Action Generation – How do we generate novel actions? To address this question, we investigate the cortico-basal ganglia mechanisms underlying dopamine control of voluntary movement.
Using an inducible and reversible pharmacogenetic approach in dopamine transporter knock-out mice (DAT-KO) we have shown that dopamine rapidly modulates changes in synchrony and oscillatory neural activity in corticostriatal circuits, and that these changes correlate with changes in movement. We are currently investigating the relative involvement of dopamine type 1 (D1) and type 2 (D2) receptors on corticostriatal synchrony, and using optogenetics to determine the role of different striatal cell types on striatal synchrony and action initiation.
Action Improvement – How do we improve the performance of an action? To address this question, we investigate the molecular, cellular, and circuit mechanisms mediating the different phases of skill learning.
We found that iteration of an action changes the nature of the action, more specifically, that different molecular and circuit mechanisms are involved in the early and late phases of skill learning. Overtraining of a novel motor skill rendered the performance of
this skill less dopamine-dependent. Also, extended training led to functional reorganization of the striatal circuits through subregion and pathway-specific synaptic plasticity.
Actions and Outcomes – How do we learn that particular actions can produce specific outcomes? To address this question, we investigate the differences between goal-directed actions and habits.
Extended training can induce a shift from voluntary goal-directed actions, which are governed by action-outcome contingencies and are sensitive to the value of the outcome, to habits which are less sensitive to changes in the value of the outcome. We established instrumental paradigms to reliably study habit formation in mice, and confirmed that different areas of the dorsal striatum are important for goal-directed actions and habits. Using these paradigms, we showed that endocannabinoids are critical for habit formation. We are currently investigating the role of nigrostriatal dopaminergic projections in goal-directed actions and habits.
In order to have an understanding of the mechanisms of action from molecules to systems we developed new genetically modified mice to manipulate and visualize plasticity in corticostriatal circuits. We also generated new microelectrode arrays for in-vivo simultaneous recording of multiple cortico-basal ganglia regions in behaving mice.