Adjunct Associate Professor of Neurology, University of
California San Francisco
Associate Investigator, Ernest Gallo Clinic and Research Center
Scientific Program Manager, Wheeler Center for the Neurobiology of Addiction
Tel: (510) 985-3927
Fax: (510) 985-3101
My research is focused on understanding the neural circuits that underlie motivation and goal-directed behavior and how these circuits are altered with drug addiction. Combining behavior, pharmacology, and slice electrophysiology, we are determining the acute and chronic actions of drugs of abuse and relating these actions to changes in behaviors.
The ventral tegmental area (VTA) and the nucleus accumbens are two brain regions that have been shown to be critically involved in the rewarding properties of many drugs of abuse. Interestingly, these same brain regions involved in reinforcing rewarding behaviors are also involved in aversion. Specifically, an animal will avoid an environment paired with microinjection of kappa opioid receptor agonists into either the nucleus accumbens or the VTA. We are using a combination of fluorescent tracing, electrophysiology and histology to determine whether specific subpopulations of neurons in these brain regions are activated by rewarding or aversive stimuli.
A fundamental step toward understanding how any neural circuit operates is to understand how individual synapses transfer information from one neuron to the next. At most synapses, the release of neurotransmitter is highly dependent on the history of activity at that synapse. We are interested in understanding this short-term plasticity, how it differs at different synapses and how it is altered by neuromodulators such as dopamine or opioid peptides. Changes in short-term plasticity at a synapse can have profound effects on the activity of a neural circuit, and therefore, the behavior of the organism. Thus, we are investigating how short-term synaptic plasticity is affected following exposure to drugs of abuse. Drugs of abuse produce profound behavioral effects in animal models. Studying the mechanisms underlying these behaviors not only has the potential to provide therapeutic interventions for treating drug addiction, but also provides an excellent general model for pursuing a causal link between synaptic modifications and changes in behavior.
Xia, Y. F., Margolis, E. B. and Hjelmstad G. O. (2010) Substance P inhibits GABA(B) receptor signaling in the ventral tegmental area. J. Physiol. (Lond.) 588 (9) 1541-1549. Abstract
Margolis, E. B., Hjelmstad, G. O., Fields, H. L. and Mitchell, J. M. (2008) Delta Opioid Receptor Expression in the Ventral Tegmental Area Protects Against Elevated Alcohol Consumption. J. Neurosci. 28(48):12672-81. Abstract
Margolis, E. B., Mitchell, J. M., Ishikawa, J., Hjelmstad, G. O. and Fields, H. L. (2008) Midbrain dopamine neurons: projection target determines action potential duration and dopamine D2 receptor inhibition. J Neurosci. 28(36): 8908-8913. Abstract
Xia, Y. F. and Hjelmstad, G. O. (2008) Acute amphetamine exposure selectively desensitizes kappa opioid receptors in the nucleus accumbens. Neuropsychopharmacology 33: 892-900. Abstract
Fields, H. L., Margolis, E., Hjelmstad, G. O., and Nicola, S. M. (2007) Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement. Ann. Rev. Neurosci. 30: 289-316. Abstract
Warrier, A. and Hjelmstad G. O. (2007) Protein kinase inhibitors reduce GABA but not glutamate release in the nucleus accumbens. Neuropharmacology 53 (8): 925-929. Abstract
Margolis, E., Lock, H., Hjelmstad, G. O. and Fields, H. L. (2006) The ventral tegmental area revisited; Is there an electrophysiological marker for dopaminergic neurons? J. Physiol. (Lond) 577 (3): 907-913. Abstract
Hjelmstad, G. O. (2006) Interactions between asynchronous release and short-term plasticity in the nucleus accumbens slice. J. Neurophysiol. 95 (3): 2020-2023. Abstract
Margolis, E., Lock, H., Chefer, V., Shippenberg, T. S., Hjelmstad, G. O. and Fields, H. L. (2006) Kappa opioids selectively control dopaminergic neurons projecting to the prefrontal cortex. Proc. Natl. Acad. Sci. USA. 103 (8): 2938-2942. AbstractFull publication list