma, Kaizong; Rapoport, Stanley I.; Rao, Jagadeesh S.

2013-01-01

Background Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in schizophrenic (SCZ) patients, often as percent of total lipid concentration or incomplete lipid profile. In this study, we quantified absolute concentrations (nmol/g wet weight) of several lipid classes and their constituent fatty acids in postmortem prefrontal cortex of SCZ patients (n = 10) and age-matched controls (n = 10). Methods Lipids were extracted, fractionated with thin layer chromatography and assayed. Results Mean total lipid, phospholipid, individual phospholipids, plasmalogen, triglyceride and cholesteryl ester concentrations did not differ significantly between the groups. Compared to controls, SCZ brains showed significant increases in several monounsaturated and polyunsaturated fatty acids in cholesteryl ester. Significant increases or decreases occurred in palmitoleic, linoleic, γ-linolenic and n-3 docosapentaenoic acid in total lipids, triglycerides or phospholipids. Conclusion These changes suggest disturbed prefrontal cortex fatty acid concentrations, particularly within cholesteryl esters, as a pathological aspect of schizophrenia. PMID:23428160

Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain.

PubMed

Kobayashi, Eiji; Nakano, Masako; Kubota, Kenta; Himuro, Nobuaki; Mizoguchi, Shougo; Chikenji, Takako; Otani, Miho; Mizue, Yuka; Nagaishi, Kanna; Fujimiya, Mineko

2018-01-26

Although the cognitive impairment in Alzheimer's disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.

Fatty acid composition of the postmortem prefrontal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hamazaki, Kei; Maekawa, Motoko; Toyota, Tomoko; Dean, Brian; Hamazaki, Tomohito; Yoshikawa, Takeo

2015-06-30

Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, in the frontal cortex (particularly the orbitofrontal cortex) of patients with depression, schizophrenia, or bipolar disorder. However, the results from regions in the frontal cortex other than the orbitofrontal cortex are inconsistent. In this study we investigated whether patients with schizophrenia, bipolar disorder, or major depressive disorder have abnormalities in PUFA levels in the prefrontal cortex [Brodmann area (BA) 8]. In postmortem studies, fatty acids in the phospholipids of the prefrontal cortex (BA8) were evaluated by thin layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to previous studies, we found no significant differences in the levels of PUFAs or other fatty acids in the prefrontal cortex (BA8) between patients and controls. Subanalysis by sex also showed no significant differences. No significant differences were found in any individual fatty acids between suicide and non-suicide cases. These psychiatric disorders might be characterized by very specific fatty acid compositions in certain areas of the brain, and BA8 might not be involved in abnormalities of PUFA metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Corticofugal modulation of peripheral auditory responses

PubMed Central

Terreros, Gonzalo; Delano, Paul H.

2015-01-01

The auditory efferent system originates in the auditory cortex and projects to the medial geniculate body (MGB), inferior colliculus (IC), cochlear nucleus (CN) and superior olivary complex (SOC) reaching the cochlea through olivocochlear (OC) fibers. This unique neuronal network is organized in several afferent-efferent feedback loops including: the (i) colliculo-thalamic-cortico-collicular; (ii) cortico-(collicular)-OC; and (iii) cortico-(collicular)-CN pathways. Recent experiments demonstrate that blocking ongoing auditory-cortex activity with pharmacological and physical methods modulates the amplitude of cochlear potentials. In addition, auditory-cortex microstimulation independently modulates cochlear sensitivity and the strength of the OC reflex. In this mini-review, anatomical and physiological evidence supporting the presence of a functional efferent network from the auditory cortex to the cochlear receptor is presented. Special emphasis is given to the corticofugal effects on initial auditory processing, that is, on CN, auditory nerve and cochlear responses. A working model of three parallel pathways from the auditory cortex to the cochlea and auditory nerve is proposed. PMID:26483647

[Studies on HPLC chromatogram of phenolic constituents of Cortex Magnoliae Officinalis].

PubMed

Huang, Wen-hua; Guo, Bao-lin; Si, Jin-ping

2005-07-01

To study the chemical characteristic, to identify the different forms and to establish the new standard for the quality control of Cortex Magnoliae Officinalis. HPLC method was used with acetonitrile-water (63:37) as the mobile phase at room temperature. The chromatographic column was Lichrospher 100 RP-18e (4.6 mm x 250 mm, 5 microm). The flow rate was 1 mL x min(-1), and the detection wavelength was 294 nm. The chromatograms of 45 individuals from 13 seed resources of Cortex Magnolia Officinalis were recorded. The chemical characteristics analysis and comparability' s calculation of seed resources were made. It was proposed that the area ratio of peak 5 to 6 (characteristic I) and the area ratio of peak 5 and 6 to the total peak areas (characteristic II) are the identification characteristics for different seed resources of Cortex Magnoliae Officinalis. This method can be used effectively to identify the high quality seed resource of Cortex Magnoliae Officinalis.

In vitro and in vivo analyses of the Bacillus anthracis spore cortex lytic protein SleL

PubMed Central

Lambert, Emily A.; Sherry, Nora

2012-01-01

The bacterial endospore is the most resilient biological structure known. Multiple protective integument layers shield the spore core and promote spore dehydration and dormancy. Dormancy is broken when a spore germinates and becomes a metabolically active vegetative cell. Germination requires the breakdown of a modified layer of peptidoglycan (PG) known as the spore cortex. This study reports in vitro and in vivo analyses of the Bacillus anthracis SleL protein. SleL is a spore cortex lytic enzyme composed of three conserved domains: two N-terminal LysM domains and a C-terminal glycosyl hydrolase family 18 domain. Derivatives of SleL containing both, one or no LysM domains were purified and characterized. SleL is incapable of digesting intact cortical PG of either decoated spores or purified spore sacculi. However, SleL derivatives can hydrolyse fragmented PG substrates containing muramic-δ-lactam recognition determinants. The muropeptides that result from SleL hydrolysis are the products of N-acetylglucosaminidase activity. These muropeptide products are small and readily released from the cortex matrix. Loss of the LysM domain(s) decreases both PG binding and hydrolysis activity but these domains do not appear to determine specificity for muramic-δ-lactam. When the SleL derivatives are expressed in vivo, those proteins lacking one or both LysM domains do not associate with the spore. Instead, these proteins remain in the mother cell and are apparently degraded. SleL with both LysM domains localizes to the coat or cortex of the endospore. The information revealed by elucidating the role of SleL and its domains in B. anthracis sporulation and germination is important in designing new spore decontamination methods. By exploiting germination-specific lytic enzymes, eradication techniques may be greatly simplified. PMID:22343356

Neurotoxicological effects of nicotine on the embryonic development of cerebellar cortex of chick embryo during various stages of incubation.

PubMed

El-Beltagy, Abd El-Fattah B M; Abou-El-Naga, Amoura M; Sabry, Dalia M

2015-10-01

Long-acting nicotine is known to exert pathological effects on almost all tissues including the cerebellar cortex. The present work was designed to elucidate the effect of nicotine on the development of cerebellar cortex of chick embryo during incubation period. The fertilized eggs of hen (Gallus gallus domesticus) were injected into the air space by a single dose of long acting nicotine (1.6 mg/kg/egg) at the 4th day of incubation. The embryos were taken out of the eggs on days 8, 12 and 16 of incubation. The cerebellum of the control and treated embryos at above ages were processed for histopathological examination. The TEM were examined at 16th day of incubation. The results of the present study revealed that, exposure to long-acting nicotine markedly influence the histogenesis of cerebellar cortex of chick embryo during the incubation period. At 8th day of incubation, nicotine delayed the differentiation of the cerebellar analge; especially the external granular layer (EGL) and inner cortical layer (ICL). Furthermore, at 12th day of incubation, the cerebellar foliation was irregular and the Purkinje cells not recognized. By 16th day of incubation, the cerebellar foliations were irregular with interrupted cerebellar cortex and irregular arrangement of Purkinje cells. Immunohistochemical analysis for antibody P53 protein revealed that the cerebellar cortex in all stages of nicotine treated groups possessed a moderate to weak reaction for P53 protein however; this reaction was markedly stronger in the cerebellar cortex of control groups. Moreover, the flow cytometric analysis confirmed that the percentage of apoptosis in control group was significantly higher compared with that of nicotine treated group. At the TEM level, the cerebellar Purkinje cells of 16th day of treated groups showed multiple subcellular alterations in compared with those of the corresponding control group. Such changes represented by appearing of vacuolated mitochondria, cisternal fragmentation of RER, irregular grooves of Golgi tubules. Also, multiple cytoplasmic vacuoles and aggregation of Nissl granules were recorded around pyknotic nucleus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Distinct expression patterns for type II topoisomerases IIA and IIB in the early foetal human telencephalon.

PubMed

Harkin, Lauren F; Gerrelli, Dianne; Gold Diaz, Diana C; Santos, Chloe; Alzu'bi, Ayman; Austin, Caroline A; Clowry, Gavin J

2016-03-01

TOP2A and TOP2B are type II topoisomerase enzymes that have important but distinct roles in DNA replication and RNA transcription. Recently, TOP2B has been implicated in the transcription of long genes in particular that play crucial roles in neural development and are susceptible to mutations contributing to neurodevelopmental conditions such as autism and schizophrenia. This study maps their expression in the early foetal human telencephalon between 9 and 12 post-conceptional weeks. TOP2A immunoreactivity was restricted to cell nuclei of the proliferative layers of the cortex and ganglionic eminences (GE), including the ventricular zone and subventricular zone (SVZ) closely matching expression of the proliferation marker KI67. Comparison with sections immunolabelled for NKX2.1, a medial GE (MGE) marker, and PAX6, a cortical progenitor cell and lateral GE (LGE) marker, revealed that TOP2A-expressing cells were more abundant in MGE than the LGE. In the cortex, TOP2B is expressed in cell nuclei in both proliferative (SVZ) and post-mitotic compartments (intermediate zone and cortical plate) as revealed by comparison with immunostaining for PAX6 and the post-mitotic neuron marker TBR1. However, co-expression with KI67 was rare. In the GE, TOP2B was also expressed by proliferative and post-mitotic compartments. In situ hybridisation studies confirmed these patterns of expression, except that TOP2A mRNA is restricted to cells in the G2/M phase of division. Thus, during early development, TOP2A is likely to have a role in cell proliferation, whereas TOP2B is expressed in post-mitotic cells and may be important in controlling expression of long genes even at this early stage. © 2015 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

Social Isolation During the Critical Period Reduces Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Cell in Mouse Prefrontal Cortex.

PubMed

Yamamuro, Kazuhiko; Yoshino, Hiroki; Ogawa, Yoichi; Makinodan, Manabu; Toritsuka, Michihiro; Yamashita, Masayuki; Corfas, Gabriel; Kishimoto, Toshifumi

2018-03-01

Juvenile social experience is crucial for the functional development of forebrain regions, especially the prefrontal cortex (PFC). We previously reported that social isolation for 2 weeks after weaning induces prefrontal cortex dysfunction and hypomyelination. However, the effect of social isolation on physiological properties of PFC neuronal circuit remained unknown. Since hypomyelination due to isolation is prominent in deep-layer of medial PFC (mPFC), we focused on 2 types of Layer-5 pyramidal cells in the mPFC: prominent h-current (PH) cells and nonprominent h-current (non-PH) cells. We found that a 2-week social isolation after weaning leads to a specific deterioration in action potential properties and reduction in excitatory synaptic inputs in PH cells. The effects of social isolation on PH cells, which involve reduction in functional glutamatergic synapses and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate charge ratio, are specific to the 2 weeks after weaning and to the mPFC. We conclude that juvenile social experience plays crucial roles in the functional development in a subtype of Layer-5 pyramidal cells in the mPFC. Since these neurons project to subcortical structures, a deficit in social experience during the critical period may result in immature neural circuitry between mPFC and subcortical targets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Playing the electric light orchestra—how electrical stimulation of visual cortex elucidates the neural basis of perception

PubMed Central

Cicmil, Nela; Krug, Kristine

2015-01-01

Vision research has the potential to reveal fundamental mechanisms underlying sensory experience. Causal experimental approaches, such as electrical microstimulation, provide a unique opportunity to test the direct contributions of visual cortical neurons to perception and behaviour. But in spite of their importance, causal methods constitute a minority of the experiments used to investigate the visual cortex to date. We reconsider the function and organization of visual cortex according to results obtained from stimulation techniques, with a special emphasis on electrical stimulation of small groups of cells in awake subjects who can report their visual experience. We compare findings from humans and monkeys, striate and extrastriate cortex, and superficial versus deep cortical layers, and identify a number of revealing gaps in the ‘causal map′ of visual cortex. Integrating results from different methods and species, we provide a critical overview of the ways in which causal approaches have been used to further our understanding of circuitry, plasticity and information integration in visual cortex. Electrical stimulation not only elucidates the contributions of different visual areas to perception, but also contributes to our understanding of neuronal mechanisms underlying memory, attention and decision-making. PMID:26240421

Pain-processing abnormalities in bipolar I disorder, bipolar II disorder, and schizophrenia: A novel trait marker for psychosis proneness and functional outcome?

PubMed

Minichino, Amedeo; Delle Chiaie, Roberto; Cruccu, Giorgio; Piroso, Serena; Di Stefano, Giulia; Francesconi, Marta; Bersani, Francesco Saverio; Biondi, Massimo; Truini, Andrea

2016-11-01

Overlapping neural system dysfunctions, mainly involving the secondary somatosensory cortex (S2), the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC), seem to be related to both pain-perception abnormalities and psychotic symptoms in schizophrenia (SCZ) and bipolar disorder (BD). Laser-evoked potentials (LEPs) were used to investigate pain-perception and central pain-processing abnormalities in SCZ, bipolar I disorder (BD-I), and bipolar II disorder (BD-II), and to evaluate their relationship with history of psychosis, and social-cognitive and functional impairments. Twenty patients with SCZ, 17 patients with BD-I, and 21 patients with BD-II who were all under similar pharmacological treatment underwent clinical, functional, and neuro-psychological assessment. LEPs were analyzed in patients and 19 healthy subjects (HS). LEPs elicit responses reflecting the activity of the S2 (N1 wave) and the ACC/AIC cortices (N2/P2 complex). A four-group ANOVA was conducted between patients and HS to compare pain-perceptive thresholds (PThs), N1, and N2/P2-LEP components. Compared to HS: (i) patients with SCZ showed pain-processing and pain-perception abnormalities, as revealed by significantly higher PTh (P<.01), and lower N1 (P<.01) and N2/P2 (P<.01) amplitudes, (ii) patients with BD-I showed only pain-processing abnormalities, as revealed by significantly lower N1 (P<.05) and N2 (P<.01) amplitudes; and patients with BD-II did not differ for any of the LEP variables investigated. N1 and N2 amplitudes negatively correlated to history of psychosis (P<.01), social-cognition (P<.05), and real-world functioning (P<.01) measures in the whole group of patients. To the best of our knowledge, this is the first study comparing central pain processing in patients with SCZ, BD-I, and BD-II. Our results suggest that pain-processing abnormalities may represent a novel locus of interest for research investigating trait markers of the psychosis spectrum. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Experience-Dependent Synaptic Plasticity in V1 Occurs without Microglial CX3CR1

PubMed Central

Stevens, Beth

2017-01-01

Brief monocular deprivation (MD) shifts ocular dominance and reduces the density of thalamic synapses in layer 4 of the mouse primary visual cortex (V1). We found that microglial lysosome content is also increased as a result of MD. Previous studies have shown that the microglial fractalkine receptor CX3CR1 is involved in synaptic development and hippocampal plasticity. We therefore tested the hypothesis that neuron-to-microglial communication via CX3CR1 is an essential component of visual cortical development and plasticity in male mice. Our data show that CX3CR1 is not required for normal development of V1 responses to visual stimulation, multiple forms of experience-dependent plasticity, or the synapse loss that accompanies MD in layer 4. By ruling out an essential role for fractalkine signaling, our study narrows the search for understanding how microglia respond to active synapse modification in the visual cortex. SIGNIFICANCE STATEMENT Microglia in the visual cortex respond to monocular deprivation with increased lysosome content, but signaling through the fractalkine receptor CX3CR1 is not an essential component in the mechanisms of visual cortical development or experience-dependent synaptic plasticity. PMID:28951447

14-3-3 coordinates microtubules, Rac, and myosin II to control cell mechanics and cytokinesis

PubMed Central

Zhou, Qiongqiong; Kee, Yee-Seir; Poirier, Christopher C.; Jelinek, Christine; Osborne, Jonathan; Divi, Srikanth; Surcel, Alexandra; Will, Marie E.; Eggert, Ulrike S.; Müller-Taubenberger, Annette; Iglesias, Pablo A.; Cotter, Robert J.; Robinson, Douglas N.

2010-01-01

Summary Background During cytokinesis, regulatory signals are presumed to emanate from the mitotic spindle. However, what these signals are and how they lead to the spatiotemporal changes in the cortex structure, mechanics, and regional contractility are not well understood in any system. Results To investigate pathways that link the microtubule network to the cortical changes that promote cytokinesis, we used chemical genetics in Dictyostelium to identify genetic suppressors of nocodazole, a microtubule depolymerizer. We identified 14-3-3 and found that it is enriched in the cortex, helps maintain steady state microtubule length, contributes to normal cortical tension, modulates actin wave formation, and controls the symmetry and kinetics of cleavage furrow contractility during cytokinesis. Furthermore, 14-3-3 acts downstream of a Rac small GTPase (RacE), associates with myosin II heavy chain and is needed to promote myosin II bipolar thick filament remodeling. Conclusion 14-3-3 connects microtubules, Rac and myosin II to control several aspects of cortical dynamics, mechanics, and cytokinesis cell shape change. Further, 14-3-3 interacts directly with myosin II heavy chain to promote bipolar thick filament remodeling and distribution. Overall, 14-3-3 appears to integrate several critical cytoskeletal elements that drive two important processes cytokinesis shape change and cell mechanics. PMID:20951045

What Is the Evidence for Inter-laminar Integration in a Prefrontal Cortical Minicolumn?

PubMed

Opris, Ioan; Chang, Stephano; Noga, Brian R

2017-01-01

The objective of this perspective article is to examine columnar inter-laminar integration during the executive control of behavior. The integration hypothesis posits that perceptual and behavioral signals are integrated within the prefrontal cortical inter-laminar microcircuits. Inter-laminar minicolumnar activity previously recorded from the dorsolateral prefrontal cortex (dlPFC) of nonhuman primates, trained in a visual delay match-to-sample (DMS) task, was re-assessed from an integrative perspective. Biomorphic multielectrode arrays (MEAs) played a unique role in the in vivo recording of columnar cell firing in the dlPFC layers 2/3 and 5/6. Several integrative aspects stem from these experiments: 1. Functional integration of perceptual and behavioral signals across cortical layers during executive control. The integrative effect of dlPFC minicolumns was shown by: (i) increased correlated firing on correct vs. error trials; (ii) decreased correlated firing when the number of non-matching images increased; and (iii) similar spatial firing preference across cortical-striatal cells during spatial-trials, and less on object-trials. 2. Causal relations to integration of cognitive signals by the minicolumnar turbo-engines. The inter-laminar integration between the perceptual and executive circuits was facilitated by stimulating the infra-granular layers with firing patterns obtained from supra-granular layers that enhanced spatial preference of percent correct performance on spatial trials. 3. Integration across hierarchical levels of the brain. The integration of intention signals (visual spatial, direction) with movement preparation (timing, velocity) in striatum and with the motor command and posture in midbrain is also discussed. These findings provide evidence for inter-laminar integration of executive control signals within brain's prefrontal cortical microcircuits.

Cellular and laminar expression of Dab-1 during the postnatal critical period in cat visual cortex and the effects of dark rearing.

PubMed

Kiser, Paul J; Liu, Zijing; Wilt, Steven D; Mower, George D

2011-04-06

This study describes postnatal critical period changes in cellular and laminar expression of Dab-1, a gene shown to play a role in controlling neuronal positioning during embryonic brain development, in cat visual cortex and the effects of dark rearing (DR). At 1week, there is dense cellular staining which is uniform across cortical layers and very light neuropil staining. At the peak of the critical period (5weeks), dense cell staining is largely restricted to large pyramidal cells of deep layer III and layer V, there is faint cell body staining throughout all cortical layers, neuropil staining is markedly increased and uniform in layers III to VI. This dramatic change in laminar and cellular labeling is independent of visual input, since immunostaining is similar in 5-week DR cats. By 10weeks, the mature laminar and cellular staining pattern is established and the major subsequent change is a further reduction in the density of cellular staining in all cortical layers. Neuropil staining is pronounced and uniform across cortical layers. These developmental changes are altered by DR. Quantification by cell counts indicated that age and DR interact such that differences in cellular expression are opposite in direction between 5- and 20-week-old cats. This bidirectional regulation of cellular expression is the same in all cortical laminae. The bidirectional regulation of cellular expression matches the effects of age and DR on physiological plasticity during the critical period as assessed by ocular dominance shifts in response to monocular deprivation. Copyright © 2011 Elsevier B.V. All rights reserved.

Texture Segregation Causes Early Figure Enhancement and Later Ground Suppression in Areas V1 and V4 of Visual Cortex.

