This application focuses on two aspects of plasticity in the adult nervous system. 1) The long-term impact of synaptic use and disuse on the chemistry of a neuron. The adaptability of the nervous system in response to changes in the environment is essential for the survival of an animal. With the exception of sensory neurons which receive information about the environment directly, most nerve cells receive such information only indirectly through changes in their synaptic and humoral inputs. It is the ability of neurons to change in response to changes in these inputs which ultimately produces many of the behavioral and physiological adaptations necessary for survival. In this application we propose to study the effects of changes in synaptic activity on two classes of proteins with key roles in synaptic physiology: the enzymes which regulate the rates of synthesis of specific neurotransmitters and the receptors which mediate the postsynaptic effects of these transmitters. In addition we propose to examine the possible modulatory effects of glucocorticoids on these trans-synaptic processes. 2) Mechanisms which allow certain neural systems to recover after partial damage. We have studied this problem in the pineal gland using the known dependence of the activity of the enzyme serotonin N-acetyltransferase (NAT) on sympathetic nerve activity to measure changes in synaptic stimulation. We have observed that following unilateral denervation of the pineal gland, a midline structure innervated by both superior cervical ganglia, NAT activity is initially greatly depressed; however within 32 h normal levels of enzyme activity are restored. We propose to study the mechanism of this rapid recovery process and in particular to test our hypothesis that the disappearance of norepinephrine uptake sites in the degenerating neurons increases the effectiveness of the norepinephrine released by the surviving neurons in stimulating their target cells. These studies on neural plasticity are relevant to our understanding of the long-term biochemical changes which underlie normal psychological processes such as learning and memory and to our understanding of the biochemical bases of specific mental illness and their treatments.
