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 Repjournal_title
Scientific reportsauthors
Deng D,Masri S,Yao L,Ma X,Cao X,Yang S,Bao S,Zhou Qdoi
10.1038/s41598-020-68652-5subject
Has Abstractpub_date
2020-07-20 00:00:00pages
11969issue
1issn
2045-2322pii
10.1038/s41598-020-68652-5journal_volume
10pub_type
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