PubMed

Poort, Jasper; Self, Matthew W; van Vugt, Bram; Malkki, Hemi; Roelfsema, Pieter R

2016-10-01

Segregation of images into figures and background is fundamental for visual perception. Cortical neurons respond more strongly to figural image elements than to background elements, but the mechanisms of figure-ground modulation (FGM) are only partially understood. It is unclear whether FGM in early and mid-level visual cortex is caused by an enhanced response to the figure, a suppressed response to the background, or both.We studied neuronal activity in areas V1 and V4 in monkeys performing a texture segregation task. We compared texture-defined figures with homogeneous textures and found an early enhancement of the figure representation, and a later suppression of the background. Across neurons, the strength of figure enhancement was independent of the strength of background suppression.We also examined activity in the different V1 layers. Both figure enhancement and ground suppression were strongest in superficial and deep layers and weaker in layer 4. The current-source density profiles suggested that figure enhancement was caused by stronger synaptic inputs in feedback-recipient layers 1, 2, and 5 and ground suppression by weaker inputs in these layers, suggesting an important role for feedback connections from higher level areas. These results provide new insights into the mechanisms for figure-ground organization. © The Author 2016. Published by Oxford University Press.

Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits.

PubMed

Kohara, Keigo; Pignatelli, Michele; Rivest, Alexander J; Jung, Hae-Yoon; Kitamura, Takashi; Suh, Junghyup; Frank, Dominic; Kajikawa, Koichiro; Mise, Nathan; Obata, Yuichi; Wickersham, Ian R; Tonegawa, Susumu

2014-02-01

The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.

Enlargement of Axo-Somatic Contacts Formed by GAD-Immunoreactive Axon Terminals onto Layer V Pyramidal Neurons in the Medial Prefrontal Cortex of Adolescent Female Mice Is Associated with Suppression of Food Restriction-Evoked Hyperactivity and Resilience to Activity-Based Anorexia

PubMed Central

Chen, Yi-Wen; Wable, Gauri Satish; Chowdhury, Tara Gunkali; Aoki, Chiye

2016-01-01

Many, but not all, adolescent female mice that are exposed to a running wheel while food restricted (FR) become excessive wheel runners, choosing to run even during the hours of food availability, to the point of death. This phenomenon is called activity-based anorexia (ABA). We used electron microscopic immunocytochemistry to ask whether individual differences in ABA resilience may correlate with the lengths of axo-somatic contacts made by GABAergic axon terminals onto layer 5 pyramidal neurons (L5P) in the prefrontal cortex. Contact lengths were, on average, 40% greater for the ABA-induced mice, relative to controls. Correspondingly, the proportion of L5P perikaryal plasma membrane contacted by GABAergic terminals was 45% greater for the ABA mice. Contact lengths in the anterior cingulate cortex correlated negatively and strongly with the overall wheel activity after FR (R = −0.87, P < 0.01), whereas those in the prelimbic cortex correlated negatively with wheel running specifically during the hours of food availability of the FR days (R = −0.84, P < 0.05). These negative correlations support the idea that increases in the glutamic acid decarboxylase (GAD) terminal contact lengths onto L5P contribute toward ABA resilience through suppression of wheel running, a behavior that is intrinsically rewarding and helpful for foraging but maladaptive within a cage. PMID:25979087

Layer 2/3 pyramidal cells in the medial prefrontal cortex moderate stress induced depressive behaviors

PubMed Central

Shrestha, Prerana; Mousa, Awni; Heintz, Nathaniel

2015-01-01

Major depressive disorder (MDD) is a prevalent illness that can be precipitated by acute or chronic stress. Studies of patients with Wolfram syndrome and carriers have identified Wfs1 mutations as causative for MDD. The medial prefrontal cortex (mPFC) is known to be involved in depression and behavioral resilience, although the cell types and circuits in the mPFC that moderate depressive behaviors in response to stress have not been determined. Here, we report that deletion of Wfs1 from layer 2/3 pyramidal cells impairs the ability of the mPFC to suppress stress-induced depressive behaviors, and results in hyperactivation of the hypothalamic–pituitary–adrenal axis and altered accumulation of important growth and neurotrophic factors. Our data identify superficial layer 2/3 pyramidal cells as critical for moderation of stress in the context of depressive behaviors and suggest that dysfunction in these cells may contribute to the clinical relationship between stress and depression. DOI: http://dx.doi.org/10.7554/eLife.08752.001 PMID:26371510

Deep Learning Predicts Correlation between a Functional Signature of Higher Visual Areas and Sparse Firing of Neurons.

PubMed

Zhuang, Chengxu; Wang, Yulong; Yamins, Daniel; Hu, Xiaolin

2017-01-01

Visual information in the visual cortex is processed in a hierarchical manner. Recent studies show that higher visual areas, such as V2, V3, and V4, respond more vigorously to images with naturalistic higher-order statistics than to images lacking them. This property is a functional signature of higher areas, as it is much weaker or even absent in the primary visual cortex (V1). However, the mechanism underlying this signature remains elusive. We studied this problem using computational models. In several typical hierarchical visual models including the AlexNet, VggNet, and SHMAX, this signature was found to be prominent in higher layers but much weaker in lower layers. By changing both the model structure and experimental settings, we found that the signature strongly correlated with sparse firing of units in higher layers but not with any other factors, including model structure, training algorithm (supervised or unsupervised), receptive field size, and property of training stimuli. The results suggest an important role of sparse neuronal activity underlying this special feature of higher visual areas.

Deep Learning Predicts Correlation between a Functional Signature of Higher Visual Areas and Sparse Firing of Neurons

PubMed Central

Zhuang, Chengxu; Wang, Yulong; Yamins, Daniel; Hu, Xiaolin

2017-01-01

Visual information in the visual cortex is processed in a hierarchical manner. Recent studies show that higher visual areas, such as V2, V3, and V4, respond more vigorously to images with naturalistic higher-order statistics than to images lacking them. This property is a functional signature of higher areas, as it is much weaker or even absent in the primary visual cortex (V1). However, the mechanism underlying this signature remains elusive. We studied this problem using computational models. In several typical hierarchical visual models including the AlexNet, VggNet, and SHMAX, this signature was found to be prominent in higher layers but much weaker in lower layers. By changing both the model structure and experimental settings, we found that the signature strongly correlated with sparse firing of units in higher layers but not with any other factors, including model structure, training algorithm (supervised or unsupervised), receptive field size, and property of training stimuli. The results suggest an important role of sparse neuronal activity underlying this special feature of higher visual areas. PMID:29163117

Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism.

PubMed

Chauhan, Abha; Gu, Feng; Essa, Musthafa M; Wegiel, Jerzy; Kaur, Kulbir; Brown, William Ted; Chauhan, Ved

2011-04-01

Mitochondria play important roles in generation of free radicals, ATP formation, and in apoptosis. We studied the levels of mitochondrial electron transport chain (ETC) complexes, that is, complexes I, II, III, IV, and V, in brain tissue samples from the cerebellum and the frontal, parietal, occipital, and temporal cortices of subjects with autism and age-matched control subjects. The subjects were divided into two groups according to their ages: Group A (children, ages 4-10 years) and Group B (adults, ages 14-39 years). In Group A, we observed significantly lower levels of complexes III and V in the cerebellum (p<0.05), of complex I in the frontal cortex (p<0.05), and of complexes II (p<0.01), III (p<0.01), and V (p<0.05) in the temporal cortex of children with autism as compared to age-matched control subjects, while none of the five ETC complexes was affected in the parietal and occipital cortices in subjects with autism. In the cerebellum and temporal cortex, no overlap was observed in the levels of these ETC complexes between subjects with autism and control subjects. In the frontal cortex of Group A, a lower level of ETC complexes was observed in a subset of autism cases, that is, 60% (3/5) for complexes I, II, and V, and 40% (2/5) for complexes III and IV. A striking observation was that the levels of ETC complexes were similar in adult subjects with autism and control subjects (Group B). A significant increase in the levels of lipid hydroperoxides, an oxidative stress marker, was also observed in the cerebellum and temporal cortex in the children with autism. These results suggest that the expression of ETC complexes is decreased in the cerebellum and the frontal and temporal regions of the brain in children with autism, which may lead to abnormal energy metabolism and oxidative stress. The deficits observed in the levels of ETC complexes in children with autism may readjust to normal levels by adulthood. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism

PubMed Central

Chauhan, Abha; Gu, Feng; Essa, Musthafa M.; Wegiel, Jerzy; Kaur, Kulbir; Brown, William Ted; Chauhan, Ved

2016-01-01

Mitochondria play important roles in generation of free radicals, ATP formation, and in apoptosis. We studied the levels of mitochondrial electron transport chain (ETC) complexes, that is, complexes I, II, III, IV, and V, in brain tissue samples from the cerebellum and the frontal, parietal, occipital, and temporal cortices of subjects with autism and age-matched control subjects. The subjects were divided into two groups according to their ages: Group A (children, ages 4–10 years) and Group B (adults, ages 14–39 years). In Group A, we observed significantly lower levels of complexes III and V in the cerebellum (p < 0.05), of complex I in the frontal cortex (p < 0.05), and of complexes II (p < 0.01), III (p<0.01), and V (p < 0.05) in the temporal cortex of children with autism as compared to age-matched control subjects, while none of the five ETC complexes was affected in the parietal and occipital cortices in subjects with autism. In the cerebellum and temporal cortex, no overlap was observed in the levels of these ETC complexes between subjects with autism and control subjects. In the frontal cortex of Group A, a lower level of ETC complexes was observed in a subset of autism cases, that is, 60% (3/5) for complexes I, II, and V, and 40% (2/5) for complexes III and IV. A striking observation was that the levels of ETC complexes were similar in adult subjects with autism and control subjects (Group B). A significant increase in the levels of lipid hydroperoxides, an oxidative stress marker, was also observed in the cerebellum and temporal cortex in the children with autism. These results suggest that the expression of ETC complexes is decreased in the cerebellum and the frontal and temporal regions of the brain in children with autism, which may lead to abnormal energy metabolism and oxidative stress. The deficits observed in the levels of ETC complexes in children with autism may readjust to normal levels by adulthood. PMID:21250997

Body Topography Parcellates Human Sensory and Motor Cortex.

PubMed

Kuehn, Esther; Dinse, Juliane; Jakobsen, Estrid; Long, Xiangyu; Schäfer, Andreas; Bazin, Pierre-Louis; Villringer, Arno; Sereno, Martin I; Margulies, Daniel S

2017-07-01

The cytoarchitectonic map as proposed by Brodmann currently dominates models of human sensorimotor cortical structure, function, and plasticity. According to this model, primary motor cortex, area 4, and primary somatosensory cortex, area 3b, are homogenous areas, with the major division lying between the two. Accumulating empirical and theoretical evidence, however, has begun to question the validity of the Brodmann map for various cortical areas. Here, we combined in vivo cortical myelin mapping with functional connectivity analyses and topographic mapping techniques to reassess the validity of the Brodmann map in human primary sensorimotor cortex. We provide empirical evidence that area 4 and area 3b are not homogenous, but are subdivided into distinct cortical fields, each representing a major body part (the hand and the face). Myelin reductions at the hand-face borders are cortical layer-specific, and coincide with intrinsic functional connectivity borders as defined using large-scale resting state analyses. Our data extend the Brodmann model in human sensorimotor cortex and suggest that body parts are an important organizing principle, similar to the distinction between sensory and motor processing. © The Author 2017. Published by Oxford University Press.

Laminar- and Target-Specific Amygdalar Inputs in Rat Primary Gustatory Cortex.

PubMed

Haley, Melissa S; Fontanini, Alfredo; Maffei, Arianna

2016-03-02

The primary gustatory cortex (GC) receives projections from the basolateral nucleus of the amygdala (BLA). Behavioral and electrophysiological studies demonstrated that this projection is involved in encoding the hedonic value of taste and is a source of anticipatory activity in GC. Anatomically, this projection is largest in the agranular portion of GC; however, its synaptic targets and synaptic properties are currently unknown. In vivo electrophysiological recordings report conflicting evidence about BLA afferents either selectively activating excitatory neurons or driving a compound response consistent with the activation of inhibitory circuits. Here we demonstrate that BLA afferents directly activate excitatory neurons and two distinct populations of inhibitory neurons in both superficial and deep layers of rat GC. BLA afferents recruit different proportions of excitatory and inhibitory neurons and show distinct patterns of circuit activation in the superficial and deep layers of GC. These results provide the first circuit-level analysis of BLA inputs to a sensory area. Laminar- and target-specific differences of BLA inputs likely explain the complexity of amygdalocortical interactions during sensory processing. Projections from the basolateral nucleus of the amygdala (BLA) to the cortex convey information about the emotional value and the expectation of a sensory stimulus. Although much work has been done to establish the behavioral role of BLA inputs to sensory cortices, very little is known about the circuit organization of BLA projections. Here we provide the first in-depth analysis of connectivity and synaptic properties of the BLA input to the gustatory cortex. We show that BLA afferents activate excitatory and inhibitory circuits in a layer-specific and pattern-specific manner. Our results provide important new information about how neural circuits establishing the hedonic value of sensory stimuli and driving anticipatory behaviors are organized at the synaptic level. Copyright © 2016 the authors 0270-6474/16/362623-15$15.00/0.

Zinc histochemistry reveals circuit refinement and distinguishes visual areas in the developing ferret cerebral cortex.

PubMed

Khalil, Reem; Levitt, Jonathan B

2013-09-01

A critical question in brain development is whether different brain circuits mature concurrently or with different timescales. To characterize the anatomical and functional development of different visual cortical areas, one must be able to distinguish these areas. Here, we show that zinc histochemistry, which reveals a subset of glutamatergic processes, can be used to reliably distinguish visual areas in juvenile and adult ferret cerebral cortex, and that the postnatal decline in levels of synaptic zinc follows a broadly similar developmental trajectory in multiple areas of ferret visual cortex. Zinc staining in all areas examined (17, 18, 19, 21, and Suprasylvian) is greater in the 5-week-old than in the adult. Furthermore, there is less laminar variation in zinc staining in the 5-week-old visual cortex than in the adult. Despite differences in staining intensity, areal boundaries can be discerned in the juvenile as in the adult. By 6 weeks of age, we observe a significant decline in visual cortical synaptic zinc; this decline was most pronounced in layer IV of areas 17 and 18, with much less change in higher-order extrastriate areas during the important period in visual cortical development following eye opening. By 10 weeks of age, the laminar pattern of zinc staining in all visual areas is essentially adultlike. The decline in synaptic zinc in the supra- and infragranular layers in all areas proceeds at the same rate, though the decline in layer IV does not. These results suggest that the timecourse of synaptic zinc decline is lamina specific, and further confirm and extend the notion that at least some aspects of cortical maturation follow a similar developmental timecourse in multiple areas. The postnatal decline in synaptic zinc we observe during the second postnatal month begins after eye opening, consistent with evidence that synaptic zinc is regulated by sensory experience.

High-frequency gamma oscillations coexist with low-frequency gamma oscillations in the rat visual cortex in vitro.

PubMed

Oke, Olaleke O; Magony, Andor; Anver, Himashi; Ward, Peter D; Jiruska, Premysl; Jefferys, John G R; Vreugdenhil, Martin

2010-04-01

Synchronization of neuronal activity in the visual cortex at low (30-70 Hz) and high gamma band frequencies (> 70 Hz) has been associated with distinct visual processes, but mechanisms underlying high-frequency gamma oscillations remain unknown. In rat visual cortex slices, kainate and carbachol induce high-frequency gamma oscillations (fast-gamma; peak frequency approximately 80 Hz at 37 degrees C) that can coexist with low-frequency gamma oscillations (slow-gamma; peak frequency approximately 50 Hz at 37 degrees C) in the same column. Current-source density analysis showed that fast-gamma was associated with rhythmic current sink-source sequences in layer III and slow-gamma with rhythmic current sink-source sequences in layer V. Fast-gamma and slow-gamma were not phase-locked. Slow-gamma power fluctuations were unrelated to fast-gamma power fluctuations, but were modulated by the phase of theta (3-8 Hz) oscillations generated in the deep layers. Fast-gamma was spatially less coherent than slow-gamma. Fast-gamma and slow-gamma were dependent on gamma-aminobutyric acid (GABA)(A) receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and gap-junctions, their frequencies were reduced by thiopental and were weakly dependent on cycle amplitude. Fast-gamma and slow-gamma power were differentially modulated by thiopental and adenosine A(1) receptor blockade, and their frequencies were differentially modulated by N-methyl-D-aspartate (NMDA) receptors, GluK1 subunit-containing receptors and persistent sodium currents. Our data indicate that fast-gamma and slow-gamma both depend on and are paced by recurrent inhibition, but have distinct pharmacological modulation profiles. The independent co-existence of fast-gamma and slow-gamma allows parallel processing of distinct aspects of vision and visual perception. The visual cortex slice provides a novel in vitro model to study cortical high-frequency gamma oscillations.

Somatosensory cortical remodelling after rehabilitation and clinical benefit of in writer's cramp.

PubMed

Bleton, Jean Pierre; Vidailhet, Marie; Bourdain, Frédéric; Ducorps, Antoine; Schwartz, Denis; Delmaire, Christine; Lehéricy, Stéphane; Renault, Bernard; Garnero, Line; Meunier, Sabine

2011-05-01

In order to explore the pathophysiological basis of a new rehabilitation therapy in writer's cramp (WC), healthy controls, untreated WC patients and WC patients who recovered a legible handwriting after rehabilitation were explored using magnetoencephalography, and the somatosensory evoked fields of fingers I, II, III and V in the sensory cortex were studied. In the cortex controlling the dystonic limb, the size of the hand representation in the trained patients was similar to that of healthy controls, and significantly different from that of untrained patients. Trained patients exhibited 'super-normal' reorganisation of the finger maps. In the cortex controlling the non-dystonic limb, there was little difference between trained and untrained patients, and the hand representation was enlarged and disorganised. The authors hypothesise that prolonged tailored rehabilitation in WC may induce long-term plasticity phenomena, lateralised to the cortex controlling the dystonic hand.

“Subpial Fan Cell” — A Class of Calretinin Neuron in Layer 1 of Adult Monkey Prefrontal Cortex

PubMed Central

Gabbott, Paul L. A.

2016-01-01

Layer 1 of the cortex contains populations of neurochemically distinct neurons and afferent fibers which markedly affect neural activity in the apical dendritic tufts of pyramidal cells. Understanding the causal mechanisms requires knowledge of the cellular architecture and synaptic organization of layer 1. This study has identified eight morphological classes of calretinin immunopositive (CRet+) neurons (including Cajal-Retzius cells) in layer 1 of the prefrontal cortex (PFC) in adult monkey (Macaca fasicularis), with a distinct class — termed “subpial fan (SPF) cell” — described in detail. SPF cells were rare horizontal unipolar CRet+ cells located directly beneath the pia with a single thick primary dendrite that branched into a characteristic fan-like dendritic tree tangential to the pial surface. Dendrites had spines, filamentous processes and thorny branchlets. SPF cells lay millimeters apart with intralaminar axons that ramified widely in upper layer 1. Such cells were GABA immunonegative (-) and occurred in areas beyond PFC. Interspersed amidst SPF cells displaying normal structural integrity were degenerating CRet+ neurons (including SPF cells) and clumps of lipofuscin-rich cellular debris. The number of degenerating SPF cells increased during adulthood. Ultrastructural analyses indicated SPF cell somata received asymmetric (A — presumed excitatory) and symmetric (S — presumed inhibitory) synaptic contacts. Proximal dendritic shafts received mainly S-type and distal shafts mostly A-type input. All dendritic thorns and most dendritic spines received both synapse types. The tangential areal density of SPF cell axonal varicosities varied radially from parent somata — with dense clusters in more distal zones. All boutons formed A-type contacts with CRet- structures. The main post-synaptic targets were dendritic shafts (67%; mostly spine-bearing) and dendritic spines (24%). SPF-SPF cell innervation was not observed. Morphometry of SPF cells indicated a unique class of CRet+/GABA- neuron in adult monkey PFC — possibly a subtype of persisting Cajal-Retzius cell. The distribution and connectivity of SPF cells suggest they act as integrative hubs in upper layer 1 during postnatal maturation. The main synaptic output of SPF cells likely provides a transminicolumnar excitatory influence across swathes of apical dendritic tufts — thus affecting information processing in discrete patches of layer 1 in adult monkey PFC. PMID:27147978

Is orbital volume associated with eyeball and visual cortex volume in humans?

PubMed

Pearce, Eiluned; Bridge, Holly

2013-01-01

In humans orbital volume increases linearly with absolute latitude. Scaling across mammals between visual system components suggests that these larger orbits should translate into larger eyes and visual cortices in high latitude humans. Larger eyes at high latitudes may be required to maintain adequate visual acuity and enhance visual sensitivity under lower light levels. To test the assumption that orbital volume can accurately index eyeball and visual cortex volumes specifically in humans. Structural Magnetic Resonance Imaging (MRI) techniques are employed to measure eye and orbit (n = 88) and brain and visual cortex (n = 99) volumes in living humans. Facial dimensions and foramen magnum area (a proxy for body mass) were also measured. A significant positive linear relationship was found between (i) orbital and eyeball volumes, (ii) eyeball and visual cortex grey matter volumes and (iii) different visual cortical areas, independently of overall brain volume. In humans the components of the visual system scale from orbit to eye to visual cortex volume independently of overall brain size. These findings indicate that orbit volume can index eye and visual cortex volume in humans, suggesting that larger high latitude orbits do translate into larger visual cortices.

Is orbital volume associated with eyeball and visual cortex volume in humans?

