Increasing endogenous activity of NMDARs on GABAergic neurons increases inhibition, alters sensory processing and prevents noise-induced tinnitus.

Abstract:

:Selective enhancement of GABAergic inhibition is thought to impact many vital brain functions and interferes with the genesis and/or progression of numerous brain disorders. Here, we show that selectively increasing NMDA receptor activity in inhibitory neurons using an NMDAR positive allosteric modulator (PAM) elevates spiking activity of inhibitory neurons in vitro and in vivo. In vivo infusion of PAM increases spontaneous and sound-evoked spiking in inhibitory and decreases spiking in excitatory neurons, and increases signal-to-noise ratio in the primary auditory cortex. In addition, PAM infusion prior to noise trauma prevents the occurrence of tinnitus and reduction in GABAergic inhibition. These results reveal that selectively enhancing endogenous NMDAR activity on the GABAergic neurons can effectively enhance inhibitory activity and alter excitatory-inhibitory balance, and may be useful for preventing diseases that involve reduced inhibition as the major cause.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Deng D,Masri S,Yao L,Ma X,Cao X,Yang S,Bao S,Zhou Q

doi

10.1038/s41598-020-68652-5

subject

Has Abstract

pub_date

2020-07-20 00:00:00

pages

11969

issue

1

issn

2045-2322

pii

10.1038/s41598-020-68652-5

journal_volume

10

pub_type

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