Effect of drugs of Abuse on Dendritic Physiology

Over the past 10 years, it has become increasingly apparent that alterations of ion channel and receptor functions are the main factors underlying the powerful short- and long-term effects of alcohol on human behavior. Most ion channels and receptors are found in the membrane of dendrites, which represent about 90% of the total neuronal membrane surface. Dendrites, the extension of neuron cell bodies, are specialized for receiving and processing the vast majority of incoming neuronal signals. Despite the obvious importance of this neuronal compartment, very little is known about the ways alcohol modulates dendritic channels and receptors.
In an effort to further our understanding of the cellular mechanisms of alcohol, we will compare the acute and chronic effects of ethanol on biophysical and pharmacological properties of a subpopulation of potassium channels called Maxi K or BK channels. These channels present the unique characteristics of being activated by changes of both membrane potential and intracellular calcium. Several key features led us to place the BK channels at the heart of this study. First, our group has recently found that BK channels are expressed in the membrane of soma and dendrites. Second, BK channels, at least somatic ones, are sensitive to EtOH. Third, BK channels are critical modulators of spike shape and action potential patterning, two phenomena that determine the final neuronal output. Thus, ethanol effects on this potassium channel are likely to play a major role in the way it modulates neuronal integration. We will focus our efforts on neurons of the nucleus accumbens, a structure best known for mediating the reinforcing effects of drugs of abuse such as alcohol and opiates.

Education
Ph.D. in Neuroscience, Université Pierre et Marie Curie, Paris, France 1991
Master in Neuroscience Université Pierre et Marie Curie, Paris, France, 1987-1988
Bachelor of Animal Physiology, Université Pierre et Marie Curie, Paris, 1983-1987

Research Training
Senior Research Associate. Dept of Neuropharmacology, The Scripps Research Institute, 1993-2001.
Postdoctoral fellow The Max Planck Institute, Munich, Germany, 1992-1993.
Graduate research Fellow. INSERM U161, 1988-1991.

Selected Publications

Martin, G., Puig, S.I., Pietrzykowski, A., Zadek, P.,Emery, P., and Treistman. S.N. (2004) Restricted cellular localization of a specific BK-channel subtype controls ethanol sensitivity in the nucleus accumbens, J. Neurosci. 24(29):6563-72).

Pietrzykowski, A., Martin, G., Puig, S. and Treistman, (2004) S.N. Alcohol Tolerance in BK Channels of Neuronal Terminals is Intrinsic, and Includes Two Components: Decreased Channel Sensitivity to Ethanol and Decreased Channel Density. J Neurosci. 24(38):8322-32.

Martin G and Siggins, G.R. (2002) Electrophysiological Evidence of the Expression of a Glycine Receptor in Freshly-Isolated Neurons from Nucleus Accumbens J Pharmacol Exp Ther 302:1135-1145

Martin G, Ahmed SH, Blank T, Spiess J, Koob GF and Siggins G.R. (1999) Chronic morphine treatment alters NMDA receptor-mediated synaptic transmission in the nucleus accumbens. J. Neurosci 19:9081-9089

Martin G. Przewlocki R and Siggins G.R. (1999) Effect of different metabotropic glutamate receptor agonists on nucleus accumbens NMDA-EPSCs in morphine tolerant Rats. J Pharmacol Exp Ther 288:30-35

Martin G., Nie Z.and Siggins G.R (1997) Mu opioid receptors modulate N-methyl-aspartate receptor-mediated responses in nucleus accumbens neurons. J Neurosci 17: 11-22

Martin G. Nie Z and Siggins G.R. (1997) Metabotropic glutamate receptors regulate N-Methyl-D-Asparate-synaptic transmission in nucleus Accumbens neurons. J Neurophysiol 79:3028-3038.

Siggins G.R Martin G, Yuan X, Nie Z.and Madamba S (1995) Opiate modulation of glutamatergic transmission in nucleus accumbens in vitro. Analgesia 1:4-6, 728-733

Martin G., Oliveras J.L. and Montagne-Clavel J (1992) Involvement of ventromedial medulla "multimodal, multireceptive" neurons in opiate spinal descending control system: a single-unit study of the effect of morphine in the awake, freely moving rat. J Neurosci., 12:1511-1522.