Paper Chase

Paper Chase is a research database designed to offer abstracts of research articles published in journals that have a highly rated impact factor as determined by ISI Impact Factor and PageRank. Abstracts are organized by date, with the most recently published papers listed first.

Feb 13, 2020 9
Vol. 9,

Paradoxical network excitation by glutamate release from VGluT3+ GABAergic interneurons.

Authors: Pelkey KA, Calvigioni D, Fang C, Vargish G, Ekins T, Auville K, Wester JC, Lai M, Mackenzie-Gray Scott C, Yuan X, Hunt S, Abebe D, Xu Q, Dimidschstein J, Fishell G, Chittajallu R, McBain CJ
In violation of Dale's principle several neuronal subtypes utilize more than one classical neurotransmitter. Molecular identification of vesicular glutamate transporter three and cholecystokinin expressing cortical interneurons (CCK+VGluT3+INTs) has prompted speculation of GABA/glutamate corelease from these cells for almost two decades despite a lack of direct evidence. We unequivocally demonstrate CCK+VGluT3+INT-mediated GABA/glutamate cotransmission onto principal cells in adult mice using paired recording and optogenetic approaches. Although under normal conditions, GABAergic inhibition dominates CCK+VGluT3+INT signaling, glutamatergic signaling becomes predominant when glutamate decarboxylase (GAD) function is compromised. CCK+VGluT3+INTs 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 CCK+VGluT3+INTs is amplified, they promote paradoxical network hyperexcitability which may be relevant to disorders involving GAD dysfunction such as schizophrenia or vitamin B6 deficiency.