加巴能
谷氨酸受体
NMDA受体
兴奋毒性
神经科学
抑制性突触后电位
化学
兴奋性突触后电位
生物
受体
生物化学
作者
Lulu Yao,Yi Rong,Xiaoyan Ma,Haifu Li,Di Deng,Yongjun Chen,Sungchil Yang,Tao Peng,Tao Ye,Feng Liang,Nenggui Xu,Qiang Zhou
标识
DOI:10.1101/2021.10.17.464733
摘要
Abstract The NMDA subtype glutamate receptors (NMDARs) play important roles in both physiological and pathological processes in the brain. Comparing to their critical roles in synaptic modifications and excitotoxicity in the excitatory neurons, much less is understood about the functional contributions of NMDARs to the inhibitory/GABAergic neurons. By using selective NMDAR inhibitors and potentiators, we here show that NMDARs bi-directionally modulate the intrinsic excitability (defined as spontaneous/evoked spiking activity and EPSP-spike coupling) in the inhibitory/GABAergic neurons. This modulation depends on GluN2C/2D-but not GluN2A/2B-containing NMDARs. We further show that NMDAR modulator EU1794-4 mostly enhances extrasynaptic NMDAR activity, and by using it we demonstrate a significant contribution of extrasynaptic NMDARs to the modulation of intrinsic excitability in the inhibitory neurons. Altogether, this bidirectional modulation of intrinsic excitability reveals a previously less appreciated importance of NMDARs in the second-to-second functioning of inhibitory/GABAergic neurons.
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