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Neuroscience Graduate Program at UCSF

Faculty - Howard Fields, M.D./Ph.D.

Neural Circuitry Underlying Pain Modulation


Research Description

My research group studies the neurobiology of motivation, both pain and pleasure. We are interested in how addictive drugs alter behavior. In particular, our current research focuses on how opioids contribute to motivated behaviors and addiction. There are several distinct opioid receptors: mu, kappa, and delta, and endogenous opioids: endorphins, enkephalins, dynorphins and endomorphins. Our goal is to determine how each of these endogenous opioids and their receptors regulate motivation and reinforcement. We use both behavioral pharmacology and electrophysiology in awake behaving rodents. We also use in vitro electrophysiology in the relevant brain regions to identify the synaptic mechanisms that control neuron firing and consequently behavior. We also use immunocytochemical and tract tracing methods to answer questions of circuitry.

Our current focus is on a circuit that includes the midbrain dopaminergic regions and their downstream targets in the nucleus accumbens and medial prefrontal cortex. We are studying opioid control of these midbrain dopaminergic neurons and their neighboring non-dopamine neurons. We have found that opioid actions differ depending upon the projection target of the neuron under study. We are also studying dopamine inputs to nucleus accumbens neurons in awake behaving rats.

Laboratory members are also engaged in studying the neural basis of decision making in humans using behavioral testing and functional MRI. We plan to apply this approach to the study of addiction in humans.

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Current Projects

See research summary (above).

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Lab Members

Fred Ambroggi
Postdoctoral Fellow

Amy Chang
MSTP Student

Greg Hjelmstad
Adjunct Assistant Professor
Ph.D. UCSF
Opioid and dopamine actions in nucleus accumbens

Michael Krause
Postdoctoral Fellow

Elyssa Margolis
Postdoctoral Fellow
Opioid regulation of mesolimbic dopamine neurons

Jennifer Mitchell
Research Scientist
Peptidergic control of motivated behaviors

Sharif Taha
Postdoctoral Fellow
Neural circuit basis of palatability

Claire Wilcox
Postdoctoral Fellow

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Selected Publications

Kim, J.A., Pollak, K., Hjelmstad, G.O., Fields, H.L.  A single cocaine exposure enhances both opioid reward and aversion through a VTA-dependent mechanism.  Proc Natl Acad Sci U S A.  101:5664-5669, 2004.

Johansen, J.P., Fields, H.L.,  Glutamatergic activation of neurons in the anterior cingulate cortex is necessary and sufficient to produce an aversive teaching signal.  Nature Neuroscience, 7: 398-403, 2004.

Taha, S., Fields, H.L.  Encoding of palatability and appetitive behaviors by distinct neuronal populations in  the nucleus accumbens. J. Neuroscience, 25:1193-202, 2005.

Margolis, E.B., Lock, H., Chefer, V., Shippenberg, T., Hjelmstad, G.O., Fields, H.L.   Kappa opioids selectively control dopaminergic neurons projecting to the prefrontal cortex. PNAS, 103: 2938-2942, 2006.

Taha, S., Fields, H.L.  Inhibitions of nucleus accumbens neurons encode a gating signal for reward-directed behavior. J. Neuroscience 26(1):217-222, 2006.

Keltner, J.R., Furst, A., Fan, C.,Redfern, R., Inglis, B., Fields, H.L.  Isolating the modulatory effect of expectancy upon pain transmission: An FMRI study.  J. Neuroscience 26(16):4437-4443, 2006.

German, P., Fields, H.L.  How prior reward experience biases exploratory movements: a probabilistic model. J. Neurophysiol., 97:2083-93, 2007.

German, P., Fields, H.L.  Nucleus Accumbens neurons persistently encode locations associated with morphine reward. J. Neurophysiol.,97:2094-106, 2007.

Woolley, J.D., Lee, B.S., Fields, H.L. Nucleus accumbens opioids regulate flavor based preferences in food consumption. Neuroscience, 143:309-317, 2007.

Margolis, E.B.,  Lock, H., Hjelmstad, G.O., Fields, H.L.  The ventral tegmental area revisited: Is there an electrophysiological marker for dopaminergic neurons?  J. Physiol. 577: 907-924, 2006 originally published on line Sept 7, 2006.

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Howard Fields, M.D./Ph.D.



Email

hlf@phy.ucsf.edu

Phone

510-985-3971

Physical Address

5858 Horton Street
Suite 200
Emeryville, CA

Mailing Address

Ernest Gallo Clinic and Research Center
5858 Horton Street
Suite 200
Emeryville, CA 94608

For Internal Campus Mail

Box 0453

Other Websites

PIBS Website

Wheeler Center for the Neurobiology of Addiction

Keck Center for Integrative Neuroscience