Activation of muscarinic receptors induces a long-lasting enhancement of Purkinje cell responses to glutamate.
The cerebellar cortex contains diffusely distributed cholinergic fibers and both muscarinic and nicotinic receptors. Behavioral studies suggest that an important function of this cholinergic innervation may be to modulate the effects of afferent input to the cerebellar cortex. The present study compared the effects of the muscarinic agonist bethanechol on basal firing rates and on glutamate-evoked firing of Purkinje cells in the vermis of the cerebellum of anesthetized rats. Microiontophoretic application of bethanechol produced a slowly developing, long-lasting enhancement of glutamate-evoked firing which was often disassociated from the bethanechol effect on the basal firing rate. Bethanechol increased the glutamate response of 22/33 Purkinje 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 glutamate response. For 7/33 Purkinje cells, bethanechol decreased the glutamate-evoked response. However, this decrease did not appear to be mediated by muscarinic receptors because it was not blocked by scopolamine and it was mimicked by application of the vehicle alone. Acetylcholine application produced a long-lasting increase in the glutamate response of 4/5 Purkinje cells that was similar to the bethanechol effect. These data indicate that the cerebellar cholinergic system exerts a prominent modulatory influence on Purkinje cell excitability by acting through muscarinic receptors.
Andre
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Dipartimento di Fisiologia e Biochimica, Università di Pisa, Italy.
Pompeiano
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O
White
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D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D008297:Male; D018727:Muscarinic Antagonists; D009474:Neurons / Q000187:drug effects; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012016:Reference Values; D012601:Scopolamine / Q000494:pharmacology; D013997:Time Factors
D001626:Bethanechol Compounds; D005971:Glutamates; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D018723:Bethanechol; D018698:Glutamic Acid; D012601:Scopolamine; D000109:Acetylcholine