Developmental visual cortex plasticity, the susceptibility of the brain to be modified by the environmental changes during postnatal development, is deemed representative of many life-sustaining neural functions such as learning, memory, sensory plasticity and aging. Furthermore, this process underlies the formation of normal neural connections, which is assailed by conditions that prevent normal sensory stimulation, including strabismus and childhood cataract. A research plan is proposed to study the ultastructural basis of developmental plasticity, combining tract-tracing, immunocytochemistry and electron microscopy techniques for qualitative and quantitative ultrastructural analysis. The long term objective of this research is to understand the roles of the glutamate and the cholinergic receptors in activity dependent synaptic modifications that underlie the critical period of visual plasticity. A newly developed technique will be used to dually identify developing thalamocortical(TC) axons and the chemically specified target sites to determine afferent-target relationships between thalamic terminals and the neurotransmitter receptors. Specifically, 1) the morphological properties of sites contacted by thalamocortical axons, and the GABA content of the targets, 2) the connection pattern of TC axons on NMDA, metabotropic and AMPA type glutamate receptors, and 3) the relationships between TC axons and the muscarinic receptors, will be examined in visual cortex layer IV and the subplate, before, during and after the critical period of visual plasticity. The specific goals of the proposed research address the identification of transient cellular mechanisms that lead to refinement and segregation of thalamic axons into ocular dominance columns, and to termination of early cortical plasticity by synaptic consolidation. The knowledge on how the neural proteins that are implicated in plasticity are structurally utilized by neural circuitry may provide insights in understanding the mechanisms of normal brain function as well as the conditions result from the sensory deprivation.
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