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Molecular Changes in the Sensorimotor Cortex During Learning and Recall: Tracking and Manipulating PKMĪ¶
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Francis, Joseph T., Goodman, Jeffrey
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Spring 2017
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2017-05-08
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Doctoral Dissertation
Adobe PDF, 3.21 MB
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Procedural learning and memories, such as those associated with learning how to ride a bike, are believed to be supported by plasticity and reorganization of the sensorimotor cortex. Several studies utilizing a rodent reaching task, as that used in the current work, have shown that procedural learning is accompanied by enhanced synaptic strength and structural modification in the sensorimotor cortex at distinct layers (e.g. layers II/III and V). However, an investigation that causally links these changes with synaptic molecular machinery and behavior has been elusive.
This study aims to fill this gap in our current understanding by tracking changes in task performance as well as layer specific modifications in key molecules, atypical protein kinase M zeta (PKMĪ¶) and postsynaptic density protein 95 (PSD-95), that have been shown necessary for the maintenance of long-term potentiation (LTP) and activity-dependent synapse stabilization respectively. Our results demonstrate that PKMĪ¶ levels decrease in S1 during an early pause in learning on day 3, and both PKMĪ¶ and PSD-95 peak in S1 and M1 once the performance has reached an asymptote on day 9. Continued daily practice after day 9 is accompanied by sustained higher levels of PKMĪ¶, but not PSD-95. Past this correlation, we utilized genetic and pharmacological methods to causally perturb PKMĪ¶ during and after learning. We found results indicating the importance of PKMĪ¶ both during learning and in maintaining the procedural memory engram. Taken together, we propose a model integrating PKMĪ¶-dependent LTP and PSD-95-assisted synaptogenesis as the molecular mechanisms to encode and store motor memory traces in sensorimotor cortex.
Citation
Gao, P. (2017). Molecular Changes in the Sensorimotor Cortex During Learning and Recall: Tracking and Manipulating PKMĪ¶. [Doctoral dissertation, SUNY Downstate Health Sciences University]. SUNY Open Access Repository. https://soar.suny.edu/handle/20.500.12648/15915
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Doctoral Dissertation