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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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