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Stimulation of α1-adrenoceptors facilitates GABAergic transmission onto pyramidal neurons in the medial prefrontal cortex.

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.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Luo F,Tang H,Cheng ZY

doi

10.1016/j.neuroscience.2015.04.070

subject

Has Abstract

pub_date

2015-08-06 00:00:00

pages

63-74

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(15)00422-4

journal_volume

300

pub_type

杂志文章

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