Overview  

Research in the Howe lab is focused on three major questions:

• How do neural circuits motivate action to seek desired outcomes?

• How do neural circuits promote or inhibit particular actions?

• How do neural circuits to learn to predict positive and negative outcomes and the optimal actions to approach or avoid those outcomes?

A central function of all nervous systems is to determine when and how an organism should move based upon its current environment and feedback from prior experience. Although often subconscious, these processes are core features of our everyday experience. Research has identified the basal ganglia, a collection of deep brain nuclei, as being central to motivating and learning appropriate actions to seek desired outcomes or avoid undesired ones.  Dysfunction of the basal ganglia, such as in Parkinson’s disease, Huntington’s Disease, and drug addiction, can result in profound deficits in learning, action control, and outcome-directed evaluation and behavior.  Our lab’s mission is to provide a deeper mechanistic understanding of how basal ganglia circuits operate to control these functions under normal and pathological conditions.

Approach

Our goal is to derive general principles of basal ganglia circuit operation that govern motivation, action control and learning. To this end, we develop and utilize a range of technologies that enable the investigation of cell type and neurotransmitter specific signaling in the striatum, the principal basal ganglia input nucleus, at multiple spatial scales with rapid (10s of ms) temporal resolution in behaving mice. To measure dynamics across populations of neurons throughout the striatum, we employ fiber photometry and cellular resolution two-photon imaging, which enable us to record neurotransmitter release and calcium signals from genetically distinct neuronal sub-types. We also utilize high resolution two-photon imaging (see movie below) to investigate signals at sub-cellular scale in specific axons and dendrites in striatum microcircuits. Finally, we use carefully targeted optogenetic approaches guided by our signal measurements to test links between cell-type specific inputs and outputs and behavior. These approaches allow us to identify fundamental input/output operations that form the basis of basal ganglia computation. Studies are carried out in behaving mice performing tasks in virtual reality designed to capture key aspects of action control and learning in changing environments.