CENTRAL VESTIBULAR NETWORKS IN THE GUINEA-PIG - FUNCTIONAL-CHARACTERIZATION IN THE ISOLATED WHOLE-BRAIN IN-VITRO

The isolated, in vitro whole brain of guinea-pig was used to assess so me of the main physiological and pharmacological properties of the ves tibule-ocular pathways in this species. Extracellular and intracellula r recordings were obtained from the vestibular, abducens and oculomoto r nuclei, as well as from the abducens and oculomotor nerves, while in puts from the vestibular afferents, the visual pathways and the spinal cord were activated. The three main types of medial Vestibular nucleu s neurons (A, B and B+LTS), previously described on slices, were also identified in the isolated brain. They had similar membrane properties in both preparations. Eighty-five per cent of cells recorded in the v estibular nucleus responded with monosynaptic, excitatory postsynaptic potentials (latency 1.05-1.9ms) to stimulation of the ipsilateral ves tibular nerve, and were thus identified as second-order vestibular neu rons. In addition, stimulation of the contralateral vestibular afferen ts revealed in most cases a disynaptic or trisynaptic, commissural inh ibition. Second-order vestibular neurons displayed in the isolated bra in a high degree of variability of their spontaneous activity, as in a lert guinea-pigs. Type PI neurons always exhibited a regular firing, w hile type B and B+LTS cells could have very irregular patterns of spon taneous discharge. Thus, type A and type B neurons might correspond, r espectively, to the tonic and phasic vestibular neurons described in v ivo. The regularity of spontaneous discharge was positively correlated with the amplitude of spike after hyperpolarization, and there was a trend for irregular neurons to be excited from ipsilateral vestibular afferents at shorter latencies than regular units. Synaptic activation could trigger subthreshold plateau potentials and low-threshold spike s in some of the second-order vestibular neurons. As a second step, th e pharmacology of the synaptic transmission between primary vestibular afferents and second-order neurons was assessed using specific antago nists of the glutamatergic receptors. Both the synaptic field potentia ls and excitatory postsynaptic potentials elicited in the medial vesti bular nucleus by single shock stimulation of the ipsilateral vestibula r nerve were largely or, sometimes, totally blocked by 6-cyano-7-nitro quinoxaline-2,3-dione, indicating a dominating role of lpha-amino-3-hy droxy-5-methyl-4-isoxazolepropionic acid receptor-mediated glutamaterg ic transmission. The remaining component of the responses was complete ly or partially suppressed by DL-2-amino-5-phosphonovaleric acid in 35 % of the cases, suggesting a concomitant, moderate involvement of N-me thyl-D-asparate receptors. In addition, a synaptic response resistant to both antagonists; but sensitive to a zero Ca2+/high Mg2+ containing solution, was often observed. Finally,recordings from abducens and oc ulomotor complexes confirmed the existence in the guinea-pig of strong bilateral, disynaptic excitatory and inhibitory inputs from vestibula r afferents to motoneurons of extraocular muscles, which contribute to generation of the vestibule-ocular reflex. The functional integrity o f vestibular-related pathways in the isolated brain was additionally c hecked by stimulation of the spinal cord and optic tract. Stimulation of the spinal cord evoked, in addition to antidromic responses in the vestibular nucleus, short-latency synaptic responses in both the vesti bular nucleus and abducens motoneurons, suggesting possible recruitmen t of spinal afferents. Activation of visual pathways at the level of t he optic chiasm often induced long latency responses in the various st ructures under study. These results demonstrate that the in vitro isol ated brain can be readily used for detailed, functional studies of the neuronal networks underlying gaze and posture control. (C) 1997 IBRO. Published by Elsevier Science Ltd.