The goal of the proposed experiments is to understand the mechanisms and rules which govern the modification of synaptic strength in the cerebral cortex throughout life. Three hypotheses about experience-dependent cortical plasticity will be tested; namely, 1) that the enduring effect of limited periods of abnormal somatic sensory experience on cortical synapses is greatest in early postnatal life, 2) that operative N-methyl-D-Aspartate (NMDA) receptors are necessary for experience-dependent synaptic modification in cortex at all ages and 3) that NMDA effects will be greatest in the input zone (layer IV) early in life, greatest in the associational zone (layers II + III) later in life and absent from all layers in extreme old age. Four sets of experiments are proposed to test these postulates: 1) Studies of the effect of sensory deprivation g aU but 1 whisker for 30 days), beginning at postnatal ages ranging from newborn to old age, on the """"""""cortical domain"""""""" of the single """"""""used"""""""" or """"""""experienced"""""""" whisker, 2) Studies to determine whether this type of sensory deprivation effect depends on cortical and/or subcortical plasticity, 3) Studies of the effect of blocking NMDA receptors with D-APV on cortical cell responses to sensory stimulation before and after the end of the above defined critical period and 4) Studies of the effect of chronic administration of NMDA receptor blockers on experiencedependent expansion of the cortical domains. These experiments will describe the extent of use. dependent changes induced in whisker to barrel field system throughout the normal lifespan of a rat. They will show the degree to which cortical neurons in each layer are depend upon NMDA receptors to effect the synaptic modification required for these changes. If changes in the cortical domain of a single whisker do occur, but do not depend upon NMDA receptors, the results may emphasize the need to consider additional or even alterative mechanisms. The detailed nature of the experiments will provide information to guide future studies on the mechanisms underlying, activity-dependent cortical plasticity.
