Inferior olive inactivation decreases the excitability of the intracerebellar and lateral vestibular nuclei in the rat.

Abstract

SUMMARY1. In rats under sodium pentobarbitone anaesthesia the inferior olive region has been reversibly inactivated by applying a cooling probe to the ventral surface of the medulla. Unitary activity has been recorded from the fastigial, interpositus and Deiters nuclei.2. Identification of units was based on the presence of a dye spot, left by the recording micropipette. In the Deiters nucleus, an additional criterion ofidentification was the antidromic activation from spinal cord stimulation.3. Following cooling of the inferior olive of one side, we have observed suppression of the activity of all the fourteen Deiters neurones and of seventeen out of twenty neurones recorded from the intracerebellar nuclei.4. In two out of seven Deiters neurones tested the antidromic invasion elicited by spinal cord stimulation was suppressed.5. In rats, whose inferior olive was previously destroyed, cooling ofthe inferior olive region was not followed by the powerful depression of spike activity seen in the vestibular and cerebellar nuclei cells in the intact rats.6. These results indicate that the olivocerebellar system is very important in regulating the level of excitability of the subcerebellar structures and therefore in controlling both postural mechanisms and the processing of information relating to sensorimotor integration. INTRODUCTIONThe inferior olive projects to the entire cerebellar cortex (Brodal, 1940) and it is likely to be the only source of climbing fibres (Eccles, Ito & Szentaigothai, 1967;Armstrong, 1974;Montarolo, Raschi & Strata, 1980). Its important role in cerebellar function and consequently in motor control is widely accepted (Armstrong, 1978). Evidence for such an assumption is provided by the fact that in rats an inferior olive lesion induces motor disorders, which are as severe as those following cerebellectomy (Llinas, Walton, Hillman & Sotelo, 1975).It has been recently suggested that one function of the inferior olive is to exert a powerful tonic control on the excitability of the Purkinje cells ofthe cerebellar cortex and consequently ofthe neurones ofthe intracerebellar and Deiters nuclei (Montarolo,

Cerebellar Dysfunction Explains the Extinction-Like Abolition of Conditioned Eyeblinks After NBQX Injections in the Inferior Olive

“…When the stimulation resumed, CRs were immediately absent on the background of already suppressed IN activity. This stimulation-independent and NBQX-induced suppression of IN firing rate is consistent with previous reports of the tonic effects of blocking IO input to the cerebellum (Benedetti et al, 1983;Bengtsson et al, 2004). It appears that NBQX downregulated the firing rate of the IO and this upregulated the activity of Purkinje cells in the cerebellar cortex (Batini et al, 1985;Lang, 2001;Bengtsson et al, 2004).…”

“…Authors of these behavioral studies speculated that a tonic dysfunction of the cerebellar circuit could explain this effect. Specifically, they suggested that CR deficits were caused by a nonspecific tonic suppression of activity in cerebellar nuclei that is known to be associated with IO lesions/inactivations (Benedetti et al, 1983;Zbarska et al, 2007). These findings were challenged by reports that lesioning (McCormick et al, 1985) or inactivating (Medina et al, 2002) the IO produces not an immediate, but gradual, extinction-like suppression of CRs.…”

“…Confirming these predictions experimentally has been difficult because blocking the IO input to the cerebellum produces incapacitating shifts in tonic activity within eyeblink circuits. Inactivating the IO increases the firing rate of cerebellar Purkinje cells, which in turn inhibit cerebellar output nuclei (Montarolo et al, 1982;Benedetti et al, 1983;Batini et al, 1985). This physiological mechanism interferes with testing the learning-related function of the IO.…”

Role of cerebellum in adaptive modification of reflex blinks.

“…The results of inferior olive inactivation, however, argue against this possibility. As reported previously (Benedetti et al 1983;Batini et al 1985), inactivation of the inferior olive increases the level of tonic Purkinje cell simple spike activity (Fig. 5).…”

Functional Relations of Cerebellar Modules of the Cat

“…Despite the low rate, climbing fiber discharge strongly influences Purkinje cell simple spike discharge, and elimination of olivary input causes simple spike discharge to rapidly increase to a high regular rate (Colin et al, 1980;Rawson and Tilokskulchai, 1981;Montarolo et al, 1982;Strata and Montarolo, 1982). Simple spike discharge inhibits cerebellar nuclear cells (Ito et al, 1964), so a high rate of simple spike discharge effectively turns off cells in the cerebellar nuclei (Benedetti et al, 1983), which reduces discharge in cerebellar targets such as the magnocellular red nucleus (RNm) (Bardin et al, 1983;Billard and Daniel, 1985). Although the previous studies relied on anesthetized preparations, it is likely that the circuit operates in a similar fashion in the awake animal, since blocking glutamate receptors in the IO reduces discharge in the cerebellar nuclei of conscious rabbits (Zbarska et al, 2008).…”