The Experts below are selected from a list of 108 Experts worldwide ranked by ideXlab platform
David A Lewis - One of the best experts on this subject based on the ideXlab platform.
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postnatal development of synaptic structure proteins in pyramidal neuron axon initial segments in monkey prefrontal cortex
The Journal of Comparative Neurology, 2009Co-Authors: Dianne A Cruz, Emily M Lovallo, Steven Stockton, Matthew N Rasband, David A LewisAbstract:In the primate prefrontal cortex (PFC), the functional maturation of the synaptic connections of certain classes of GABA neurons is very complex. For example, the levels of both pre- and post-synaptic proteins that regulate GABA neurotransmission from the Chandelier class of cortical interneurons to the axon initial segment (AIS) of pyramidal neurons undergo marked changes during both the perinatal period and adolescence in the monkey PFC. In order to understand the potential molecular mechanisms associated with these developmental refinements, we quantified the relative densities, laminar distributions, and lengths of pyramidal neuron AIS immunoreactive for ankyrin-G, sIV spectrin, or gephyrin, three proteins involved in regulating synapse structure and receptor localization, in the PFC of rhesus monkeys ranging in age from birth through adulthood. Ankyrin-G- and sIV spectrin-labeled AIS declined in density and length during the first six months postnatal, but then remained stable through adolescence and into adulthood. In contrast, the density of gephyrin-labeled AIS was stable until approximately 15 months of age and then markedly declined during adolescence. Thus, molecular determinants of the structural features that define GABA inputs to pyramidal neuron AIS in monkey PFC undergo distinct developmental trajectories with different types of changes occurring during the perinatal period and adolescence. In concert with previous data, these findings reveal a two-phase developmental process of GABAergic synaptic stability and GABA neurotransmission at Chandelier Cell inputs to pyramidal neurons that likely contributes to the protracted maturation of behaviors mediated by primate PFC circuitry.
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postnatal development of parvalbumin and gaba transporter immunoreactive axon terminals in monkey prefrontal cortex
The Journal of Comparative Neurology, 2002Co-Authors: Susan L Erickson, David A LewisAbstract:In the primate prefrontal cortex, the axon terminals of the Chandelier class of inhibitory local circuit neurons have a distinctive time course of postnatal development. In this study, we sought to determine whether the axon terminals of other classes of local circuit neurons are also refined during postnatal development. We examined postnatal changes in the density of punctate structures immunoreactive for the calcium binding protein parvalbumin, which identifies a subset of gamma-aminobutyric acid (GABA) -containing terminals, in the prefrontal cortex of 35 rhesus monkeys ranging in age from newborn to adult. In area 46, the density of parvalbumin- immunoreactive puncta in the superficial and middle layers was extremely low in the newborn animals, then increased more than 10-fold to adult levels, which were achieved by 3 to 4 years of age. In layer V, a band of labeled puncta present in the newborn animals also increased in density until 3 to 4 years of age. Developmental changes of parvalbumin-immunoreactive puncta in area 9 were similar to those in area 46. In contrast, the density of punctate structures labeled with an antibody against a GABA membrane transporter (GAT-1) did not change across development, suggesting that the number of GABAergic terminals is stable over time, but that the level of parvalbumin protein within the terminals varies. The time course of the observed changes in these parvalbumin-labeled terminals is markedly different from that of parvalbumin-immunoreactive Chandelier Cell terminal clusters. These findings suggest that morphologically specialized classes of inhibitory interneurons assume prominence within the prefrontal cortical network at different stages of postnatal development. J. Comp. Neurol. 448:186–202, 2002. © 2002 Wiley-Liss, Inc.
