Contributions of calcium-dependent and calcium-independent mechanisms to presynaptic inhibition at a cerebellar synapse.
Activation of either adenosine A1 receptors or GABAB receptors inhibits many excitatory synapses in the mammalian brain. However, the extent to which different mechanisms contribute to such synaptic modulation is unclear. We examined the manner in which activation of adenosine A1 receptors and GABAB receptors modulates synaptic strength at the granule cell to Purkinje cell synapse in rat cerebellar slices. Optical determination of presynaptic calcium influx revealed that presynaptic calcium channels were modulated by 2-chloroadenosine (2CA) and baclofen, agonists of the adenosine A1 receptor and the GABAB receptor, respectively. 2CA and baclofen differentially affected three classes of calcium channels without altering the shape of the presynaptic volley, suggesting that changes in presynaptic waveform do not contribute significantly to synaptic modulation. 2CA affected neither the amplitude nor the frequency of spontaneous miniature postsynaptic currents, whereas baclofen reduced the frequency by approximately 40% without affecting the amplitude. In addition, 2CA and baclofen do not change either fiber excitability or presynaptic residual calcium. Taken together, our data indicate that activation of the adenosine A1 receptor reduces synaptic strength by modulating presynaptic calcium channels. Baclofen modulates presynaptic calcium channels as well but also affects release processes downstream from calcium entry.
Dittman
J S
JS
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Regehr
W G
WG
D015762:2-Chloroadenosine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002531:Cerebellum / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects; D009433:Neural Inhibition / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D018377:Neurotransmitter Agents; D018080:Receptors, GABA-B; D018047:Receptors, Purinergic P1; D015762:2-Chloroadenosine; D001418:Baclofen; D002118:Calcium