The Role of PAK Signaling in Synaptic Transmission and Plasticity and Social Memory in Mice
Abstract
Social interactions are essential to our mental health and their deficits are hallmark characteristics in numerous brain disorders. Various subregions within the medial temporal lobe have been implicated in social memory, however, the underlying molecular and cellular mechanisms that tune these particular neural circuits in memory processing remain unclear. PAKs (p21-activated kinases) are a family of serine/threonine protein kinases that are target enzymes of the Rho family small GTPases and central regulators of both the actin cytoskeleton and neuronal morphology. PAK 1 and 3 are involved in the regulation of the structural and functional properties of the synapse, including dendritic spine morphology, synaptic transmission and plasticity, and learning and memory. Recent human and animal studies have revealed that perturbations in PAKs are implicated in several neurological and mental disorders including autism spectrum disorders (ASD) and intellectual disability (ID). These disorders are often characterized by social impairments, yet the cellular correlates within the neural circuits that subserve PAK function in social behaviour remains unknown. In this thesis, I explore five objectives which elucidates the role of PAK signaling in the entorhinal cortical perforant projections to the dentate gyrus (EC-DG) in social memory retrieval. First, I characterize the biochemical and cellular properties of a novel transgenic mouse model where the expression of a dominant negative…
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Evidence Hub reads this as a thesis, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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