Molecular mechanisms of memory formation : using activity regulated genes to identify active neural circuits
2014
A fundamental goal in neuroscience is to understand
mechanisms underlying the ability to create memories from sensory
experience. While large structures such as the hippocampus are
known to be critical for certain types of learning, memories are
ultimately thought to be represented in sparsely distributed
neuronal ensembles within these larger structures. Currently, there
are few tools that allow for the identification and manipulation of
these ensembles, which has limited our understanding of the
molecular and cellular processes underlying learning and memory. We
have previously reported that the activity-regulated transcription
factor Npas4 is selectively induced in a sparse population of CA3
following contextual fear conditioning. Global knockout or
selective deletion of Npas4 in CA3 both resulted in impaired
contextual memory, and restoration of Npas4 in CA3 was sufficient
to reverse the deficit in global knockout mice. Taking advantage of
the critical role of Npas4 in contextual memory formation, we
developed a set of novel molecular tools to gain access to cell
populations activated by experience. Using this system, we
identified and manipulated the properties of neurons activated by
behavioral experience in a variety of neural circuits in mice,
rats, and Drosophila. We believe that the tools developed in this
thesis can provide a major advancement in the field, and will allow
researchers to target any neural circuit activated by experience in
a variety of species.
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