Brainstem nucleus incertus controls contextual memory formation

2019. június 18.
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 GABAergic neurons of the mouse nucleus incertus (NI) selectively inhibit somatostatin-positive interneurons in the hippocampus, both mono-synaptically and indirectly via the inhibition of their sub-cortical 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.

Nucleus incertus (NI) activation prevents memory formation. NI GABAergic neurons regulate contextual memory formation by inhibiting somatostatin interneurons (SOM IN) directly in hippocampus (A) and indirectly via inhibition of their excitatory inputs in the medial septum (MS). Pairing optical stimulation (B) with aversive stimuli (C), eliminates fear memory-formation, while control mice display normal fear (freezing) after exposure to the same environment a day later (D).

Szőnyi A, Sos KE, Nyilas R, Schlingloff D, Domonkos A, Takács VT, Pósfai B, Hegedüs P, Priestley JB, Gundlach AL, Gulyás AI, Varga V, Losonczy A, Freund TF, Nyiri G.
Brainstem nucleus incertus controls contextual memory formation.
Science. 2019 May 24;364(6442). doi: 10.1126/science.aaw0445.