Anatol Kreitzer, PhD

To address the functional properties of basal ganglia motor circuits, my laboratory applies a variety of experimental approaches. We perform whole-cell patch-clamp electrophysiology in brain slices, which allows us to record and analyze the properties of synaptic currents from individual neurons. Optical imaging and optical stimulation provide techniques to monitor activity in larger populations of neurons and within microcircuits. We also utilize transgenic animals designed to allow in vitro and in vivo identification and modification of basal ganglia circuit function. Additionally, we use genetic and pharmacological animal models of human disease, as well as a battery of behavioral testing procedures.

A major focus of the laboratory is the striatum, which forms the input nucleus of the basal ganglia. Striatal projection neurons target either the substantia nigra pars reticulata (direct pathway) or the lateral globus pallidus (indirect pathway). Imbalances between neural activity in these two circuits have been proposed to underlie the profound motor deficits observed in PD and HD. We have described important differences in the cellular and synaptic properties of striatal medium spiny neurons in these pathways, including the selective expression of a form of long-term synaptic depression (LTD) mediated by endocannabinoid signalling and regulated by dopamine at indirect pathway synapses. Current studies are aimed at elucidating additional pathway-specific mechanisms of neuromodulation and synaptic plasticity in the striatum and their role in basal ganglia circuit function and motor control.