PubMed Central

Pearce, Eiluned; Bridge, Holly

2013-01-01

Background In humans orbital volume increases linearly with absolute latitude. Scaling across mammals between visual system components suggests that these larger orbits should translate into larger eyes and visual cortices in high latitude humans. Larger eyes at high latitudes may be required to maintain adequate visual acuity and enhance visual sensitivity under lower light levels. Aim To test the assumption that orbital volume can accurately index eyeball and visual cortex volumes specifically in humans. Subjects & Methods Structural Magnetic Resonance Imaging (MRI) techniques are employed to measure eye and orbit (N=88), and brain and visual cortex (N=99) volumes in living humans. Facial dimensions and foramen magnum area (a proxy for body mass) were also measured. Results A significant positive linear relationship was found between (i) orbital and eyeball volumes, (ii) eyeball and visual cortex grey matter volumes, (iii) different visual cortical areas, independently of overall brain volume. Conclusion In humans the components of the visual system scale from orbit to eye to visual cortex volume independently of overall brain size. These findings indicate that orbit volume can index eye and visual cortex volume in humans, suggesting that larger high latitude orbits do translate into larger visual cortices. PMID:23879766

Mo/Si multilayers with enhanced TiO II- and RuO II-capping layers

NASA Astrophysics Data System (ADS)

Yulin, Sergiy; Benoit, Nicolas; Feigl, Torsten; Kaiser, Norbert; Fang, Ming; Chandhok, Manish

2008-03-01

The lifetime of Mo/Si multilayer-coated projection optics is one of the outstanding issues on the road of commercialization of extreme-ultraviolet lithography (EUVL). The application of Mo/Si multilayer optics in EUVL requires both sufficient radiation stability and also the highest possible normal-incidence reflectivity. A serious problem of conventional high-reflective Mo/Si multilayers capped by silicon is the considerable degradation of reflective properties due to carbonization and oxidation of the silicon surface layer under exposure by EUV radiation. In this study, we focus on titanium dioxide (TiO II) and ruthenium dioxide (RuO II) as promising capping layer materials for EUVL multilayer coatings. The multilayer designs as well as the deposition parameters of the Mo/Si systems with different capping layers were optimized in terms of maximum peak reflectivity at the wavelength of 13.5 nm and longterm stability under high-intensive irradiation. Optimized TiO II-capped Mo/Si multilayer mirrors with an initial reflectivity of 67.0% presented a reflectivity drop of 0.6% after an irradiation dose of 760 J/mm2. The reflectivity drop was explained by the partial oxidation of the silicon sub-layer. No reflectivity loss after similar irradiation dose was found for RuO II-capped Mo/Si multilayer mirrors having initial peak reflectivity of 66%. In this paper we present data on improved reflectivity of interface-engineered TiO II- and RuO II-capped Mo/Si multilayer mirrors due to the minimization of both interdiffusion processes inside the multilayer stack and absorption loss in the oxide layer. Reflectivities of 68.5% at the wavelength of 13.4 nm were achieved for both TiO II- and RuO II-capped Mo/Si multilayer mirrors.

All-vapor processing of p-type tellurium-containing II-VI semiconductor and ohmic contacts thereof

DOEpatents

McCandless, Brian E.

2001-06-26

An all dry method for producing solar cells is provided comprising first heat-annealing a II-VI semiconductor; enhancing the conductivity and grain size of the annealed layer; modifying the surface and depositing a tellurium layer onto the enhanced layer; and then depositing copper onto the tellurium layer so as to produce a copper tellurium compound on the layer.

Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition.

PubMed

Stein, Anna; Goldmeier, Silvia; Voltolini, Sarah; Setogutti, Enio; Feldman, Carlos; Figueiredo, Eduardo; Eick, Renato; Irigoyen, Maria; Rigatto, Katya

2012-07-01

The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients. R2* quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50 ± 5.3 years) underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI). A multiple fast gradient-echo sequence was used to acquire R2*/T2* images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location). The images were post-processed to generate R2* maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg). The results were compared using an ANOVA for repeated measurements (mean + standard deviation) followed by the Tukey test. ClinicalTrials.gov: NCT01545479. A significant difference (p<0.001) in renal oxygenation (R2*) was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08 ± 0.56 ms, medulla = 17.21 ± 1.47 ms and cortex = 10.30 ± 0.44 ms, medulla = 16.06 ± 1.74 ms, respectively; and left kidney, cortex= 11.79 ± 1.85 ms, medulla = 17.03 ± 0.88 ms and cortex = 10.89 ± 0.91 ms, medulla = 16.43 ± 1.49 ms, respectively. This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.

Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation.

PubMed

Hanken, Katrin; Bosse, Mona; Möhrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

2016-01-01

Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1.5 mA) was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20 min of a 40-min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5 mA) over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. tDCS was delivered for 20 min before patients performed a 20-min lasting visual vigilance task. Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in RT associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation. Anodal tDCS over the right parietal cortex can counteract the increase in RTs during vigilance performance, but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

Multiple zonal projections of the nucleus reticularis tegmenti pontis to the cerebellar cortex of the rat.

PubMed

Serapide, M F; Parenti, R; Pantò, M R; Zappalà, A; Cicirata, F

2002-06-01

Compartmentalization (alternating labelled and unlabelled stripes) of mossy fibre terminals was found in the cerebellar cortex after iontophoretic injections of biotinylated dextran amine into discrete regions of the nucleus reticularis tegmenti pontis (NRTP). The zonal pattern was only observed when volumes of nuclear tissue ranging from 4.5 x 106 to 17.66 x 106 microm3 were impregnated. Up to nine compartments (i.e. up to five stripes separated by four interstripes) were found in crus I and in vermal lobule VI. Up to seven compartments (four stripes and three interstripes) were found in crus II; up to five compartments (three stripes and two interstripes) were identified in the lobulus simplex, the paraflocculus and vermal lobules IV, V and VII; up to three compartments (two stripes and one interstripe) were identified in the paramedian lobule and, finally, up to two compartments (one stripe and one interstripe) were identified in the copula pyramidis, in the flocculus and in vermal lobules II, III, VIII and IX. The projections of the NRTP are arranged according to a divergent/convergent projection pattern. From single injections in the NRTP, projections were traced to a set of cortical stripes widely distributed over the cerebellar cortex. The set of stripes labelled from different regions of the NRTP partially overlapped but complete overlap was never found. This finding revealed that the topographic combination of the projections of the NRTP to the cerebellar cortex is specific for each region of the NRTP. Finally, the projections to single cortical areas were arranged according to a pattern of compartmentalization that is specific for each cortical area, independent of the site of injection in the NRTP and of the number of stripes evident in the cortex.

Combining tractography and cortical measures to test system-specific hypotheses in multiple sclerosis

PubMed Central

Gorgoraptis, Nikos; Wheeler-Kingshott, Claudia AM; Jenkins, Thomas M; Altmann, Daniel R; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2010-01-01

The objective was to test three motor system-specific hypotheses in multiple sclerosis patients: (i) corticospinal tract and primary motor cortex imaging measures differ between multiple sclerosis patients and controls; (ii) in patients, these measures correlate with disability; (iii) in patients, corticospinal tract measures correlate with measures of the ipsilateral primary motor cortex. Eleven multiple sclerosis patients with a history of hemiparesis attributable to a lesion within the contralateral corticospinal tract, and 12 controls were studied. We used two advanced imaging techniques: (i) diffusion-based probabilistic tractography, to obtain connectivity and fractional anisotropy of the corticospinal tract; and (ii) FreeSurfer, to measure volume, thickness, surface area, and curvature of precentral and paracentral cortices. Differences in these measures between patients and controls, and relationships between each other and to clinical scores, were investigated. Patients showed lower corticospinal tract fractional anisotropy and smaller volume and surface area of the precentral gyrus than controls. In patients, corticospinal tract connectivity and paracentral cortical volume, surface area, and curvature were lower with increasing disability; lower connectivity of the affected corticospinal tract was associated with greater surface area of the ipsilateral paracentral cortex. Corticospinal tract connectivity and new measures of the primary motor cortex, such as surface area and curvature, reflect the underlying white and grey matter damage that contributes to disability. The correlation between lower connectivity of the affected corticospinal tract and greater surface area of the ipsilateral paracentral cortex suggests the possibility of cortical adaptation. Combining tractography and cortical measures is a useful approach in testing hypotheses which are specific to clinically relevant functional systems in multiple sclerosis, and can be applied to other neurological diseases. PMID:20215478

Adrenocortical Carcinoma—Patient Version

Cancer.gov

Adrenocortical carcinoma is a rare cancer which forms in the cortex (outer layer) of an adrenal gland. There are two adrenal glands. One sits on top of each kidney. Start here to find information on adrenocortical carcinoma treatment and research.

The thalamus as a monitor of motor outputs.

PubMed Central

Guillery, R W; Sherman, S M

2002-01-01

Many of the ascending pathways to the thalamus have branches involved in movement control. In addition, the recently defined, rich innervation of 'higher' thalamic nuclei (such as the pulvinar) from pyramidal cells in layer five of the neocortex also comes from branches of long descending axons that supply motor structures. For many higher thalamic nuclei the clue to understanding the messages that are relayed to the cortex will depend on knowing the nature of these layer five motor outputs and on defining how messages from groups of functionally distinct output types are combined as inputs to higher cortical areas. Current evidence indicates that many and possibly all thalamic relays to the neocortex are about instructions that cortical and subcortical neurons are contributing to movement control. The perceptual functions of the cortex can thus be seen to represent abstractions from ongoing motor instructions. PMID:12626014

Characterization of Two (3H) Ketanserin Recognition Sites in Rat Striatum

DTIC Science & Technology

1987-01-01

autoradiography to be localized to The 5-HT, sites are proposed to activate adenylate layer IV of the cortex and striatum ( Pazos et al., cyclase (Barbaccia et al...Chuang (1987). assumption has not been completely tested. Since its introduction as a selective radioligand for Pazos et al. (1985) recently confirmed...cniorophenylalanine. 1833 B S-3 1834 B. L. ROT!! ET AL. enriched in striatum and cortex. Pazos et al. (1985) mAt Tris-Cl, pH 7.40 at 25°C) at 4C. A crude membrane

Cortical Thickness, Surface Area and Subcortical Volume Differentially Contribute to Cognitive Heterogeneity in Parkinson's Disease.

PubMed

Gerrits, Niels J H M; van Loenhoud, Anita C; van den Berg, Stan F; Berendse, Henk W; Foncke, Elisabeth M J; Klein, Martin; Stoffers, Diederick; van der Werf, Ysbrand D; van den Heuvel, Odile A

2016-01-01

Parkinson's disease (PD) is often associated with cognitive deficits, although their severity varies considerably between patients. Recently, we used voxel-based morphometry (VBM) to show that individual differences in gray matter (GM) volume relate to cognitive heterogeneity in PD. VBM does, however, not differentiate between cortical thickness (CTh) and surface area (SA), which might be independently affected in PD. We therefore re-analyzed our cohort using the surface-based method FreeSurfer, and investigated (i) CTh, SA, and (sub)cortical GM volume differences between 93 PD patients and 45 matched controls, and (ii) the relation between these structural measures and cognitive performance on six neuropsychological tasks within the PD group. We found cortical thinning in PD patients in the left pericalcarine gyrus, extending to cuneus, precuneus and lingual areas and left inferior parietal cortex, bilateral rostral middle frontal cortex, and right cuneus, and increased cortical surface area in the left pars triangularis. Within the PD group, we found negative correlations between (i) CTh of occipital areas and performance on a verbal memory task, (ii) SA and volume of the frontal cortex and visuospatial memory performance, and, (iii) volume of the right thalamus and scores on two verbal fluency tasks. Our primary findings illustrate that i) CTh and SA are differentially affected in PD, and ii) VBM and FreeSurfer yield non-overlapping results in an identical dataset. We argue that this discrepancy is due to technical differences and the subtlety of the PD-related structural changes.

Onset of Tlx-3 expression in the chick cerebellar cortex correlates with the morphological development of fissures and delineates a posterior transverse boundary.

PubMed

Logan, Cairine; Millar, Cassie; Bharadia, Vinay; Rouleau, Katherine

2002-06-24

Recent studies have shown that the mammalian cerebellar cortex can be subdivided into a reproducible array of zones and stripes. In particular, discontinuous patterns of gene expression together with mutational analysis suggest that there are at least four distinct transverse zones along the rostrocaudal axis in mouse: the anterior zone (lobules I-V), the central zone (lobules VI and VII), the posterior zone (lobules VIII and IX), and the nodular zone (lobule X). Here we show that the divergent homeobox-containing transcription factor, Tlx- 3 (also known as Hox11L2 or Rnx) is transiently expressed in external granule cells in a distinct transverse domain of the developing chick cerebellar cortex. Expression is first detected at Hamburger and Hamilton (HH) stage 35. Interestingly, Tlx-3 mRNA expression is initially confined to, and coincident with, the morphological development of fissures. Slightly later, at HH stage 38, expression extends throughout the developing external granular layer (EGL) of lobules I-IXab. Notably, no Tlx-3 expression was detected in lobules IXc and X at any developmental time point examined. Expression is noticeably stronger in nonproliferating cells located in the deep layer of the EGL. Tlx-3 expression is downregulated as granule cells migrate inward to form the internal granule layer and is undetectable shortly after birth. These results suggest that Tlx-3 is expressed as granule cells become postmitotic and suggest that Tlx-3 may play a role in the differentiation of distinct neuronal populations in the cerebellum. Copyright 2002 Wiley-Liss, Inc.

The laminar and temporal structure of stimulus information in the phase of field potentials of auditory cortex.

PubMed

Szymanski, Francois D; Rabinowitz, Neil C; Magri, Cesare; Panzeri, Stefano; Schnupp, Jan W H

2011-11-02

Recent studies have shown that the phase of low-frequency local field potentials (LFPs) in sensory cortices carries a significant amount of information about complex naturalistic stimuli, yet the laminar circuit mechanisms and the aspects of stimulus dynamics responsible for generating this phase information remain essentially unknown. Here we investigated these issues by means of an information theoretic analysis of LFPs and current source densities (CSDs) recorded with laminar multi-electrode arrays in the primary auditory area of anesthetized rats during complex acoustic stimulation (music and broadband 1/f stimuli). We found that most LFP phase information originated from discrete "CSD events" consisting of granular-superficial layer dipoles of short duration and large amplitude, which we hypothesize to be triggered by transient thalamocortical activation. These CSD events occurred at rates of 2-4 Hz during both stimulation with complex sounds and silence. During stimulation with complex sounds, these events reliably reset the LFP phases at specific times during the stimulation history. These facts suggest that the informativeness of LFP phase in rat auditory cortex is the result of transient, large-amplitude events, of the "evoked" or "driving" type, reflecting strong depolarization in thalamo-recipient layers of cortex. Finally, the CSD events were characterized by a small number of discrete types of infragranular activation. The extent to which infragranular regions were activated was stimulus dependent. These patterns of infragranular activations may reflect a categorical evaluation of stimulus episodes by the local circuit to determine whether to pass on stimulus information through the output layers.

Experimental Traumatic Brain Injury Results in Long-Term Recovery of Functional Responsiveness in Sensory Cortex but Persisting Structural Changes and Sensorimotor, Cognitive, and Emotional Deficits.

PubMed

Johnstone, Victoria P A; Wright, David K; Wong, Kendrew; O'Brien, Terence J; Rajan, Ramesh; Shultz, Sandy R

2015-09-01

Traumatic brain injury (TBI) is a leading cause of death worldwide. In recent studies, we have shown that experimental TBI caused an immediate (24-h post) suppression of neuronal processing, especially in supragranular cortical layers. We now examine the long-term effects of experimental TBI on the sensory cortex and how these changes may contribute to a range of TBI morbidities. Adult male Sprague-Dawley rats received either a moderate lateral fluid percussion injury (n=14) or a sham surgery (n=12) and 12 weeks of recovery before behavioral assessment, magnetic resonance imaging, and electrophysiological recordings from the barrel cortex. TBI rats demonstrated sensorimotor deficits, cognitive impairments, and anxiety-like behavior, and this was associated with significant atrophy of the barrel cortex and other brain structures. Extracellular recordings from ipsilateral barrel cortex revealed normal neuronal responsiveness and diffusion tensor MRI showed increased fractional anisotropy, axial diffusivity, and tract density within this region. These findings suggest that long-term recovery of neuronal responsiveness is owing to structural reorganization within this region. Therefore, it is likely that long-term structural and functional changes within sensory cortex post-TBI may allow for recovery of neuronal responsiveness, but that this recovery does not remediate all behavioral deficits.

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

PubMed Central

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

2004-01-01

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

Raman Microspectroscopic Mapping with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) Applied to the High-Pressure Polymorph of Titanium Dioxide, TiO2-II.

PubMed

Smith, Joseph P; Smith, Frank C; Ottaway, Joshua; Krull-Davatzes, Alexandra E; Simonson, Bruce M; Glass, Billy P; Booksh, Karl S

2017-08-01

The high-pressure, α-PbO 2 -structured polymorph of titanium dioxide (TiO 2 -II) was recently identified in micrometer-sized grains recovered from four Neoarchean spherule layers deposited between ∼2.65 and ∼2.54 billion years ago. Several lines of evidence support the interpretation that these layers represent distal impact ejecta layers. The presence of shock-induced TiO 2 -II provides physical evidence to further support an impact origin for these spherule layers. Detailed characterization of the distribution of TiO 2 -II in these grains may be useful for correlating the layers, estimating the paleodistances of the layers from their source craters, and providing insight into the formation of the TiO 2 -II. Here we report the investigation of TiO 2 -II-bearing grains from these four spherule layers using multivariate curve resolution-alternating least squares (MCR-ALS) applied to Raman microspectroscopic mapping. Raman spectra provide evidence of grains consisting primarily of rutile (TiO 2 ) and TiO 2 -II, as shown by Raman bands at 174 cm -1 (TiO 2 -II), 426 cm -1 (TiO 2 -II), 443 cm -1 (rutile), and 610 cm -1 (rutile). Principal component analysis (PCA) yielded a predominantly three-phase system comprised of rutile, TiO 2 -II, and substrate-adhesive epoxy. Scanning electron microscopy (SEM) suggests heterogeneous grains containing polydispersed micrometer- and submicrometer-sized particles. Multivariate curve resolution-alternating least squares applied to the Raman microspectroscopic mapping yielded up to five distinct chemical components: three phases of TiO 2 (rutile, TiO 2 -II, and anatase), quartz (SiO 2 ), and substrate-adhesive epoxy. Spectral profiles and spatially resolved chemical maps of the pure chemical components were generated using MCR-ALS applied to the Raman microspectroscopic maps. The spatial resolution of the Raman microspectroscopic maps was enhanced in comparable, cost-effective analysis times by limiting spectral resolution and optimizing spectral acquisition parameters. Using the resolved spectra of TiO 2 -II generated from MCR-ALS analysis, a Raman spectrum for pure TiO 2 -II was estimated to further facilitate its identification.

State transitions of actin cortices in vitro and in vivo

NASA Astrophysics Data System (ADS)

Tan, Tzer Han; Keren, Kinneret; Mackintosh, Fred; Schmidt, Christoph; Fakhri, Nikta

Most animal cells are enveloped by a thin layer of actin cortex which governs the cell mechanics. A functional cortex must be rigid to provide mechanical support while being flexible to allow for rapid restructuring events such as cell division. To satisfy these requirements, the actin cortex is highly dynamic with fast actin turnover and myosin-driven contractility. The regulatory mechanism responsible for the transition between a mechanically stable state and a restructuring state is not well understood. Here, we develop a technique to map the dynamics of reconstituted actin cortices in emulsion droplets using IR fluorescent single-walled carbon nanotubes (SWNTs). By increasing crosslinker concentration, we find that a homogeneous cortex transitions to an intermediate state with broken rotational symmetry and a globally contractile state which further breaks translational symmetry. We apply this new dynamic mapping technique to cortices of live starfish oocytes in various developmental stages. To identify the regulatory mechanism for steady state transitions, we subject the oocytes to actin and myosin disrupting drugs.

Neural coding in barrel cortex during whisker-guided locomotion

PubMed Central

Sofroniew, Nicholas James; Vlasov, Yurii A; Hires, Samuel Andrew; Freeman, Jeremy; Svoboda, Karel

2015-01-01

Animals seek out relevant information by moving through a dynamic world, but sensory systems are usually studied under highly constrained and passive conditions that may not probe important dimensions of the neural code. Here, we explored neural coding in the barrel cortex of head-fixed mice that tracked walls with their whiskers in tactile virtual reality. Optogenetic manipulations revealed that barrel cortex plays a role in wall-tracking. Closed-loop optogenetic control of layer 4 neurons can substitute for whisker-object contact to guide behavior resembling wall tracking. We measured neural activity using two-photon calcium imaging and extracellular recordings. Neurons were tuned to the distance between the animal snout and the contralateral wall, with monotonic, unimodal, and multimodal tuning curves. This rich representation of object location in the barrel cortex could not be predicted based on simple stimulus-response relationships involving individual whiskers and likely emerges within cortical circuits. DOI: http://dx.doi.org/10.7554/eLife.12559.001 PMID:26701910

Regulation of cerebral cortex development by Rho GTPases: insights from in vivo studies

PubMed Central

Azzarelli, Roberta; Kerloch, Thomas; Pacary, Emilie

2015-01-01

The cerebral cortex is the site of higher human cognitive and motor functions. Histologically, it is organized into six horizontal layers, each containing unique populations of molecularly and functionally distinct excitatory projection neurons and inhibitory interneurons. The stereotyped cellular distribution of cortical neurons is crucial for the formation of functional neural circuits and it is predominantly established during embryonic development. Cortical neuron development is a multiphasic process characterized by sequential steps of neural progenitor proliferation, cell cycle exit, neuroblast migration and neuronal differentiation. This series of events requires an extensive and dynamic remodeling of the cell cytoskeleton at each step of the process. As major regulators of the cytoskeleton, the family of small Rho GTPases has been shown to play essential functions in cerebral cortex development. Here we review in vivo findings that support the contribution of Rho GTPases to cortical projection neuron development and we address their involvement in the etiology of cerebral cortex malformations. PMID:25610373

A new Pb{sup II}(ethylenediaminetetraacetate) coordination polymer with a two-dimensional layer structure

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

Zhao, D., E-mail: iamzd@hpu.edu.cn; Zhang, R. H.; Li, F. F.

