Stress undermines reward-guided cognitive performance through synaptic depression in the lateral habenula

Weighing alternatives during reward pursuit is a vital cognitive computation that, when disrupted by stress, yields aspects of neuropsychiatric disorders. To examine the neural mechanisms underlying these phenomena, we employed a behavioral task in which mice were confronted by a reward and its omis...

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Detalles Bibliográficos
Autores: Nuno Perez, Alvaro, Trusel, Massimo, Lalive, Arnaud L., Congiu, Mauro, Gastaldo, Denise, Tchenio, Anna, Lecca, Salvatore, Soiza Reilly, Mariano, Bagni, Claudia, Mameli, Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/175287
Acceso en línea:http://hdl.handle.net/11336/175287
Access Level:acceso abierto
Palabra clave:AMPA RECEPTORS
LATERAL HABENULA
REWARD-GUIDED BEHAVIORS
STRESS
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario:Weighing alternatives during reward pursuit is a vital cognitive computation that, when disrupted by stress, yields aspects of neuropsychiatric disorders. To examine the neural mechanisms underlying these phenomena, we employed a behavioral task in which mice were confronted by a reward and its omission (i.e., error). The experience of error outcomes engaged neuronal dynamics within the lateral habenula (LHb), a subcortical structure that supports appetitive behaviors and is susceptible to stress. A high incidence of errors predicted low strength of habenular excitatory synapses. Accordingly, stressful experiences increased error choices while decreasing glutamatergic neurotransmission onto LHb neurons. This synaptic adaptation required a reduction in postsynaptic AMPA receptors (AMPARs), irrespective of the anatomical source of glutamate. Bidirectional control of habenular AMPAR transmission recapitulated and averted stress-driven cognitive deficits. Thus, a subcortical synaptic mechanism vulnerable to stress underlies behavioral efficiency during cognitive performance.