Noradrenergic and cholinergic modulations of corticocerebellar activity modify the gain of vestibulospinal reflexes.

Abstract

In addition to mossy fibers and climbing fibers, the cerebellar cortex receives noradrenergic and cholinergic afferents. Since the Purkinje (P) cells of the cerebellar vermis (culmen) respond to roll tilt of the animal with a discharge pattern that is out of phase with respect to that of the related lateral vestibular neurons, thus exerting a facilitatory influence on the gain of the vestibulospinal (VS) reflex, we tested the effects of local microinjection into the anterior vermis of noradrenergic and cholinergic agents on these reflexes. In decerebrate cats, unilateral microinjection in the paramedial zone B of the culmen of 0.25 microliters of small doses of alpha 1-, alpha 2-, and beta-noradrenergic agonists (i.e., metoxamine, clonidine, and isoproterenol, respectively) increased the response gain (in impulses/second per deg) of the EMG response of the ipsilateral and to some extent also of the contralateral triceps brachii to animal tilt (at 0.15 Hz, +/- 10 degrees). On the other hand local injection of the corresponding antagonists (i.e., prazosin, yohimbine, and propranolol) either decreased the gain of the ipsilateral triceps brachii to labyrinth stimulation or else prevented the occurrence of the effects induced by the corresponding agonists. An increase in gain of the VS reflexes was also elicited in other experiments by unilateral microinjection either of the nonselective cholinergic agonist carbachol or of the anticholinesterase eserine sulfate. Thus, the effects could be produced by increasing the naturally present amount of acetylcholine. Further experiments indicated that a bilateral increase in the response gain of the triceps brachii to labyrinth stimulation occurred after microinjection of a selective muscarinic (bethanechol) or nicotinic agonist (nicotine), while just the opposite result was obtained after microinjection of the corresponding muscarinic (scopolamine) and nicotinic (hexamethonium, D-tubocurarine) blockers. The effects of the noradrenergic and cholinergic agonists, which persisted for about two hours after the injection, were site specific and dose dependent. It appears, therefore, that the noradrenergic and cholinergic afferents to the cerebellar vermis intervene in the gain regulation of the VS reflexes, possibly by increasing the amplitude of modulation of the P cells to labyrinth stimulation.