In vitro studies of medial vestibular nucleus neurones

• Main Author: Sulaiman, Mohd Roslan
• Published: University of Edinburgh 1999
• Subjects: 612.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662594

This thesis describes electrophysiological studies of rat medial vestibular nucleus (MVN) neurones <I>in vitro</I>, in which the actions of opioids and the opioid-receptor like agonist nociceptin, were characterised. In addition the changes in the intrinsic membrane properties of the MVN neurones during the behavioural recovery after unilateral vestibular deafferentation ("vestibular compensation", a model of lesion-induced plasticity in the adult brain), were investigated. In the first part of this thesis, using agonists and antagonists selective for opioid receptor subtypes, the presence of δ- but not μ- or κ-opioid receptors was demonstrated on spontaneously active MVN neurones <I>in vitro</I>. The majority (80%) of spontaneously active MVN neurones were inhibited in dose-dependent manner by the δ-opioid receptor agonist [D-Ala<SUP>2</SUP>, D-Leu<SUP>5</SUP>]-enkephalin (DADLE) but not the μ-opioid receptor agonists, morphine and κ-opioid receptor agonist, U50 488H. The inhibitory actions of DADLE persisted after blockade of synaptic transmission and were effectively antagonised by naloxone and naltrindole. In whole cell current clamp recordings, the DADDLE-induced inhibition was accompanied by a membrane hyperpolarisation and a decreased cell input resistance. In voltage clamp experiments, DADLE induced an outward current that was reduced but not abolished by tetraethylammonium bromide (TEA). The degree of DADLE-induced inhibition were dependent on post-natal age, such that the responses to DADLE were smaller in younger animals and increased significantly with age. In the second part, the effect of nociceptin/orphanin FQ (N/OFQ), the recently discovered endogenous ligand for the opioid receptor like-1 (ORL<SUB>1</SUB>) receptor was examined on spontaneously active MVN neurones. In the final part of this thesis, the changes in intrinsic membrane properties and the action potential firing characteristics of identified Type A and Type B MVN neurones in the rostral region of the MVN were studied during the early stage of vestibular compensation.