Natural hypothalamic circuit dynamics underlying object memorization

• Published in: Nature communications 2019-06, Vol.10 (1), p.2505-2505, Article 2505
• Main Authors: Kosse, Christin, Burdakov, Denis
• Format: Article
• Language: English
• Subjects: 14; 14/34; 42; 42/44; 631/378; 631/443/376; Animals; Brain; Channel gating; Glutamate Decarboxylase - metabolism; Humanities and Social Sciences; Hypothalamic Hormones - metabolism; Hypothalamus; Hypothalamus - cytology; Hypothalamus - metabolism; Hypothalamus - physiology; Melanin; Melanin-concentrating hormone; Melanins - metabolism; Memory; Memory - drug effects; Memory - physiology; Mice; multidisciplinary; Neural Inhibition - physiology; Neural Pathways; Neurons; Neurons - metabolism; Object recognition; Optogenetics; Pattern recognition; Piperidines - pharmacology; Pituitary Hormones - metabolism; Receptors, Pituitary Hormone - antagonists & inhibitors; Receptors, Pituitary Hormone - metabolism; Recognition, Psychology - drug effects; Recognition, Psychology - physiology; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-10484-7

Brain signals that govern memory formation remain incompletely identified. The hypothalamus is implicated in memory disorders, but how its rapidly changing activity shapes memorization is unknown. During encounters with objects, hypothalamic melanin-concentrating hormone (MCH) neurons emit brief signals that reflect object novelty. Here we show that targeted optogenetic silencing of these signals, performed selectively during the initial object encounters (i.e. memory acquisition), prevents future recognition of the objects. We identify an upstream inhibitory microcircuit from hypothalamic GAD65 neurons to MCH neurons, which constrains the memory-promoting MCH cell bursts. Finally, we demonstrate that silencing the GAD65 cells during object memory acquisition improves future object recognition through MCH-receptor-dependent pathways. These results provide causal evidence that object-associated signals in genetically distinct but interconnected hypothalamic neurons differentially control whether the brain forms object memories. This gating of memory formation by hypothalamic activity establishes appropriate behavioral responses to novel and familiar objects. Hypothalamus is implicated in memory disorders but the neural mechanisms are unknown. Here, the authors report that MCH expressing hypothalamic neurons respond to novel object exposure, are inhibited by local GAD65 expressing neurons and these local circuit interactions are causally involved in object memory formation.