Development of Synaptic Plasticity in Visual Cortex

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DESCRIPTION (provided by applicant): Synapses in the cerebral cortex undergo dynamic alterations in their efficiency throughout life. In particular, the neurons of the primary visual cortex can use such synaptic plasticity to perform parallel computations on aspects of visual processing. Such activity-dependent changes in synaptic signaling have been suggested to contribute to visual perception, cognitive performance, skill-learning, developmental re-organization and refinement of functional visual cortical synaptic networks and adaptive responses after injury. These forms of plasticity undergo dramatic changes in their robustness, modulation by intrinsic and extrinsic factors and underlying molecular processes during postnatal development. However, the developmental regulation of these forms of functional synaptic plasticity has received less attention. We utilize an experimental model of neocortical synaptic plasticity that is based on serial correlations of synaptic input with activation of the postsynaptic neuron to characterize the initial intracellular calcium triggering events that generally lead to long term synaptic potentiation (LTP). Interestingly, in the neonatal visual cortex, when the identical serial correlations are applied to neurons of the same class (layer 2/3 pyramidal neurons), the synaptic plasticity that occurs (LTP or long term synaptic depression - LTD) varies between individual cells. A variety of sources of calcium including NMDA receptors, metabotropic glutamate receptors, inositide trisphosphate receptors (IPaRs), ryanodine receptors and voltage activated calcium channels all contribute to this process in these neonatal visual cortical neurons. The outcome of LTP or LTD in the neonatal cortex is predicted by the intracellular dendritic calcium transient's kinetic profile that occurs during the individual correlations and the kinetics of the cumulative calcium wave that spreads to the cell body. This protocol offers a unique window into the initial underlying calcium signaling processes that determines polarity of synaptic changes in the visual cortex during postnatal development and provides a new provocative view of how kinetics and amplitude of the very first calcium signals may be critical in the subsequent downstream activation of plasticity. This project also provides the first comprehensive analysis of unitary synaptic connections between individual layer 4 and layer 2/3 neurons with dual patch recording from synaptically coupled pairs with analysis of plasticity and calcium signaling at those connections. We determine the effects of intrinsic cellular differences, maturation, previous experience (metaplasticity) and calcium sources on the signaling and plasticity processes.