Journal
CEREBRAL CORTEX
Volume 21, Issue 11, Pages 2450-2460Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhr007
Keywords
cannabinoid 1 receptor; GABA; GABA membrane transporter 1; glutamic acid decarboxylase; parvalbumin
Categories
Funding
- National Institutes of Health [MH051234, MH084053, MH071533, MH085108]
- BMS foundation
- Bristol-Myers Squibb
- Curridium Ltd
- Pfizer
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Subclasses of gamma-aminobutyric acid (GABA) interneurons differentially influence cortical network activity. The contribution of differences in GABA synthesis and reuptake in axon boutons to cell type-specific functions is unknown. GABA is synthesized within boutons by glutamic acid decarboxylase 65 (GAD65) and GAD67, while GAT1 is responsible for GABA reuptake. Using an imaging methodology capable of determining the colocalization frequency of different immunocytochemical labels in the same bouton and the quantification of the fluorescence intensity of each label in these same structures, we assessed the bouton levels of GAD65, GAD67, and GAT1 in parvalbumin-expressing chandelier (PVch) and basket (PVb) neurons and cannabinoid 1 receptor-expressing basket (CB1r(b)) neurons in the monkey prefrontal cortex. We show that PVch boutons almost exclusively contained GAD67, relative to GAD65, whereas CB1r(b) boutons contained mostly GAD65. In contrast, both GAD65 and GAD67 were easily detected in PVb boutons. Furthermore, in comparison with PVch boutons, CB1r(b) boutons expressed low to undetectable levels of GAT1. Our findings provide a new basis for the distinctive functional roles of these perisomatic-innervating interneurons in cortical circuits. In addition, they strongly suggest that altered levels of GAD67 or GAD65, as seen in some psychiatric diseases, would have cell type-specific consequences on the modulation of GABA neurotransmission.
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