Cellular and Systems Mechanisms of L&M
Siena, Italy
May 29, 2017


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May 29, 2017
Alcino J. Silva

Integrative Center for Learning and MemoryDepartments of Neurobiology, Psychiatry, and Psychology, UCLA

Molecular, cellular, and circuit mechanisms that link memories across time
Studies of the molecular, cellular and circuit mechanisms of learning and memory have focused almost exclusively on how single memories are acquired, stored and edited. By comparison, very little is known about the mechanisms that integrate and link memories across time. Recent studies from our laboratory showed that learning triggers CREB activation and a subsequent temporary increase in neuronal excitability in these circuits that for a time biases the allocation of a subsequent memory to the neuronal ensemble encoding the first memory. Recently, we have used state of the art in vivo imaging methods and other approaches to show that in the hippocampus, this mechanism can link memories across time, such that the recall of one memory increases the likelihood of recalling the other memory. Interestingly, we also showed that this mechanism is disrupted in older mice, and that artificially manipulating neuronal excitability with a chemo-genetically strategy can rescue these deficits, a result that implicates this mechanism in memory linking and in age-related cognitive decline.

Memory: from molecular and cellular mechanisms to treatments.
Mouse model studies in our laboratory have uncovered mechanisms and treatments for learning and memory disorders, including Neurofibromatosis type I, Tuberous Sclerosis, Noonan Syndrome and DISC1. We have also identified cognitive enhancers that could be used when etiology is uncertain. We will review these and other related findings that illustrate how insights into the biology of molecular and cellular processes in the brain are changing the way we understand and envision treating learning and memory disorders. Adult treatments could one day help the millions of people affected with neurodevelopmental and other learning & memory disorders.