Molecular mechanisms of memory formation : using activity regulated genes to identify active neural circuits

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2014

Author dc:creator

• Ramamoorthi, Kartik

Advisor dc:contributor.advisor

• Yingxi Lin.

• Brain and Cognitive Sciences.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/87459

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/87459