Amy Zhou

Repeated stimulation of thalamic input to the nucleus accumbens elicits a compulsive phenotype in mice

Supervisor: Dr. Jonathan Britt

Compulsive behavior is a common feature of many psychiatric diseases, including obsessive compulsive disorder (OCD), and Tourette’s syndrome. While the neural mechanisms that promote compulsive behaviours remain uncertain, rodent and human research has implicated disruptions of basal ganglia circuitry. Recent research has focused specifically on the role of the nucleus accumbens (NAc) and its glutamatergic afferents in driving repetitive behaviours. For example, hyperactivity of the orbitofrontal cortex (OFC)-NAc pathway is correlated with compulsive behaviour in OCD patient populations. Similarly, repeated stimulation of the OFC-NAc pathway elicits compulsive behaviour in mice, but the role of other NAc glutamate afferents remains unclear. Here, we optogenetically stimulate paraventricular thalamus (PVT) and ventral hippocampus (vHPC) inputs to the NAc in mice to characterize their influence on compulsive behaviours. Our model of compulsion incorporates measures of repetitive self-grooming, behaviour in an open field test (OFT), and reversal learning (RLT). Understanding the neural underpinnings of these behaviours in a mouse model are critical to understanding human manifestations of compulsive behaviour.

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