2016-12-15

A new Pb{sup II}−edta{sup 4–} coordination polymer, Pb{sub 2}(edta)(H{sub 2}O){sub 0.76} (edta{sup 4–} = ethylenediaminetetraacetate) was synthesized under hydrothermal condition. Single crystal X-ray analysis reveals that it represents a novel two-dimensional (2D) Pb{sup 2+}–edta{sup 4–} layer structure with a (4,8{sup 2})-topology. Each edta{sup 4–} ligand employs its four carboxylate O and two N atoms to chelate one Pb{sup II} atom (hexa-coordinated) and connects five Pb{sup II} atoms (ennea-coordinated) via its four carboxylate groups to form 2D layer framework. Adjacent layers are packed into the overall structure through vander Waals interactions.

Method of manufacturing semiconductor having group II-group VI compounds doped with nitrogen

DOEpatents

Compaan, Alvin D.; Price, Kent J.; Ma, Xianda; Makhratchev, Konstantin

2005-02-08

A method of making a semiconductor comprises depositing a group II-group VI compound onto a substrate in the presence of nitrogen using sputtering to produce a nitrogen-doped semiconductor. This method can be used for making a photovoltaic cell using sputtering to apply a back contact layer of group II-group VI compound to a substrate in the presence of nitrogen, the back coating layer being doped with nitrogen. A semiconductor comprising a group II-group VI compound doped with nitrogen, and a photovoltaic cell comprising a substrate on which is deposited a layer of a group II-group VI compound doped with nitrogen, are also included.

Compensating Level-Dependent Frequency Representation in Auditory Cortex by Synaptic Integration of Corticocortical Input

PubMed Central

Happel, Max F. K.; Ohl, Frank W.

2017-01-01

Robust perception of auditory objects over a large range of sound intensities is a fundamental feature of the auditory system. However, firing characteristics of single neurons across the entire auditory system, like the frequency tuning, can change significantly with stimulus intensity. Physiological correlates of level-constancy of auditory representations hence should be manifested on the level of larger neuronal assemblies or population patterns. In this study we have investigated how information of frequency and sound level is integrated on the circuit-level in the primary auditory cortex (AI) of the Mongolian gerbil. We used a combination of pharmacological silencing of corticocortically relayed activity and laminar current source density (CSD) analysis. Our data demonstrate that with increasing stimulus intensities progressively lower frequencies lead to the maximal impulse response within cortical input layers at a given cortical site inherited from thalamocortical synaptic inputs. We further identified a temporally precise intercolumnar synaptic convergence of early thalamocortical and horizontal corticocortical inputs. Later tone-evoked activity in upper layers showed a preservation of broad tonotopic tuning across sound levels without shifts towards lower frequencies. Synaptic integration within corticocortical circuits may hence contribute to a level-robust representation of auditory information on a neuronal population level in the auditory cortex. PMID:28046062

The evolution of cortical development: the synapsid-diapsid divergence.

PubMed

Goffinet, Andre M

2017-11-15

The cerebral cortex covers the rostral part of the brain and, in higher mammals and particularly humans, plays a key role in cognition and consciousness. It is populated with neuronal cell bodies distributed in radially organized layers. Understanding the common and lineage-specific molecular mechanisms that orchestrate cortical development and evolution are key issues in neurobiology. During evolution, the cortex appeared in stem amniotes and evolved divergently in two main branches of the phylogenetic tree: the synapsids (which led to present day mammals) and the diapsids (reptiles and birds). Comparative studies in organisms that belong to those two branches have identified some common principles of cortical development and organization that are possibly inherited from stem amniotes and regulated by similar molecular mechanisms. These comparisons have also highlighted certain essential features of mammalian cortices that are absent or different in diapsids and that probably evolved after the synapsid-diapsid divergence. Chief among these is the size and multi-laminar organization of the mammalian cortex, and the propensity to increase its area by folding. Here, I review recent data on cortical neurogenesis, neuronal migration and cortical layer formation and folding in this evolutionary perspective, and highlight important unanswered questions for future investigation. © 2017. Published by The Company of Biologists Ltd.

Ultastructural analysis on acetylcholinesterase localization in the cerebellar cortex of teleosts.

PubMed

Contestabile, A; Villani, L; Ciani, F

1977-12-28

The histochemical localization of acetylcholinesterase (AChE) was studied by electron microscopy in the cerebellar cortex of the goldfish and the catfish. The patterns of enzyme distribution show noticeable differences in the two teleost species at the level of the corresponding cerebellar structures. Among the most distinctive features is the prevailing intracellular localization of enzyme activity in the goldfish and the prevailing extracellular localization in the catfish in the molecular layer and, to a lesser extent, the granular layer. Only quantitative differences in the ability to synthesize AChE can be recorded among the different cerebellar neurons in the two species, since all these neurons exhibit different amounts of enzyme activity linked to their cytoplasmic structures. Comparing the results obtained with those of previous histochemical, experimental and developmental researches, the hypothesis seems well founded that the embryonic pool of cerebellar neurons is made up of AChE-synthesizing nruroblasts which, during development, loss or maintain to a different the mechanisms for AChE synthesis. In addition the light and electron microscope histochemistry reveals at different levels of resolution that the final pattern of AChE distribution in the cerebellar cortex is the sum of different degress of AChE synthesis by cerebellar neurons and different degrees of enzyme release in extracellular spaces.

Synaptic Circuit Organization of Motor Corticothalamic Neurons

PubMed Central

Yamawaki, Naoki

2015-01-01

Corticothalamic (CT) neurons in layer 6 constitute a large but enigmatic class of cortical projection neurons. How they are integrated into intracortical and thalamo-cortico-thalamic circuits is incompletely understood, especially outside of sensory cortex. Here, we investigated CT circuits in mouse forelimb motor cortex (M1) using multiple circuit-analysis methods. Stimulating and recording from CT, intratelencephalic (IT), and pyramidal tract (PT) projection neurons, we found strong CT↔ CT and CT↔ IT connections; however, CT→IT connections were limited to IT neurons in layer 6, not 5B. There was strikingly little CT↔ PT excitatory connectivity. Disynaptic inhibition systematically accompanied excitation in these pathways, scaling with the amplitude of excitation according to both presynaptic (class-specific) and postsynaptic (cell-by-cell) factors. In particular, CT neurons evoked proportionally more inhibition relative to excitation (I/E ratio) than IT neurons. Furthermore, the amplitude of inhibition was tuned to match the amount of excitation at the level of individual neurons; in the extreme, neurons receiving no excitation received no inhibition either. Extending these studies to dissect the connectivity between cortex and thalamus, we found that M1-CT neurons and thalamocortical neurons in the ventrolateral (VL) nucleus were remarkably unconnected in either direction. Instead, VL axons in the cortex excited both IT and PT neurons, and CT axons in the thalamus excited other thalamic neurons, including those in the posterior nucleus, which additionally received PT excitation. These findings, which contrast in several ways with previous observations in sensory areas, illuminate the basic circuit organization of CT neurons within M1 and between M1 and thalamus. PMID:25653383

Anatomical Evidence for Classical and Extra-classical Receptive Field Completion Across the Discontinuous Horizontal Meridian Representation of Primate Area V2

PubMed Central

Jeffs, Janelle; Ichida, Jennifer M.; Federer, Frederick

2009-01-01

In primates, a split of the horizontal meridian (HM) representation at the V2 rostral border divides this area into dorsal (V2d) and ventral (V2v) halves (representing lower and upper visual quadrants, respectively), causing retinotopically neighboring loci across the HM to be distant within V2. How is perceptual continuity maintained across this discontinuous HM representation? Injections of neuroanatomical tracers in marmoset V2d demonstrated that cells near the V2d rostral border can maintain retinotopic continuity within their classical and extra-classical receptive field (RF), by making both local and long-range intra- and interareal connections with ventral cortex representing the upper visual quadrant. V2d neurons located <0.9–1.3 mm from the V2d rostral border, whose RFs presumably do not cross the HM, make nonretinotopic horizontal connections with V2v neurons in the supra- and infragranular layers. V2d neurons located <0.6–0.9 mm from the border, whose RFs presumably cross the HM, in addition make retinotopic local connections with V2v neurons in layer 4. V2d neurons also make interareal connections with upper visual field regions of extrastriate cortex, but not of MT or MTc outside the foveal representation. Labeled connections in ventral cortex appear to represent the “missing” portion of the connectional fields in V2d across the HM. We conclude that connections between dorsal and ventral cortex can create visual field continuity within a second-order discontinuous visual topography. PMID:18755777

Frequency-band signatures of visual responses to naturalistic input in ferret primary visual cortex during free viewing.

PubMed

Sellers, Kristin K; Bennett, Davis V; Fröhlich, Flavio

2015-02-19

Neuronal firing responses in visual cortex reflect the statistics of visual input and emerge from the interaction with endogenous network dynamics. Artificial visual stimuli presented to animals in which the network dynamics were constrained by anesthetic agents or trained behavioral tasks have provided fundamental understanding of how individual neurons in primary visual cortex respond to input. In contrast, very little is known about the mesoscale network dynamics and their relationship to microscopic spiking activity in the awake animal during free viewing of naturalistic visual input. To address this gap in knowledge, we recorded local field potential (LFP) and multiunit activity (MUA) simultaneously in all layers of primary visual cortex (V1) of awake, freely viewing ferrets presented with naturalistic visual input (nature movie clips). We found that naturalistic visual stimuli modulated the entire oscillation spectrum; low frequency oscillations were mostly suppressed whereas higher frequency oscillations were enhanced. In average across all cortical layers, stimulus-induced change in delta and alpha power negatively correlated with the MUA responses, whereas sensory-evoked increases in gamma power positively correlated with MUA responses. The time-course of the band-limited power in these frequency bands provided evidence for a model in which naturalistic visual input switched V1 between two distinct, endogenously present activity states defined by the power of low (delta, alpha) and high (gamma) frequency oscillatory activity. Therefore, the two mesoscale activity states delineated in this study may define the degree of engagement of the circuit with the processing of sensory input. Copyright © 2014 Elsevier B.V. All rights reserved.

Enlargement of Axo-Somatic Contacts Formed by GAD-Immunoreactive Axon Terminals onto Layer V Pyramidal Neurons in the Medial Prefrontal Cortex of Adolescent Female Mice Is Associated with Suppression of Food Restriction-Evoked Hyperactivity and Resilience to Activity-Based Anorexia.

PubMed

Chen, Yi-Wen; Wable, Gauri Satish; Chowdhury, Tara Gunkali; Aoki, Chiye

2016-06-01

Many, but not all, adolescent female mice that are exposed to a running wheel while food restricted (FR) become excessive wheel runners, choosing to run even during the hours of food availability, to the point of death. This phenomenon is called activity-based anorexia (ABA). We used electron microscopic immunocytochemistry to ask whether individual differences in ABA resilience may correlate with the lengths of axo-somatic contacts made by GABAergic axon terminals onto layer 5 pyramidal neurons (L5P) in the prefrontal cortex. Contact lengths were, on average, 40% greater for the ABA-induced mice, relative to controls. Correspondingly, the proportion of L5P perikaryal plasma membrane contacted by GABAergic terminals was 45% greater for the ABA mice. Contact lengths in the anterior cingulate cortex correlated negatively and strongly with the overall wheel activity after FR (R = -0.87, P < 0.01), whereas those in the prelimbic cortex correlated negatively with wheel running specifically during the hours of food availability of the FR days (R = -0.84, P < 0.05). These negative correlations support the idea that increases in the glutamic acid decarboxylase (GAD) terminal contact lengths onto L5P contribute toward ABA resilience through suppression of wheel running, a behavior that is intrinsically rewarding and helpful for foraging but maladaptive within a cage. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Developmental remodeling of corticocortical feedback circuits in ferret visual cortex

PubMed Central

Khalil, Reem; Levitt, Jonathan B.

2014-01-01

Visual cortical areas in the mammalian brain are linked through a system of interareal feedforward and feedback connections, which presumably underlie different visual functions. We characterized the refinement of feedback projections to primary visual cortex (V1) from multiple sources in juvenile ferrets ranging in age from four to ten weeks postnatal. We studied whether the refinement of different aspects of feedback circuitry from multiple visual cortical areas proceeds at a similar rate in all areas. We injected the neuronal tracer cholera toxin B (CTb) into V1, and mapped the areal and laminar distribution of retrogradely labeled cells in extrastriate cortex. Around the time of eye opening at four weeks postnatal, the retinotopic arrangement of feedback appears essentially adultlike; however, Suprasylvian cortex supplies the greatest proportion of feedback, whereas area 18 supplies the greatest proportion in the adult. The density of feedback cells and the ratio of supragranular/infragranular feedback contribution declined in this period at a similar rate in all cortical areas. We also find significant feedback to V1 from layer IV of all extrastriate areas. The regularity of cell spacing, the proportion of feedback arising from layer IV, and the tangential extent of feedback in each area all remained essentially unchanged during this period, except for the infragranular feedback source in area 18 which expanded. Thus, while much of the basic pattern of cortical feedback to V1 is present before eye opening, there is major synchronous reorganization after eye opening, suggesting a crucial role for visual experience in this remodeling process. PMID:24665018

Developmental Injury to the Cerebellar Cortex Following Hydroxyurea Treatment in Early Postnatal Life: An Immunohistochemical and Electron Microscopic Study.

PubMed

Martí, Joaquín; Molina, Vanesa; Santa-Cruz, M C; Hervás, José P

2017-02-01

Postnatal development of the cerebellar cortex was studied in rats administered with a single dose (2 mg/g) of the cytotoxic agent hydroxyurea (HU) on postnatal day (P) 9 and collected at appropriate times ranging from 6 h to 45 days. Quantification of several parameters such as the density of pyknotic, mitotic, BrdU-positive, and vimentin-stained cells revealed that HU compromises the survival of the external granular layer (EGL) cells. Moreover, vimentin immunocytochemistry revealed overexpression and thicker immunoreactive glial processes in HU-treated rats. On the other hand, we also show that HU leads to the activation of apoptotic cellular events, resulting in a substantial number of dying EGL cells, as revealed by TUNEL staining and at the electron microscope level. Additionally, we quantified several features of the cerebellar cortex of rats exposed to HU in early postnatal life and collected in adulthood. Data analysis indicated that the analyzed parameters were less pronounced in rats administered with this agent. Moreover, we observed several alterations in the cerebellar cortex cytoarchitecture of rats injected with HU. Anomalies included ectopic placement of Purkinje cells and abnormities in the dendritic arbor of these macroneurons. Ectopic granule cells were also found in the molecular layer. These findings provide a clue for investigating the mechanisms of HU-induced toxicity during the development of the central nervous system. Our results also suggest that it is essential to avoid underestimating the adverse effects of this hydroxylated analog of urea when administered during early postnatal life.

Developmental remodeling of corticocortical feedback circuits in ferret visual cortex.

PubMed

Khalil, Reem; Levitt, Jonathan B

2014-10-01

Visual cortical areas in the mammalian brain are linked through a system of interareal feedforward and feedback connections, which presumably underlie different visual functions. We characterized the refinement of feedback projections to primary visual cortex (V1) from multiple sources in juvenile ferrets ranging in age from 4-10 weeks postnatal. We studied whether the refinement of different aspects of feedback circuitry from multiple visual cortical areas proceeds at a similar rate in all areas. We injected the neuronal tracer cholera toxin B (CTb) into V1 and mapped the areal and laminar distribution of retrogradely labeled cells in extrastriate cortex. Around the time of eye opening at 4 weeks postnatal, the retinotopic arrangement of feedback appears essentially adult-like; however, suprasylvian cortex supplies the greatest proportion of feedback, whereas area 18 supplies the greatest proportion in the adult. The density of feedback cells and the ratio of supragranular/infragranular feedback contribution declined in this period at a similar rate in all cortical areas. We also found significant feedback to V1 from layer IV of all extrastriate areas. The regularity of cell spacing, the proportion of feedback arising from layer IV, and the tangential extent of feedback in each area all remained essentially unchanged during this period, except for the infragranular feedback source in area 18, which expanded. Thus, while much of the basic pattern of cortical feedback to V1 is present before eye opening, there is major synchronous reorganization after eye opening, suggesting a crucial role for visual experience in this remodeling process. © 2014 Wiley Periodicals, Inc.

Auditory Cortex Basal Activity Modulates Cochlear Responses in Chinchillas

PubMed Central

León, Alex; Elgueda, Diego; Silva, María A.; Hamamé, Carlos M.; Delano, Paul H.

2012-01-01

Background The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. Methodology/Principal Findings Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. Conclusions/Significance These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects suggests that there are at least two functional pathways from the auditory cortex to the cochlea. PMID:22558383

Inactivation of the infragranular striate cortex broadens orientation tuning of supragranular visual neurons in the cat.

PubMed

Allison, J D; Bonds, A B

1994-01-01

Intracortical inhibition is believed to enhance the orientation tuning of striate cortical neurons, but the origin of this inhibition is unclear. To examine the possible influence of ascending inhibitory projections from the infragranular layers of striate cortex on the orientation selectivity of neurons in the supragranular layers, we measured the spatiotemporal response properties of 32 supragranular neurons in the cat before, during, and after neural activity in the infragranular layers beneath the recorded cells was inactivated by iontophoretic administration of GABA. During GABA iontophoresis, the orientation tuning bandwidth of 15 (46.9%) supragranular neurons broadened as a result of increases in response amplitude to stimuli oriented about +/- 20 degrees away from the preferred stimulus angle. The mean (+/- SD) baseline orientation tuning bandwidth (half width at half height) of these neurons was 13.08 +/- 2.3 degrees. Their mean tuning bandwidth during inactivation of the infragranular layers increased to 19.59 +/- 2.54 degrees, an increase of 49.7%. The mean percentage increase in orientation tuning bandwidth of the individual neurons was 47.4%. Four neurons exhibited symmetrical changes in their orientation tuning functions, while 11 neurons displayed asymmetrical changes. The change in form of the orientation tuning functions appeared to depend on the relative vertical alignment of the recorded neuron and the infragranular region of inactivation. Neurons located in close vertical register with the inactivated infragranular tissue exhibited symmetric changes in their orientation tuning functions. The neurons exhibiting asymmetric changes in their orientation tuning functions were located just outside the vertical register. Eight of these 11 neurons also demonstrated a mean shift of 6.67 +/- 5.77 degrees in their preferred stimulus orientation. The magnitude of change in the orientation tuning functions increased as the delivery of GABA was prolonged. Responses returned to normal approximately 30 min after the delivery of GABA was discontinued. We conclude that inhibitory projections from neurons within the infragranular layers of striate cortex in cats can enhance the orientation selectivity of supragranular striate cortical neurons.

Bipolar H II regions produced by cloud-cloud collisions

NASA Astrophysics Data System (ADS)

Whitworth, Anthony; Lomax, Oliver; Balfour, Scott; Mège, Pierre; Zavagno, Annie; Deharveng, Lise

2018-05-01

We suggest that bipolar H II regions may be the aftermath of collisions between clouds. Such a collision will produce a shock-compressed layer, and a star cluster can then condense out of the dense gas near the center of the layer. If the clouds are sufficiently massive, the star cluster is likely to contain at least one massive star, which emits ionizing radiation, and excites an H II region, which then expands, sweeping up the surrounding neutral gas. Once most of the matter in the clouds has accreted onto the layer, expansion of the H II region meets little resistance in directions perpendicular to the midplane of the layer, and so it expands rapidly to produce two lobes of ionized gas, one on each side of the layer. Conversely, in directions parallel to the midplane of the layer, expansion of the H II region stalls due to the ram pressure of the gas that continues to fall towards the star cluster from the outer parts of the layer; a ring of dense neutral gas builds up around the waist of the bipolar H II region, and may spawn a second generation of star formation. We present a dimensionless model for the flow of ionized gas in a bipolar H II region created according to the above scenario, and predict the characteristics of the resulting free-free continuum and recombination-line emission. This dimensionless model can be scaled to the physical parameters of any particular system. Our intention is that these predictions will be useful in testing the scenario outlined above, and thereby providing indirect support for the role of cloud-cloud collisions in triggering star formation.

Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex

PubMed Central

Ku, Shih-pi; Nakamura, Nozomu H.; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M.

2017-01-01

The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc, which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval. PMID:28790897

Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex.

PubMed

Ku, Shih-Pi; Nakamura, Nozomu H; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M

2017-01-01

The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc , which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval.

Effect of prenatal exposure to ethanol on the ultrastructure of layer V of mature rat somatosensory cortex.

PubMed

al-Rabiai, S; Miller, M W

1989-12-01

Recent data have shown that the structure and function of layer V pyramidal neurons, e.g. corticospinal neurons, is altered by prenatal exposure to ethanol. We examined the effect of ethanol on the ultrastructure of layer V in somatosensory cortex. Timed pregnant rats were fed a diet containing 6.7% (v/v) ethanol (E) or pair-fed a nutritionally matched control diet (C). Thirty-day-old offspring of these mothers were prepared by standard electron microscopic techniques. The somata of pyramidal and local circuit neurons and the neuropil were analysed. Prenatal exposure to ethanol induced alterations in the somata of both populations of neurons. The parallel stacking of cisternae characteristic of C-treated rats was disorganized in E-treated rats. Moreover, the Golgi complex and lysosomes occupied a larger fraction of the somata of E-treated rats. The number and frequency of symmetric axosomatic synapses, but not asymmetric axosomatic synapses, formed by both types of neurons were significantly greater in E-treated rats. Gestational exposure to ethanol produced a variety of changes in the neuropil. Dendrites, particularly dendritic shafts, occupied less space in E-treated rats. In contrast, axons accounted for significantly more of the neuropil in E-treated rats than in controls. This increase in axonal space was due to a significantly greater coverage by non-myelinated axons and a significantly smaller coverage by myelinated axons in E-treated rats than in C-treated rats. Although the overall frequency of synapses was similar in both treatment groups, there were significantly more asymmetric synapses in E-treated rats, and most of these were axospinous synapses. These differences may contribute to documented physiological changes such as the lower rate of glucose utilization in layer V of somatosensory cortex of E-treated rats and they may underlie the mental retardation which is characteristic of children with foetal alcohol syndrome.

