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Hippocampal CB1 receptors control incidental associations

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.
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https://hal.inrae.fr/hal-02626385
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Submitted on : Tuesday, May 26, 2020 - 5:14:59 PM
Last modification on : Monday, December 13, 2021 - 1:54:20 PM

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Arnau Busquets-Garcia, José F. Oliveira da Cruz, Geoffrey Terral, Antonio C. Pagano Zottola, Edgar Soria-Gomez, et al.. Hippocampal CB1 receptors control incidental associations. Neuron, Elsevier, 2018, 99 (6), pp.1247-1259. ⟨10.1016/j.neuron.2018.08.014⟩. ⟨hal-02626385⟩

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