GABA(B) receptor activation modulates GABA(A) receptor-mediated inhibition in chicken nucleus magnocellularis neurons.
Neurons of nucleus magnocellularis (NM), a division of avian cochlear nucleus that performs precise temporal encoding, receive glutamatergic excitatory input solely from the eighth nerve and GABAergic inhibitory input primarily from the ipsilateral superior olivary nucleus. GABA activates both ligand-gated Cl- channels [GABA(A) receptors (GABA(A)Rs)] and G protein-coupled receptors (GABA(B) receptors). The net effect of GABA(A)R-mediated input to NM is inhibitory, although depolarizing. Several studies have shown that this shunting, inhibitory GABAergic input can evoke action potentials in postsynaptic NM neurons, which could interfere with their temporal encoding. While this GABA-mediated firing is limited by a low-voltage-activated K+ conductance, we have found evidence for a second mechanism. We investigated modulation of GABA(A)R-mediated responses by GABA(B)Rs using whole cell recording techniques. Bath-applied baclofen, a GABA(B)R agonist, produced dose-dependent suppression of evoked inhibitory postsynaptic currents (eIPSCs). This suppression was blocked by CGP52432, a potent and selective GABA(B)R antagonist. Baclofen reduced the frequency but not the amplitude of miniature IPSCs (mIPSCs) and did not affect postsynaptic currents elicited by puff application of a specific GABA(A)R agonist muscimol, suggesting a presynaptic mechanism for the GABA(B)R-mediated modulation. Firing of NM neurons by synaptic stimulation of GABAergic inputs to NM was eliminated by baclofen. However, endogenous GABA(B)R activity in the presynaptic inhibitory terminals was not observed. We propose that presynaptic GABA(B)Rs function as autoreceptors, regulating synaptic strength of GABA(A)R-mediated inhibition, and prevent NM neurons from generating firing during activation of the inhibitory inputs.
Lu
Yong
Y
Virginia Merrill Bloedel Hearing Research Center, Deptartment of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, WA, USA.
Burger
R Michael
RM
Rubel
Edwin W
EW
D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002642:Chick Embryo; D017626:Cochlear Nucleus / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010721:Phosphinic Acids / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000528:radiation effects; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000528:radiation effects
D001596:Benzylamines; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C083008:CGP 52432; D001418:Baclofen; D008274:Magnesium; D002118:Calcium