Modulation of synaptic depression of the calyx of Held synapse by GABA(B) receptors and spontaneous activity.
The calyx of Held synapse of the medial nucleus of the trapezoid body is a giant axosomatic synapse in the auditory brainstem, which acts as a relay synapse showing little dependence of its synaptic strength on firing frequency. The main mechanism that is responsible for its resistance to synaptic depression is its large number of release sites with low release probability. Here, we investigated the contribution of presynaptic GABA(B) receptors and spontaneous activity to release probability both in vivo and in vitro in young-adult mice. Maximal activation of presynaptic GABA(B) receptors by baclofen reduced synaptic output by about 45% in whole-cell voltage clamp slice recordings, which was accompanied by a reduction in short-term depression. A similar reduction in transmission was observed when baclofen was applied in vivo by microiontophoresis during juxtacellular recordings using piggyback electrodes. No significant change in synaptic transmission was observed during application of the GABA(B) receptor antagonist CGP54626 both during in vivo and slice recordings, suggesting a low ambient GABA concentration. Interestingly, we observed that synapses with a high spontaneous frequency showed almost no synaptic depression during auditory stimulation, whereas synapses with a low spontaneous frequency did depress during noise bursts. Our data thus suggest that spontaneous firing can tonically reduce release probability in vivo. In addition, our data show that the ambient GABA concentration in the auditory brainstem is too low to activate the GABA(B) receptor at the calyx of Held significantly, but that activation of GABA(B) receptors can reduce sound-evoked synaptic depression.
J. G. G. Borst: Department of Neuroscience, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. g.borst@erasmusmc.nl.
Tiantian
T
Wang
Silviu I
SI
Rusu
Bohdana
B
Hruskova
Rostislav
R
Turecek
J Gerard G
JG
Borst
D000161:Acoustic Stimulation; D000200:Action Potentials; D000367:Age Factors; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D036881:Long-Term Synaptic Depression; D051379:Mice; D008810:Mice, Inbred C57BL; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D055366:Synaptic Potentials; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000378:metabolism / Q000502:physiology
D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C107353:CGP 54626; D001418:Baclofen