Substance P excites GABAergic neurons in the mouse central amygdala through neurokinin 1 receptor activation

Journal of Neurophysiology
Ludmila SosulinaHans-Christian Pape

Abstract

Substance P (SP) is implicated in stress regulation and affective and anxiety-related behavior. Particularly high expression has been found in the main output region of the amygdala complex, the central amygdala (CE). Here we investigated the cellular mechanisms of SP in CE in vitro, taking advantage of glutamic acid decarboxylase-green fluorescent protein (GAD67-GFP) knockin mice that yield a reliable labeling of GABAergic neurons, which comprise 95% of the neuronal population in the lateral section of CE (CEl). In GFP-positive neurons within CEl, SP caused a membrane depolarization and increase in input resistance, associated with an increase in action potential firing frequency. Under voltage-clamp conditions, the SP-specific membrane current reversed at -101.5 ± 2.8 mV and displayed inwardly rectifying properties indicative of a membrane K(+) conductance. Moreover, SP responses were blocked by the neurokinin type 1 receptor (NK1R) antagonist L-822429 and mimicked by the NK1R agonist [Sar(9),Met(O2)(11)]-SP. Immunofluorescence staining confirmed localization of NK1R in GFP-positive neurons in CEl, predominantly in PKCδ-negative neurons (80%) and in few PKCδ-positive neurons (17%). Differences in SP responses were not observe...Continue Reading

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Citations

Jun 14, 2017·Brain Structure & Function·Kazuko MizutaniFumino Fujiyama
Jun 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Marie BarbierPierre-Yves Risold
Nov 19, 2019·Neuropeptides·Kanwal IftikharSumbul Zehra
Jun 26, 2021·Frontiers in Cellular Neuroscience·Yuqi RenMinmin Luo
Jan 23, 2021·CNS & Neurological Disorders Drug Targets·Viktor S KokhanGjumrakch Aliev

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