Brainstem nucleus incertus controls contextual memory formation

Szőnyi, András and Sós, Katalin Eszter and Nyilas, Rita and Schlingloff, Dániel and Domonkos, Andor and Takács, Virág and Pósfai, Balázs and Hegedüs, Panna and Gulyás, Attila and Varga, Viktor and Losonczy, Attila and Freund, Tamás and Nyíri, Gábor (2019) Brainstem nucleus incertus controls contextual memory formation. SCIENCE, 364 (6442). 752-+. ISSN 0036-8075

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Abstract

Hippocampal pyramidal cells encode memory engrams, which guide adaptive behavior. Selection of engram-forming cells is regulated by somatostatin-positive dendrite-targeting interneurons, which inhibit pyramidal cells that are not required for memory formation. Here, we found that gamma-aminobutyric acid ( GABA)-releasing neurons of the mouse nucleus incertus (NI) selectively inhibit somatostatin-positive interneurons in the hippocampus, both monosynaptically and indirectly through the inhibition of their subcortical excitatory inputs. We demonstrated that NI GABAergic neurons receive monosynaptic inputs from brain areas processing important environmental information, and their hippocampal projections are strongly activated by salient environmental inputs in vivo. Optogenetic manipulations of NI GABAergic neurons can shift hippocampal network state and bidirectionally modify the strength of contextual fear memory formation. Our results indicate that brainstem NI GABAergic cells are essential for controlling contextual memories.

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