Noradrenergic regulation of GABAergic inhibition of main olfactory bulb mitral cells varies as a function of concentration and receptor subtype.
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 this 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 GABA(A) receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs/mIPSCs) recorded in mitral cells. Low doses of NE suppressed sIPSCs and mIPSCs because of activation of alpha2 receptors. Intermediate concentrations of NE increased sIPSCs and mIPSCs primarily because of activation of alpha1 receptors. In 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 seems 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.
Nai
Qiang
Q
Dept. of Anatomy, Univ. of Tennessee Health Science Ctr., 855 Monroe Ave., Suite 515, Memphis, TN 38163, USA. qnai@utmem.edu
Dong
Hong-Wei
HW
Hayar
Abdallah
A
Linster
Christiane
C
Ennis
Matthew
M
D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011222:Prazepam / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000145:classification / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D011941:Receptors, Adrenergic; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D011222:Prazepam; D009638:Norepinephrine