Contextual modulation of primary visual cortex by auditory signals.

PubMed

Petro, L S; Paton, A T; Muckli, L

2017-02-19

Early visual cortex receives non-feedforward input from lateral and top-down connections (Muckli & Petro 2013 Curr. Opin. Neurobiol. 23, 195-201. (doi:10.1016/j.conb.2013.01.020)), including long-range projections from auditory areas. Early visual cortex can code for high-level auditory information, with neural patterns representing natural sound stimulation (Vetter et al. 2014 Curr. Biol. 24, 1256-1262. (doi:10.1016/j.cub.2014.04.020)). We discuss a number of questions arising from these findings. What is the adaptive function of bimodal representations in visual cortex? What type of information projects from auditory to visual cortex? What are the anatomical constraints of auditory information in V1, for example, periphery versus fovea, superficial versus deep cortical layers? Is there a putative neural mechanism we can infer from human neuroimaging data and recent theoretical accounts of cortex? We also present data showing we can read out high-level auditory information from the activation patterns of early visual cortex even when visual cortex receives simple visual stimulation, suggesting independent channels for visual and auditory signals in V1. We speculate which cellular mechanisms allow V1 to be contextually modulated by auditory input to facilitate perception, cognition and behaviour. Beyond cortical feedback that facilitates perception, we argue that there is also feedback serving counterfactual processing during imagery, dreaming and mind wandering, which is not relevant for immediate perception but for behaviour and cognition over a longer time frame.This article is part of the themed issue 'Auditory and visual scene analysis'. © 2017 The Authors.

Contextual modulation of primary visual cortex by auditory signals

PubMed Central

Paton, A. T.

2017-01-01

Early visual cortex receives non-feedforward input from lateral and top-down connections (Muckli & Petro 2013 Curr. Opin. Neurobiol. 23, 195–201. (doi:10.1016/j.conb.2013.01.020)), including long-range projections from auditory areas. Early visual cortex can code for high-level auditory information, with neural patterns representing natural sound stimulation (Vetter et al. 2014 Curr. Biol. 24, 1256–1262. (doi:10.1016/j.cub.2014.04.020)). We discuss a number of questions arising from these findings. What is the adaptive function of bimodal representations in visual cortex? What type of information projects from auditory to visual cortex? What are the anatomical constraints of auditory information in V1, for example, periphery versus fovea, superficial versus deep cortical layers? Is there a putative neural mechanism we can infer from human neuroimaging data and recent theoretical accounts of cortex? We also present data showing we can read out high-level auditory information from the activation patterns of early visual cortex even when visual cortex receives simple visual stimulation, suggesting independent channels for visual and auditory signals in V1. We speculate which cellular mechanisms allow V1 to be contextually modulated by auditory input to facilitate perception, cognition and behaviour. Beyond cortical feedback that facilitates perception, we argue that there is also feedback serving counterfactual processing during imagery, dreaming and mind wandering, which is not relevant for immediate perception but for behaviour and cognition over a longer time frame. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044015

Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.

PubMed

Matsumoto, Naoyuki; Hoshiba, Yoshio; Morita, Kazuya; Uda, Natsu; Hirota, Miwako; Minamikawa, Maki; Ebisu, Haruka; Shinmyo, Yohei; Kawasaki, Hiroshi

2017-03-15

Although periventricular nodular heterotopia (PNH) is often found in the cerebral cortex of people with thanatophoric dysplasia (TD), the pathophysiology of PNH in TD is largely unknown. This is mainly because of difficulties in obtaining brain samples of TD patients and a lack of appropriate animal models for analyzing the pathophysiology of PNH in TD. Here we investigate the pathophysiological mechanisms of PNH in the cerebral cortex of TD by utilizing a ferret TD model which we recently developed. To make TD ferrets, we electroporated fibroblast growth factor 8 (FGF8) into the cerebral cortex of ferrets. Our immunohistochemical analyses showed that PNH nodules in the cerebral cortex of TD ferrets were mostly composed of cortical neurons, including upper layer neurons and GABAergic neurons. We also found disorganizations of radial glial fibers and of the ventricular lining in the TD ferret cortex, indicating that PNH may result from defects in radial migration of cortical neurons along radial glial fibers during development. Our findings provide novel mechanistic insights into the pathogenesis of PNH in TD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Correlation of the mechanical and structural properties of cortical rachis keratin of rectrices of the Toco Toucan (Ramphastos toco).

PubMed

Bodde, S G; Meyers, M A; McKittrick, J

2011-07-01

Mechanical characterization of the cortex of rectrices (tail feathers) of the Toco Toucan (Ramphastos toco) has been carried out by tensile testing of the rachis cortex in order to systematically determine Young's modulus and maximum tensile strength gradients on the surfaces and along the length of the feather. Of over seventy-five samples tested, the average Young's modulus was found to be 2.56±0.09 GPa, and maximum tensile strength was found to be 78±6 MPa. The Weibull modulus for all sets is greater than one and less than four, indicating that measured strength is highly variable. The highest Weibull moduli were reported for dorsal samplings. Dorsal and ventral surfaces of the cortex are both significantly stiffer and stronger than lateral rachis cortex. On the dorsal surface, cortex sampled from the distal end of the feather was found to be least stiff and weakest compared to that sampled from proximal and middle regions along the length of the feather. Distinctive fracture patterns correspond to failure in the superficial cuticle layer and the bulk of the rachis cortex. In the cuticle, where supramolecular keratinous fibers are oriented tangentially, evidence of ductile tearing was observed. In the bulk cortex, where the fibers are bundled and oriented longitudinally, patterns suggestive of near-periodic aggregation and brittle failure were observed. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Up-regulation of intrarenal renin-angiotensin system contributes to renal damage in high-salt induced hypertension rats].

PubMed

Wu, Hai-yan; Liang, Yao-xian; Bai, Qiong; Zhuang, Zhen; A, La-ta; Zheng, Dan-xia; Wang, Yue

2015-02-18

To test the hypothesis that in a high-salt induced hypertension in normal rats, whether the changes of intrarenal renin-agiotensin system (RAS) play a critical role in renal damage and could be reflected by urinary angiotensinogen (AGT). In the study, 27 normotensive male Wistar-Kyoto rats were divided into control group [0.3% (mass faction) NaCl in chow, n=9, NS], high-salt diet group [8% (mass faction) NaCl in chow, n=9, HS] and high-salt diet with Losartan group [8% (mass faction) NaCl in chow and 20 mg/(kg×d) Losartan in gavages, n=9, HS+L)], and were fed for six weeks. The blood pressure was monitored and urine samples were collected every 2 weeks. AGTs in plasma, kidney and urine were measured by ELISA kits. The renal cortex expression of mRNA and protein of AGT were measured by Real-time PCR and immunohistochemistry (IHC). The renin activity and ANG II were measured by radioimmunoassay (RIA) kits. Compared with NS, the systolic blood pressure (SBP) [(156 ± 2) mmHg vs. (133 ± 3) mmHg, P<0.05] increased significantly at the end of the 2nd week, and the urinary protein [(14.07 ± 2.84) mg/24 h vs. (7.62 ± 3.02) mg/24 h, P<0.05] increased significantly at the end of the 6th week in HS. Compared with HS, there was no significant difference in SBP (P>0.05) but the proteinuria [(9.69 ± 2.73) mg/24 h vs. (14.07 ± 2.84) mg/24 h, P<0.01] decreased significantly in HS+L. Compared with NS, there was no significant difference in the plasma renin activity, angiotensinogen and ANG II level in HS (P>0.05), but the renal cortex renin content [(8.72 ± 1.98) ng/(mL × h) vs. (4.37 ± 1.26) ng/(mL × h), P<0.05], AGT formation [(4.02 ± 0.60) ng/mg vs. (2.59 ± 0.42) ng/mg, P<0.01], ANG II level [(313.8 ± 48.76) pmol/L vs. (188.9 ± 46.95) pmol/L, P<0.05] were increased significantly in HS, and the urinary AGT and ANG II excretion rates increased significantly (P<0.05). Compared with HS, the plasma renin activity, angiotensinogen and ANG II level were significantly increased (P<0.05), but the renal cortex renin content, AGT formation, ANG II level significantly decreased (P<0.05), and the urinary AGT and ANG II excretion rates decreased significantly in HS+L (P<0.05). The urinary AGT excretion rates were positively correlated with the AGT level in the renal cortex (P<0.05). Up-regulation of intarenal RAS may contribute to renal damage in high-salt induced hypertension rats. Urinary AGT may reflect the status of intrarenal RAS.

Assessing the significance of Palaeolithic engraved cortexes. A case study from the Mousterian site of Kiik-Koba, Crimea

PubMed Central

d’Errico, Francesco; Stepanchuk, Vadim

2018-01-01

Twenty-Seven Lower and Middle Paleolithic sites from Europe and the Middle East are reported in the literature to have yielded incised stones. At eleven of these sites incisions are present on flint cortexes. Even when it is possible to demonstrate that the engravings are ancient and human made, it is often difficult to distinguish incisions resulting from functional activities such as butchery or use as a cutting board, from those produced deliberately, and even more difficult to identify the scope of the latter. In this paper we present results of the analysis of an engraved cortical flint flake found at Kiik-Koba, a key Mousterian site from Crimea, and create an interpretative framework to guide the interpretation of incised cortexes. The frame of inference that we propose allows for a reasoned evaluation of the actions playing a role in the marking process and aims at narrowing down the interpretation of the evidence. The object comes from layer IV, the same layer in which a Neanderthal child burial was unearthed, which contains a para-Micoquian industry of Kiik-Koba type dated to between c.35 and 37 cal kyr BP. The microscopic analysis and 3D reconstruction of the grooves on the cortex of this small flint flake, demonstrate that the incisions represent a deliberate engraving made by a skilled craftsman, probably with two different points. The lines are nearly perfectly framed into the cortex, testifying of well controlled motions. This is especially the case considering the small size of the object, which makes this a difficult task. The production of the engraving required excellent neuromotor and volitional control, which implies focused attention. Evaluation of the Kiik-Koba evidence in the light of the proposed interpretative framework supports the view that the engraving was made with a representational intent. PMID:29718916

Assessing the significance of Palaeolithic engraved cortexes. A case study from the Mousterian site of Kiik-Koba, Crimea.

PubMed

Majkić, Ana; d'Errico, Francesco; Stepanchuk, Vadim

2018-01-01

Twenty-Seven Lower and Middle Paleolithic sites from Europe and the Middle East are reported in the literature to have yielded incised stones. At eleven of these sites incisions are present on flint cortexes. Even when it is possible to demonstrate that the engravings are ancient and human made, it is often difficult to distinguish incisions resulting from functional activities such as butchery or use as a cutting board, from those produced deliberately, and even more difficult to identify the scope of the latter. In this paper we present results of the analysis of an engraved cortical flint flake found at Kiik-Koba, a key Mousterian site from Crimea, and create an interpretative framework to guide the interpretation of incised cortexes. The frame of inference that we propose allows for a reasoned evaluation of the actions playing a role in the marking process and aims at narrowing down the interpretation of the evidence. The object comes from layer IV, the same layer in which a Neanderthal child burial was unearthed, which contains a para-Micoquian industry of Kiik-Koba type dated to between c.35 and 37 cal kyr BP. The microscopic analysis and 3D reconstruction of the grooves on the cortex of this small flint flake, demonstrate that the incisions represent a deliberate engraving made by a skilled craftsman, probably with two different points. The lines are nearly perfectly framed into the cortex, testifying of well controlled motions. This is especially the case considering the small size of the object, which makes this a difficult task. The production of the engraving required excellent neuromotor and volitional control, which implies focused attention. Evaluation of the Kiik-Koba evidence in the light of the proposed interpretative framework supports the view that the engraving was made with a representational intent.

Effects of noise-induced hearing loss on parvalbumin and perineuronal net expression in the mouse primary auditory cortex.

PubMed

Nguyen, Anna; Khaleel, Haroun M; Razak, Khaleel A

2017-07-01

Noise induced hearing loss is associated with increased excitability in the central auditory system but the cellular correlates of such changes remain to be characterized. Here we tested the hypothesis that noise-induced hearing loss causes deterioration of perineuronal nets (PNNs) in the auditory cortex of mice. PNNs are specialized extracellular matrix components that commonly enwrap cortical parvalbumin (PV) containing GABAergic interneurons. Compared to somatosensory and visual cortex, relatively less is known about PV/PNN expression patterns in the primary auditory cortex (A1). Whether changes to cortical PNNs follow acoustic trauma remains unclear. The first aim of this study was to characterize PV/PNN expression in A1 of adult mice. PNNs increase excitability of PV+ inhibitory neurons and confer protection to these neurons against oxidative stress. Decreased PV/PNN expression may therefore lead to a reduction in cortical inhibition. The second aim of this study was to examine PV/PNN expression in superficial (I-IV) and deep cortical layers (V-VI) following noise trauma. Exposing mice to loud noise caused an increase in hearing threshold that lasted at least 30 days. PV and PNN expression in A1 was analyzed at 1, 10 and 30 days following the exposure. No significant changes were observed in the density of PV+, PNN+, or PV/PNN co-localized cells following hearing loss. However, a significant layer- and cell type-specific decrease in PNN intensity was seen following hearing loss. Some changes were present even at 1 day following noise exposure. Attenuation of PNN may contribute to changes in excitability in cortex following noise trauma. The regulation of PNN may open up a temporal window for altered excitability in the adult brain that is then stabilized at a new and potentially pathological level such as in tinnitus. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamics of Aerenchyma Distribution in the Cortex of Sulfate-deprived Adventitious Roots of Maize

PubMed Central

BOURANIS, DIMITRIS L.; CHORIANOPOULOU, STYLIANI N.; KOLLIAS, CHARALAMBOS; MANIOU, PHILIPPA; PROTONOTARIOS, VASSILIS E.; SIYIANNIS, VASSILIS F.; HAWKESFORD, MALCOLM J.

2006-01-01

• Background and Aims Aerenchyma formation in maize adventitious roots is induced in nutrient solution by the deprivation of sulfate (S) under well-oxygenated conditions. The aim of this research was to examine the extent of aerenchyma formation in the cortex of sulfate-deprived adventitious roots along the root axis, in correlation with the presence of reactive oxygen species (ROS), calcium levels and pH of cortex cells and root lignification. • Methods The morphometry of the second whorl of adventitious (W2) roots, subject to S-deprivation conditions throughout development, was recorded in terms of root length and lateral root length and distribution. W2 roots divided into sectors according to the mean length of lateral roots, and cross-sections of each were examined for aerenchyma. In-situ detection of alterations in ROS presence, calcium levels and pH were performed by means of fluorescence microscopy using H2DCF-DA, fluo-3AM and BCECF, respectively. Lignification was detected using the Wiesner test. • Key Results S-deprivation reduced shoot growth and enhanced root proliferation. Aerenchyma was found in the cortex of 77 % of the root length, particularly in the region of emerging or developing lateral roots. The basal and apical sectors had no aerenchyma and no aerenchyma connection was found with the shoot. S-deprivation resulted in alterations of ROS, calcium levels and pH in aerenchymatous sectors compared with the basal non-aerenchymatous region. Lignified epidermal layers were located at the basal and the proximal sectors. S-deprivation resulted in shorter lateral roots in the upper sectors and in a limited extension of the lignified layers towards the next lateral root carrying sector. • Conclusions Lateral root proliferation is accompanied by spatially localized induced cell death in the cortex of developing young maize adventitious roots during S-deprivation. PMID:16481362

Elaboration of the Visual Pathways from the Study of War-Related Cranial Injuries: The Period from the Russo-Japanese War to World War I.

PubMed

Lanska, Douglas J

2016-01-01

As a result of the wars in the early 20th century, elaboration of the visual pathways was greatly facilitated by the meticulous study of visual defects in soldiers who had suffered focal injuries to the visual cortex. Using relatively crude techniques, often under difficult wartime circumstances, investigators successfully mapped key features of the visual pathways. Studies during the Russo- Japanese War (1904-1905) by Tatsuji Inouye (1881-1976) and during World War I by Gordon Holmes (1876-1965), William Lister (1868-1944), and others produced increasingly refined retinotopic maps of the primary visual cortex, which were later supported and refined by studies during and after World War II. Studies by George Riddoch (1888-1947) during World War I also demonstrated that some patients could still perceive motion despite blindness caused by damage to their visual cortex and helped to establish the concept of functional partitioning of visual processes in the occipital cortex. © 2016 S. Karger AG, Basel.

Mitochondrial Damage: A Diagnostic and Metabolic Approach in Traumatic Brain Injury and Post-Traumatic Disorder

DTIC Science & Technology

2013-01-29

Scanning Confocal Microscope (Zeiss- Pascal) using 20x obj. and edited using Zeiss Image Examiner Ver 5.0. The iso-cortical pyramidal layers 1 and 2 are...NeuN immunoreactivity is seen in the neuronal cytoplasm and especially apical dendrites of pyramidal neurons (white arrows), which facilitates the...identification of the pyramidal cell morphology in the outer pyramidal cell layer of neo-cortex (see picture A, depicted as py). Cortical Pyramidal

A Connectionist Simulation of Attention and Vector Comparison: The Need for Serial Processing in Parallel Hardware

DTIC Science & Technology

1991-01-01

visual and three-layer connectionist network, in that the input layer of memory processing is serial, and is likely to represent each module is... Selective attention gates visual University Press. processing in the extrastnate cortex. Science, 229:782-784. Treasman, A.M. (1985). Preartentive...AD-A242 225 A CONNECTIONIST SIMULATION OF ATTENTION AND VECTOR COMPARISON: THE NEED FOR SERIAL PROCESSING IN PARALLEL HARDWARE Technical Report AlP

Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging.

PubMed

Pabba, Mohan; Scifo, Enzo; Kapadia, Fenika; Nikolova, Yuliya S; Ma, Tianzhou; Mechawar, Naguib; Tseng, George C; Sibille, Etienne

2017-10-01

The orbitofrontal cortex (OFC) is vulnerable to normal and pathologic aging. Currently, layer resolution large-scale proteomic studies describing "normal" age-related alterations at OFC are not available. Here, we performed a large-scale exploratory high-throughput mass spectrometry-based protein analysis on OFC layer 2/3 from 15 "young" (15-43 years) and 18 "old" (62-88 years) human male subjects. We detected 4193 proteins and identified 127 differentially expressed (DE) proteins (p-value ≤0.05; effect size >20%), including 65 up- and 62 downregulated proteins (e.g., GFAP, CALB1). Using a previously described categorization of biological aging based on somatic tissues, that is, peripheral "hallmarks of aging," and considering overlap in protein function, we show the highest representation of altered cell-cell communication (54%), deregulated nutrient sensing (39%), and loss of proteostasis (35%) in the set of OFC layer 2/3 DE proteins. DE proteins also showed a significant association with several neurologic disorders; for example, Alzheimer's disease and schizophrenia. Notably, despite age-related changes in individual protein levels, protein co-expression modules were remarkably conserved across age groups, suggesting robust functional homeostasis. Collectively, these results provide biological insight into aging and associated homeostatic mechanisms that maintain normal brain function with advancing age. Copyright © 2017 Elsevier Inc. All rights reserved.

Somatosensory map expansion and altered processing of tactile inputs in a mouse model of fragile X syndrome.

