Abstract
A contemporary view of the synapse is that it is a highly sophisticated computation device that transmits information between neurons. Synaptic transmission can be achieved with a small number of synapse proteins, yet vertebrate synapses have in excess of one thousand proteins. Traditional models, formulated before the complexity of synapse proteomes was known, posited that other signaling proteins in synapses were there to control synaptic strength and cause learning by strengthening ensembles of neurons.
In the Genes to Cognition (G2C) program which has been completed the largest unbiased mouse genetic study of postsynaptic proteins where synaptic physiology and behavior have been rigorously quantified. The comparative testing allows scientists, for the first time, to identify the postsynaptic proteins with the strongest and most important phenotypes.
A new model of synapse function in behavior was proposed, where the complexity of the proteome specifies the behavioral components of the behavioral repertoire of innate and learned behaviors. The data does not support the LTP model of learning, but instead, suggests an alternative mechanism of learning that does not depend on long-term synaptic strength.
The G2C program also compared, for the first time, a large number of mouse lines carrying mutations in intellectual disability, autism and schizophrenia genes. This analysis shows common signatures of behavioral and electrophysiological “endophenotypes” and “spectrums” and that the disorders cause a shift from genetically determined optimal responses.
About the speaker
Prof Seth Grant graduated from Sydney University followed by postdoctoral research at Cold Spring Harbor Laboratory and Columbia University. He joined The University of Edinburgh in 1994 and moved to the Wellcome Trust Sanger Institute in Cambridge in 2003. In 2011, Prof Grant returned to The University of Edinburgh and is currently the Professor of Molecular Neuroscience.
Prof Grant’s research focuses on the study of genes and proteins that control the synapses between nerve cells. Multiprotein machines comprising many different protein components are responsible for basic innate and learned behaviors and dysfunction in many brain diseases. His recent work shows that these mechanisms are conserved between mice and humans opening new avenues for diagnosis and therapeutic discoveries.
Prof Grant held additional appointments including the John Cade Visiting Professor at The University of Melbourne (2005), Honorary Professorship at Cambridge University (2007) and was elected the Fellow of the Royal Society of Edinburgh (2011).
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