Zoom Colloquium: Synapses Lost & Found: Critical periods, Amblyopia & Alzheimer's disease

Synapses Lost & Found: Critical periods, Amblyopia & Alzheimer's disease

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Carla Shatz, Sapp Family Provostial Professor, The Catherine Holman Johnson Director of Stanford Bio-X & Prof., of Biology & Neurobiology


Arvind Chandna

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Abstract - The brain is the most incredible computational machine imaginable, with trillions of synaptic connections. How are connections wired up in development? Wiring happens sequentially first by forming a basic scaffold of connectivity according to genetic blueprints that define strict molecular guidance cues. Then the exact details of each circuit emerge by pruning and sculpting synapses from the immature pattern of connections. The decision-making process that determines which synaptic connections remain and which are pruned is also genetically specified and requires neural function. Even before birth, the brain generates its own internal neural activity to jump-start the sculpting process. After birth sensory systems mature and experience of the external world takes over to influence brain wiring during developmental critical periods. Neural activity and sensory experience regulate expression of sets of genes including several previously thought to act only in the immune system. These activity-regulated genes- including Major Histocompatibility Class I family members and Paired immunoglobulin-like receptor B- are required in neurons for pruning and sculpting synapses during development. Unexpectedly PirB signaling may also contribute to excessive synapse pruning in Alzheimer’s disease and PirB blockade can restore visual function in a mouse model of Amblyopia. Thus, the baby's brain is not a miniature version of the adult, but rather is a dynamically changing structure in which neural activity and experience ultimately select and stabilize essential details of neural circuitry that make each of us different from one another.


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