PubMed

Juczewski, Konrad; von Richthofen, Helen; Bagni, Claudia; Celikel, Tansu; Fisone, Gilberto; Krieger, Patrik

2016-12-01

Fragile X syndrome (FXS) is a common inherited form of intellectual disability caused by the absence or reduction of the fragile X mental retardation protein (FMRP) encoded by the FMR1 gene. In humans, one symptom of FXS is hypersensitivity to sensory stimuli, including touch. We used a mouse model of FXS (Fmr1 KO) to study sensory processing of tactile information conveyed via the whisker system. In vivo electrophysiological recordings in somatosensory barrel cortex showed layer-specific broadening of the receptive fields at the level of layer 2/3 but not layer 4, in response to whisker stimulation. Furthermore, the encoding of tactile stimuli at different frequencies was severely affected in layer 2/3. The behavioral effect of this broadening of the receptive fields was tested in the gap-crossing task, a whisker-dependent behavioral paradigm. In this task the Fmr1 KO mice showed differences in the number of whisker contacts with platforms, decrease in the whisker sampling duration and reduction in the whisker touch-time while performing the task. We propose that the increased excitability in the somatosensory barrel cortex upon whisker stimulation may contribute to changes in the whisking strategy as well as to other observed behavioral phenotypes related to tactile processing in Fmr1 KO mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Modulation of AMPA receptor mediated current by nicotinic acetylcholine receptor in layer I neurons of rat prefrontal cortex

PubMed Central

Tang, Bo; Luo, Dong; Yang, Jie; Xu, Xiao-Yan; Zhu, Bing-Lin; Wang, Xue-Feng; Yan, Zhen; Chen, Guo-Jun

2015-01-01

Layer I neurons in the prefrontal cortex (PFC) exhibit extensive synaptic connections with deep layer neurons, implying their important role in the neural circuit. Study demonstrates that activation of nicotinic acetylcholine receptors (nAChRs) increases excitatory neurotransmission in this layer. Here we found that nicotine selectively increased the amplitude of AMPA receptor (AMPAR)-mediated current and AMPA/NMDA ratio, while without effect on NMDA receptor-mediated current. The augmentation of AMPAR current by nicotine was inhibited by a selective α7-nAChR antagonist methyllycaconitine (MLA) and intracellular calcium chelator BAPTA. In addition, nicotinic effect on mEPSC or paired-pulse ratio was also prevented by MLA. Moreover, an enhanced inward rectification of AMPAR current by nicotine suggested a functional role of calcium permeable and GluA1 containing AMPAR. Consistently, nicotine enhancement of AMPAR current was inhibited by a selective calcium-permeable AMPAR inhibitor IEM-1460. Finally, the intracellular inclusion of synthetic peptide designed to block GluA1 subunit of AMPAR at CAMKII, PKC or PKA phosphorylation site, as well as corresponding kinase inhibitor, blocked nicotinic augmentation of AMPA/NMDA ratio. These results have revealed that nicotine increases AMPAR current by modulating the phosphorylation state of GluA1 which is dependent on α7-nAChR and intracellular calcium. PMID:26370265

Facilitation and Restoration of Cognitive Function in Primate Prefrontal Cortex by a Neuroprosthesis that Utilizes Minicolumn-Specific Neural Firing

PubMed Central

Hampson, Robert E.; Gerhardt, Greg A.; Marmarelis, Vasilis; Song, Dong; Opris, Ioan; Santos, Lucas; Berger, Theodore W.; Deadwyler, Sam A.

2012-01-01

Problem addressed Maintenance of cognitive control is a major concern for many human disease condition, therefore a major goal of human neuroprosthetics is to facilitate and/or recover cognitive function when such circumstances impair appropriate decision making. Methodology Nonhuman primates trained to perform a delayed match to sample (DMS) were employed to record mini-columnar activity in the prefrontal cortex (PFC) via custom designed conformal multielectrode arrays that provided inter-laminar recordings from neurons in PFC layer 2/3 and layer 5. Such recordings were analyzed via a previously demonstrated nonlinear multi-input multi-output (MIMO) neuroprosthesis in rodents, which extracted and characterized multi-columnar firing patterns during DMS performance. Results The MIMO model verified that the conformal recorded individual PFC minicolumns responded to entrained target selections in patterns critical for successful DMS performance. This allowed substitution of task-related layer 5 neuron firing patterns with electrical stimulation in the same recording regions during columnar transmission from layer 2/3 at the time of target selection. Such stimulation facilitated normal task performance, but more importantly, recovered performance when applied as a neuroprosthesis following pharmacological disruption of decision making in the same task. Significance and potential impact These findings provide the first successful application of a neuroprosthesis in primate brain designed specifically to restore or repair disrupted cognitive function. PMID:22976769

Information processing occurs via critical avalanches in a model of the primary visual cortex

NASA Astrophysics Data System (ADS)

Bortolotto, G. S.; Girardi-Schappo, M.; Gonsalves, J. J.; Pinto, L. T.; Tragtenberg, M. H. R.

2016-01-01

We study a new biologically motivated model for the Macaque monkey primary visual cortex which presents power-law avalanches after a visual stimulus. The signal propagates through all the layers of the model via avalanches that depend on network structure and synaptic parameter. We identify four different avalanche profiles as a function of the excitatory postsynaptic potential. The avalanches follow a size-duration scaling relation and present critical exponents that match experiments. The structure of the network gives rise to a regime of two characteristic spatial scales, one of which vanishes in the thermodynamic limit.

Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy.

PubMed

Lyoo, C H; Jeong, Y; Ryu, Y H; Lee, S Y; Song, T J; Lee, J H; Rinne, J O; Lee, M S

2008-02-01

To study the effect of disease duration on the clinical, neuropsychological and [(18)F]-deoxyglucose (FDG) PET findings in patients with mixed type multiple system atrophy (MSA), this study included 16 controls and 37 mixed-type MSA patients with a shorter than a 3-year history of cerebellar or parkinsonian symptoms. We classified the patients into three groups according to the duration of parkinsonian or cerebellar symptoms (Group I =

Redox Reactions between Mn(II) and Hexagonal Birnessite Change Its Layer Symmetry.

PubMed

Zhao, Huaiyan; Zhu, Mengqiang; Li, Wei; Elzinga, Evert J; Villalobos, Mario; Liu, Fan; Zhang, Jing; Feng, Xionghan; Sparks, Donald L

2016-02-16

Birnessite, a phyllomanganate and the most common type of Mn oxide, affects the fate and transport of numerous contaminants and nutrients in nature. Birnessite exhibits hexagonal (HexLayBir) or orthogonal (OrthLayBir) layer symmetry. The two types of birnessite contain contrasting content of layer vacancies and Mn(III), and accordingly have different sorption and oxidation abilities. OrthLayBir can transform to HexLayBir, but it is still vaguely understood if and how the reverse transformation occurs. Here, we show that HexLayBir (e.g., δ-MnO2 and acid birnessite) transforms to OrthLayBir after reaction with aqueous Mn(II) at low Mn(II)/Mn (in HexLayBir) molar ratios (5-24%) and pH ≥ 8. The transformation is promoted by higher pH values, as well as smaller particle size, and/or greater stacking disorder of HexLayBir. The transformation is ascribed to Mn(III) formation via the comproportionation reaction between Mn(II) adsorbed on vacant sites and the surrounding layer Mn(IV), and the subsequent migration of the Mn(III) into the vacancies with an ordered distribution in the birnessite layers. This study indicates that aqueous Mn(II) and pH are critical environmental factors controlling birnessite layer structure and reactivity in the environment.

Intrinsic electrophysiological properties of entorhinal cortex stellate cells and their contribution to grid cell firing fields

PubMed Central

Pastoll, Hugh; Ramsden, Helen L.; Nolan, Matthew F.

2012-01-01

The medial entorhinal cortex (MEC) is an increasingly important focus for investigation of mechanisms for spatial representation. Grid cells found in layer II of the MEC are likely to be stellate cells, which form a major projection to the dentate gyrus. Entorhinal stellate cells are distinguished by distinct intrinsic electrophysiological properties, but how these properties contribute to representation of space is not yet clear. Here, we review the ionic conductances, synaptic, and excitable properties of stellate cells, and examine their implications for models of grid firing fields. We discuss why existing data are inconsistent with models of grid fields that require stellate cells to generate periodic oscillations. An alternative possibility is that the intrinsic electrophysiological properties of stellate cells are tuned specifically to control integration of synaptic input. We highlight recent evidence that the dorsal-ventral organization of synaptic integration by stellate cells, through differences in currents mediated by HCN and leak potassium channels, influences the corresponding organization of grid fields. Because accurate cellular data will be important for distinguishing mechanisms for generation of grid fields, we introduce new data comparing properties measured with whole-cell and perforated patch-clamp recordings. We find that clustered patterns of action potential firing and the action potential after-hyperpolarization (AHP) are particularly sensitive to recording condition. Nevertheless, with both methods, these properties, resting membrane properties and resonance follow a dorsal-ventral organization. Further investigation of the molecular basis for synaptic integration by stellate cells will be important for understanding mechanisms for generation of grid fields. PMID:22536175

Rebound spiking in layer II medial entorhinal cortex stellate cells: Possible mechanism of grid cell function

PubMed Central

Shay, Christopher F.; Ferrante, Michele; Chapman, G. William; Hasselmo, Michael E.

2015-01-01

Rebound spiking properties of medial entorhinal cortex (mEC) stellate cells induced by inhibition may underlie their functional properties in awake behaving rats, including the temporal phase separation of distinct grid cells and differences in grid cell firing properties. We investigated rebound spiking properties using whole cell patch recording in entorhinal slices, holding cells near spiking threshold and delivering sinusoidal inputs, superimposed with realistic inhibitory synaptic inputs to test the capacity of cells to selectively respond to specific phases of inhibitory input. Stellate cells showed a specific phase range of hyperpolarizing inputs that elicited spiking, but non-stellate cells did not show phase specificity. In both cell types, the phase range of spiking output occurred between the peak and subsequent descending zero crossing of the sinusoid. The phases of inhibitory inputs that induced spikes shifted earlier as the baseline sinusoid frequency increased, while spiking output shifted to later phases. Increases in magnitude of the inhibitory inputs shifted the spiking output to earlier phases. Pharmacological blockade of h-current abolished the phase selectivity of hyperpolarizing inputs eliciting spikes. A network computational model using cells possessing similar rebound properties as found in vitro produces spatially periodic firing properties resembling grid cell firing when a simulated animal moves along a linear track. These results suggest that the ability of mEC stellate cells to fire rebound spikes in response to a specific range of phases of inhibition could support complex attractor dynamics that provide completion and separation to maintain spiking activity of specific grid cell populations. PMID:26385258

An autopsy case of cortical superficial siderosis with persistent abnormal behavior.

PubMed

Torii, Youta; Iritani, Shuji; Fujishiro, Hiroshige; Sekiguchi, Hirotaka; Habuchi, Chikako; Umeda, Kentaro; Matsunaga, Shinji; Mimuro, Maya; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

2016-12-01

In recent years, MRI has revealed cortical superficial siderosis (cSS), which exhibits hemosiderin deposition in only the cortical surface. However, the associations between the histological findings and clinical symptoms of cSS remain unclear. We herein report an autopsy case of a 75-year-old Japanese man with cSS with persistent abnormal behavior according to cognitive impairment, hallucination and delusion. At 73 years of age, the patient presented with unusual behavior that indicated auditory hallucination and delusion. One year later, he was admitted to the hospital for malignant lymphoma. On admission, cognitive impairment was detected by a screening test. Soon after hospitalization, he presented with active delirium including visual hallucination and delusion. The patient's excited behavior was improved by the administration of a major tranquilizer. However, the abnormal behavior and cognitive impairment persisted. At 75 years of age, he died of heart failure. A neuropathological investigation revealed hemosiderin depositions in the superficial layer of the cortex in the medial and lateral frontal lobe, the lateral temporal lobe, the parietal lobe, and the medial and lateral occipital lobe. Neuritic plaques and diffuse plaques were extensively observed, which corresponded to Braak stage C and CERAD B, although NFTs were observed that corresponded to Braak stage II. Cortical amyloid angiopathy was not observed in any regions. Ischemic change of brain was also mild. Our report suggests that localized deposition of hemosiderin in the cortex might affect the manifestation of cognitive impairments and hallucination. Further clinicopathological studies are needed to clarify the clinical manifestations of patients with cSS. © 2016 Japanese Society of Neuropathology.

Spectral, thermal and optical-electrical properties of the layer-by-layer deposited thin film of nano Zn(II)-8-hydroxy-5-nitrosoquinolate complex.

PubMed

Haggag, Sawsan M S; Farag, A A M; Abdelrafea, Mohamed

2013-06-01

Zinc(II)-8-hydroxy-5-nitrosoquinolate, [Zn(II)-(HNOQ)2], was synthesized and assembled as a deposited thin film of nano-metal complex by a rapid, direct, simple and efficient procedure based on layer-by-layer chemical deposition technique. Stoichiometric identification and structural characterization of [Zn(II)-(HNOQ)2] were confirmed by electron impact mass spectrometry (EI-MS) and Fourier Transform infrared spectroscopy (FT-IR). Surface morphology was studied by using a scanning electron microscope imaging (SEM) and the particle size was found to be in the range of 23-49 nm. Thermal stability of [Zn(II)-(HNOQ)2] was studied and the thermal parameters were evaluated using thermal gravimetric analysis (TGA). The current density-voltage measurements showed that the current flow is dominated by a space charge limited and influenced by traps under high bias. The optical properties of [Zn(II)-(HNOQ)2] thin films were found to exhibit two direct allowed transitions at 2.4 and 1.0 eV, respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

3D Reconstruction and Standardization of the Rat Vibrissal Cortex for Precise Registration of Single Neuron Morphology

PubMed Central

Egger, Robert; Narayanan, Rajeevan T.; Helmstaedter, Moritz; de Kock, Christiaan P. J.; Oberlaender, Marcel

2012-01-01

The three-dimensional (3D) structure of neural circuits is commonly studied by reconstructing individual or small groups of neurons in separate preparations. Investigation of structural organization principles or quantification of dendritic and axonal innervation thus requires integration of many reconstructed morphologies into a common reference frame. Here we present a standardized 3D model of the rat vibrissal cortex and introduce an automated registration tool that allows for precise placement of single neuron reconstructions. We (1) developed an automated image processing pipeline to reconstruct 3D anatomical landmarks, i.e., the barrels in Layer 4, the pia and white matter surfaces and the blood vessel pattern from high-resolution images, (2) quantified these landmarks in 12 different rats, (3) generated an average 3D model of the vibrissal cortex and (4) used rigid transformations and stepwise linear scaling to register 94 neuron morphologies, reconstructed from in vivo stainings, to the standardized cortex model. We find that anatomical landmarks vary substantially across the vibrissal cortex within an individual rat. In contrast, the 3D layout of the entire vibrissal cortex remains remarkably preserved across animals. This allows for precise registration of individual neuron reconstructions with approximately 30 µm accuracy. Our approach could be used to reconstruct and standardize other anatomically defined brain areas and may ultimately lead to a precise digital reference atlas of the rat brain. PMID:23284282

Arc/Arg3.1 mRNA expression reveals a subcellular trace of prior sound exposure in adult primary auditory cortex.

PubMed

Ivanova, T N; Matthews, A; Gross, C; Mappus, R C; Gollnick, C; Swanson, A; Bassell, G J; Liu, R C

2011-05-05

Acquiring the behavioral significance of sound has repeatedly been shown to correlate with long term changes in response properties of neurons in the adult primary auditory cortex. However, the molecular and cellular basis for such changes is still poorly understood. To address this, we have begun examining the auditory cortical expression of an activity-dependent effector immediate early gene (IEG) with documented roles in synaptic plasticity and memory consolidation in the hippocampus: Arc/Arg3.1. For initial characterization, we applied a repeated 10 min (24 h separation) sound exposure paradigm to determine the strength and consistency of sound-evoked Arc/Arg3.1 mRNA expression in the absence of explicit behavioral contingencies for the sound. We used 3D surface reconstruction methods in conjunction with fluorescent in situ hybridization (FISH) to assess the layer-specific subcellular compartmental expression of Arc/Arg3.1 mRNA. We unexpectedly found that both the intranuclear and cytoplasmic patterns of expression depended on the prior history of sound stimulation. Specifically, the percentage of neurons with expression only in the cytoplasm increased for repeated versus singular sound exposure, while intranuclear expression decreased. In contrast, the total cellular expression did not differ, consistent with prior IEG studies of primary auditory cortex. Our results were specific for cortical layers 3-6, as there was virtually no sound driven Arc/Arg3.1 mRNA in layers 1-2 immediately after stimulation. Our results are consistent with the kinetics and/or detectability of cortical subcellular Arc/Arg3.1 mRNA expression being altered by the initial exposure to the sound, suggesting exposure-induced modifications in the cytoplasmic Arc/Arg3.1 mRNA pool. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of microgravity on muscle and cerebral cortex: a suggested interaction

NASA Astrophysics Data System (ADS)

D'Amelio, F.; Fox, R. A.; Wu, L. C.; Daunton, N. G.; Corcoran, M. L.

The ``slow'' antigravity muscle adductor longus was studied in rats after 14 days of spaceflight (SF). The techniques employed included standard methods for light microscopy, neural cell adhesion molecule (N-CAM) immunocytochemistry and electron microscopy. Light and electron microscopy revealed myofiber atrophy, segmental necrosis and regenerative myofibers. Regenerative myofibers were N-CAM immunoreactive (N-CAM-IR). The neuromuscular junctions showed axon terminals with a decrease or absence of synaptic vesicles, degenerative changes, vacant axonal spaces and changes suggestive of axonal sprouting. No alterations of muscle spindles was seen either by light or electron microscopy. These observations suggest that muscle regeneration and denervation and synaptic remodeling at the level of the neuromuscular junction may take place during spaceflight. In a separate study, GABA immunoreactivity (GABA-IR) was evaluated at the level of the hindlimb representation of the rat somatosensory cortex after 14 days of hindlimb unloading by tail suspension (``simulated'' microgravity). A reduction in number of GABA-immunoreactive cells with respect to the control animals was observed in layer Va and Vb. GABA-IR terminals were also reduced in the same layers, particularly those terminals surrounding the soma and apical dendrites of pyramidal cells in layer Vb. On the basis of previous morphological and behavioral studies of the neuromuscular system after spaceflight and hindlimb suspension it is suggested that after limb unloading there are alterations of afferent signaling and feedback information from intramuscular receptors to the cerebral cortex due to modifications in the reflex organization of hindlimb muscle groups. We propose that the changes observed in GABA immunoreactivity of cells and terminals is an expression of changes in their modulatory activity to compensate for the alterations in the afferent information.

Arc/Arg3.1 mRNA expression reveals a sub-cellular trace of prior sound exposure in adult primary auditory cortex

PubMed Central

Ivanova, Tamara; Matthews, Andrew; Gross, Christina; Mappus, Rudolph C.; Gollnick, Clare; Swanson, Andrew; Bassell, Gary J.; Liu, Robert C.

2011-01-01

Acquiring the behavioral significance of a sound has repeatedly been shown to correlate with long term changes in response properties of neurons in the adult primary auditory cortex. However, the molecular and cellular basis for such changes is still poorly understood. To address this, we have begun examining the auditory cortical expression of an activity-dependent effector immediate early gene (IEG) with documented roles in synaptic plasticity and memory consolidation in the hippocampus: Arc/Arg3.1. For initial characterization, we applied a repeated 10 minute (24 hour separation) sound exposure paradigm to determine the strength and consistency of sound-evoked Arc/Arg3.1 mRNA expression in the absence of explicit behavioral contingencies for the sound. We used 3D surface reconstruction methods in conjunction with fluorescent in-situ hybridization (FISH) to assess the layer-specific sub-cellular compartmental expression of Arc/Arg3.1 mRNA. We unexpectedly found that both the intranuclear and cytoplasmic patterns of expression depended on the prior history of sound stimulation. Specifically, the percentage of neurons with expression only in the cytoplasm increased for repeated versus singular sound exposure, while intranuclear expression decreased. In contrast, the total cellular expression did not differ, consistent with prior IEG studies of primary auditory cortex. Our results were specific for cortical layers 3–6, as there was virtually no sound driven Arc/Arg3.1 mRNA in layers 1–2 immediately after stimulation. Our results are consistent with the kinetics and/or detectability of cortical sub-cellular Arc/Arg3.1 mRNA expression being altered by the initial exposure to the sound, suggesting exposure-induced modifications in the cytoplasmic Arc/Arg3.1 mRNA pool. PMID:21334422

Augmenting responses evoked in area 17 of the cat by intracortical axon collaterals of cortico-geniculate cells.

PubMed Central

Ferster, D; Lindström, S

1985-01-01

Evoked potentials were recorded in the visual cortex of the cat after electrical stimulation of the lateral geniculate nucleus (l.g.n.). The primary response, mediated by geniculo-cortical fibres, was depressed at stimulation frequencies above 7 Hz and replaced by a late potential, the incremental response, which gradually increased in amplitude with successive stimuli. The incremental response was a negative-positive potential in the depth of the cortex with the negative component having maximal amplitude in layer 4. The response reversed polarity in layer 1 to become a positive-negative potential at the surface. The latency of the negative component of the incremental response was about 3.5-4 ms in layer 4, compared to about 1.5 and 2.5 ms for the mono- and disynaptic components of the primary response. The incremental response could only be evoked from the l.g.n. and the optic radiation, not from the optic tract, superior colliculus or other surrounding structures. Within the l.g.n., the effect was only evoked from stimulation sites in approximate retinotopic register with the recording site in the cortex. Low threshold points were found in the A laminae, completely overlapping with the low threshold points for the primary response. Thresholds increased steeply when the stimulation electrode was lowered into the C laminae. The incremental response could still be evoked ten days after the destruction of all cells in the l.g.n. complex by kainic acid. It is concluded that the described incremental response is identical to the augmenting response of Dempsey & Morison (1943) and is mediated by intracortical axon collaterals of antidromically activated cortico-geniculate neurones. Images Plate 1 PMID:4057097

Laminar circuit organization and response modulation in mouse visual cortex

PubMed Central

Olivas, Nicholas D.; Quintanar-Zilinskas, Victor; Nenadic, Zoran; Xu, Xiangmin

2012-01-01

The mouse has become an increasingly important animal model for visual system studies, but few studies have investigated local functional circuit organization of mouse visual cortex. Here we used our newly developed mapping technique combining laser scanning photostimulation (LSPS) with fast voltage-sensitive dye (VSD) imaging to examine the spatial organization and temporal dynamics of laminar circuit responses in living slice preparations of mouse primary visual cortex (V1). During experiments, LSPS using caged glutamate provided spatially restricted neuronal activation in a specific cortical layer, and evoked responses from the stimulated layer to its functionally connected regions were detected by VSD imaging. In this study, we first provided a detailed analysis of spatiotemporal activation patterns at specific V1 laminar locations and measured local circuit connectivity. Then we examined the role of cortical inhibition in the propagation of evoked cortical responses by comparing circuit activity patterns in control and in the presence of GABAa receptor antagonists. We found that GABAergic inhibition was critical in restricting layer-specific excitatory activity spread and maintaining topographical projections. In addition, we investigated how AMPA and NMDA receptors influenced cortical responses and found that blocking AMPA receptors abolished interlaminar functional projections, and the NMDA receptor activity was important in controlling visual cortical circuit excitability and modulating activity propagation. The NMDA receptor antagonist reduced neuronal population activity in time-dependent and laminar-specific manners. Finally, we used the quantitative information derived from the mapping experiments and presented computational modeling analysis of V1 circuit organization. Taken together, the present study has provided important new information about mouse V1 circuit organization and response modulation. PMID:23060751

Altered Gradients of Glutamate and Gamma-Aminobutyric Acid Transcripts in the Cortical Visuospatial Working Memory Network in Schizophrenia.

