The role of central and peripheral synaptic activity in the developmental death of motoneurons.

Funded Activity Summary

Information processing in the nervous system relies on the effective communication between neurons and their target cells which make up our neuronal circuitry. At the centre of all this is the synapse, the specialized contact between a neuron and its target cell, be it another neuron in the brain or a target organ such as skeletal muscle. Our primary goal is to determine how the formation of synaptic connections during development regulates neuronal survival. In this proposal we have focussed on the neuromotor system as it is a well characterised part of the nervous system. During development, 50% of motoneurons die at a time when they are making contact with skeletal muscle, and when contacts onto motoneurons by other neurons are being established. We believe that the formation of effective synaptic contacts onto motoneurons, as well as connections by motoneurons onto muscle are the key regulators of motoneuron survival. We are in a position to be able to address what regulates motoneuron death; as we have a number of mice which lack key molecules needed for the formation of specialisations that allow neuronal contacts to be made between motor neurons and their muscle, and with other neurons within the spinal cord. By examining the function of motoneurons, counting them and screening for molecular changes in these mice, we will be able to dissect out the mechanism of how a motoneurons' fate is determined during developmental motoneuron death. This research could help in developing strategies aimed at improving neuronal connections to improve neuronal viability. Our research will have important implications for our understanding about the basis of adult neuro-degenerative diseases, such as motor neuron disease and Alzheimer's, which are in part characterised by a molecular breakdown in neuronal connections that ultimately result in neuronal death.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $463,145.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cellular Nervous System

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Developmental motoneuron death | Glycinergic , GABAergic transmission | Motor neuron disease | Nervous system development | Nervous system disorders | Neural Development | Neuromuscular diseases | Neuromuscular junction | Neuronal cell death | Neuronal death

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