Role of Muscarinic Receptors in the Cerebellar Control of the Vestibulospinal Reflex Gain: Cellular Mechanisms

Abstract

Most of the inhibitory Purkinje (P-) cells of the cerebellar anterior vermis fire out-of-phase with respect to the excitatory vestibulospinal neurons during roll tilt of the animal, thus exerting a positive influence on the gain of the vestibulospinal reflex (VSR). The responses of these P-cells depend on activation of glutamatergic excitatory mossy fibers-granule cells, but they are likely to be shaped by GABAergic inhibitory interneurons. The cerebellar cortex contains cholinergic fibers and both muscarinic and nicotinic receptors. In decerebrate cats intravermal injection of the muscarinic agonist bethanechol increased the VSR gain. The cellular mechanisms underlying these gain changes were studied in anesthetized Sprague-Dawley rats by microiontophoresis. Application of bethanechol (10-60 nA, 300 s) increased the response of vermal P-cells to pulses of glutamate (22/33 cells) or GABA (23/25 cells). These effects, which were blocked by the muscarinic antagonist scopolamine, lasted up to 15-40 min and occurred regardless of whether bethanecol altered the basal firing rate of the cells. We propose that the increase of P-cell responses to both excitatory and inhibitory neurotransmitters following activation of muscarinic receptors enhances the amplitude of modulation of these neurons to animal tilt, thus increasing the gain of the VSR.

Key Words:

• cerebellum
• Purkinje cells
• muscurinic receptors
• glutamate
• GABA
• neuromodulation