Anatol Kreitzer, PhD

Associate Professor
Physiology
415-734-2507

Synaptic Plasticity and Circuit Function in the Basal Ganglia

The control of movement is among the most fundamental functions of the nervous system. The basal ganglia, and the striatum in particular, play a critical role in the learning, selection, and initiation of appropriate actions. Individuals suffering from movement disorders such as Parkinson’s Disease (PD) or dystonia have profound difficulties performing appropriate movements, yet the cellular and synaptic basis of these disorders is not well understood. A thorough understanding of the mechanisms underlying circuit function in the basal ganglia, both in health and disease, will provide a framework that can be used to develop novel treatments for neurological disorders.

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. We utilize in vivo single-unit recordings in awake behaving mice. Both in vitro and in vivo experiments take advantage of recently-developed optogenetic techniques to identify and selectively stimulate different cell types. In vivo recording/optogenetic experiments are integrated with sophisticated behavioral monitoring techniques, allowing a detailed picture of neural activity in specified cell types in vivo during behavior.

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. More recently, we have characterized the functional role of the direct and indirect pathways in behaving animals, using optogenetic methods. 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. 

Current Projects

  1. Mechanisms and function of synaptic plasticity in basal ganglia circuits
  2. Synaptic plasticity and dendritic integration of thalamostriatal and corticostriatal inputs
  3. The role of tonic and phasic dopamine signaling in the striatum
  4. The role of striatal microcircuits in striatal function and dysfunction
  5. Regulation of basal ganglia output nuclei by direct and indirect pathway activity
  6. The pathophysiology of Parkinson’s disease and dystonia
  7. The role of direct and indirect pathways in motor learning 

Lab Members

Chris Donahue, PhD
Postdoctoral Fellow
christopher.donahue@gladstone.ucsf.edu

Arnaud Lalive
Postdoctoral Fellow
arnaud.lalive@gladstone.ucsf.edu

Tony Lien
Postdoctoral Fellow
tony.lien@gladstone.ucsf.edu

Scott Owen
Postdoctoral Fellow
scott.owen@gladstone.ucsf.edu

Max Liu
Neuroscience Graduate Student
max.liu@ucsf.edu

Tom Roseberry
Neuroscience Graduate Student
thomas.roseberry@ucsf.edu

Delanie Schulte
Research Associate
delanie.schulte@gladstone.ucsf.edu

Lab Website

Publications: