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Reciprocal Alterations in Pre- and Postsynaptic Inhibitory Markers at Chandelier Cell Inputs to Pyramidal Neurons in Schizophrenia


Volk, D W (2002). Reciprocal Alterations in Pre- and Postsynaptic Inhibitory Markers at Chandelier Cell Inputs to Pyramidal Neurons in Schizophrenia. Cerebral Cortex, 12(10):1063-1070.

Abstract

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 α2 subunit of the GABAA receptor is preferentially localized at pyramidal neuron AIS, we quantified α2 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 α2-labeled AIS per mm2 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 α2-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 neuro-transmission 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

Abstract

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 α2 subunit of the GABAA receptor is preferentially localized at pyramidal neuron AIS, we quantified α2 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 α2-labeled AIS per mm2 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 α2-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 neuro-transmission 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

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:Unspecified
Scopus Subject Areas:Life Sciences > Cognitive Neuroscience
Life Sciences > Cellular and Molecular Neuroscience
Language:English
Date:1 October 2002
Deposited On:25 Sep 2018 12:53
Last Modified:31 Jul 2020 07:30
Publisher:Oxford University Press
ISSN:1047-3211
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/cercor/12.10.1063
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101093cercor12101063 (Library Catalogue)

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