A dual-pathway architecture enables chronic stress to disrupt agency and promote habit formation

Abstract

Chronic stress can change how we learn and, thus, how we make decisions by promoting the formation of inflexible, potentially maladaptive, habits. Here we investigated the neuronal circuit mechanisms that enable this. Using a multifaceted approach in male and female mice, we reveal a dual pathway, amygdala-striatal, neuronal circuit architecture by which a recent history of chronic stress shapes learning to disrupt flexible goal-directed behavior in favor of inflexible habits. Chronic stress inhibits activity of basolateral amygdala projections to the dorsomedial striatum to impede the action-outcome learning that supports flexible, goal-directed decisions. Stress also increases activity in direct central amygdala projections to the dorsomedial striatum to promote the formation of rigid, inflexible habits. Thus, stress exerts opposing effects on two amygdala-striatal pathways to promote premature habit formation. These data provide neuronal circuit insights into how chronic stress shapes learning and decision making, and help understand how stress can lead to the disrupted decision making and pathological habits that characterize substance use disorders and other psychiatric conditions.

Habit learning shapes activity dynamics in the central nucleus of the amygdala

“…Here, we report that activity in the central nucleus of the amygdala (CeA) changes dynamically with habit formation. Greater cFos expression in the CeA was observed after extended training on the plus-maze, aligning with prior studies that detail a critical role for the CeA in habit formation 8,12 . Through in-vivo single-unit recordings, we show that CeA neurons are modulated by specific task-related events on a plus-maze task.…”

“…While no explicit chunking motifs were observed, the emphasis on the outcome event in CeA activity emerged late in training, as habits formed, and then decayed after reward devaluation. These results add to a growing body of literature implicating the CeA in appetitive learning processes, including habit formation 8,12,[24][25][26] , and add confirmation to recent work showing reward-related changes in CeA activity that reflect reward preference 13 as well as reward-related signals that reflect stress-facilitated habit-learning in the CeA-to-dorsomedial striatum (DMS) pathway 12 .…”

“…This striking persistence in motivation to receive the CeA-stimulation-paired outcomes could reflect an underlying function for the CeA in tagging reward events with motivational salience. In this view, our finding that reward-related activity grows in the CeA as behaviors become over-trained and habitual, which is also observed when stress exposure exacerbates habit formation 12 , could cause behavioral persistence because of increased motivational value of that reward event. By extension, it is possible to consider that some forms of habit-like behaviors, defined by insensitivity to aversive shock or insensitivity to reward devaluation, could result from a motivational saliency process rather than a stimulus-response-(reinforcement) learning process.…”

“…Thus, this circuit could be potentially involved presently during habit formation on our task. An alternative to this hypothesized network comes from a report that highlights CeA projections to the DMS that govern habit formation after animals undergo a chronic unpredictable stress protocol 12 . There, experimenters used fiber photometry to show elevated CeA calcium activity following outcome collection, but only in animals that had undergone a stress protocol and were thus reliant on habit responding.…”

“…Stimulation of the CeA can increase motivated behaviors to the point of compulsion [9][10][11] . Recent work has noted that the CeA and its outputs are preferentially engaged during stress-induced accelerated habit formation and in potentially addictive behaviors like ethanolseeking 12,13 . However, unlike research on other habit-promoting brain areas 14,15 , little is known about what changes in CeA electrophysiological activity relate to habit learning under normal conditions.…”