Floccular modulation of vestibuloocular pathways and cerebellum-related plasticity: An in vitro whole brain study

The isolated whole brain (IWB) preparation of the guinea pig was used to in vestigate the floccular modulation of vestibular-evoked responses in abduce ns and oculomotor nerves and abducens nucleus; for identification of floccu lus target neurons (FTNs) in the vestibular nuclei and intracellular study of some of their physiological properties; to search for possible flocculus -dependent plasticity at the FTN level by pairing of vestibular nerve and f loccular stimulations; and to study the possibility of induction of longter m depression (LTD) in Purkinje cells by paired stimulation of the inferior olive and vestibular nerve. Stimulation of the flocculus had only effects o n responses evoked from the ipsilateral (with respect to the stimulated flo cculus) vestibular nerve. Floccular stimulation significantly inhibited the vestibular-evoked discharges in oculomotor nerves on both sides and the in hibitory field potential in the ipsilateral abducens nucleus while the exci tatory responses in the contralateral abducens nerve and nucleus were free from such inhibition. Eleven second-order vestibular neurons were found to receive a short-latency monosynaptic inhibitory input from the flocculus an d were thus characterized as FTNs. Monosynaptic inhibitory postsynaptic pot entials from the flocculus were bicuculline sensitive, suggesting a GABA(A) -ergic transmission from Purkinje cells to FTNs. Two of recorded FTNs could be identified as vestibulospinal neurons by their antidromic activation fr om the cervical segments of the spinal cord. Several pairing paradigms were investigated in which stimulation of the flocculus could precede, coincide with, or follow the vestibular nerve stimulation. None of them led to long -term modification of responses in the abducens nucleus or oculomotor nerve evoked by activation of vestibular afferents. On the other hand, pairing o f the inferior olive and vestibular nerve stimulation resulted in approxima tely a 30% reduction of excitatory postsynaptic potentials evoked in Purkin je cells by the vestibular nerve stimulation. This reduction was pairing-sp ecific and lasted throughout the entire recording time of the neurons. Thus in the IWB preparation, we were able to induce a LTD in Purkinje cells, bu t we failed to detect traces of flocculus-dependent plasticity at the level of FTNs in vestibular nuclei. Although these data cannot rule out the poss ibility of synaptic modifications in FTNs and/or at other brain stem sites under different experimental conditions, they are in favor of the hypothesi s that the LTD in the flocculus could be the essential mechanism of cellula r plasticity in the vestibuloocular pathways.