The corticostriatal system in health and disease

The purpose of this proposal is to improve our understanding of how different parts of the cerebral cortex interact with each other and with basal ganglia circuits to generate purposeful behaviors, and how these processes become dysfunctional in disease conditions known to involve cortico-basal ganglia motor systems.

To achieve this, we will combine:- Optical imaging, via mini-scope/2p-microscope technology, of genetically encoded calcium and dopamine sensors - informing about electrophysiological and neurochemical signaling- Targeted manipulations of pre-/postsynaptic neurons in corticostriatal circuits via combinatorial expression of light/chemo-activated ion-channels- Chronic multi-structure recordings of activity in distributed brain structures across behavioral/pathological states.

We aim to study:The information processing of multisensory association areas and premotor areas converging on specific cell populations in striatum that underlies the selection of motor actions in goal-directed behaviorThe pathophysiological processes, at the network and cellular level, in cortico-basal ganglia circuits that cause motor symptoms in Parkinson’s disease (PD) and in levodopa-induced dyskinesia (LID) This will be performed in awake head-fixed or freely behaving rodents under a 4-year period.This proposal will give insights into fundamental brain functions with implications for several fields of research, and will accelerate the development of new therapies for brain disease.