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TitleGuiding synaptic plasticity: Novel roles for netrin-1 in synaptic plasticity and memory formation in the adult brain.
Publication TypeJournal Article
Year of Publication2020
AuthorsGlasgow, Stephen D., Edward S. Ruthazer, and Timothy E. Kennedy
JournalJ Physiol
Date Published2020 Feb 03
ISSN1469-7793
Abstract

Adult neural plasticity engages mechanisms that change synapse structure and function, yet many of the underlying events bear a striking similarity to processes that occur during the initial establishment of neural circuits during development. It is a long-standing hypothesis that the molecular mechanisms critical for neural development may also regulate synaptic plasticity related to learning and memory in adults. Netrins were initially described as chemoattractant guidance cues that direct cell and axon migration during embryonic development, yet they continue to be expressed by neurons in the adult brain. Recent findings have identified roles for netrin-1 in synaptogenesis during postnatal maturation, and in synaptic plasticity in the adult mammalian brain, regulating AMPA glutamate receptor trafficking at excitatory synapses. These findings provide an example of a conserved developmental guidance cue that is expressed by neurons in the adult brain and functions as a key regulator of activity-dependent synaptic plasticity. Notably, in humans, genetic polymorphisms in netrin-1 and its receptors have been linked to neurodevelopmental and neurodegenerative disorders. The molecular mechanisms associated with the synaptic function of netrin-1 therefore present new therapeutic targets for neuropathologies associated with memory dysfunction. Here, we summarize recent findings that link netrin-1 signalling to synaptic plasticity, and discuss the implications of these discoveries for the neurobiological basis of memory consolidation.

DOI10.1113/JP278704
Alternate JournalJ Physiol
PubMed ID32017127
Grant ListPJT-366649 / / Canadian Institutes of Health Research to TEK /
FDN-143238 / / ESR /