Forming long-term memories is crucial for adaptive behavior and survival in changing environments. The molecular consolidation processes which underlie the formation of these long-term memories are dependent on protein synthesis in excitatory and SST-expressing neurons. A centrally important, parallel process to this involves the removal of the memory constraint quinone reductase 2 (QR2), which has been recently shown to enhance memory consolidation for novel experiences in the cortex and hippocampus, via redox modulation. However, it is unknown within which cell type in the cortex removal of QR2 occurs, nor how this affects neuronal function. Here, we use novel taste learning in the mouse anterior insular cortex (aIC) to show that similarly to mRNA translation, QR2 removal occurs in excitatory and SST-expressing neurons. Interestingly, both novel taste and QR2 inhibition reduce excitability specifically within SST, but not excitatory neurons. Furthermore, reducing QR2 expression in SST, but not in PV or excitatory neurons, is sufficient to enhance taste memory. Thus, QR2 mediated intrinsic property changes of SST interneurons in the aIC is a central removable factor to allow novel taste memory formation. This previously unknown involvement of QR2 and SST interneurons in re-setting aIC activity hours following learning, describes a molecular mechanism to define cell circuits for novel information. Therefore, the QR2 pathway in SST interneurons provides a fresh new avenue by which to tackle age-related cognitive deficits, while shedding new light onto the functional machinations of long-term memory formation for novel information.
Bibliographical noteFunding Information:
This work was supported by the Israel Academy of Sciences and Humanities Grant 258/20 and the Deutsche Forschungsgemeinschaft Grant 3619/13 (to K. R.). N.G. is a recipient of the University of Haifa President Fellowship for Excellent PhD students. H.K. is a recipient of the Edmond de Rothschild?s scholarship.
This work was supported by the Israel Academy of Sciences and Humanities Grant 258/20 and the Deutsche Forschungsgemeinschaft Grant 3619/13 (to K. R.). N.G. is a recipient of the University of Haifa President Fellowship for Excellent PhD students. H.K. is a recipient of the Edmond de Rothschild’s scholarship.
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ASJC Scopus subject areas
- Neuroscience (all)