NMDAR plasticity and metaplasticity in early odor preference learning in rats

Mukherjee, Bandhan (2019) NMDAR plasticity and metaplasticity in early odor preference learning in rats. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Early odor preference learning is a classical conditioning behavioral model which can be used to understand the molecular mechanism of learning and memory, and synaptic plasticity. In this thesis the research is focused on the role of N-methyl D-aspartate receptor (NMADR) plasticity and metaplasticity in early odor preference learning. In Chapter 2, we investigated the differential roles of L-type calcium channel (LTCC) and NMDAR in early odor preference learning. The results suggest that the NMDAR is crucial for creating stimulus-specific memory and LTCC is required for maintenance of the memory. Activation of LTCC without NMDAR can cause loss of input specificity and as a result, generalization of the memory. Chapter 3 depicts that, the effect of altered number of NMDARs in the anterior piriform cortex (aPC) can significantly modifies future learning and synaptic plasticity. Here we show that NMDARs are down regulated at 3hr following the early odor preference learning. Repeated training at 3hr leads to unlearning and this unlearning is mediated by NMDAR itself. Inhibition of the NMDAR prior to retraining at 3hr, blocks unlearning. In continuation of Chapter 3, we have characterized the molecular mechanism underlying the NMDAR mediated unlearning in Chapter 4. Calcineurine and metabotropic glutamate receptor (mGluR) plays a vital role in NMDAR downregulation at 3hr following early odor preference training. In Chapter 5, we have investigated whether NMDAR plasticity and its mediated metaplasiticity observed in the early odor preference learning can be induced by stronger trainings that produce prolonged memories. Previous research has shown that infusing trichostatin A (TSA), a histone deacetylation inhibitor, in the olfactory bulb (OB) extends odor preference memory up to 5 days. Our data suggests that OB TSA infusion prevents NMDAR down-regulation and unlearning. These outcomes argue that it is critical to understand the metaplastic effects of training which have implications for learning optimization.

Item Type: Thesis (Doctoral (PhD))
URI: http://research.library.mun.ca/id/eprint/13748
Item ID: 13748
Additional Information: Includes bibliographical references (pages 213-288).
Keywords: NMDAR, Synaptic Plasticity, Memory, Learning and Unlearning, Synaptic tagging, LTP and LTD, HDAC
Department(s): Medicine, Faculty of
Date: May 2019
Date Type: Submission
Medical Subject Heading: Receptors, N-Methyl-D-Aspartate; Memory--drug effects.

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