Objective
In this project the efforts of six different laboratories using both similar and complementary methodological approaches will be used to study the mechanisms of acetylcholinergic, serotonergic, dopaminergic, enkephalinergic and glutamatergic monosynaptic transmission both in situ and in culture. Both local classical and distant hormonal-like transmissions will be investigated.
The research will analyse the mechanisms of the modulation of these synapses by their own endogenously released signal molecules and exogenous signal molecules. These monosynaptic connections are well defined in the laboratories of the participating groups. Comparisons will be made of the background mechanisms underlying synaptic modulation and regulation at different types of synapses, using gastropod molluscs (Lymnaea and Aplysia - one of the best understood neurobiological paradigms), amphibia and mammals. The sources and actions of nitric oxide and another putative gaseous neuromodulator, carbon monoxide (CO) will also be studied.
The main objectives of this project are: to study the properties of the presynaptic receptors and of the molecular mechanisms by which they achieve changes in the efficacy of the synapse using an identified cholinergic synapse in Aplysia; to study desensitization, both as short-term and long-term forms of plasticity at vertebrate neuromuscular junctions and to analyse the molecular mechanism of desensitisation, nonquantal secretion of scetylcholine and its interactions with quantal release; to model monosynaptic transmissions in culture between putative central glutamatergic neurones of mammals to study the possible ontogenetic peculiarities of LTP and its transmitter modulation in central neurones in the course of their differentiation in culture; to model hormonal-like transmissions in vivo and in culture using identified tonically active monoaminergic and opioid systems in gastropods; to study metabolic regulation of tonic activity of transmitter specific systems in vivo and in culture; to reconstruct, in culture, an identified neuronal circuit and to study its modulation by mono-aminergic and opioid system; and to study the actions of NO and to identify putative sources of endogenous CO in the nervous system of Lymnaea for further studies of the physiology of this unique intercellular modulator.
Topic(s)
Call for proposal
Data not availableFunding Scheme
Data not availableCoordinator
LS2 9NQ Leeds
United Kingdom