PubMed

Hoftman, Gil D; Dienel, Samuel J; Bazmi, Holly H; Zhang, Yun; Chen, Kehui; Lewis, David A

2018-04-15

Visuospatial working memory (vsWM), which is impaired in schizophrenia, requires information transfer across multiple nodes in the cerebral cortex, including visual, posterior parietal, and dorsolateral prefrontal regions. Information is conveyed across these regions via the excitatory projections of glutamatergic pyramidal neurons located in layer 3, whose activity is modulated by local inhibitory gamma-aminobutyric acidergic (GABAergic) neurons. Key properties of these neurons differ across these cortical regions. Consequently, in schizophrenia, alterations in the expression of gene products regulating these properties could disrupt vsWM function in different ways, depending on the region(s) affected. Here, we quantified the expression of markers of glutamate and GABA neurotransmission selectively in layer 3 of four cortical regions in the vsWM network from 20 matched pairs of schizophrenia and unaffected comparison subjects. In comparison subjects, levels of glutamate transcripts tended to increase, whereas GABA transcript levels tended to decrease, from caudal to rostral, across cortical regions of the vsWM network. Composite measures across all transcripts revealed a significant effect of region, with the glutamate measure lowest in the primary visual cortex and highest in the dorsolateral prefrontal cortex, whereas the GABA measure showed the opposite pattern. In schizophrenia subjects, the expression levels of many of these transcripts were altered. However, this disease effect differed across regions, such that the caudal-to-rostral increase in the glutamate measure was blunted and the caudal-to-rostral decline in the GABA measure was enhanced in the illness. Differential alterations in layer 3 glutamate and GABA neurotransmission across cortical regions may contribute to vsWM deficits in schizophrenia. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Alterations in a Unique Class of Cortical Chandelier Cell Axon Cartridges in Schizophrenia.

PubMed

Rocco, Brad R; DeDionisio, Adam M; Lewis, David A; Fish, Kenneth N

2017-07-01

The axons of chandelier cells (ChCs) target the axon initial segment of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of axon initial segments detectable by immunoreactivity for the α2 subunit of the GABA A receptor is higher in layers 2/superficial 3 of the prefrontal cortex. These findings were interpreted as compensatory responses to lower GABA levels in ChCs. However, we recently found that in schizophrenia, ChC cartridge boutons contain normal levels of the 67 kDa isoform of glutamic acid decarboxylase (GAD67) protein, the enzyme responsible for GABA synthesis in these boutons. To understand these findings we quantified the densities of ChC cartridges immunoreactive for vesicular GABA transporter (vGAT+), which is present in all cartridge boutons, and the subset of cartridges that contain calbindin (CB+). Prefrontal cortex tissue sections from 20 matched pairs of schizophrenia and unaffected comparison subjects were immunolabeled for vGAT, GAD67, and CB. The mean density of vGAT+/CB+ cartridges was 2.7-fold higher, exclusively in layer 2 of schizophrenia subjects, whereas the density of vGAT+/CB- cartridges did not differ between subject groups. Neither vGAT, CB, or GAD67 protein levels per ChC bouton nor the number of boutons per cartridge differed between subject groups. Our findings of a greater density of CB+ ChC cartridges in prefrontal cortex layer 2 from schizophrenia subjects suggests that the normal developmental pruning of these cartridges is blunted in the illness. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Differential distribution of vesicular glutamate transporters in the rat cerebellar cortex.

PubMed

Hioki, H; Fujiyama, F; Taki, K; Tomioka, R; Furuta, T; Tamamaki, N; Kaneko, T

2003-01-01

The chemical organization of excitatory axon terminals in the rat cerebellar cortex was examined by immunocytochemistry and in situ hybridization histochemistry of vesicular glutamate transporters 1 and 2 (VGluT1 and VGluT2). Chemical depletion of the inferior olivary complex neurons by 3-acetylpyridine treatment almost completely removed VGluT2 immunoreactivity from the molecular layer, leaving VGluT1 immunoreactivity apparently intact. On the other hand, neuronal deprivation of the cerebellar cortex by kainic acid injection induced a large loss of VGluT1 immunoreactivity in the molecular layer. In the cerebellar granular layer, both VGluT1 and VGluT2 immunoreactivities were found in mossy fiber terminals, and the two immunoreactivities were mostly colocalized in single-axon terminals. Signals for mRNA encoding VGluT2 were found in the inferior olivary complex, and those for VGluT1 and VGluT2 mRNAs were observed in most brainstem precerebellar nuclei sending mossy fibers, such as the pontine, pontine tegmental reticular, lateral reticular and external cuneate nuclei. These results indicate that climbing and parallel fibers selectively use VGluT2 and VGluT1, respectively, whereas mossy fibers apply both VGluT1 and VGluT2 together to accumulate glutamate into synaptic vesicles. Since climbing-fiber and parallel-fiber terminals are known to make depressing and facilitating synapses, respectively, VGluT1 and VGluT2 might have distinct properties associated with those synaptic characteristics. Thus, it would be the next interesting issue to determine whether mossy-fiber terminals co-expressing VGluT1 and VGluT2 show synaptic facilitation or depression.

Inferior parietal lobule projections to anterior inferotemporal cortex (area TE) in macaque monkey.

PubMed

Zhong, Yong-Mei; Rockland, Kathleen S

2003-05-01

Parietal cortical areas have generally been considered as part of the dorsal stream and, as such, only indirectly connected with inferotemporal cortex. In this report we demonstrate, by using the anterograde tracer BDA, that much of the inferior parietal lobule (IPL) has direct connections to anterior-ventral TE (TEav) around the anterior middle temporal sulcus (amts). Connections from area PG terminate in layers 1 and 5 as well as 4; and those from area PF, target layer 6 of TEav, with a small secondary focus in layer 4 of anterior-dorsal TE. Connections from areas PG and PF are relatively sparse; but those from the mid-IPL region (approximately area PFG), which terminate in layer 4, are light to moderate. In confirmation of these results, injections of retrograde tracers in TEav produce labeled neurons in the IPL. These are most numerous in layer 3 at the border of areas PG and PFG, but also occur in layer 5/6. These laminar patterns are more complex than the classical 'feedforward' or 'feedback' patterns associated with early sensory areas. Branched collaterals are common; and three of seven reconstructed axons branched to both TEav and to the lateral bank of the occipito-temporal sulcus, itself a major source of inputs to TEav. The existence of connections from the IPL preferentially to TEav and the amts provides another example where direct 'bypass' connections operate in parallel with multiple indirect routes. It provides further evidence for the differential connectivity of subdivisions within anterior TE and is consistent with recent evidence from functional magnetic resonance imaging studies that the region around the amts may be part of a network involved in three- dimensional shape, which is distributed across both 'what' and 'where' processing streams.

Intracortical circuits amplify sound-evoked activity in primary auditory cortex following systemic injection of salicylate in the rat

PubMed Central

Chrostowski, Michael; Salvi, Richard J.; Allman, Brian L.

2012-01-01

A high dose of sodium salicylate temporarily induces tinnitus, mild hearing loss, and possibly hyperacusis in humans and other animals. Salicylate has well-established effects on cochlear function, primarily resulting in the moderate reduction of auditory input to the brain. Despite decreased peripheral sensitivity and output, salicylate induces a paradoxical enhancement of the sound-evoked field potential at the level of the primary auditory cortex (A1). Previous electrophysiologic studies have begun to characterize changes in thalamorecipient layers of A1; however, A1 is a complex neural circuit with recurrent intracortical connections. To describe the effects of acute systemic salicylate treatment on both thalamic and intracortical sound-driven activity across layers of A1, we applied current-source density (CSD) analysis to field potentials sampled across cortical layers in the anesthetized rat. CSD maps were normally characterized by a large, short-latency, monosynaptic, thalamically driven sink in granular layers followed by a lower amplitude, longer latency, polysynaptic, intracortically driven sink in supragranular layers. Following systemic administration of salicylate, there was a near doubling of both granular and supragranular sink amplitudes at higher sound levels. The supragranular sink amplitude input/output function changed from becoming asymptotic at approximately 50 dB to sharply nonasymptotic, often dominating the granular sink amplitude at higher sound levels. The supragranular sink also exhibited a significant decrease in peak latency, reflecting an acceleration of intracortical processing of the sound-evoked response. Additionally, multiunit (MU) activity was altered by salicylate; the normally onset/sustained MU response type was transformed into a primarily onset response type in granular and infragranular layers. The results from CSD analysis indicate that salicylate significantly enhances sound-driven response via intracortical circuits. PMID:22496535

Layer- and cell-type-specific subthreshold and suprathreshold effects of long-term monocular deprivation in rat visual cortex.

PubMed

Medini, Paolo

2011-11-23

Connectivity and dendritic properties are determinants of plasticity that are layer and cell-type specific in the neocortex. However, the impact of experience-dependent plasticity at the level of synaptic inputs and spike outputs remains unclear along vertical cortical microcircuits. Here I compared subthreshold and suprathreshold sensitivity to prolonged monocular deprivation (MD) in rat binocular visual cortex in layer 4 and layer 2/3 pyramids (4Ps and 2/3Ps) and in thick-tufted and nontufted layer 5 pyramids (5TPs and 5NPs), which innervate different extracortical targets. In normal rats, 5TPs and 2/3Ps are the most binocular in terms of synaptic inputs, and 5NPs are the least. Spike responses of all 5TPs were highly binocular, whereas those of 2/3Ps were dominated by either the contralateral or ipsilateral eye. MD dramatically shifted the ocular preference of 2/3Ps and 4Ps, mostly by depressing deprived-eye inputs. Plasticity was profoundly different in layer 5. The subthreshold ocular preference shift was sevenfold smaller in 5TPs because of smaller depression of deprived inputs combined with a generalized loss of responsiveness, and was undetectable in 5NPs. Despite their modest ocular dominance change, spike responses of 5TPs consistently lost their typically high binocularity during MD. The comparison of MD effects on 2/3Ps and 5TPs, the main affected output cells of vertical microcircuits, indicated that subthreshold plasticity is not uniquely determined by the initial degree of input binocularity. The data raise the question of whether 5TPs are driven solely by 2/3Ps during MD. The different suprathreshold plasticity of the two cell populations could underlie distinct functional deficits in amblyopia.

p57KIP2 regulates radial glia and intermediate precursor cell cycle dynamics and lower layer neurogenesis in developing cerebral cortex

PubMed Central

Mairet-Coello, Georges; Tury, Anna; Van Buskirk, Elise; Robinson, Kelsey; Genestine, Matthieu; DiCicco-Bloom, Emanuel

2012-01-01

During cerebral cortex development, precise control of precursor cell cycle length and cell cycle exit is required for balanced precursor pool expansion and layer-specific neurogenesis. Here, we defined the roles of cyclin-dependent kinase inhibitor (CKI) p57KIP2, an important regulator of G1 phase, using deletion mutant mice. Mutant mice displayed macroencephaly associated with cortical hyperplasia during late embryogenesis and postnatal development. Embryonically, proliferation of radial glial cells (RGC) and intermediate precursors (IPC) was increased, expanding both populations, with greater effect on IPCs. Furthermore, cell cycle re-entry was increased during early corticogenesis, whereas cell cycle exit was augmented at middle stage. Consequently, neurogenesis was reduced early, whereas it was enhanced during later development. In agreement, the timetable of early neurogenesis, indicated by birthdating analysis, was delayed. Cell cycle dynamics analyses in mutants indicated that p57KIP2 regulates cell cycle length in both RGCs and IPCs. By contrast, related CKI p27KIP1 controlled IPC proliferation exclusively. Furthermore, p57KIP2 deficiency markedly increased RGC and IPC divisions at E14.5, whereas p27KIP1 increased IPC proliferation at E16.5. Consequently, loss of p57KIP2 increased primarily layer 5-6 neuron production, whereas loss of p27KIP1 increased neurons specifically in layers 2-5. In conclusion, our observations suggest that p57KIP2 and p27KIP1 control neuronal output for distinct cortical layers by regulating different stages of precursor proliferation, and support a model in which IPCs contribute to both lower and upper layer neuron generation. PMID:22223678

Motor cortex guides selection of predictable movement targets

PubMed Central

Woodgate, Philip J.W.; Strauss, Soeren; Sami, Saber A.; Heinke, Dietmar

2016-01-01

The present paper asks whether the motor cortex contributes to prediction-based guidance of target selection. This question was inspired by recent evidence that suggests (i) recurrent connections from the motor system into the attentional system may extract movement-relevant perceptual information and (ii) that the motor cortex cannot only generate predictions of the sensory consequences of movements but may also operate as predictor of perceptual events in general. To test this idea we employed a choice reaching task requiring participants to rapidly reach and touch a predictable or unpredictable colour target. Motor cortex activity was modulated via transcranial direct current stimulation (tDCS). In Experiment 1 target colour repetitions were predictable. Under such conditions anodal tDCS facilitated selection versus sham and cathodal tDCS. This improvement was apparent for trajectory curvature but not movement initiation. Conversely, where no predictability of colour was embedded reach performance was unaffected by tDCS. Finally, the results of a key-press experiment suggested that motor cortex involvement is restricted to tasks where the predictable target colour is movement-relevant. The outcomes are interpreted as evidence that the motor system contributes to the top-down guidance of selective attention to movement targets. PMID:25835319

Cancer 'survivor-care': II. Disruption of prefrontal brain activation top-down control of working memory capacity as possible mechanism for chemo-fog/brain (chemotherapy-associated cognitive impairment).

PubMed

Raffa, R B

2013-08-01

Cancer chemotherapy-associated cognitive impairments (termed 'chemo-fog' or 'chemo-brain'), particularly in memory, have been self-reported or identified in cancer survivors previously treated with chemotherapy. Although a variety of deficits have been detected, a consistent theme is a detriment in visuospatial working memory. The parietal cortex, a major site of storage of such memory, is implicated in chemotherapy-induced damage. However, if the findings of two recent publications are combined, the (pre)frontal cortex might be an equally viable target. Two recent studies, one postulating a mechanism for 'top-down control' of working memory capacity and another visualizing chemotherapy-induced alterations in brain activation during working memory processing, are reviewed and integrated. A computational model and the proposal that the prefrontal cortex plays a role in working memory via top-down control of parietal working memory capacity is consistent with a recent demonstration of decreased frontal hyperactivation following chemotherapy. Chemotherapy-associated impairment of visuospatial working memory might include the (pre)frontal cortex in addition to the parietal cortex. This provides new opportunity for basic science and clinical investigation. © 2013 John Wiley & Sons Ltd.

A three-layered model of primate prefrontal cortex encodes identity and abstract categorical structure of behavioral sequences.

PubMed

Hinaut, Xavier; Dominey, Peter Ford

2011-01-01

Categorical encoding is crucial for mastering large bodies of related sensory-motor experiences, but what is its neural substrate? In an effort to respond to this question, recent single-unit recording studies in the macaque lateral prefrontal cortex (LPFC) have demonstrated two characteristic forms of neural encoding of the sequential structure of the animal's sensory-motor experience. One population of neurons encodes the specific behavioral sequences. A second population of neurons encodes the sequence category (e.g. ABAB, AABB or AAAA) and does not differentiate sequences within the category (Shima, K., Isoda, M., Mushiake, H., Tanji, J., 2007. Categorization of behavioural sequences in the prefrontal cortex. Nature 445, 315-318.). Interestingly these neurons are intermingled in the lateral prefrontal cortex, and not topographically segregated. Thus, LPFC may provide a neurophysiological basis for sensorimotor categorization. Here we report on a neural network simulation study that reproduces and explains these results. We model a cortical circuit composed of three layers (infragranular, granular, and supragranular) of 5*5 leaky integrator neurons with a sigmoidal output function, and we examine 1000 such circuits running in parallel. Crucially the three layers are interconnected with recurrent connections, thus producing a dynamical system that is inherently sensitive to the spatiotemporal structure of the sequential inputs. The model is presented with 11 four-element sequences following Shima et al. We isolated one subpopulation of neurons each of whose activity predicts individual sequences, and a second population that predicts category independent of the specific sequence. We argue that a richly interconnected cortical circuit is capable of internally generating a neural representation of category membership, thus significantly extending the scope of recurrent network computation. In order to demonstrate that these representations can be used to create an explicit categorization capability, we introduced an additional neural structure corresponding to the striatum. We showed that via cortico-striatal plasticity, neurons in the striatum could produce an explicit representation both of the identity of each sequence, and its category membership. Copyright © 2011 Elsevier Ltd. All rights reserved.

Perirhinal cortex and temporal lobe epilepsy

PubMed Central

Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo

2013-01-01

The perirhinal cortex—which is interconnected with several limbic structures and is intimately involved in learning and memory—plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus. PMID:24009554

Use of separate ZnTe interface layers to form ohmic contacts to p-CdTe films

DOEpatents

Gessert, T.A.

1999-06-01

A method of is disclosed improving electrical contact to a thin film of a p-type tellurium-containing II-VI semiconductor comprising: depositing a first undoped layer of ZnTe on a thin film of p-type tellurium containing II-VI semiconductor with material properties selected to limit the formation of potential barriers at the interface between the p-CdTe and the undoped layer, to a thickness sufficient to control diffusion of the metallic-doped ZnTe into the p-type tellurium-containing II-VI semiconductor, but thin enough to minimize affects of series resistance; depositing a second heavy doped p-type ZnTe layer to the first layer using an appropriate dopant; and depositing an appropriate metal onto the outer-most surface of the doped ZnTe layer for connecting an external electrical conductor to an ohmic contact. 11 figs.

Use of separate ZnTe interface layers to form OHMIC contacts to p-CdTe films

DOEpatents

Gessert, Timothy A.

1999-01-01

A method of improving electrical contact to a thin film of a p-type tellurium-containing II-VI semiconductor comprising: depositing a first undoped layer of ZnTe on a thin film of p-type tellurium containing II-VI semiconductor with material properties selected to limit the formation of potential barriers at the interface between the p-CdTe and the undoped layer, to a thickness sufficient to control diffusion of the metallic-doped ZnTe into the p-type tellurim-containing II-VI semiconductor, but thin enough to minimize affects of series resistance; depositing a second heavy doped p-type ZnTe layer to the first layer using an appropriate dopant; and depositing an appropriate metal onto the outer-most surface of the doped ZnTe layer for connecting an external electrical conductor to an ohmic contact.

3D segmentations of neuronal nuclei from confocal microscope image stacks

PubMed Central

LaTorre, Antonio; Alonso-Nanclares, Lidia; Muelas, Santiago; Peña, José-María; DeFelipe, Javier

2013-01-01

In this paper, we present an algorithm to create 3D segmentations of neuronal cells from stacks of previously segmented 2D images. The idea behind this proposal is to provide a general method to reconstruct 3D structures from 2D stacks, regardless of how these 2D stacks have been obtained. The algorithm not only reuses the information obtained in the 2D segmentation, but also attempts to correct some typical mistakes made by the 2D segmentation algorithms (for example, under segmentation of tightly-coupled clusters of cells). We have tested our algorithm in a real scenario—the segmentation of the neuronal nuclei in different layers of the rat cerebral cortex. Several representative images from different layers of the cerebral cortex have been considered and several 2D segmentation algorithms have been compared. Furthermore, the algorithm has also been compared with the traditional 3D Watershed algorithm and the results obtained here show better performance in terms of correctly identified neuronal nuclei. PMID:24409123

3D segmentations of neuronal nuclei from confocal microscope image stacks.

PubMed

Latorre, Antonio; Alonso-Nanclares, Lidia; Muelas, Santiago; Peña, José-María; Defelipe, Javier

2013-01-01

In this paper, we present an algorithm to create 3D segmentations of neuronal cells from stacks of previously segmented 2D images. The idea behind this proposal is to provide a general method to reconstruct 3D structures from 2D stacks, regardless of how these 2D stacks have been obtained. The algorithm not only reuses the information obtained in the 2D segmentation, but also attempts to correct some typical mistakes made by the 2D segmentation algorithms (for example, under segmentation of tightly-coupled clusters of cells). We have tested our algorithm in a real scenario-the segmentation of the neuronal nuclei in different layers of the rat cerebral cortex. Several representative images from different layers of the cerebral cortex have been considered and several 2D segmentation algorithms have been compared. Furthermore, the algorithm has also been compared with the traditional 3D Watershed algorithm and the results obtained here show better performance in terms of correctly identified neuronal nuclei.

Mapping oxygen concentration in the awake mouse brain

PubMed Central

Lyons, Declan G; Parpaleix, Alexandre; Roche, Morgane; Charpak, Serge

2016-01-01

Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism. DOI: http://dx.doi.org/10.7554/eLife.12024.001 PMID:26836304

Brain State Effects on Layer 4 of the Awake Visual Cortex

PubMed Central

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

2014-01-01

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

Mapping oxygen concentration in the awake mouse brain.

PubMed

Lyons, Declan G; Parpaleix, Alexandre; Roche, Morgane; Charpak, Serge

2016-02-02

Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism.

Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist

PubMed Central

Huys, Raoul; Jirsa, Viktor K.; Darokhan, Ziauddin; Valentiniene, Sonata; Roland, Per E.

2016-01-01

Neurons in the primary visual cortex spontaneously spike even when there are no visual stimuli. It is unknown whether the spiking evoked by visual stimuli is just a modification of the spontaneous ongoing cortical spiking dynamics or whether the spontaneous spiking state disappears and is replaced by evoked spiking. This study of laminar recordings of spontaneous spiking and visually evoked spiking of neurons in the ferret primary visual cortex shows that the spiking dynamics does not change: the spontaneous spiking as well as evoked spiking is controlled by a stable and persisting fixed point attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix). The functional advantage of this organization is that it avoids the need for a system reorganization following visual stimulation, and impedes the transition of spontaneous spiking to evoked spiking and the propagation of spontaneous spiking from layer 4 to layers 2–3. PMID:26778982

A Quantitative Analysis of Neurons with Kv3 Potassium Channel Subunits–Kv3.1b and Kv3.2–in Macaque Primary Visual Cortex

PubMed Central

Constantinople, Christine M.; Disney, Anita A; Maffie, Jonathan; Rudy, Bernardo; Hawken, Michael J

2010-01-01

Voltage-gated potassium channels that are composed of Kv3 subunits exhibit distinct electrophysiological properties: activation at more depolarized potentials than other voltage-gated K+ channels and fast kinetics. These channels have been shown to contribute to the high-frequency firing of fast-spiking (FS) GABAergic interneurons in the rat and mouse brain. In the rodent neocortex, there are distinct patterns of expression for the Kv3.1b and Kv3.2 channel subunits and of co-expression of these subunits with neurochemical markers, such as the calcium-binding proteins parvalbumin (PV) and calbindin D-28K (CB). The distribution of Kv3 channels and interrelationship with calcium-binding protein expression has not been investigated in primate cortex. We used immunoperoxidase and immunofluorescent labeling and stereological counting techniques to characterize the laminar and cell-type distributions of Kv3-ir neurons in macaque V1. We found that across the cortical layers ~25% of both Kv3.1b- and Kv3.2-ir neurons are non-GABAergic. In contrast all Kv3-ir neurons in rodent cortex are GABAergic (Chow et al., 1999). The putatively excitatory Kv3-ir neurons were mostly located in layers 2, 3 and 4b. Further, the proportion of Kv3-ir neurons that express PV or CB also differs between macaque V1 and rodent cortex. These data indicate that, within the population of cortical neurons, a broader population of neurons, encompassing cells of a wider range of morphological classes may be capable of sustaining high-frequency firing in macaque V1. PMID:19634181

Spine Formation and Maturation in the Developing Rat Auditory Cortex

PubMed Central

Schachtele, Scott J.; Losh, Joe; Dailey, Michael E.; Green, Steven H.

2013-01-01

The rat auditory cortex is organized as a tonotopic map of sound frequency. This map is broadly tuned at birth and is refined during the first 3 weeks postnatal. The structural correlates underlying tonotopic map maturation and reorganization during development are poorly understood. We employed fluorescent dye ballistic labeling (“DiOlistics”) alone, or in conjunction with immunohistochemistry, to quantify synaptogenesis in the auditory cortex of normal hearing rats. We show that the developmental appearance of dendritic protrusions, which include both immature filopodia and mature spines, on layers 2/3, 4, and 5 pyramidal and layer 4 spiny nonpyramidal neurons occurs in three phases: slow addition of dendritic protrusions from postnatal day 4 (P4) to P9, rapid addition of dendritic protrusions from P9 to P19, and a final phase where mature protrusion density is achieved (>P21). Next, we combined DiOlistics with immunohistochemical labeling of bassoon, a presynaptic scaffolding protein, as a novel method to categorize dendritic protrusions as either filopodia or mature spines in cortex fixed in vivo. Using this method we observed an increase in the spine-to-filopodium ratio from P9–P16, indicating a period of rapid spine maturation. Previous studies report mature spines as being shorter in length compared to filopodia. We similarly observed a reduction in protrusion length between P9 and P16, corroborating our immunohistochemical spine maturation data. These studies show that dendritic protrusion formation and spine maturation occur rapidly at a time previously shown to correspond to auditory cortical tonotopic map refinement (P11–P14), providing a structural correlate of physiological maturation. PMID:21800311

A discrete transition zone between cuticle and cortex layers of a human hair fibre: changes observed in the presence of breast cancer.

PubMed

Lyman, Donald; Gerstmann, Paula

2017-01-01

Attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopy of hair fibres shows a discrete transition zone (DTZ) between the hard protective cuticle layer and the softer elongated cortical cells of the cortex. The DTZ is composed of flattened orthocortical cells located on the outer perimeter of the cortex and appears to range in thickness between 2 and 3.6 μm. The inner surface of the DTZ, adjacent to the elongated cortical cells that make up the core of the hair fibre, is irregular. ATR-FT-IR analyses of these flattened orthocortical cells indicate major changes in the molecular structure of keratins found in this transition zone. Other studies have identified cells that produce keratins that are distinct from alpha keratins found in the elongated heterocortical cells in the hair fibre core. These distinct keratins appear to be produced in the lower region of the hair follicle at the interface between the cuticle and cortex. The DTZ is also the region where ATR-FT-IR spectroscopy studies identified changes in C-H bending of lipid esters indicative of breast cancer. Lipid ester absorption bands at 1738 and 1732 cm -1 , present in non-cancer hair, are absent in the cancer hair and a new ester band absorbing at 1736 cm -1 is observed. When the breast cancer is clinically removed, the 1736 cm -1 ester band absorption and the increase in the 1446-1456 C-H-bending absorption ratio are no longer observed. This suggests that biomarkers produced by the breast cancer interact with stem or other cells near the lower region of the follicle, controlling the amount and type of lipid esters in the DTZ.

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

PubMed Central

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

2002-01-01

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

Laminar microvascular transit time distribution in the mouse somatosensory cortex revealed by Dynamic Contrast Optical Coherence Tomography

PubMed Central

Merkle, Conrad W.; Srinivasan, Vivek J.

2015-01-01

The transit time distribution of blood through the cerebral microvasculature both constrains oxygen delivery and governs the kinetics of neuroimaging signals such as blood-oxygen-level-dependent functional Magnetic Resonance Imaging (BOLD fMRI). However, in spite of its importance, capillary transit time distribution has been challenging to quantify comprehensively and efficiently at the microscopic level. Here, we introduce a method, called Dynamic Contrast Optical Coherence Tomography (DyC-OCT), based on dynamic cross-sectional OCT imaging of an intravascular tracer as it passes through the field-of-view. Quantitative transit time metrics are derived from temporal analysis of the dynamic scattering signal, closely related to tracer concentration. Since DyC-OCT does not require calibration of the optical focus, quantitative accuracy is achieved even deep in highly scattering brain tissue where the focal spot degrades. After direct validation of DyC-OCT against dilution curves measured using a fluorescent plasma label in surface pial vessels, we used DyC-OCT to investigate the transit time distribution in microvasculature across the entire depth of the mouse somatosensory cortex. Laminar trends were identified, with earlier transit times and less heterogeneity in the middle cortical layers. The early transit times in the middle cortical layers may explain, at least in part, the early BOLD fMRI onset times observed in these layers. The layer-dependencies in heterogeneity may help explain how a single vascular supply manages to deliver oxygen to individual cortical layers with diverse metabolic needs. PMID:26477654

Laminar microvascular transit time distribution in the mouse somatosensory cortex revealed by Dynamic Contrast Optical Coherence Tomography.

PubMed

Merkle, Conrad W; Srinivasan, Vivek J

2016-01-15

The transit time distribution of blood through the cerebral microvasculature both constrains oxygen delivery and governs the kinetics of neuroimaging signals such as blood-oxygen-level-dependent functional Magnetic Resonance Imaging (BOLD fMRI). However, in spite of its importance, capillary transit time distribution has been challenging to quantify comprehensively and efficiently at the microscopic level. Here, we introduce a method, called Dynamic Contrast Optical Coherence Tomography (DyC-OCT), based on dynamic cross-sectional OCT imaging of an intravascular tracer as it passes through the field-of-view. Quantitative transit time metrics are derived from temporal analysis of the dynamic scattering signal, closely related to tracer concentration. Since DyC-OCT does not require calibration of the optical focus, quantitative accuracy is achieved even deep in highly scattering brain tissue where the focal spot degrades. After direct validation of DyC-OCT against dilution curves measured using a fluorescent plasma label in surface pial vessels, we used DyC-OCT to investigate the transit time distribution in microvasculature across the entire depth of the mouse somatosensory cortex. Laminar trends were identified, with earlier transit times and less heterogeneity in the middle cortical layers. The early transit times in the middle cortical layers may explain, at least in part, the early BOLD fMRI onset times observed in these layers. The layer-dependencies in heterogeneity may help explain how a single vascular supply manages to deliver oxygen to individual cortical layers with diverse metabolic needs. Copyright © 2015 Elsevier Inc. All rights reserved.

The subrhinal paleocortex in the hedgehog tenrec: a multiarchitectonic characterization and an analysis of its connections with the olfactory bulb.

PubMed

Künzle, H; Radtke-Schuller, S

2000-12-01

In the Madagascan hedgehog tenrec, Echinops telfairi, the entire paleocortical region (PCx) subjacent to the rhinal indentation is composed of three layers and occupies up to two thirds of the lateral hemisphere. A clear differentiation of PCx into its presumed constituents, the piriform cortex and the entorhinal cortex, as seen in other mammals, has not been obtained so far. To gain insight into location and intrinsic organization of these areas in a basal placental mammal we investigated the tenrec's PCx using cyto-, myelo- and chemoarchitectural criteria (zinc, acetylcholinesterase, NADPh-diaphorase, Wisteria floribunda agglutinin, parvalbumin, calbindin, calretinin) and analysed its connections with the olfactory bulb. The layers 2 and 3 of the tenrec's PCx differed from the corresponding layers in the rat. The layer 2 showed a complex distribution of corticobulbar cells but could not be subdivided, in contrast to layer 3. Additional cell groups in the depth of PCx were tentatively compared with subdivisions of the endopiriform region. The architectural and connectional features varied clearly along the rostrocaudal and dorso-ventral extents of PCx and gave hints for the presence of different paleocortical subdivisions. With the possible exception of an area located at the most caudal tip of the dorsomedial hemisphere, however, no conclusive evidence was obtained for the presence of a multilayered, entorhinal region. The bulbar projections to the PCx were very extensive and almost exclusively ipsilateral. The laterality of the projection is similar to that in higher mammals, but differs from that in the erinaceous hedgehog.

The connectivity of the brain: multi-level quantitative analysis.

PubMed

Murre, J M; Sturdy, D P

1995-11-01

We develop a mathematical formalism or calculating connectivity volumes generated by specific topologies with various physical packing strategies. We consider four topologies (full, random, nearest-neighbor, and modular connectivity) and three physical models: (i) interior packing, where neurons and connection fibers are intermixed, (ii) sheeted packing where neurons are located on a sheet with fibers running underneath, and (iii) exterior packing where the neurons are located at the surfaces of a cube or sphere with fibers taking up the internal volume. By extensive cross-referencing of available human neuroanatomical data we produce a consistent set of parameters for the whole brain, the cerebral cortex, and the cerebellar cortex. By comparing these inferred values with those predicted by the expressions, we draw the following general conclusions for the human brain, cortex, and cerebellum: (i) Interior packing is less efficient than exterior packing (in a sphere). (ii) Fully and randomly connected topologies are extremely inefficient. More specifically we find evidence that different topologies and physical packing strategies might be used at different scales. (iii) For the human brain at a macro-structural level, modular topologies on an exterior sphere approach the data most closely. (iv) On a mesostructural level, laminarization and columnarization are evidence of the superior efficiency of organizing the wiring as sheets. (v) Within sheets, microstructures emerge in which interior models are shown to be the most efficient. With regard to interspecies similarities and differences we conjecture (vi) that the remarkable constancy of number of neurons per underlying square millimeter of cortex may be the result of evolution minimizing interneuron distance in grey matter, and (vii) that the topologies that best fit the human brain data should not be assumed to apply to other mammals, such as the mouse for which we show that a random topology may be feasible for the cortex.

Majewski osteodysplastic primordial dwarfism type II (MOPD II) complicated by stroke: clinical report and review of cerebral vascular anomalies.

PubMed

Brancati, Francesco; Castori, Marco; Mingarelli, Rita; Dallapiccola, Bruno

2005-12-15

We report on a 2 9/12-year-old boy with disproportionate short stature, microcephaly, subtle craniofacial dysmorphisms, and generalized skeletal dysplasia, who developed a left hemiparesis. Brain neuroimaging disclosed a complex cerebral vascular anomaly (CVA) with stenosis of the right anterior cerebral artery and telangiectatic collateral vessels supplying the cerebral cortex, consistent with moyamoya disease. Based on clinical and skeletal features, a diagnosis of Majewski osteodysplastic primordial dwarfism type II (MOPD II) was established. Review of 16 published patients with CVA affected by either Seckel syndrome or MOPD II suggested that CVA is preferentially associated to the latter subtype affecting about 1/4 of the patients. 2005 Wiley-Liss, Inc.

Lhx2 Expression in Postmitotic Cortical Neurons Initiates Assembly of the Thalamocortical Somatosensory Circuit.

PubMed

Wang, Chia-Fang; Hsing, Hsiang-Wei; Zhuang, Zi-Hui; Wen, Meng-Hsuan; Chang, Wei-Jen; Briz, Carlos G; Nieto, Marta; Shyu, Bai Chuang; Chou, Shen-Ju

2017-01-24

Cortical neurons must be specified and make the correct connections during development. Here, we examine a mechanism initiating neuronal circuit formation in the barrel cortex, a circuit comprising thalamocortical axons (TCAs) and layer 4 (L4) neurons. When Lhx2 is selectively deleted in postmitotic cortical neurons using conditional knockout (cKO) mice, L4 neurons in the barrel cortex are initially specified but fail to form cellular barrels or develop polarized dendrites. In Lhx2 cKO mice, TCAs from the thalamic ventral posterior nucleus reach the barrel cortex but fail to further arborize to form barrels. Several activity-regulated genes and genes involved in regulating barrel formation are downregulated in the Lhx2 cKO somatosensory cortex. Among them, Btbd3, an activity-regulated gene controlling dendritic development, is a direct downstream target of Lhx2. We find that Lhx2 confers neuronal competency for activity-dependent dendritic development in L4 neurons by inducing the expression of Btbd3. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The stimulus-evoked population response in visual cortex of awake monkey is a propagating wave

PubMed Central

Muller, Lyle; Reynaud, Alexandre; Chavane, Frédéric; Destexhe, Alain

2014-01-01

Propagating waves occur in many excitable media and were recently found in neural systems from retina to neocortex. While propagating waves are clearly present under anaesthesia, whether they also appear during awake and conscious states remains unclear. One possibility is that these waves are systematically missed in trial-averaged data, due to variability. Here we present a method for detecting propagating waves in noisy multichannel recordings. Applying this method to single-trial voltage-sensitive dye imaging data, we show that the stimulus-evoked population response in primary visual cortex of the awake monkey propagates as a travelling wave, with consistent dynamics across trials. A network model suggests that this reliability is the hallmark of the horizontal fibre network of superficial cortical layers. Propagating waves with similar properties occur independently in secondary visual cortex, but maintain precise phase relations with the waves in primary visual cortex. These results show that, in response to a visual stimulus, propagating waves are systematically evoked in several visual areas, generating a consistent spatiotemporal frame for further neuronal interactions. PMID:24770473

Thalamic nuclei convey diverse contextual information to layer 1 of visual cortex

PubMed Central

Imhof, Fabia; Martini, Francisco J.; Hofer, Sonja B.

2017-01-01

Sensory perception depends on the context within which a stimulus occurs. Prevailing models emphasize cortical feedback as the source of contextual modulation. However, higher-order thalamic nuclei, such as the pulvinar, interconnect with many cortical and subcortical areas, suggesting a role for the thalamus in providing sensory and behavioral context – yet the nature of the signals conveyed to cortex by higher-order thalamus remains poorly understood. Here we use axonal calcium imaging to measure information provided to visual cortex by the pulvinar equivalent in mice, the lateral posterior nucleus (LP), as well as the dorsolateral geniculate nucleus (dLGN). We found that dLGN conveys retinotopically precise visual signals, while LP provides distributed information from the visual scene. Both LP and dLGN projections carry locomotion signals. However, while dLGN inputs often respond to positive combinations of running and visual flow speed, LP signals discrepancies between self-generated and external visual motion. This higher-order thalamic nucleus therefore conveys diverse contextual signals that inform visual cortex about visual scene changes not predicted by the animal’s own actions. PMID:26691828

Human Pluripotent Stem-Cell-Derived Cortical Neurons Integrate Functionally into the Lesioned Adult Murine Visual Cortex in an Area-Specific Way.

PubMed

Espuny-Camacho, Ira; Michelsen, Kimmo A; Linaro, Daniele; Bilheu, Angéline; Acosta-Verdugo, Sandra; Herpoel, Adèle; Giugliano, Michele; Gaillard, Afsaneh; Vanderhaeghen, Pierre

2018-05-29

The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex. The transplanted human neurons expressed the appropriate repertoire of markers of six cortical layers, projected axons to specific visual cortical targets, and were synaptically active within the adult brain. Moreover, transplant maturation and integration were much less efficient following transplantation into the lesioned motor cortex, as previously observed for transplanted mouse cortical neurons. These data constitute an important milestone for the potential use of human PSC-derived cortical cells for the reassembly of cortical circuits and emphasize the importance of cortical areal identity for successful transplantation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Removal of GaAs growth substrates from II-VI semiconductor heterostructures

NASA Astrophysics Data System (ADS)

Bieker, S.; Hartmann, P. R.; Kießling, T.; Rüth, M.; Schumacher, C.; Gould, C.; Ossau, W.; Molenkamp, L. W.

2014-04-01

We report on a process that enables the removal of II-VI semiconductor epilayers from their GaAs growth substrate and their subsequent transfer to arbitrary host environments. The technique combines mechanical lapping and layer selective chemical wet etching and is generally applicable to any II-VI layer stack. We demonstrate the non-invasiveness of the method by transferring an all-II-VI magnetic resonant tunneling diode. High resolution x-ray diffraction proves that the crystal integrity of the heterostructure is preserved. Transport characterization confirms that the functionality of the device is maintained and even improved, which is ascribed to completely elastic strain relaxation of the tunnel barrier layer.

Impaired inhibitory control of cortical synchronization in fragile X syndrome.

PubMed

Paluszkiewicz, Scott M; Olmos-Serrano, Jose Luis; Corbin, Joshua G; Huntsman, Molly M

2011-11-01

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by severe cognitive impairments, sensory hypersensitivity, and comorbidities with autism and epilepsy. Fmr1 knockout (KO) mouse models of FXS exhibit alterations in excitatory and inhibitory neurotransmission, but it is largely unknown how aberrant function of specific neuronal subtypes contributes to these deficits. In this study we show specific inhibitory circuit dysfunction in layer II/III of somatosensory cortex of Fmr1 KO mice. We demonstrate reduced activation of somatostatin-expressing low-threshold-spiking (LTS) interneurons in response to the group I metabotropic glutamate receptor (mGluR) agonist 3,5-dihydroxyphenylglycine (DHPG) in Fmr1 KO mice, resulting in impaired synaptic inhibition. Paired recordings from pyramidal neurons revealed reductions in synchronized synaptic inhibition and coordinated spike synchrony in response to DHPG, indicating a weakened LTS interneuron network in Fmr1 KO mice. Together, these findings reveal a functional defect in a single subtype of cortical interneuron in Fmr1 KO mice. This defect is linked to altered activity of the cortical network in line with the FXS phenotype.

Ventromedial prefrontal cortex supports affective future simulation by integrating distributed knowledge

PubMed Central

Benoit, Roland G.; Szpunar, Karl K.; Schacter, Daniel L.

2014-01-01

Although the future often seems intangible, we can make it more concrete by imagining prospective events. Here, using functional MRI, we demonstrate a mechanism by which the ventromedial prefrontal cortex supports such episodic simulations, and thereby contributes to affective foresight: This region supports processes that (i) integrate knowledge related to the elements that constitute an episode and (ii) represent the episode’s emergent affective quality. The ventromedial prefrontal cortex achieves such integration via interactions with distributed cortical regions that process the individual elements. Its activation then signals the affective quality of the ensuing episode, which goes beyond the combined affective quality of its constituting elements. The integrative process further augments long-term retention of the episode, making it available at later time points. This mechanism thus renders the future tangible, providing a basis for farsighted behavior. PMID:25368170

Ventromedial prefrontal cortex supports affective future simulation by integrating distributed knowledge.

PubMed

Benoit, Roland G; Szpunar, Karl K; Schacter, Daniel L

2014-11-18

Although the future often seems intangible, we can make it more concrete by imagining prospective events. Here, using functional MRI, we demonstrate a mechanism by which the ventromedial prefrontal cortex supports such episodic simulations, and thereby contributes to affective foresight: This region supports processes that (i) integrate knowledge related to the elements that constitute an episode and (ii) represent the episode's emergent affective quality. The ventromedial prefrontal cortex achieves such integration via interactions with distributed cortical regions that process the individual elements. Its activation then signals the affective quality of the ensuing episode, which goes beyond the combined affective quality of its constituting elements. The integrative process further augments long-term retention of the episode, making it available at later time points. This mechanism thus renders the future tangible, providing a basis for farsighted behavior.