Neuroscience Graduate Program at UCSF
Neural Circuitry of Motivation
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.
See research summary (above).
Daicia Allen, Staff Research Associate
Fred Ambroggi, PhD, Postdoctoral Fellow
Allison Coker, Graduate Student
Peter Fong, Staff Research Associate
Gregory Hjelmstad, PhD, Associate Investigator
Elyssa Margolis, PhD, Associate Investigator
Jennifer Mitchell, PhD, Project Director, Clinical Studies
Naomi Odean, Staff Research Associate
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.
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.
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.
Krause, M., German, P.W., Taha, S.A., FIELDS, H.L., A pause in nucleus accumbens neuron firing is required to initiate and maintain feeding. J. Neuroscience, 30:4746-56, 2010.
Margolis, E.B., Mitchell, J.M., Hjelmstad, G.O., FIELDS, H.L., Stress unmasks a novel opioid synaptic mechanism in midbrain dopamine neurons. J. Physiol. 2011 Jun 20.(e-pub)
Howard Fields, M.D./Ph.D.
Ernest Gallo Clinic and Research Center
5858 Horton Street, Suite 200
Emeryville, CA 94608