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The Journal of Neuroscience, December 1, 2000, 20(23):8651-8658
GABA Spillover from Single Inhibitory Axons Suppresses Low-Frequency Excitatory Transmission at the Cerebellar Glomerulus
Simon J. Mitchell and R. Angus Silver Department of Physiology, University College London, London, WC1E 6BT, United Kingdom
GABA type B receptors (GABAB-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 GABAB-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 GABAB-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°C) presynaptic GABAB-Rs were not tonically activated by spontaneous GABA release from Golgi cells, which fire at ~8 Hz in slices at this temperature. However, tonic activation could be induced by blocking GABA uptake or by lowering temperature. GABAB-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.
Key words: transmitter spillover; GABAB; heteroreceptor; presynaptic; glutamate; synaptic transmission
Copyright © 2000 Society for Neuroscience 0270-6474/00/20238651-08$05.00/0
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