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Authors & Affiliations
Krisztián Zichó, Réka Z. Sebestény, Katalin E. Sos, Péter Papp, Albert M. Barth, Erik Misák, Áron Orosz, Márton I. Mayer, Gábor Nyiri
Abstract
Fear-related memory traces are encoded by sparse populations of hippocampal principal neurons that are recruited based on their inhibitory–excitatory balance during memory formation. Later, the re-activation of the same principal neurons can recall the memory. The details of this mechanism are still unclear. Here, we investigated whether disinhibition could play a major role in this process. Using optogenetic behavioral experiments we found that when fear was associated with the inhibition of mouse hippocampal somatostatin positive interneurons, the re-inhibition of the same interneurons could recall fear memory. Pontine nucleus incertus neurons selectively inhibit hippocampal somatostatin cells. We also found that when fear was associated with the activity of these incertus neurons or fibers, the re-activation of the same incertus neurons or fibers could also recall fear memory. These incertus neurons showed correlated activity with hippocampal principal neurons during memory recall and were strongly innervated by memory-related neocortical centers, from which the inputs could also control hippocampal disinhibition in vivo. Nonselective inhibition of these hippocampal somatostatin or incertus neurons impaired memory recall. Our data suggest a novel disinhibition-based memory mechanism in the hippocampus that is supported by local somatostatin interneurons and their pontine brainstem inputs. Funding: This project was supported by the ÚNKP-20-3-SE-31, ÚNKP-21-3-SE-9 and ÚNKP-23-3-II-SE-24 New National Excellence Program of the Ministry of Innovation and by the EFOP-3.6.3-VEKOP-16-2017-00009 Semmelweis 250+ Excellence PhD Fellowship.