The Department of Biomedicine

BBB Seminar: Sjoukje D. Kuipers

From neurogenesis to synaptic plasticity: ARChing the gap

Sjoukje D. Kuipers,
Department of Biomedicine and K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen

Psychiatric and neurologic disorders take an enormous toll on society. Elucidating their disease mechanisms in hopes of better defining treatment strategies and preventive therapies is a major driving force for both basic and clinical research. Failing adult neurogenesis is increasingly considered a factor in the pathogenesis and course of such disorders. The hippocampus is a major site of adult neurogenesis, a process in which hippocampal stem cells and their offspring give rise to mature, and functionally integrated granule cell neurons. Given the very nature of the hippocampus and its role in cognition, most notably learning and memory, disturbed neurogenesis in this structure may contribute to at least the hippocampal aspects common to these diseases. Despite the excitement of such putative links between neurogenesis and neuropsychiatric pathologies, however, there remain major gaps in our understanding. Research on the mechanisms that control progression through maturation and integration as well as electrophysiological development of cells in the early stages indicates the importance of both intrinsic properties of the cell as well as the hippocampal microenvironment, but research on the molecular basis of adult hippocampal neurogenesis, maturation and survival are needed to help explain its exact role in neuropsychiatric disorders particularly with regard to their hippocampal aspects. Recent studies from our laboratory designed to explore a potential marker for functional newborn cell integration have yielded surprising findings to suggest a new and unexpected early role for activity-regulated cytoskeletal associated protein or Arc/Arg3.1, in adult-born dentate granule cell survival and maturation, distinct from its functions in long-term potentiation (LTP), long-term depression (LTD), and homeostatic synaptic plasticity. The findings presented here may shed some light into the stringent selection process that governs the maturation and functional integration of adult-born dentate granule cells in physiological and possibly pathological conditions such as major depression or Alzheimer’s disease where putative dysregulation of the Arc protein is also implicated in underlying synaptic plasticity impairments.

Chair: Clive R. Bramham, Department of Biomedicine