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51 altered gaba transporter 1 mrna expression in prefrontal cortical neurons in schizophrenia
Biological Psychiatry, 2000Co-Authors: David W Volk, Mark C Austin, Joseph N Pierri, David A LewisAbstract:Within the prefrontal cortex (PFC) of schizophrenic subjects, recent studies suggest that alterations in markers of GABA neurotransmission, including decreased immunoreactivity for the GABA membrane transporter, GAT-1, may be most prominent in the Chandelier Cell subpopulation of GABA neurons (PNAS 95:5341, 1998). In order to explore one possible mechanism for these findings, we tested the hypothesis that GAT-1 mRNA expression is decreased in a subset of PFC GABA neurons in schizophrenia. Tissue sections containing PFC area 9 from 10 schizophrenic subjects, each matched to one control subject for sex, age, and postmortem interval, were processed for in situ hybridization histochemistry with S-labeled oligonucleotide probes for GAT-1 mRNA and exposed to nuclear emulsion. The density of labeled neurons was decreased in the schizophrenic subjects by 21–32% in layers 1–5 but was unchanged in layer 6. In contrast, mean grain density per labeled neuron, a relative measure of the Cellular level of GAT-1 mRNA expression, did not differ between schizophrenic and control subjects. These findings indicate that GAT-1 mRNA expression is relatively unaltered in the majority of PFC GABA neurons in schizophrenic subjects, but is reduced below a detectable level in a subset of GABA neurons. Furthermore, the magnitude and laminar pattern of these results were strikingly similar to our previous study of GAD67 mRNA expression in the same subjects (Arch Gen Psych, in press). Thus, markers of both GABA synthesis and uptake appear to be altered at the level of gene expression in a subset of GABA neurons, and the resulting changes in GABA neurotransmission may contribute to PFC dysfunction in schizophrenia.
Dianne A Cruz - One of the best experts on this subject based on the ideXlab platform.
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postnatal development of synaptic structure proteins in pyramidal neuron axon initial segments in monkey prefrontal cortex
The Journal of Comparative Neurology, 2009Co-Authors: Dianne A Cruz, Emily M Lovallo, Steven Stockton, Matthew N Rasband, David A LewisAbstract:In the primate prefrontal cortex (PFC), the functional maturation of the synaptic connections of certain classes of GABA neurons is very complex. For example, the levels of both pre- and post-synaptic proteins that regulate GABA neurotransmission from the Chandelier class of cortical interneurons to the axon initial segment (AIS) of pyramidal neurons undergo marked changes during both the perinatal period and adolescence in the monkey PFC. In order to understand the potential molecular mechanisms associated with these developmental refinements, we quantified the relative densities, laminar distributions, and lengths of pyramidal neuron AIS immunoreactive for ankyrin-G, sIV spectrin, or gephyrin, three proteins involved in regulating synapse structure and receptor localization, in the PFC of rhesus monkeys ranging in age from birth through adulthood. Ankyrin-G- and sIV spectrin-labeled AIS declined in density and length during the first six months postnatal, but then remained stable through adolescence and into adulthood. In contrast, the density of gephyrin-labeled AIS was stable until approximately 15 months of age and then markedly declined during adolescence. Thus, molecular determinants of the structural features that define GABA inputs to pyramidal neuron AIS in monkey PFC undergo distinct developmental trajectories with different types of changes occurring during the perinatal period and adolescence. In concert with previous data, these findings reveal a two-phase developmental process of GABAergic synaptic stability and GABA neurotransmission at Chandelier Cell inputs to pyramidal neurons that likely contributes to the protracted maturation of behaviors mediated by primate PFC circuitry.
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selective alterations in postsynaptic markers of Chandelier Cell inputs to cortical pyramidal neurons in subjects with schizophrenia
Neuropsychopharmacology, 2009Co-Authors: Dianne A Cruz, Emily M Lovallo, Cassandra L Weaver, Darlene S Melchitzky, David LewisAbstract:Markers of GABA neurotransmission between Chandelier neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons, are altered in the dorsolateral prefrontal cortex (dlPFC) of subjects with schizophrenia. For example, immunoreactivity for the GABA membrane transporter (GAT1) is decreased in presynaptic Chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. To understand the nature and functional significance of these alterations, we determined the density, laminar distribution, and length of AIS immunoreactive (IR) for ankryin-G and βIV spectrin, two proteins involved in the regulation of synapse structure and ion channel clustering at AIS, in dlPFC area 46 from 14 matched triads of subjects with schizophrenia or major depressive disorder (MDD) and normal comparison participants. The density of ankyrin-G-IR AIS in the superficial, but not in the deep, cortical layers was significantly decreased by 15–19% in the subjects with schizophrenia relative to the other participant groups. In contrast, no group differences were present in the density of βIV spectrin-IR AIS. The length of labeled AIS did not differ across participant groups for either ankyrin-G or βIV spectrin. The density of ankyrin-G-IR AIS was not altered in the dlPFC of macaque monkeys chronically exposed to antipsychotic medications. Given the important role of ankyrin-G in the recruitment and stabilization of sodium channels and other integral membrane proteins to AIS, our findings suggest that these processes are selectively altered in superficial layer pyramidal neurons in subjects with schizophrenia.
