Contributions of striatal circuits to interval timing

In our daily lives, we constantly need to adapt our behavior based upon changing circumstances around us. Often, we need to time our actions so that we act precisely when we need to. Picture driving a car down a busy street – failure to stop, accelerate, or change lanes precisely when needed can result in disastrous or even deadly consequences. In common neurological diseases such as Parkinson’s disease and Huntington’s disease which involve dysfunction of the basal ganglia, patients have impairments in the ability to estimate time and act precisely when they need to. Critically, these deficits in timing predict broader cognitive dysfunction in domains such as attention, working memory, and impulse control.

Importantly, the basal ganglia are comprised of two distinct neural subsystems – the direct and indirect pathways – which are thought to facilitate and inhibit movement, respectively. However, it remains unknown how these systems contribute to basic cognitive functions, such as timing.

Therefore, in this thesis, I aimed to understand how the striatum facilitates timed action by training mice on a simple interval timing task. Firstly, I examined how neurons within the striatum adapted as mice gained experience with a novel interval timing paradigm. Then, I used cell-type specific optogenetics and electrophysiology to specifically investigate how neurons in the direct and indirect pathways facilitate timed action. Finally, I lesioned dopaminergic neurons projecting to the striatum to examine how timed behavior is impacted by conditions like Parkinson’s disease which involve striatal dopamine depletion.