Postdoctoral Research Fellow
A position is available from July, 2008 in Neurology for an experienced and self-motivated post-doctoral fellow. The successful applicant will conduct electrophysiology research in striatal synaptic plasticity at the University of Washington, Seattle. A proven track record of experience performing whole-cell patch clamp recordings in brain slices is essential. The fellow will expand their skills by integrating optical, behavioral and electrophysiological recordings to determine the effect of repeated psychostimulants on corticostriatal activity in the dorsal and ventral striatum.
Candidates must have an MD or a PhD in biological sciences. Applications should include a cover letter describing research interests and past accomplishments, curriculum vita, bibliography and the names of 3 references. Strong analytical, writing, communication (in English) and problem solving skills are desired.
To apply, please send materials to:
Nigel S. Bamford
Summary of Proposed Research Project
The basal ganglia play an important role in habit formation and substance dependence. Excitatory glutamatergic projections from the cerebral cortex innervate the basal ganglia at the striatal medium spiny neuron, which also receives modulatory dopamine projections from midbrain nuclei as well as cholinergic inputs from tonically activated striatal interneurons. Psychostimulants and other drugs of abuse are known to produce alterations in these neurotransmitters, suggesting their implicit involvement in the synaptic mechanisms underlying dependence.
The Bamford laboratory has shown that dopamine depresses the release of glutamate from a subset of cortical terminals, providing filtering of cortical information to the striatum. Repeated use of psychostimulants in mice prevents striatal filtering by producing a chronic striatal depression in withdrawal that is renormalized by drug reinstatement. This effect is dose dependent, long lasting (>140 days) and is dependent on a new D1 receptor effect seen only in animals with previous psychostimulant experience. During withdrawal, a psychostimulant challenge produces a paradoxical increase in glutamate release by activating cholinergic-releasing interneurons. These mechanisms extend to locomotor sensitization and drug intake escalation – both hallmarks of addiction.
The Bamford laboratory offers students and fellows a unique opportunity to determine how changes in striatal synapses might produce alterations in animal behavior. The Bamford laboratory uses a combination of behavioral, optical and electrophysiological experiments to determine the effects of repeated psychostimulants on striatal function. Students can utilize a newly developed imaging technique that allows direct visualization of presynaptic release from cortical projections in murine striatal slice preparations. These optical studies can be integrated with whole-cell patch clamp recordings to delineate the characteristics of the corticostriatal pathway and the effects of dopamine transmission at the striatal medium spiny neuron. In vivo manipulations of transgenic and wild-type mice will provide models with which to investigate synaptic plasticity that occurs following repeated use of psychostimulants. The outcome of these investigations will demonstrate how alterations in dopamine release produce corticostriatal plasticity, show mechanistically how aberrant striatal excitation might lead to certain animal behaviors, and will provide further insights into pharmacological alternatives for the treatment of addiction.