GABA spillover from single inhibitory axons suppresses low-frequency excitatory transmission at the cerebellar glomerulus.
GABA type B receptors (GABA(B)-Rs) are present on excitatory terminals throughout the CNS, but surprisingly little is known about their role in modulating neurotransmission under physiological conditions. We have investigated activation of GABA(B)-Rs on excitatory terminals within the cerebellar glomerulus, a structure where glutamatergic excitatory and GABAergic inhibitory terminals are in close apposition and make axodendritic synapses onto granule cells. Application of the GABA(B)-R agonist baclofen depressed evoked mossy fiber EPSCs by 54% at 1 Hz. The amplitude of miniature EPSCs recorded in tetrodotoxin was unchanged in the presence of baclofen, but the frequency was significantly reduced, indicating a purely presynaptic action of baclofen under our recording conditions. At physiological temperature (37 degrees C) presynaptic GABA(B)-Rs were not tonically activated by spontaneous GABA release from Golgi cells, which fire at approximately 8 Hz in slices at this temperature. However, tonic activation could be induced by blocking GABA uptake or by lowering temperature. GABA(B)-Rs were activated at physiological temperature when Golgi cell firing was increased above the basal level by stimulating a single inhibitory Golgi cell input at 50 Hz, suppressing the mossy fiber-evoked EPSC by 24% at 1 Hz. Furthermore, glutamate release was selectively inhibited at low-frequency mossy fiber inputs (<10 Hz) during Golgi cell stimulation. Our findings suggest that GABA spillover in the glomerulus modulates sensory input to the cerebellar cortex.
Mitchell
S J
SJ
Department of Physiology, University College London, London, WC1E 6BT, United Kingdom.
Silver
R A
RA
D000818:Animals; D001369:Axons / Q000378:metabolism*; D001418:Baclofen / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D066298:In Vitro Techniques; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013696:Temperature; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D001418:Baclofen