Stimulation of α1-adrenoceptors facilitates GABAergic transmission onto pyramidal neurons in the medial prefrontal cortex. (6th August 2015)

• Record Type: Journal Article
• Authors: Luo, F.; Tang, H.; Cheng, Z.-y.
• Is Part Of: Neuroscience. Volume 300(2015)
• Page Start: 63
• Page End: 74
• Publication Date: 2015-08-06
• Subjects: ACSF artificial cerebrospinal fluid -- AP-5 dl-2-amino-5-phophonovaleric acid -- APs action potentials -- DNQX 6, 7-dinitroquinoxaline-2, 3-dione -- EGTA ethylene glycol tetraacetic acid -- eIPSCs evoked IPSCs -- FS fast-spiking -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- mIPSCs miniature IPSCs -- mPFC medial prefrontal cortex -- NMDA N-methyl-d-aspartic acid -- PFC prefrontal cortex -- Phe phenylephrine -- PPF paired-pulse facilitation -- PTX picrotoxin -- RMPs resting membrane potentials -- sIPSCs spontaneous IPSCs -- TTX tetrodotoxin -- α1-ARs α1-adrenoceptors; α1-adrenoceptor -- GABAergic transmission -- medial prefrontal cortex -- rat; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.04.070
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Phenylephrine enhances GABAergic transmission onto pyramidal neurons. Phenylephrine enhances GABA release probability and number of releasable vesicles. Phenylephrine depolarizes GABAergic interneurons through the inhibition of Kirs. Abstract: Whereas activation of α1 -adrenoceptors (α1 -ARs) modulates glutamatergic transmission, the roles of α1 -ARs in GABAergic transmission in the medial prefrontal cortex (mPFC) are elusive. Here, we examined the effects of the α1 -AR agonist phenylephrine (Phe) on GABAergic transmission onto pyramidal neurons in the deep layers of the mPFC. We found that bath application of Phe dose-dependently increased the amplitude of evoked IPSCs (eIPSCs). Phe increased the frequency but not the amplitude of miniature IPSCs (mIPSCs). Ca 2+ influx through T-type voltage-gated calcium channels is required for Phe-induced increases in GABA release. Phe increases GABA release probability and the number of releasable vesicles. Phe depolarizes the fast-spiking (FS) interneurons without effects on the firing rate of action potentials (APs) of interneurons. Phe-induced depolarization is independent of extracellular Na +, Ca 2+ and T-type calcium channels, but requires inward rectifier K + channels (Kirs). The present study demonstrates that Phe enhances GABAergic transmission onto mPFC pyramidal neurons through inhibiting interneurons Kirs, which further depolarizes interneurons leading to increase in Ca 2+ influx via T-type calcium channels. Our results may provide a cellular and molecular mechanism that helps explain α1 -AR-induced PFC dysfunction.