Pharmacology
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Larry Zweifel, Ph.D.,
Assistant Professor

joint with Psychiatry & Behavioral Sciences


Publications
Email: larryz@uw.edu
Box 357280
HSB J-631

Office: 206.685-6155
Fax: 206.685.3822
 

 

 

 

 

 

 

The brain is comprised of numerous discrete nuclei defined by anatomical location, structure, function, and gene expression profiles. Interconnections of the excitatory and inhibitory neurons within and between these structures are the basic components of neural circuits. Electrochemical signals within a circuit generate activity patterns that ultimately provide the substrate upon which the brain performs functional operations.

My lab is particularly interested in the limbic system of the brain. Comprised of multiple interconnected and parallel circuits, the limbic system is critical for determining where we are, where we have been, what we are doing, what we plan to do, and how all of it makes us feel. Perturbations in the functioning of one or multiple components of the limbic system are a major contributor to mental disorders, affecting approximately 1 in 4 adults. My research is directed toward understanding how a small group of neurons located in the ventral midbrain that synthesize and release the neurotransmitter dopamine influence activity patterns within the limbic system to direct behavior.

Dopamine release into target brain regions can either be tonic (low steady levels of neurotransmitter) or phasic (transient high concentrations of neurotransmitter), and these patterns are thought to play distinct roles in modulating the function of the limbic system. The mechanisms responsible for determining these patterns of activity are thought to involve distinct neurotransmitter systems impinging upon dopamine neurons, as well as a complement of neurotransmitter receptors and ion channels. To dissect how selective afferents, neurotransmitter systems, neurotransmitter receptors, and ion channels regulate patterns of dopamine neuron activity, we utilize a multi-disciplinary approach involving conditional gene activation or inactivation and combinatorial viral vector approaches to alter expression of genes at numerous levels within the circuit. Multiunit in vivo electrophysiology and fiber-optic fluorescence microscopy are used to monitor activity patterns and intracellular signaling events within select neural populations. These techniques are integrated with behavioral assays to provide the ultimate link between sensory input, generation of activity within a circuit, and behavioral output.



Recent Publications 

Manipulating gene expression in projection-specific neuronal populations using combinatorial viral approaches. - ABSTRACT

View all recent publications