In vivo dissection of neural circuits for switching of motor actions


September 30, 2015 - 1:00pm
NW 243
About the Speaker
Gil Mandelbaum (Sabatini Lab)

To select and generate appropriate motor actions that lead to “reward”, animals must integrate past experiences, current inputs from the environment, and predictions about the future. Studies show that the basal ganglia (BG) circuits both assess reward value of response options and are implicated in translating the animal’s reward value predications into the execution of motor actions. However, many current models of action selection do not consider unexpected events that require animals to switch between previously learned actions. Furthermore, the circuits that allow for such action switching are poorly understood.

To address what circuits may take part in action switching we use a combination of viral tracing, slice physiology, and in vivo physiology in mice. We identified a candidate circuit for action switching that includes the parafasicular nucleus (PF) of the thalamus. We find that PF neurons send outputs to multiple functional regions and most cell types of the striatum while also receiving a distinct projection from primary motor cortex.

Thus, forming a non-canonical 'reversed' basal ganglia loop.

Guided by these findings, we performed in vivo loss of function experiments in PF while the animal perform a cued two-choice task, resulting in a contralateral motor bias independent of the specific sensory stimuli presented to the animal. We further supported this notion with extracellular recordings from PF in vivo.

Finally, we designed a system that allows for closed-loop optogenetic perturbations when the animal is performing a limited-sensory motor switching task. To complement this, we also designed an optic fiber that allows for homogenous and high spatial resolution light delivery in the brain. We now seek to establish a causal role of the cortical-PF-striatal loop in action switching.