Pathological Plasticity in Fragile X Syndrome

[摘要] Deficits in neuronal plasticity are common hallmarks of many neurodevelopmental disorders. In the case of fragile-X syndrome (FXS), disruption in the function of a single gene,FMR1, results in a variety of neurological consequences directly related to problems with the development, maintenance, and capacity of plastic neuronal networks. In this paper, we discuss current research illustrating the mechanisms underlying plasticity deficits in FXS. These processes include synaptic, cell intrinsic, and homeostatic mechanisms both dependent on and independent of abnormal metabotropic glutamate receptor transmission. We place particular emphasis on how identified deficits may play a role in developmental critical periods to produce neuronal networks with permanently decreased capacity to dynamically respond to changes in activity central to learning, memory, and cognition in patients with FXS. Characterizing early developmental deficits in plasticity is fundamental to develop therapies that not only treat symptoms but also minimize the developmental pathology of the disease.

[学科分类] 精神健康和精神病学