Research in the Gall laboratory is focused on mechanisms of neuronal plasticity in the adult brain and, in particular, on the role of regulated changes in neurotrophic factor gene expression and adhesive interactions in plasticity and neuronal protection. Studies in this laboratory and elsewhere have demonstrated that within the adult brain neuronal and glial gene expression is quite dynamic and is regulated by such diverse influences as levels of neuronal activity, hormonal interactions, and adhesive interactions with matrix proteins. We were the first to demonstrate that the expression of different classes of neurotrophic factor genes is regulated by physiological activity and by neuronal degeneration. These results indicate that different trophic "programs" are activated by different functional demands placed on the nervous system and that these programs coordinate complex cellular responses that are likely to play critical roles in processes as activity-dependent neuronal plasticity (i.e., learning) and reactive synaptogenesis following brain damage. Recent studies have extended our analyses to the consideration of the role of adhesion proteins in regulating neurotrophic factor expression and synaptic plasticity. In particular, we have found that integrins, that serve as receptors for extracellular matrix proteins, are concentrated at synapses, regulate tyrosine kinase signaling cascades within the synapse and, ultimately, regulate the properties of codistributed neurotransmitter receptors and ion channels. Moreover, through effects on calcium influx the integrins regulate neuronal gene expression of neurotrophins. Current studies are resolving integrin-mediated signaling activities and the nature of functional interactions between these adhesion proteins and the transmission and trophic functions of the synapse.