Our long-term goal is to understand the role of cellular and molecular processes in mediating memory formation. Toward that end, we are employing fear conditioning which is an especially useful behavioural paradigm for studying the molecular basis of long-term memory. The prevailing hypothesis is that learning and memory depend on signalling molecules that affect synaptic efficacy.
The specific aim of this proposal is to provide a comprehensive assessment of the role of myosin light chain kinase (MLCK) in various cellular processes underlying fear memory formation in the lateral nucleus of the amygdala (LA), a brain area mediating fear conditioning. MLCK has been shown to be intimately involved in synaptic transmission and structural plasticity, events believed to underlie long-term memory formation. Although MLCK is involved in such central neuronal functions, its role in memory formation is not well understood.
In this proposal we will address several questions, as follows:
- Is MLCK involved in fear memory formation and extinction?
- How does MLCK regulate synaptic plasticity in LA in brain circuits involved in fear conditioning?
- What signalling pathways regulate MLCK activity in LA during fear conditioning?
- Does MLCK regulate dendritic spine structural changes in LA of fear-conditioned animals?
Toward answering such questions, we intend to use a combination of behavioural, electrophysiological, molecular and anatomical techniques. Our preliminary results show that MLCK activity in LA regulates fear memory acquisition and synaptic plasticity in the auditory thalamus-LA pathway involved in fear conditioning.
Since MLCK is essential for central neuronal processes, we expect that our research program will provide further insights into the cellular and molecular mechanisms of learning and memory. The proposed studies could also contribute to the understanding of fear-related disorders and to the development of therapeutic drugs.
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