Award details

Role of gap junctions and electrical synapses during vertebrate development with special reference to the spinal motor system

Reference	BB/C000846/1
Principal Investigator / Supervisor	Professor Keith Sillar
Co-Investigators / Co-Supervisors	Dr William Heitler
Institution	University of St Andrews
Department	Biology
Funding type	Research
Value (£)	217,187
Status	Completed
Type	Research Grant
Start date	10/01/2005
End date	09/05/2008
Duration	40 months

Abstract

Gap junctions are intercellular channels formed by connexin proteins that allow direct, low resistance, electrical and biochemical communication between neighbouring cells. In adults, changes in such coupling are known to contribute to certain neurological states, including epilepsy and ischemia. An important function of gap junctions and electrical coupling within the developing CNS is to synchronise the activity of groups of neurons, a role that has been demonstrated in numerous brain regions. Gap junction-coupling decreases during development to allow individual neurons to operate more independently. However, the mechanisms that allow coupling to be regulated by neuromodulators such as serotonin, and how this modulation might be responsible for the development of networks of neurons represent major gaps in our understanding of the nervous system. Our aims are to determine the intrinsic role of gap junctions and electrical coupling in shaping locomotor patterns during vertebrate ontogeny, focusing on the spinal motor system, and to explore the endogenous neuromodulation of these connections. We will approach these aims using a simple model system, the Xenopus embryo, where electrical coupling and gap junctions contribute to the initiation and generation of rhythmic locomotor activity and membrane potential oscillations. We will test the hypothesis that a decrease in gap junctional conductance contributes to the maturation of the CPG for swimming via a de-synchronisation of motorneurone activity. In particular, the ability of 5-HT to modulate junctional conductance will be tested. In parallel, the role of gap junctions in the conduction of a cardiac-like impulse through the epithelium will be examined and the role of neuromodulatos endogenous to the skin (5-HT, nitric oxide, substance P) in regulating skin cell excitability, e.g. in response to damaging stimuli will be determined. To validate the data, and to provide a means of generating new hypotheses, computer models of these electronic networks will be developed in parallel.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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