Biphasic Npas4 expression promotes inhibitory plasticity and suppression of fear memory consolidation in mice DOI Creative Commons
David V.C. Brito, Janina Kupke, Rostislav A. Sokolov

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 17, 2023

Abstract Long-term memories are believed to be encoded by unique transcriptional signatures in the brain. The expression of immediate early genes (IEG) promotes structural and molecular changes required for memory consolidation. Recent evidence has shown that brain is equipped with mechanisms not only promote, but actively constrict formation. However, it remains unknown whether IEG may play a role suppression. Here we uncovered novel function neuronal PAS domain protein 4 (Npas4), as an inducible suppressor gene highly salient aversive experiences. Using contextual fear conditioning paradigm, found low stimulus salience leads monophasic Npas4 expression, while learning induces biphasic hippocampus. later phase requires NMDA receptor activity independent dopaminergic neurotransmission. Our vivo pharmacological genetic manipulation experiments suggested restricts consolidation promote behavioral flexibility, facilitating extinction specificity responses. Moreover, immunofluorescence electrophysiological analysis revealed concomitant increase synaptic input from cholecystokinin (CCK)-expressing interneurons. results demonstrate how experiences evoke temporal patterns fine-tune our study provides associated suppression possible mechanism balance memories, thereby evade formation maladaptive behavior.

Language: Английский

Biphasic Npas4 expression promotes inhibitory plasticity and suppression of fear memory consolidation in mice DOI Creative Commons
David V.C. Brito, Janina Kupke, Rostislav A. Sokolov

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 17, 2023

Abstract Long-term memories are believed to be encoded by unique transcriptional signatures in the brain. The expression of immediate early genes (IEG) promotes structural and molecular changes required for memory consolidation. Recent evidence has shown that brain is equipped with mechanisms not only promote, but actively constrict formation. However, it remains unknown whether IEG may play a role suppression. Here we uncovered novel function neuronal PAS domain protein 4 (Npas4), as an inducible suppressor gene highly salient aversive experiences. Using contextual fear conditioning paradigm, found low stimulus salience leads monophasic Npas4 expression, while learning induces biphasic hippocampus. later phase requires NMDA receptor activity independent dopaminergic neurotransmission. Our vivo pharmacological genetic manipulation experiments suggested restricts consolidation promote behavioral flexibility, facilitating extinction specificity responses. Moreover, immunofluorescence electrophysiological analysis revealed concomitant increase synaptic input from cholecystokinin (CCK)-expressing interneurons. results demonstrate how experiences evoke temporal patterns fine-tune our study provides associated suppression possible mechanism balance memories, thereby evade formation maladaptive behavior.

Language: Английский

Citations

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