Effects of GABAergic and noradrenergic injections into the cerebellar flocculus on vestibulo-ocular reflexes in the rabbit

Abstract

The role of the vesitibulo-cerebellum of the rabbit in the control of the vestibulo-ocular response (VOR) and optokinetic response (OKR) reflexes was investigated by bilateral microinjections, into the flocculus, of substances affecting GABAergic or noradrenergic neurotransmission. GABA, the main transmitter through which cerebellar interneurons inhibit Purkinje cells directly or indirectly, acts normally through GABAA receptors (mainly located in the granular layer) and GABAB receptors (predominantly located in the molecular layer). Despite this different distribution, floccular injections of the GABAA agonist muscimol and of the GABAB agonist baclofen had a similar effect, presumably by profound inhibition of Purkinje cells. This effect consisted of a reduction in the gain of the VOR (in darkness and in light) as well as of the OKR by at least 50%. This provides firm evidence that the net effect of normal Purkinje-cell activity in the flocculus is to enhance the VOR and OKR, rather than to inhibit these responses, as is sometimes supposed. Intrafloccular injections of the beta-noradrenergic agonist isoproterenol or the beta-noradrenergic antagonist sotalol did not affect the basic magnitude of the VOR and OKR. However, these substances markedly affected the adaptive processes, which cause the VOR and OKR to change its magnitude when this is no longer adequate in stabilizing the retinal image. By a suitable combination of vestibular and optokinetic stimuli, consistent upward changes in the gain of these reflexes could be reliably and reproducibly induced in uninjected animals. Floccular injections of sotalol impaired these adaptive changes markedly, whereas injections of isoproterenol enhanced the adaptation, particularly of the VOR measured in darkness. These findings strongly suggest that the effectuation of adaptive changes of vestibular, and possibly other, motor control systems is strongly facilitated by the noradrenergic innervation of the flocculus, which is normally provided by the locus coeruleus (LC), by way of the beta-receptor system, although the activity of this system does not directly affect the signal transmission supporting the basic reflexes as such.