The chandelier neuron in schizophrenia

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 (GAT...

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Published inDevelopmental neurobiology (Hoboken, N.J.) Vol. 71; no. 1; pp. 118 - 127
Main Author Lewis, David A.
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2011
Subjects
Animals
ankyrin‐G
Axon guidance
axon initial segment
Cortex
Cortex (prefrontal)
GABA
gamma -Aminobutyric acid A receptors
gamma -Aminobutyric acid transporter
gamma-Aminobutyric Acid - physiology
Humans
Immunoreactivity
Interneurons - metabolism
Interneurons - pathology
Mental disorders
Nervous system
Neural networks
Neurons
Neurotransmission
prefrontal cortex
Prefrontal Cortex - pathology
Presynapse
Primates
Pyramidal cells
Schizophrenia
Schizophrenia - pathology
Sodium channels
Synapses
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ISSN1932-8451
1932-846X
1932-846X
DOI10.1002/dneu.20825

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Summary: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. These alterations are most marked in cortical layers 2–3. In addition, other determinants of the function of chandelier cell‐pyramidal neuron synapses, such as ankyrin‐G (which regulates the recruitment of sodium channels to the AIS), are also selectively altered in superficial layer pyramidal neurons in subjects with schizophrenia. Each of these components of chandelier cell‐pyramidal neuron connectivity exhibits distinctive developmental trajectories in the primate DLPFC, suggesting that disturbances in these trajectories could contribute to the pathogenesis of schizophrenia. Recent findings that inputs from neocortical chandelier neurons are excitatory provide new ideas about the role of this circuitry in the pathophysiology of cortical dysfunction in schizophrenia. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 118–127, 2011
Bibliography:Conflicts of interest: David A. Lewis currently receives investigator‐initiated research support from the BMS Foundation, Bristol‐Myers Squibb, Curridium Ltd., and Pfizer and in 2007–2009 served as a consultant in the areas of target identification and validation and new compound development to AstraZeneca, BioLine RX, Bristol‐Myers Squibb, Hoffman‐Roche, Lilly, Merck, and Neurogen.
The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health.
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ISSN:1932-8451
1932-846X
1932-846X
DOI:10.1002/dneu.20825