GABA(B) modulation of GABA(A) and glycine receptor-mediated synaptic currents in hypoglossal motoneurons.
We studied the effects of GABA(B) receptor activation on either glycine or GABA(A) receptor-mediated synaptic transmission to hypoglossal motoneurons (HMs, P8-13) using a rat brainstem slice preparation. Activation of GABA(B) receptors with baclofen, a GABA(B) receptor agonist, inhibited the amplitude of evoked glycine and GABA(A) receptor-mediated inhibitory postsynaptic currents. Additionally, with blockade of postsynaptic GABA(B) receptors baclofen decreased the frequency of both glycine and GABA(A) receptor-mediated spontaneous miniature inhibitory postsynaptic currents (mIPSCs), indicating a presynaptic site of action. Conversely, the GABA(B) receptor antagonist CGP 35348 increased the frequency of glycine receptor-mediated mIPSCs. Application of the GABA transport blocker SKF 89976A decreased the frequency of glycinergic mIPSCs. Lastly, we compared the effects of baclofen on the frequency of glycine and GABA(A) receptor-mediated mIPSC during HM development. At increased postnatal ages (P8-13 versus P1-3) mIPSC frequency was more strongly reduced by baclofen. These results show that presynaptic GABA(B) receptors inhibits glycinergic and GABAergic synaptic transmission to HMs, and the presynaptic sensitivity to baclofen is increased in P8-13 versus P1-3 HMs. Further, endogenous GABA is capable of modulating inhibitory synaptic transmission to HMs.
O'Brien
Jennifer A
JA
Department of Physiology and Biophysics, School of Medicine, University of Washington, Box 357290, Seattle, WA 98195-7290, USA.
Sebe
Joy Y
JY
Berger
Albert J
AJ
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001933:Brain Stem / Q000166:cytology / Q000502:physiology; D018682:GABA Agents / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D007002:Hypoglossal Nerve / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D009557:Nipecotic Acids / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000502:physiology*; D018009:Receptors, Glycine / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D018682:GABA Agents; D058786:GABA-B Receptor Agonists; D009557:Nipecotic Acids; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D018009:Receptors, Glycine; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; D001418:Baclofen