Stress undermines reward-guided cognitive performance through synaptic depression in the lateral habenula.
Neuron
; 109(6): 947-956.e5, 2021 03 17.
Article
in En
| MEDLINE
| ID: mdl-33535028
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stress, Psychological
/
Cognition
/
Synaptic Transmission
/
Habenula
/
Neuronal Plasticity
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Neuron
Journal subject:
NEUROLOGIA
Year:
2021
Document type:
Article
Affiliation country:
Switzerland