We are a neurophysiology research laboratory studying how the cerebral cortex and basal ganglia control learning and memory, motivation, and motor behavior. We are particularly interested in understanding the actions of monoamines, i.e. dopamine, noradrenaline and serotonin within these circuits and how these neuromodulators control excitability and synaptic plasticity.
Deficits in monoaminergic systems are implicated in a wide variety of neurodegenerative and psychiatric disorders, so the research pursued in our laboratory is relevant for Parkinson’s disease, drug addiction, depression and schizophrenia. Our overall goal is to understand the mechanisms for monoaminergic control of behavior in normal and pathological conditions.
The basis of long-term changes in excitability is governed by dynamic changes in the strength of synapses: the nodes of communication between neurons. We study how learning of behavioral tasks and pathological conditions change the synaptic strength using both morphological and functional assays. One challenging aspect of monoamines is, however, that receptor activation generates a relatively slow multidimensional cellular response. The changes in the excitability in neuronal networks occur during multiple time-scales: from seconds to several hours and longer. Therefore, our methodology consists of a combination of electrophysiology, electrochemistry, imaging and biochemistry in vivo as well as in vitro.
Ongoing projects in the laboratory aim to:
1) Clarify how dopamine promotes motor learning through actions on cortical projections to the thalamus. In these studies we use a combination of electrophysiological and imaging techniques to establish the local actions of dopamine within the primary motor cortex and the interconnected thalamic circuitry. In parallel we study how optogenetic control of dopamine inputs to the motor cortex control circuit excitability and facilitate or inhibit motor learning.
2) Demonstrate the multiple mechanisms regulating dopaminergic neurotransmitter release in basal ganglia output structures. Aberrant activity in the output nuclei of the basal ganglia is a feature of Parkinson’s disease and we use rodent models of the human condition to investigate novel therapeutic strategies. In ongoing work we manipulate dopaminergic activity using optogenetic and chemogenetic techniques and investigate how this influences basal ganglia output activity.
3) Understand the mechanisms underlying dopamine-noradrenaline co-release in the frontal cortex. This project aims to characterize the actions of antidepressant drugs in the frontal cortex and how monoaminergic drugs may be utilized in cognitive-enhancing therapy. With microdialysis, carbon fiber electrochemistry and biosensors for dopamine and noradrenaline we measure neurotransmitter release in behaving rodents. In parallel we investigate how clinically relevant therapeutics regulate monoamine release.