REM sleep–active MCH neurons are involved in forgetting hippocampus-dependent memories

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Science  20 Sep 2019:
Vol. 365, Issue 6459, pp. 1308-1313
DOI: 10.1126/science.aax9238

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A brain pathway for active forgetting

Sleep affects memories via several mechanisms. Izawa et al. identified a possible new pathway in the brain: REM sleep–active hypothalamic melanin-concentrating hormone (MCH)–producing neurons, which, among others, project to the hippocampus. Surprisingly, genetic ablation of MCH neurons increased memory performance in mice. Conversely, pharmacogenetic activation of MCH neurons impaired memory. In vitro physiological experiments showed that activation of MCH fibers in hippocampal slices suppressed spiking activity of pyramidal cells. These findings indicate that the MCH pathway may become a target for memory modulation.

Science, this issue p. 1308


The neural mechanisms underlying memory regulation during sleep are not yet fully understood. We found that melanin concentrating hormone–producing neurons (MCH neurons) in the hypothalamus actively contribute to forgetting in rapid eye movement (REM) sleep. Hypothalamic MCH neurons densely innervated the dorsal hippocampus. Activation or inhibition of MCH neurons impaired or improved hippocampus-dependent memory, respectively. Activation of MCH nerve terminals in vitro reduced firing of hippocampal pyramidal neurons by increasing inhibitory inputs. Wake- and REM sleep–active MCH neurons were distinct populations that were randomly distributed in the hypothalamus. REM sleep state–dependent inhibition of MCH neurons impaired hippocampus-dependent memory without affecting sleep architecture or quality. REM sleep–active MCH neurons in the hypothalamus are thus involved in active forgetting in the hippocampus.

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