This proposal aims to identify and characterize small molecules that modulate activity and gene expression of molecular motor kinesin, a critical regulator of axonal transport in neurons. Kinesins are molecular machines that require ATPase for its activity. My previous finding suggests that modulating kinesin function enhances synaptic activity. Most importantly kinesin activity is physiologically upregulated during memory storage. I have identified kinesins that are most abundant in hippocampus and cortex of mice. Two different luminescence readouts will be used to assess the action on small molecules on kinesin activity. The first assay is based on the ATPase activity of kinesin and we measure generation of ADP. In the second assay we will identify small molecules that can potentially modulate expression of luciferase genes cloned under the control of kinesin promoter. These molecules will be useful in upregulating kinesin levels in neurons. We will characterize these molecules by testing their effect in neuronal activity and in neuronal cultures.