Paradoxical network excitation by glutamate release from VGluT3 GABAergic interneurons.

07:00 EST 13th February 2020 | BioPortfolio

Summary of "Paradoxical network excitation by glutamate release from VGluT3 GABAergic interneurons."

In violation of Dale's principle several neuronal subtypes utilize more than one classical neurotransmitter. Molecular identification of vesicular glutamate transporter 3 and cholecystokinin expressing cortical interneurons (CCKVGluT3INTs) has prompted speculation of GABA/glutamate corelease from these cells for almost two decades despite a lack of direct evidence. We unequivocally demonstrate CCKVGluT3INT mediated GABA/glutamate cotransmission onto principal cells in adult mice using paired recording and optogenetic approaches. Although under normal conditions, GABAergic inhibition dominates CCKVGluT3INT signaling, glutamatergic signaling becomes predominant when glutamate decarboxylase (GAD) function is compromised. CCKVGluT3INTs exhibit surprising anatomical diversity comprising subsets of all known dendrite targeting CCK interneurons in addition to the expected basket cells, and their extensive circuit innervation profoundly dampens circuit excitability under normal conditions. However, in contexts where the glutamatergic phenotype of CCKVGluT3INTs is amplified, they promote paradoxical network hyperexcitability which may be relevant to disorders involving GAD dysfunction such as schizophrenia or vitamin B6 deficiency.


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This article was published in the following journal.

Name: eLife
ISSN: 2050-084X


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