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postnatal development of pre and postsynaptic gaba markers at Chandelier Cell connections with pyramidal neurons in monkey prefrontal cortex
The Journal of Comparative Neurology, 2003Co-Authors: Dianne A Cruz, Stephen M Eggan, David LewisAbstract:The protracted postnatal maturation of the primate prefrontal cortex (PFC) is associated with substantial changes in the number of excitatory synapses on pyramidal neurons, whereas the total number of inhibitory synapses appears to remain constant. In this study, we sought to determine whether the developmental changes in excitatory input to pyramidal Cells are paralleled by changes in functional markers of inhibitory inputs to pyramidal neurons. The Chandelier subclass of γ-aminobutyric acid (GABA) neurons provides potent inhibitory control over pyramidal neurons by virtue of their axon terminals, which form distinct vertical structures (termed cartridges) that synapse at the axon initial segment (AIS) of pyramidal neurons. Thus, we examined the relative densities, laminar distributions, and lengths of presynaptic Chandelier axon cartridges immunoreactive for the GABA membrane transporter 1 (GAT1) or the calcium-binding protein parvalbumin (PV) and of postsynaptic pyramidal neuron AIS immunoreactive for the GABAA receptor α2 subunit (GABAA α2) in PFC area 46 of 38 rhesus monkeys (Macaca mulatta). From birth through 2 years of age, the relative densities and laminar distributions of these three markers exhibited different trajectories, suggesting developmental shifts in the weighting of at least some factors that determine inhibition at the AIS. In contrast, from 2 to 4 years of age, all three markers exhibited similar declines in density and length that paralleled the periadolescent pruning of excitatory synapses to pyramidal neurons. Across development, the predominant laminar location of PV-labeled cartridges and GABAA α2-immunoreactive AIS shifted from the middle to superficial layers, whereas the laminar distribution of GAT1-positive cartridges did not change. Together, these findings suggest that the maturation of inhibitory inputs to the AIS of PFC pyramidal neurons is a complex process that may differentially affect the firing patterns of subpopulations of pyramidal neurons at specific postnatal time points. J. Comp. Neurol. 465:385–400, 2003. © 2003 Wiley-Liss, Inc.
Alberto Munoz - One of the best experts on this subject based on the ideXlab platform.
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the distribution of Chandelier Cell axon terminals that express the gaba plasma membrane transporter gat 1 in the human neocortex
Cerebral Cortex, 2007Co-Authors: Javier Defelipe, Maria Carmen Inda, Alberto MunozAbstract:Chandelier Cells represent a unique type of cortical GABAergic interneuron whose axon terminals (Ch-terminals) form synapses exclusively with the axon initial segments of pyramidal Cells. In this study, we have used immunocytochemistry for the high-affinity plasma membrane transporter-1 (GAT-1) to analyze the distribution and density of Ch-terminals in various cytoarchitectonic and functional areas of the human neocortex. The lowest density of GAT-1-immuoreactive (-ir) Ch-terminals was detected in the primary and secondary visual (areas 17 and 18) and in the somatosensory areas (areas 3b and 1). In contrast, an intermediate density was observed in the motor area 4 and the associative frontolateral areas 45 and 46, whereas the associative frontolateral areas 9 and 10, frontal orbitary areas 11, 12, 13, 14, and 47, associative temporal areas 20, 21, 22, and 38, and cingulate areas 24 and 32 displayed the highest density of GAT-1-ir Ch-terminals. Despite these differences, the laminar distribution of GAT-1-ir Ch-terminals was similar in most cortical areas. Hence, the highest density of this transporter was observed in layer II, followed by layers III, V, VI, and IV. In most cortical areas, the density of GAT-1-ir Ch-terminals was positively correlated with the neuronal density, although a negative correlation was detected in layer III across all cortical areas. These results indicate that there are substantial differences in the distribution and density of GAT-1-ir Ch-terminals between areas and layers of the human neocortex. These differences might be related to the different functional attributes of the cortical regions examined.
