The muscarinic agonist, bethanechol, enhances GABA-induced inhibition of Purkinje cells in the cerebellar cortex.
An important function of cholinergic projections to the cerebellar cortex may be to modulate the effects of classical afferent inputs to the cerebellar cortex. This hypothesis is supported by the recent observation that cholinergic agonists act at muscarinic receptors in the cerebellar cortex to facilitate Purkinje cell responses to glutamate, the excitatory neurotransmitter of parallel fibers [Brain Res., 617 (1993) 28-36]. Since Purkinje cell excitability is influenced by inhibitory input from basket and stellate cells as well as by excitatory input from granule cells and climbing fibers, the present study investigated whether muscarinic agonists could also modify the Purkinje cell responses to GABA, the putative inhibitory transmitter of basket and stellate neurons. In anesthetized rats, microiontophoretic application of bethanechol produced a long-lasting enhancement of GABA-evoked inhibition of firing of Purkinje cells in the cerebellar vermis (22/25 cells) regardless of whether bethanechol increased, decreased or failed to alter the basal firing rate of the cell. The muscarinic antagonist scopolamine prevented the bethanechol-induced increase in the GABA response. It appears, therefore, that cholinergic activation of muscarinic receptors enhances not only the excitatory but also the inhibitory component of cerebellar cortex circuitry. Further experiments are required to investigate whether this combination of effects may potentiate the signal processing capabilities of the cerebellar cortex.
Andre
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Dipartimento di Fisiologia e Biochimica, Universita di Pisa, Italy.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology*; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects*; D004357:Drug Synergism; D004566:Electrodes; D007478:Iontophoresis; D008297:Male; D010277:Parasympathomimetics / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D001626:Bethanechol Compounds; D010277:Parasympathomimetics; D018723:Bethanechol; D005680:gamma-Aminobutyric Acid; D012601:Scopolamine