Surmeier, D. James, PhD
Chairman, Department of Physiology
Lurie 8-105 Chicago
|Areas of Research||
Brain Imaging, Mechanisms of Drug Action, Molecular Neuroscience, Motor Control, Neurobiology of Disease, Systems Neuroscience
|NU Scholar Profile|
|Recent Publications on PubMed|
The research in our lab revolves around the question of how neuromodulators shape the excitability of basal ganglia and frontal cortex neurons. These two areas share a rich monoaminergic innervation arising from the mesencephalon and medulla. Disorders in monoaminergic signaling in these forebrain structures have been implicated in a wide variety of psychomotor disorders including Parkinson’s disease, dystonia, Huntington’s disease, schizophrenia, drug abuse, depression and Tourette’s syndrome.
There are several ongoing projects in our lab. All of them are ultimately interested in determining how dopamine or serotonin change neural activity.
Unlike neurotransmitters, neuromodulators like dopamine influence neuronal activity by altering the properties of voltage-dependent and ligand-gated membrane channels. This is accomplished by G-protein coupled receptors that activate intracellular enzyme cascades. There are several obstacles to the characterization of these pathways and their cellular consequences. One is the molecular heterogeneity of participating proteins. Another is the difficulty in gaining a quantitative description of changes in channel behavior. To overcome these obstacles, we use a combination of electrophysiological, biochemical and molecular strategies. Patch clamp techniques are used to quantitatively characterize the impact of receptor activation on ion channels. Biochemical techniques are used to identify the enzymes and signaling molecules linking receptor and channel. Molecular techniques, such as single cell mRNA amplification, are used to ‘fingerprint’ neurons subjected to electrophysiological and biochemical analysis. These single cell mRNA profiles allow us not only to determine the molecular identity of elements in a particular signaling cascade but also to determine the broader functional class to which a studied neuron belongs.
The combination of these techniques has enabled us to make great strides in understanding the impact of neuromodulators, like dopamine, on forebrain function in recent years and will hopefully lead to new strategies for normalizing their signaling in disease states.
Surmeier, D.J., Song, W.-J. and Yan, Z. Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. J. Neurosci. 16:6579-6591, 1996.
Yan, Z., Song, W.-J. and Surmeier, D.J. D2 dopamine receptor reduce N-type Ca2+ currents in rat neostriatal cholinergic interneurons through a membrane-delimited, protein kinase C-insensitive pathway. J. Neurophysiol. 78:1003-1015, 1997.
Yan Z, Surmeier DJ D5 dopamine receptors enhance Zn2+-sensitive GABA(A) currents in striatal cholinergic interneurons through a PKA/PP1 cascade. Neuron 19:1115-26, 1997.
Song, W.-J., Tkatch, T., Baranauskas, G., Kitai, S.T. and Surmeier, D.J. Somatodendritic depolarization-activated potassium currents in rat neostriatal cholinergic interneurons are predominantly of the A-type and attributable to co-expression of Kv4.2 and Kv4.1 subunits. J. Neurosci. 18: 3124-3137, 1998.
Baranauskas G, Tkatch T, Surmeier DJ Delayed rectifier currents in rat globus pallidus neurons are attributable to Kv2.1 and Kv3.1/3.2 K(+) channels. J Neurosci 19:6394-404, 1999.
Mermelstein PG, Foehring RC, Tkatch T, Song WJ, Baranauskas G, Surmeier DJ Properties of Q-type calcium channels in neostriatal and cortical neurons are correlated with beta subunit expression. J Neurosci 19:7268-77, 1999.
Kelz MB, Chen J, Carlezon WA, Jr., Whisler K, Gilden L, Beckmann AM, Steffen C, Zhang YJ, Marotti L, Self DW, Tkatch T, Baranauskas G, Surmeier DJ, Neve RL, Duman RS, Picciotto MR, Nestler EJ Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine. Nature 401:272-6, 1999.