RT Journal Article
SR Electronic
T1 The Mechanism of cAMP-Mediated Enhancement at a Cerebellar Synapse
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8687
OP 8694
DO 10.1523/JNEUROSCI.17-22-08687.1997
VO 17
IS 22
A1 Chinfei Chen
A1 Wade G. Regehr
YR 1997
UL http://www.jneurosci.org/content/17/22/8687.abstract
AB Increases in cAMP have been shown previously to enhance the strength of the granule cell to Purkinje cell synapse. We have examined the mechanisms underlying this enhancement in rat cerebellar brain slices. Elevation of cAMP levels by forskolin increased synaptic currents in a dose-dependent manner. Fluorometric calcium measurements revealed that forskolin did not affect presynaptic calcium influx or resting calcium levels. The waveform of the presynaptic volley was also unaltered, indicating that changes in the presynaptic action potential did not contribute to synaptic enhancement. However, forskolin enhanced the frequency but not the size of spontaneous miniature EPSCs. There was a one-to-one correspondence between increases of spontaneous and evoked neurotransmitter release. These results suggest that forskolin increases release at this synapse via presynaptic mechanisms that do not alter calcium influx. The effect of forskolin on paired-pulse facilitation was examined to assess the relative contributions of changes in the probability of release (p) and changes in the number of functional release sites (n) to this form of enhancement. These experiments suggest that although small changes in n cannot be excluded, most of the enhancement arises from increases in p.