Journal Article

Brainstem nucleus incertus controls contextual memory formation

Hegedüs, Panna, Gulyás, Attila I., Sos, Katalin E., Priestley, James B., Nyiri, Gábor, Nyilas, Rita, Varga, Viktor, Schlingloff, Dániel, Szőnyi, András, Gundlach, Andrew L., Freund, Tamás F., Pósfai, Balázs, Domonkos, Andor, Takács, Virág T., Losonczy, Attila

2019

Overview

In the hippocampus, each memory trace is encoded by a specific subset of pyramidal cells. The other pyramidal cells must be actively excluded from the memory encoding process by inhibition, which is done by selective dendrite-targeting interneurons. Szőnyi et al. found that γ-aminobutyric acid–releasing (GABAergic) cells located in a small region in the brain stem called the nucleus incertus project to the hippocampus. The nucleus incertus again is innervated by several regions that respond to salient stimuli. Its GABAergic cells preferentially inhibit the dendrite-targeting interneurons in the hippocampus. The nucleus incertus is thus a central mediator between brain regions that are highly responsive to salient stimuli and the hippocampal circuitry involved in memory formation. Science , this issue p. eaaw0445 A brainstem regulatory mechanism for the selection of hippocampal neuronal assemblies during contextual learning is described. 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 γ-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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Air conditioners / Animals / Anxiety / Association Learning - physiology / Associative learning / Brain stem / Calcium imaging / Circuits / Coding / Conditioning (learning) / Dementia disorders / Dendrites / Dendritic structure / Disorders / Environment models / Environmental effects / Environmental information / Fear / Fear conditioning / Female / Fibers / GABAergic Neurons - physiology / Genetics / Habenula / Hippocampus / Immunoelectron microscopy / Information processing / Inhibition / Interneurons / Interneurons - chemistry / Interneurons - physiology / Light effects / Male / Memory and Learning Tests / Mice / Mice, Inbred C57BL / Neural Inhibition - physiology / Neuroimaging / Neurons / Nuclei (cytology) / Prefrontal cortex / Pyramidal Cells - chemistry / Pyramidal Cells - physiology / Rabies / Raphe Nuclei - physiology / Releasing / RESEARCH ARTICLE SUMMARY / Sensory neurons / Sensory stimuli / Septum / Somatosensory cortex / Somatostatin - analysis / Somatostatin - physiology / Stimulation / Stimuli / Stochastic processes / Theta Rhythm / γ-Aminobutyric acid