Neurobiology Research Unit (Jeff Wickens)
Outline of Research
The long-range goal of the Neurobiology Research Unit is to understand the cellular mechanisms and neural circuitry underlying learning and adaptive behavior in the mammalian brain. Our collaborative, interdisciplinary program of research is focused on the striatum of the basal ganglia and the neuromodulators, dopamine and acetylcholine, that play a central role in the mechanisms of learning. The basal ganglia are a set of forebrain nuclei thought to play a key role in adaptive behaviour through the selection of actions, goals and strategies on the basis of previous reward-related learning. They are also involved in major neurological and behavioural disorders, such as Parkinson’s disease and attention-deficit hyperactivity disorder. Central issues in basal ganglia research include the manner in which the cortical input to the basal ganglia is processed and how neuromodulators such as dopamine and acetylcholine modify and influence the operations performed on the cortical inputs.
Our specific aims are: (1) to investigate underlying mechanisms of synaptic plasticity in the striatum focusing on dendritic integration, eligibility traces, and regional specialization of plasticity mechanisms; (2) to determine the role in learning of burst firing and pauses in midbrain dopamine neurons and striatal cholinergic interneurons, and identify the neural circuitry controlling them; and, (3) to extend experimental and theoretical understanding of integrative functions of the frontostriatal system using computational and analog simulation approaches. We use a powerful and unique combination of approaches extending from cellular to behavioral levels of biological organization, including 2-photon microscopy, electrophysiology, fast-scan cyclic voltammetry, optogenetics and computational modeling. The cellular mechanisms of reinforcement are of broad, general significance for the neuroscience of learning and motivation, and of fundamental importance for clinical understanding of major neuropsychiatric disorders. Our research has the forward goal of developing better treatments for attention-deficit hyperactivity disorder and Parkinson’s disease, which are debilitating neurological disorders of great importance to children and adults.