Laminar Distribution of Subsets of GABAergic Axon Terminals in Human Prefrontal Cortex
In human prefrontal cortex (PFC), ~85% of γ-aminobutyric acid (GABA)-expressing neurons can be subdivided into non-overlapping groups by the presence of calbindin (CB), calretinin (CR) or parvalbumin (PV). Substantial research has focused on the differences in the laminar locations of the cells bodi...
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doaj-a83b285b21ad47cb89ab164b954c60582020-11-25T00:37:07ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292018-02-011210.3389/fnana.2018.00009329608Laminar Distribution of Subsets of GABAergic Axon Terminals in Human Prefrontal CortexKenneth N. Fish0Brad R. Rocco1David A. Lewis2David A. Lewis3Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesWestern Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesWestern Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesIn human prefrontal cortex (PFC), ~85% of γ-aminobutyric acid (GABA)-expressing neurons can be subdivided into non-overlapping groups by the presence of calbindin (CB), calretinin (CR) or parvalbumin (PV). Substantial research has focused on the differences in the laminar locations of the cells bodies of these neurons, with limited attention to the distribution of their axon terminals, their sites of action. We previously reported that in non-human primates subtypes of these cells are distinguishable by differences in terminal protein levels of the GABA synthesizing enzymes glutamic acid decarboxylase 65 (GAD65) and GAD67. Here we used multi-label fluorescence microscopy in human PFC to assess: (1) the laminar distributions of axon terminals containing CB, CR, or PV; and (2) the relative protein levels of GAD65, GAD67 and vesicular GABA transporter (vGAT) in CB, CR and PV terminals. The densities of the different CB, CR and PV terminal subpopulations differed across layers of the PFC. PV terminals comprised two subsets based on the presence of only GAD67 (GAD67+) or both GADs (GAD65/GAD67+), whereas CB and CR terminals comprised three subsets (GAD65+, GAD67+, or GAD65/GAD67+). The densities of the different CB, CR and PV GAD terminal subpopulations also differed across layers. Finally, within each of the three calcium-binding protein subpopulations intra-terminal protein levels of GAD and vGAT differed by GAD subpopulation. These findings are discussed in the context of the laminar distributions of CB, CR and PV cell bodies and the synaptic targets of their axons.http://journal.frontiersin.org/article/10.3389/fnana.2018.00009/fullGAD65GAD67glutamic acid decarboxylasevGAThuman PFC |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kenneth N. Fish Brad R. Rocco David A. Lewis David A. Lewis |
spellingShingle |
Kenneth N. Fish Brad R. Rocco David A. Lewis David A. Lewis Laminar Distribution of Subsets of GABAergic Axon Terminals in Human Prefrontal Cortex Frontiers in Neuroanatomy GAD65 GAD67 glutamic acid decarboxylase vGAT human PFC |
author_facet |
Kenneth N. Fish Brad R. Rocco David A. Lewis David A. Lewis |
author_sort |
Kenneth N. Fish |
title |
Laminar Distribution of Subsets of GABAergic Axon Terminals in Human Prefrontal Cortex |
title_short |
Laminar Distribution of Subsets of GABAergic Axon Terminals in Human Prefrontal Cortex |
title_full |
Laminar Distribution of Subsets of GABAergic Axon Terminals in Human Prefrontal Cortex |
title_fullStr |
Laminar Distribution of Subsets of GABAergic Axon Terminals in Human Prefrontal Cortex |
title_full_unstemmed |
Laminar Distribution of Subsets of GABAergic Axon Terminals in Human Prefrontal Cortex |
title_sort |
laminar distribution of subsets of gabaergic axon terminals in human prefrontal cortex |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroanatomy |
issn |
1662-5129 |
publishDate |
2018-02-01 |
description |
In human prefrontal cortex (PFC), ~85% of γ-aminobutyric acid (GABA)-expressing neurons can be subdivided into non-overlapping groups by the presence of calbindin (CB), calretinin (CR) or parvalbumin (PV). Substantial research has focused on the differences in the laminar locations of the cells bodies of these neurons, with limited attention to the distribution of their axon terminals, their sites of action. We previously reported that in non-human primates subtypes of these cells are distinguishable by differences in terminal protein levels of the GABA synthesizing enzymes glutamic acid decarboxylase 65 (GAD65) and GAD67. Here we used multi-label fluorescence microscopy in human PFC to assess: (1) the laminar distributions of axon terminals containing CB, CR, or PV; and (2) the relative protein levels of GAD65, GAD67 and vesicular GABA transporter (vGAT) in CB, CR and PV terminals. The densities of the different CB, CR and PV terminal subpopulations differed across layers of the PFC. PV terminals comprised two subsets based on the presence of only GAD67 (GAD67+) or both GADs (GAD65/GAD67+), whereas CB and CR terminals comprised three subsets (GAD65+, GAD67+, or GAD65/GAD67+). The densities of the different CB, CR and PV GAD terminal subpopulations also differed across layers. Finally, within each of the three calcium-binding protein subpopulations intra-terminal protein levels of GAD and vGAT differed by GAD subpopulation. These findings are discussed in the context of the laminar distributions of CB, CR and PV cell bodies and the synaptic targets of their axons. |
topic |
GAD65 GAD67 glutamic acid decarboxylase vGAT human PFC |
url |
http://journal.frontiersin.org/article/10.3389/fnana.2018.00009/full |
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