GABA spillover from single inhibitory axons suppresses low-frequency excitatory transmission at the cerebellar glomerulus

J Neurosci. 2000 Dec 1;20(23):8651-8. doi: 10.1523/JNEUROSCI.20-23-08651.2000.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Baclofen / pharmacology
  • Cerebellum / cytology
  • Cerebellum / metabolism*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • GABA-B Receptor Agonists
  • In Vitro Techniques
  • Nerve Fibers / drug effects
  • Nerve Fibers / metabolism
  • Neural Inhibition / physiology*
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Temperature
  • Tetrodotoxin / pharmacology
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • GABA Agonists
  • GABA Antagonists
  • GABA-B Receptor Agonists
  • Receptors, GABA-B
  • Tetrodotoxin
  • gamma-Aminobutyric Acid
  • Baclofen