Gregory Hjelmstad

Research Interests

Neural circuitry underlying reward and addiction

Research Summary

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.
A circuit based approach to understanding behavior requires: 1) identifying the neural circuit involved, 2) understanding how individual neurons function within that network and 3) determining what changes occur in the network that correlate to changes in behavior (i.e. learning). In the case of drug addiction, much of this circuit has been identified. 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. Therefore, we are focusing our electrophysiological studies on neurons in these two nuclei.
A fundamental step toward understanding how any neural circuit operates is to understand how individual synapses transfer information from one neuron to the next. Incoming action potentials, or spikes, produce a probabilistic release of neurotransmitter. The synaptic currents produced by this neurotransmitter is then integrated by the postsynaptic cell, where, upon reaching a threshold, it will produce an action potential of its own. The release of neurotransmitter, and thus the activity of the postsynaptic neuron, is highly dependent on the history of activity at that synapse. We are interested in understanding this history effect or 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 synaptic plasticity 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.

Selected Publications

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

Margolis, E., Hjelmstad, G. O., Bonci, A. and Fields, H. L. (2003) Kappa opioid agonists directly inhibit midbrain dopaminergic neurons. J. Neurosci. 23 (30), 9981-9986.

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

Hjelmstad, G. O. and Fields, H. L. (2001) Kappa opioid receptor inhibition of glutamatergic transmission in the nucleus accumben shell. J. Neurophysiol. 85 (3): 1153-1158.