David Lewis - One of the best experts on this subject based on the ideXlab platform.
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selective alterations in postsynaptic markers of Chandelier Cell inputs to cortical pyramidal neurons in subjects with schizophrenia
Neuropsychopharmacology, 2009Co-Authors: Dianne A Cruz, Emily M Lovallo, Cassandra L Weaver, Darlene S Melchitzky, David LewisAbstract:Markers of GABA neurotransmission between Chandelier neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons, are altered in the dorsolateral prefrontal cortex (dlPFC) of subjects with schizophrenia. For example, immunoreactivity for the GABA membrane transporter (GAT1) is decreased in presynaptic Chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. To understand the nature and functional significance of these alterations, we determined the density, laminar distribution, and length of AIS immunoreactive (IR) for ankryin-G and βIV spectrin, two proteins involved in the regulation of synapse structure and ion channel clustering at AIS, in dlPFC area 46 from 14 matched triads of subjects with schizophrenia or major depressive disorder (MDD) and normal comparison participants. The density of ankyrin-G-IR AIS in the superficial, but not in the deep, cortical layers was significantly decreased by 15–19% in the subjects with schizophrenia relative to the other participant groups. In contrast, no group differences were present in the density of βIV spectrin-IR AIS. The length of labeled AIS did not differ across participant groups for either ankyrin-G or βIV spectrin. The density of ankyrin-G-IR AIS was not altered in the dlPFC of macaque monkeys chronically exposed to antipsychotic medications. Given the important role of ankyrin-G in the recruitment and stabilization of sodium channels and other integral membrane proteins to AIS, our findings suggest that these processes are selectively altered in superficial layer pyramidal neurons in subjects with schizophrenia.
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postnatal development of pre and postsynaptic gaba markers at Chandelier Cell connections with pyramidal neurons in monkey prefrontal cortex
The Journal of Comparative Neurology, 2003Co-Authors: Dianne A Cruz, Stephen M Eggan, David LewisAbstract:The protracted postnatal maturation of the primate prefrontal cortex (PFC) is associated with substantial changes in the number of excitatory synapses on pyramidal neurons, whereas the total number of inhibitory synapses appears to remain constant. In this study, we sought to determine whether the developmental changes in excitatory input to pyramidal Cells are paralleled by changes in functional markers of inhibitory inputs to pyramidal neurons. The Chandelier subclass of γ-aminobutyric acid (GABA) neurons provides potent inhibitory control over pyramidal neurons by virtue of their axon terminals, which form distinct vertical structures (termed cartridges) that synapse at the axon initial segment (AIS) of pyramidal neurons. Thus, we examined the relative densities, laminar distributions, and lengths of presynaptic Chandelier axon cartridges immunoreactive for the GABA membrane transporter 1 (GAT1) or the calcium-binding protein parvalbumin (PV) and of postsynaptic pyramidal neuron AIS immunoreactive for the GABAA receptor α2 subunit (GABAA α2) in PFC area 46 of 38 rhesus monkeys (Macaca mulatta). From birth through 2 years of age, the relative densities and laminar distributions of these three markers exhibited different trajectories, suggesting developmental shifts in the weighting of at least some factors that determine inhibition at the AIS. In contrast, from 2 to 4 years of age, all three markers exhibited similar declines in density and length that paralleled the periadolescent pruning of excitatory synapses to pyramidal neurons. Across development, the predominant laminar location of PV-labeled cartridges and GABAA α2-immunoreactive AIS shifted from the middle to superficial layers, whereas the laminar distribution of GAT1-positive cartridges did not change. Together, these findings suggest that the maturation of inhibitory inputs to the AIS of PFC pyramidal neurons is a complex process that may differentially affect the firing patterns of subpopulations of pyramidal neurons at specific postnatal time points. J. Comp. Neurol. 465:385–400, 2003. © 2003 Wiley-Liss, Inc.
