Hippocampal CB1 Receptors Control Incidental Associations

Neuron
Arnau Busquets-GarciaGiovanni Marsicano

Abstract

By priming brain circuits, associations between low-salience stimuli often guide future behavioral choices through a process known as mediated or inferred learning. However, the precise neurobiological mechanisms of these incidental associations are largely unknown. Using sensory preconditioning procedures, we show that type 1 cannabinoid receptors (CB1R) in hippocampal GABAergic neurons are necessary and sufficient for mediated but not direct learning. Deletion and re-expression of CB1R in hippocampal GABAergic neurons abolishes and rescues mediated learning, respectively. Interestingly, paired presentations of low-salience sensory cues induce a specific protein synthesis-dependent enhancement of hippocampal CB1R expression and facilitate long-term synaptic plasticity at inhibitory synapses. CB1R blockade or chemogenetic manipulations of hippocampal GABAergic neurons upon preconditioning affect incidental associations, as revealed by impaired mediated learning. Thus, CB1R-dependent control of inhibitory hippocampal neurotransmission mediates incidental associations, allowing future associative inference, a fundamental process for everyday life, which is altered in major neuropsychiatric diseases. VIDEO ABSTRACT.

Citations

Oct 1, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sara PeñascoPedro Grandes
Apr 23, 2020·Genes·Geoffrey TerralEdgar Soria-Gómez
Jun 30, 2019·Psychopharmacology·Lilian KloftJohannes G Ramaekers
Sep 28, 2018·Nature Reviews. Neuroscience·Sian Lewis
Aug 28, 2020·Frontiers in Molecular Neuroscience·Charlotte PietteLaurent Venance
Feb 12, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lilian KloftJohannes G Ramaekers
Oct 4, 2020·Neurobiology of Learning and Memory·Ming Teng Koh, Michela Gallagher
May 13, 2021·The FEBS Journal·Almudena Robledo-MenendezEdgar Soria-Gomez
Aug 24, 2021·Frontiers in Behavioral Neuroscience·Christina IoannidouGiovanni Marsicano
Dec 14, 2021·Frontiers in Behavioral Neuroscience·Hea-Jin Kim, Hae-Young Koh
Jan 16, 2022·Molecular Neurobiology·David De Sa NogueiraKatia Befort

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