The therapeutic promise of reversibility drives much of the research into mechanisms of autism spectrum disorders (ASD). This workshop will summarize recent advances in the ability to control critical periods of brain development and the successful recovery of function by various treatments in animal models of ASD. The concepts of excitatory-inhibitory balance, regulation of protein synthesis, and microglial activation will be highlighted. Plasticity at the right time and place is central to brain development and function throughout life. Sensory systems have revealed that cortical critical periods are driven by the dynamics of excitatory-inhibitory (E-I) circuit balance, which is often impaired in ASD. Circuit rewiring is a physical process, involving the pruning and construction of new connections, requiring well-orchestrated protein synthesis. Ultimately, molecular ‘brakes’ are expressed which actively clamp down on plasticity beyond early development. Resetting E-I balance or lifting these brakes in adulthood allows the successful reactivation of critical period plasticity. Correcting E-I imbalance with pharmacological inhibitors of neurotransmission is one way to rescue Rett syndrome in mice. Signaling cascades, including the mTOR pathway, couple neurotransmitter and neurotrophin receptors to the translation regulatory machinery during the formation of long-lasting synaptic plasticity. Mutations in the negative regulators of this machinery, such as Fragile X or eIF4E, are associated with ASD. Curbing the excessive protein synthesis may reverse these disorders. A further novel target may also include microglia, which normally contribute to synaptic pruning. Wild-type bone marrow transplants arrest disease pathology and increases life expectancy in Rett syndrome models, indicating an important role for immune-glial interactions as well. This session will consider the various rescue paradigms from the biological context of normal critical periods of brain development, which may be mis-timed or mis-regulated in ASD.
Saturday, 4 May 2013: 10:30-12:30
Auditorium (Kursaal Centre)
T. K. Hensch
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