Submitted on November 5, 2008
Revised on March 4, 2009
Accepted on March 8, 2009
Noradrenergic Regulation of GABAergic Inhibition of Main Olfactory Bulb Mitral Cells Varies as a Function of Concentration and Receptor Subtype
Qiang Nai1*, Hong-Wei Dong2, Abdallah Hayar3, Christiane Linster4, and Matthew Ennis5
1 University of Tennessee, Health Science Center
2 University of Tennessee Health Science Center, Memphis, TN 38163
3 University of Arkansas for Medical Sciences
4 Cornell University
5 University of Tennessee Health Science Center
* To whom correspondence should be addressed. E-mail: qnai{at}utmem.edu.
The main olfactory bulb (MOB) receives a rich noradrenergic innervation from the pontine nucleus locus coeruleus (LC). Previous studies indicate that norepinephrine (NE) modulates the strength of GABAergic inhibition in MOB. However, the nature of this modulation and the NE receptors involved remain controversial. The goal of the present study was to investigate the role of NE receptor subtypes in modulating the GABAergic inhibition of mitral cells using patch clamp electrophysiology in rat MOB slices. NE concentration-dependently and bi-directionally modulated GABAA receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs/mIPSCs) recorded in mitral cells. Low doses of NE suppressed sIPSCs and mIPSCs due to activation of alpha2 receptors. Intermediate concentrations of NE increased sIPSCs and mIPSCs due primarily to activation of alpha1 receptors. By contrast, activation of beta receptors increased sIPSCs but not mIPSCs. These results indicate that NE release regulates the strength of GABAergic inhibition of mitral cells depending on the NE receptor subtype activated. Functionally, the differing affinity of noradrenergic receptor subtypes appears to allow for dynamic modulation of GABAergic inhibition in MOB as function of the extracellular NE concentration, which in turn, is regulated by behavioral state.
