Pramod Dash, PhD

Biography

Formation and Impairment of Memory

Research in my laboratory aims to delineate the biochemical and molecular changes that are critical for memory formation.  Experimental and clinical studies performed by a number of investigators have established that short-term memory (memories lasting for minutes-to-hours) depends on post-translation modification (e.g. phosphorylation) of proteins within neurons, whereas long-term memory (memories lasting for days-to-weeks, and in some cases, a lifetime) requires de novo protein synthesis and morphological changes.  Using a multi-disciplinary approach, we disrupt or augment specific biochemical events within the hippocampus and other brain regions to determine the aspect of memory altered as a result of these manipulations.

Working memory (memories that last for seconds) is critical for holding information “online” in order to guide goal-directed behavior.  Working memory is required for decision making and coherent thought processes, and is often impaired as a result of normal aging, and diseases such as Parkinson’s, Alzheimer’s, schizophrenia and traumatic brain injury (TBI).   It is not well understood if the biochemical and molecular mechanisms that are required for short-term memory formation also play a role in working memory.  Research in our laboratory has demonstrated that while short-term memory requires protein kinase-mediated phosphorylation of cellular substrate proteins (e.g. channels, transcription factors), these activities in prefrontal cortex neurons impair working memory.  Interestingly, prefrontal protein phosphatase activity, vis a vis calcineurin, appears to be critical for this temporary form of memory.  One of our ongoing projects is to identify the substrate proteins that are dephosphorylated during working memory with the goal of developing agents that can be used to treat working memory impairments.

TBI can profoundly alter memory formation that can markedly compromise day-to-day activities and quality of life.  These impairments can occur in the absence of overt brain damage such as is seen in persons sustaining a concussion.  Interestingly, our research has shown that the cellular and molecular mechanisms of memory impairments are not static, but evolve over time.  This suggests that a pharmacological treatment that is effective in the acute stage of injury, is unlikely to work in the chronic stage of injury.  The long-term goal of our research is to identify potential targets for therapeutic interventions to alleviate the memory disorders triggered by TBI.