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reciprocal alterations in pre and postsynaptic inhibitory markers at Chandelier Cell inputs to pyramidal neurons in schizophrenia
Cerebral Cortex, 2002Co-Authors: David W Volk, Joseph N Pierri, Jeanmarc Fritschy, Allan R Sampson, David LewisAbstract:In the prefrontal cortex of subjects with schizophrenia, markers of the synthesis and re-uptake of GABA appear to be selectively altered in a subset of interneurons that includes Chandelier Cells. Determining the effect of these disturbances in presynaptic GABA markers on inhibitory signaling requires knowledge of the status of GABAA receptors at the postsynaptic targets of Chandelier Cells, the axon initial segments (AIS) of pyramidal neurons. Because the α 2 subunit of the GABAA receptor is preferentially localized at pyramidal neuron AIS, we quantified α 2 subunit immunoreactive AIS in tissue sections containing prefrontal cortex area 46 from 14 matched triads of subjects with schizophrenia, subjects with major depression and control subjects. Systematic, random sampling revealed that the mean number of α 2-labeled AIS per mm 2 in subjects with schizophrenia was significantly (P = 0.007) increased by 113% compared to control subjects and non-significantly increased compared to subjects with major depression. Furthermore, within subjects with schizophrenia, the density of α 2-labeled AIS was negatively correlated (r = –0.49, P = 0.038) with the density of Chandelier axon terminals immunoreactive for the GABA membrane transporter. These data suggest that GABAA receptors are up-regulated at pyramidal neuron AIS in response to deficient GABA neurotransmission at Chandelier axon terminals in schizophrenia. Thus, disturbances in inhibition at the Chandelier neuron–pyramidal neuron synapse may be a critical component of prefrontal cortical dysfunction in schizophrenia.
Josh Z Huang - One of the best experts on this subject based on the ideXlab platform.
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retinal and callosal activity dependent Chandelier Cell elimination shapes binocularity in primary visual cortex
Social Science Research Network, 2019Co-Authors: Borshuen Wang, Maria Sol Bernardez Sarria, Michael C Crair, Josh Z HuangAbstract:In mammals with binocular vision, integration of the left and right visual scene begins with information at the center visual field, which are relayed from each retina in parallel and merge in the primary visual cortex (V1) through the convergence of ipsi- and contralateral geniculocortical inputs as well as trans-callosal projections between two visual hemispheres. The developmental mechanisms that assemble this binocular circuit remain incompletely understood. Using genetic methods in mice, we found that during the days before eye-opening, retinal and callosal activity drives massive apoptosis of GABAergic Chandelier Cells (ChCs) in the binocular region of V1. Blockade of ChC elimination resulted in a contralateral-dominated V1 and deficient binocular vision. As activity patterns in the retina prior to vision convey the organization of the visual field, their regulation of ChC density through the trans-callosal pathway may prime a nascent binocular territory for subsequent experience-driven tuning during the post-vision critical period.
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retinal and callosal activity dependent Chandelier Cell elimination shapes binocularity in primary visual cortex
bioRxiv, 2019Co-Authors: Borshuen Wang, Maria Sol Bernardez Sarria, Michael C Crair, Josh Z HuangAbstract:In mammalian primary visual cortex (V1), integration of the left and right visual scene into a binocular percept derives from convergent ipsi- and contralateral geniculocortical inputs and trans-callosal projections between the two hemispheres. However, the underlying developmental mechanisms remain incompletely understood. Using genetic methods in mice we found that during the days before eye-opening, retinal and callosal activity drives massive apoptosis of GABAergic Chandelier Cells (ChCs) in the binocular region of V1. Blockade of ChC elimination resulted in a contralateral-dominated V1 and deficient binocular vision. As activity patterns within and between retinas prior to vision convey organization of the visual field, their regulation of ChC density through the trans-callosal pathway may prime a nascent binocular territory for subsequent experience-driven tuning during the post-vision critical period.