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- W3141557600 abstract "Ultrapotent chemogenetics, including the chloride-permeable inhibitory PSAM 4 -GlyR receptor, were recently proposed as a powerful strategy to selectively control neuronal activity in awake, behaving animals. We aimed to validate the inhibitory function of PSAM 4 -GlyR in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) in the ventral striatum. Activation of PSAM 4 -GlyR with the uPSEM 792 ligand enhanced rather than suppressed the activity of D1-MSNs in vivo as indicated by increased c-fos expression in D1-MSNs and in vitro as indicated by cell-attached recordings from D1-MSNs in mouse brain slices. Whole-cell recordings showed that activation of PSAM 4 -GlyR depolarized D1-MSNs, attenuated GABAergic inhibition, and shifted the reversal potential of PSAM 4 -GlyR current to more depolarized potentials, perpetuating the depolarizing effect of receptor activation. These data show that ‘inhibitory’ PSAM 4 -GlyR chemogenetics may activate certain cell types and highlight the pitfalls of utilizing chloride conductances to inhibit neurons." @default.
- W3141557600 created "2021-04-13" @default.
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- W3141557600 date "2021-04-06" @default.
- W3141557600 modified "2023-10-11" @default.
- W3141557600 title "Excitation of medium spiny neurons by ‘inhibitory’ ultrapotent chemogenetics via shifts in chloride reversal potential" @default.
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- W3141557600 doi "https://doi.org/10.7554/elife.64241" @default.
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