Alterations in chandelier neuron axon terminals in the prefrontal cortex of schizophrenic subjects.

OBJECTIVE Abnormalities in prefrontal cortical gamma-aminobutyric acid (GABA) neurotransmission may contribute to cognitive dysfunction in schizophrenia. The density of chandelier neuron axon terminals (cartridges) immunoreactive for the GABA membrane transporter (GAT-1) has been reported to be reduced in the dorsolateral prefrontal cortex of schizophrenic subjects. Because cartridges regulate the output of pyramidal cells, this study analyzed the laminar distribution of GAT-1-immunoreactive cartridges to determine whether certain subpopulations of pyramidal cells are preferentially affected. METHOD Measurements were made of the density of GAT-1 -immunoreactive cartridges in layers 2-3a, 3b-4, and 6 of dorsolateral prefrontal cortex area 46 in 30 subjects with schizophrenia, each of whom was matched to one normal and one psychiatric comparison subject. GAT-1-immunoreactive cartridge density was also examined in monkeys chronically treated with haloperidol. RESULTS Relative to both comparison groups, the schizophrenic subjects had significantly lower GAT-1-immunoreactive cartridge density in layers 2-3a and 3b-4. The decrease was most common and most marked in layers 3b-4, where 80% of the schizophrenic subjects exhibited an average 50.1% decrease in cartridge density in comparison with the matched normal subjects. In contrast, GAT-1-immunoreactive cartridge density was unchanged in the haloperidol-treated monkeys. CONCLUSIONS These findings demonstrate that the density of GAT-1-immunoreactive cartridges is reduced in the majority of schizophrenic subjects and that this alteration may most prominently affect the function of pyramidal cells located in the middle cortical layers. This abnormality may reflect a number of underlying deficits, including a primary defect in dorsolateral prefrontal cortex circuitry or a secondary response to altered thalamic input to this region.

• Publication year

  1999

• Venue

  American Journal of Psychiatry

• Publication date

  1999-11-01

• Fields of study

  Medicine, Psychology

• Identifiers
  DOI 10.1176/AJP.156.11.1709PMID 10553733
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• The altered cartridge pattern may most prominently affect pyramidal cells in the middle cortical layers.

  Confidence 0.84

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review
• Chronic haloperidol treatment in monkeys does not alter GAT-1-immunoreactive cartridge density.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review
• The reduction in GAT-1-immunoreactive cartridge density is most pronounced in layers 3b-4, where 80% of schizophrenic subjects showed an average 50.1% decrease relative to matched normal subjects.

  Confidence 0.96

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review
• In dorsolateral prefrontal cortex area 46, schizophrenia is associated with lower GAT-1-immunoreactive cartridge density in layers 2-3a and 3b-4 than in matched comparison subjects.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review

• dorsolateral prefrontal cortex area 46

  brain region

  A prefrontal cortical region sampled for laminar cartridge-density measurements.

  Aliases: DLPFC area 46, area 46

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review
• gat-1-immunoreactive cartridges

  neural structure

  Chandelier neuron axon terminals in the prefrontal cortex that are labeled by immunoreactivity for the GABA membrane transporter GAT-1.

  Aliases: cartridges immunoreactive for the GABA membrane transporter (GAT-1), GAT-1 cartridges

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review
• haloperidol-treated monkeys

  animal model

  Monkeys chronically exposed to haloperidol and used as a medication comparison model.

  Aliases: monkeys chronically treated with haloperidol

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review
• layers 2-3a

  cortical layer

  A superficial laminar subdivision of cortex used as one of the measurement strata in area 46.

  Aliases: layer 2-3a

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review
• layers 3b-4

  cortical layer

  A middle cortical laminar subdivision of cortex used as one of the measurement strata in area 46.

  Aliases: layer 3b-4

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review
• normal and psychiatric comparison subjects

  control group

  Matched human comparison groups used to benchmark the schizophrenia measurements.

  Aliases: comparison subjects, matched normal and psychiatric comparison subjects

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review
• pyramidal cells

  neuron type

  Cortical projection neurons whose output is regulated by chandelier-cell cartridges at the axon initial segment.

  Aliases: pyramidal neurons

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review
• schizophrenia

  condition

  The psychiatric disorder represented by the patient group examined in the postmortem tissue measurements.

  Aliases: schizophrenic subjects

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (n259mg7uxy) reviewmexicorea (qjvnbu8xg3) review

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