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).
Adam Ferris, Staff Research Associate
Fred Ambroggi, PhD, Postdoctoral Fellow
Jocelyn Richard , PhD, Postdoctoral Fellow
Peter Fong, Staff Research Associate
Gregory Hjelmstad, PhD, Adjunct Associate Investigator
Elyssa Margolis, PhD, Adjunct Assistant Professor
Jennifer Mitchell, PhD, Adjunct Assistant Professor
Catriona Miller, Laboratory Manager
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)
Ghazizadeh A, Ambroggi F, Odean N, Fields HL. Prefrontal cortex mediates extinction of responding by two distinct neural mechanisms in accumbens shell. J Neurosci. 2012 Jan 11;32(2):726-37. doi: 10.1523/JNEUROSCI.3891-11.2012.
Mitchell JM, O'Neil JP, Janabi M, Marks SM, Jagust WJ, Fields HL. Alcohol consumption induces endogenous opioid release in the human orbitofrontal cortex and nucleus accumbens. Sci Transl Med. 2012 Jan 11;4(116):116ra6. doi: 10.1126/scitranslmed.3002902.
Kayser AS, Allen DC, Navarro-Cebrian A, Mitchell JM, Fields HL. Dopamine, corticostriatal connectivity, and intertemporal choice. J Neurosci. 2012 Jul 4;32(27):9402-9. doi: 10.1523/JNEUROSCI.1180-12.2012.
Margolis EB, Toy B, Himmels P, Morales M, Fields HL. Identification of rat ventral tegmental area GABAergic neurons. PLoS One. 2012;7(7):e42365. doi: 10.1371/journal.pone.0042365. Epub 2012 Jul 31.
Navratilova E, Xie JY, Okun A, Qu C, Eyde N, Ci S, Ossipov MH, King T, Fields HL, Porreca F. Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20709-13. doi: 10.1073/pnas.1214605109. Epub 2012 Nov 26.
Hjelmstad GO, Xia Y, Margolis EB, Fields HL. Opioid modulation of ventral pallidal afferents to ventral tegmental area neurons. J Neurosci. 2013 Apr 10;33(15):6454-9. doi: 10.1523/JNEUROSCI.0178-13.2013.
Howard Fields, M.D./Ph.D.
UCSF MC 0444
675 Nelson Rising Lane, Room 414B
San Francisco, CA. 94158