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Finding the way to memory
Date:2/4/2013

tor DCC is a critical component of synapses between neurons in the adult brain, and is required for synapses to function properly. To demonstrate this, we selectively removed DCC from a specific subset of neurons in the adult mouse brain. This results in progressive degeneration of synapses, leading to defects in synaptic plasticity and memory. The synapses continue to function in that they still communicate but, the synapses cannot adjust or change in response to new experiences. Therefore, you can't learn anymore."

Furthermore, DCC deletion from mature neurons results in changes in the shape of specialized protrusions called dendritic spines, and alters the NMDA receptor, a critical trigger for mechanisms that make changes in synaptic strength. Therefore the study reveals that DCC is required to maintain proper synapse morphology or shape, and to regulate the ability of the NMDA receptor to switch on, which ensures activity-dependent synaptic plasticity.

Mutant mice that entirely lack DCC in all cells do not survive past birth and exhibit major defects in brain development. In order to investigate the function of netrin in the adult brain, researchers from the Netherlands Cancer Institute, collaborators on this study, engineered a new strain of floxed mice, in which the DCC gene can be selectively deleted from a specific sub-set of cells. Floxing involves putting short sequences of DNA on either side of a gene sequence. An enzyme that is activated later in life then recombines the DNA and cuts out the intervening sequence deleting the gene only from specific cells. The Kennedy lab activated this enzyme only in the mature mouse brain, and limited activation to only a subset of neurons, consequently deleting the DCC gene from only from these neurons. These mice live to adulthood (DCC is made normally in all other cells in the mouse) as the enzyme only turns on and deletes DCC in specific cells in the adult brain. Although the mice otherwise appe
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Contact: Anita Kar
anita.kar@mcgill.ca
514-398-3376
McGill University
Source:Eurekalert

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