Fear memory recall involves hippocampal somatostatin interneurons

Zichó, Krisztián and Sós, Katalin Eszter and Papp, Péter and Barth, Albert and Misák, Erik and Orosz, Áron and Mayer, Márton István and Z. Sebestyén, Réka and Nyíri, Gábor (2023) Fear memory recall involves hippocampal somatostatin interneurons. PLOS BIOLOGY, 21 (6). e3002154. ISSN 1544-9173

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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 for- mation. Later, the reactivation 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 reactivation 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 mouse 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.

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