Date

2018

Department or Program

Neuroscience

Primary Wellesley Thesis Advisor

Sara Wasserman

Additional Advisor(s)

Matthew A. Wilson

Additional Advisor

Michael C. Wiest

Abstract

Place cells are pyramidal neurons in CA1, 2, and 3 of the hippocampus that fire preferentially when an animal is located in a certain position in an environment. The location to which a place cell maximally responds (its place field) is randomly assigned within an environment. Place fields can be re-assigned depending on changes to local sensory cues within an environment, a phenomenon called “remapping”. Research has established that place field formation is affected by input from the local network in the hippocampus. Interneurons in CA1 are known to provide inhibitory input into place cells, but no causal link between local inhibition and place map remapping has been demonstrated. Here, we sought to understand if directly driving local inhibitory networks in CA1 could induce place field remapping. To do this, we used optogenetic stimulation to excite interneurons while concurrently monitoring neural activity using a red-shifted calcium indicator (jRCaMP1b) in freely moving mice. Microendoscopic calcium imaging was performed over multiple days as the mouse explored an open field. After the animal had explored the field for several days, interneurons in CA1 were optogenetically activated at certain positions in the environment. Unfortunately, the low signal to noise level of the red-shifted calcium indicator prevented analysis of this dataset. In lieu of this, we analyzed data from a green fluorescent calcium indicator (GCaMP6f) that we used to initially test out our experimental technique. The results of this analysis revealed aberrant neural activity during calcium imaging sessions, suggesting that the calcium imaging technique may have unexpected, pathological effects on neural activity in the hippocampus. The work described here sets the groundwork for further concurrent use of optogenetics with calcium imaging in investigations into the cellular mechanisms behind place field formation.

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