Associate Investigator, Ernest Gallo Clinic and Research Center

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.

Recent Publications:

Margolis EB, Mitchell JM, Ishikawa J, Hjelmstad GO, Fields HL. Midbrain dopamine neurons: projection target determines action potential duration and dopamine D(2) receptor inhibition.  J Neurosci. 28(36):8908-13, 2008.

Warrier A, Hjelmstad GO. Protein kinase inhibitors reduce GABA but not glutamate release in the nucleus accumbens. Neuropharmacology 53(8): 925-9, 2007.

Xia YF, He L, Whistler JL, Hjelmstad GO. Acute amphetamine exposure selectively desensitizes kappa opioid receptors in the nucleus accumbens. Neuropsychopharmacol. advance online publication 6 June 2007.

Fields HL, Hjelmstad GO, Margolis EB, Nicola SM. Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement. Annu. Rev. Neurosci. 30, 289-316, 2007.

Margolis E, Lock H, Hjelmstad GO, Fields HL. The ventral tegmental area revisited; Is there an electrophysiological marker for dopaminergic neurons? J. Physiol. (Lond) 577(Pt 3): 907-24, 2006.

Hjelmstad GO. Interactions between asynchronous release and short-term plasticity in the nucleus accumbens slice. J. Neurophysiol. 95 (3): 2020-2023, 2006.

Margolis E, Lock H, Chefer V, Shippenberg TS, Hjelmstad GO, Fields HL. Kappa opioids selectively control dopaminergic neurons projecting to the prefrontal cortex. Proc. Natl. Acad. Sci. USA. 103 (8): 2938-2942, 2006.

Margolis E, Hjelmstad GO, Bonci A, Fields HL. Both kappa and mu opioid agonists inhibit glutamatergic input to ventral tegmental area neurons. J. Neurophysiol. 93 (6): 3086, 2005.

Hjelmstad GO. Dopamine excites nucleus accumbens neurons through the differential modulation of glutamate and GABA release. J. Neurosci. 24 (39): 8621-8628, 2004.

Nicola SM, Hopf FW, Hjelmstad GO. Contrast enhancement: A physiological effect of striatal dopamine? Cell Tissue Res. 318, 93-106, 2004.

Kim JA, Pollak KA, Hjelmstad GO, Fields HL. A single cocaine exposure enhances both opioid reward and aversion through a VTA-dependent mechanism. Proc. Natl. Acad. Sci. USA. 101 (15): 5664-5669, 2004.

Hjelmstad GO, Fields HL. Kappa opioid receptor activation in the nucleus accumbens inhibits glutamate and GABA transmission through different mechanisms. J. Neurophysiol. 89 (5), 2389-2395, 2003.

Margolis E, Hjelmstad GO, Bonci A, Fields HL. Kappa opioid agonists directly inhibit midbrain dopaminergic neurons. J. Neurosci. 23 (30), 9981-9986, 2003.

Hjelmstad GO, Fields HL. Kappa opioid receptor inhibition of glutamatergic transmission in the nucleus accumben shell. J. Neurophysiol. 85 (3): 1153-1158, 2001.

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