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 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.

Automated summary

The study revealed that weighing alternatives during reward pursuit is a vital cognitive computation that, when disrupted by stress, can lead to aspects of neuropsychiatric disorders. Mice faced with choices between rewards and errors showed increased error choices and decreased glutamatergic neurotransmission onto LHb neurons under stressful experiences. This subcortical synaptic mechanism vulnerable to stress plays a key role in behavioral efficiency during cognitive performance.