Modulation of cellular and rhythmic network activity in spinal s'l!!lPathetic rggions by 5-hydroxIDPtamine and electrical synapses

• Main Author: Pierce, Michelle Louise
• Published: University of Leeds 2008
• Subjects: 612.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491638

Rhythmic activity is a ubiquitous feature of sympathetic nerve discharge and has been postulated to be involved in sympathetic reflex control, coordinating the responses of anatomically separated sympathetic nerves and enhancing the responsiveness of the viscera to sympathetic activation. Several studies indicate that some sympathetic rhythms are generated in the spinal cord. This activity has primarily been studied in vivo or in isolated nervous system preparations. Whilst these techniques are useful for elucidating the functional consequences of such activity, a detailed description of the underlying rhythmogenic networks has not been . forthcoming. Therefore, a neonatal (10-12 day old) rat transverse spinal cord slice preparation was developed to study rhythmic network activity in the sympathetic intermediolateral cell column (IML). This thesis presents data which validate the slice preparation as a useful tool for investigating oscillations in the IML. Extracellular recordings were made from the IML, and spontaneous oscillations at 7.5-22 Hz were observed in 29% of slices. The power of these oscillations was enhanced by 5~HT and agonists of5-HT2A and 5-HT2C receptors without affecting the frequency. Furthermore, the same drugs induced similar oscillations in previously nonoscillating slices. Occasionally, action potentials could be observed occurring in phase with the oscillation. The oscillations were abolished by TTX and gap junction blockers, and were partially sensitive to blockade ofGABAA receptors. To enhance understanding of the cellular mechanisms underlying IML oscillations and their modulation by 5-HT, patch clamp recordings ofIML neurones were made.SPNs in the IML were depolarised bY5-HT28 and 5-HT2C (but not 5-HT2A) receptor activation, whereas IML intemeurones were hyperpolarised by 5-HT and the 5-HT1AI5A17 agonist 8-0H-DPAT and depolarised by agonists of5-HT2C receptors. 5-HT also modulated synaptic inputs to both types of neurone. More than 50% of SPNs displayed ongoing gap junction-mediated potentials ('spikelets') which were increased in frequency and amplitude by 5-HT2 receptor agonists. The effects of gap junctions on the firing behaviour of SPNs were significant and might explain the effects of gap junction blockade on IML oscillations. It was concluded that rhythmic IML activity depends on transmission of action potentials between SPNs via gap junctions, and is modulated by GABAergic .inputs. IML oscillations may represent a novel sympathetic rhythm, or may be analogous to the 10Hz rhythm observed in intact animals, or may represent a spinal substrate for. synchronisation ofSPN activity in response to supraspinal activity.