Friday, May 9, 2025
5/9/2025
Cell specific & compartment specific changes in translation during long term memory storage - PROJECT ABSTRACT In neurons, changes in transcription and translation are important processes underlying the process of long-term potentiation at the synaptic level. However, the compartment-specific and cell-specific variations in translation and transcription during the process of long-term memory (LTM) storage, along with the molecular mechanisms responsible for these changes, remains unclear. Previous studies have found that mRNAs differentially localize to different areas of the neuron and serve as the basis for localized translation via the actions of molecular motors, such as kinesin and dynein. The importance of these motor proteins in the process of neuronal function is well- documented, such that disruptions in the functions of these motors are associated with a range of neurodegenerative diseases. Despite the importance of these proteins, the processes of translational control that governs molecular motors during LTM remains poorly understood. This proposal seeks to understand this relationship between local translation, molecular motors, and LTM storage, utilizing the model Aplysia californica. Recent investigations into the role of axonal organelle transport during LTM identified enhanced bidirectional transport of mitochondria associated with synapse maintenance. This enhancement in transport is dependent upon translation and transcription. Building upon this finding, I hypothesize that compartment-specific regulations of translation contributed to this change in transport, and play an important role in synapse formation, maintenance, and plasticity. To test this hypothesis, puro-PLA will be used to examine the localized translation of kinesins and dynein subunits, along with dynactin, using the Aplysia SN-L7 coculture system to reconstitute synapses in vitro. In addition, puro-PLA will also be employed to examine the expression of translation regulators such as eIFs, in order to elucidate the potential direct effects these regulators have on translation. Furthermore, puromycin labelling will be used in conjunction to sensitization, tissue clearing and light-sheet microscopy to assess temporal changes in translation at a cell-specific manner within the entire Aplysia CNS. These studies will shed more light on the role of translational regulation in LTM, in both a simple circuitry and the entire nervous system. The results of these studies will further elucidate the role of translational control in axonal transport dysfunction that contribute to neurodegenerative diseases, and identify potential targets for therapeutic development.
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