Author

Ying LiFollow

Date

2019

Department or Program

Biological Chemistry

Primary Wellesley Thesis Advisor

Elizabeth S.C. Oakes

Additional Advisor(s)

Peter S.B. Finnie

Additional Advisor

Melissa A. Beers

Additional Advisor

Barbara S. Beltz

Abstract

Visual memory is a complex neurophysiological process wherein visual inputs are transduced and encoded within networks of synapsing neurons. At the core of this system are neurotransmitters and postsynaptic receptors, including N-methyl-D-aspartate (NMDA) receptors, which are necessary for visual memory in mice. Interestingly, with age there is a predictable, visual experience-dependent replacement of NMDA receptor subunit NR2B by a second subunit, NR2A. Both subunits have been implicated in regulating potentiation in the murine primary visual cortex (V1) in response to visual stimulus in other forms of plasticity, such as ocular dominance. The goal of this project was to characterize NMDA receptor subunit composition changes during the acquisition of visual memory and to elucidate the role of NR2B in stimulus-specific response potentiation (SRP) and orientation-selective habituation (OSH), which are electrophysiological and behavioral manifestations of visual memory, respectively. To this end, we measured NR2A and NR2B protein levels via Western blot in mice before and after six days of exposure to a sinusoidal grating stimulus. We also evaluated SRP and OSH in mice in which NR2B was selectively deleted by Cre recombinase or pharmacologically inhibited by either CP-101,606 or Ro 25-6981. Our preliminary findings indicate that NMDA subunit exchange in V1 is minimal during the acquisition of visual memory. We observed that the loss of NR2B does not appear to impact SRP or OSH, suggesting that the subunit does not play a role in visual memory, although these biological effects are obscured by high variance and small sample sizes. Finally, we report that DMSO—used as a pharmacological vehicle—may inhibit the acquisition, but not the consolidation of visual memory. Our work here on characterising NMDA receptor subunit NR2B explores one aspect of the biochemical basis of plasticity in V1 and suggests alternative mechanisms that underlie visual memory that warrant further investigation in order to fully understand learning and memory.

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