Poster Session 1 - B7
1Sanghavy Sivakumaran, 1Daniel W. Sparks, 1,2,3Evelyn K. Lambe
1 Dept. of Physiology, University of Toronto, Toronto, ON, Canada; 2 Dept. of OBGYN, University of Toronto, Toronto, ON, Canada; 3 Dept. of Psychiatry, University of Toronto, Toronto, ON, Canada
The ventral medial habenula (vMHb) and the interpeduncular nucleus (IPN) are targets of the drug nicotine with potential repercussions for initial physiological experiences of this addictive drug. Of note, the α5 nicotinic receptor subunit, encoded by Chrna5, appears to be protective against the development of nicotine addiction, potentially encoding aversive properties of the drug. In humans, a single nucleotide polymorphism in Chrna5 that disrupts creation of the α5 protein, has been identified among individuals who readily develop chronic nicotine dependence. In situ work using wild-type mice has suggested that normally α5 is highly expressed within the IPN but only weakly expressed within the vMHb. While the α5 subunit does not participate in the nicotinic receptor binding site, it has powerful effects on the conductance and desensitization parameters of nicotinic receptors. Here, we probe the contribution of the α5 subunit to nicotine-elicited changes in neuronal excitability in the IPN and the vMHb . For these experiments, we use whole-cell patch clamp electrophysiology in brain slices from α5+/+, α5+/-, and α5-/- mice. Initial results show that responses to nicotine are markedly attenuated in the IPN but not the vMHb of the a5-/- mice. In both regions, wild-type and heterozygous mice show nicotine-elicited increases in neuronal excitability, and the emergence of depolarization block in vMHb. In future work, we aim to examine the role of the α5 subunit in the plasticity of this pathway and how it is altered by initial exposures to nicotine in vivo. This work is necessary to characterize the role α5 plays in the neurophysiological response to initial nicotine exposures.