Role of the flocculus in mediating vestibular nucleus neuron plasticity during vestibular compensation in the rat

A R Johnston, J R Seckl, M B Dutia

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We investigated the role of the cerebellar flocculus in mediating the adaptive changes that occur in the intrinsic properties of brainstem medial vestibular nucleus (MVN) neurons during vestibular compensation. Ipsi-lesional, but not contra-lesional, flocculectomy prevented the compensatory increase in intrinsic excitability (CIE) that normally occurs in the de-afferented MVN neurons within 4 h after unilateral labyrinthectomy (UL). Flocculectomy did not, however, prevent the down-regulation of efficacy of GABA receptors that also occurs in these neurons after UL, indicating that these responses of the MVN neurons to deafferentation are discrete, parallel processes. CIE was also abolished by intra-floccular microinjection of the metabotropic glutamate receptor (mGluR) antagonist AIDA, and the protein kinase C inhibitor bisindolymaleimide I (BIS-I). The serene-threonine kinase inhibitor H-7 had no effect when microinjected at the time of deafferentation, but abolished CIE if microinjected 2 h later. These cellular effects are in line with the recently reported retardatory effects of BIS-I and H-7 on behavioural recovery after UL. They demonstrate that the increase in intrinsic excitability in MVN neurons during vestibular compensation is cerebellum dependent, and requires mGluR activation and protein phosphorylation in cerebellar cortex. Furthermore, microinjection of the glucocorticoid receptor (GR) antagonist RU38486 into the ipsi-lesional flocculus also abolished CIE in MVN neurons. Thus an important site for glucocorticoids in facilitating vestibular compensation is within the cerebellar cortex. These observations ascribe functional significance to the high levels of GR and 11-beta-HSD Type I expression in cerebellum.

Original languageEnglish
Pages (from-to)903-911
Number of pages9
JournalJournal of Physiology
Issue number3
Publication statusPublished - 15 Dec 2002


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