Involvement of a stress-responsive orbito-striatal projection in impulsive action in male rats

Background: Motor impulsivity is a symptom shared by several psychiatric disorders. Stress exacerbates impulsivity, but the neurocircuits involved are unknown. We have shown that the orbitofrontal cortex (OFC) is activated during a rodent motor impulsivity task and that chronic unpredictable stress (CUS) increases premature responding. In this study, we examine the role of the OFC projection to dorsal medial striatum (DMS) in motor control, and test whether this pathway mediates the effects of stress on impulsive action. Methods: Motor impulsivity was measured with the 1-choice serial reaction time test (1-CSRTT). To determine if OFC-DMS projections are involved in controlling impulsivity, we used pathway-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-mediated chemogenetic manipulation during 1-CSRTT. We examined stress effects on OFC-DMS neuronal activation using Fos immunohistochemistry. To assess if stress increases impulsivity through OFC-DMS projections, we chemogenetically manipulated the pathway in stressed rats during behavior. Results: We found OFC-DMS projections inhibit premature responding in a well-mastered task. Stress attenuated OFC neuronal activation, including the OFC-DMS projection neurons, during behavior. However, selectively activating the projection in stressed rats was not sufficient to abolish the stress effects. Finally, the response to stress depended on baseline trait impulsivity. Rats with low trait impulsivity were more vulnerable to stress and showed attenuated activation of OFC-DMS neurons but increased activation of other OFC cell populations. Conclusions: These results suggest the OFC-DMS pathway modulates impulsivity in concert with other OFC neuronal populations. Furthermore, stress effects are baseline-dependent and affect only low-impulsivity rats, possibly by altering the balance of activation in functionally opposing neuronal populations.