Kinase suppressor of ras (KSR) serves as a scaffolding protein for the ERK/MAP kinase cascade but has not yet been investigated within the central nervous system. As ERK activation has been shown to be important for processes of normal learning, KSR may also play an integral role in these same processes. This research seeks to investigate the role of KSR within the hippocampus in processes of learning and memory, synaptic plasticity, and signal transduction. Using KSR null mice, associative fear conditioning will be assessed as a prototypical hippocampus dependent learning paradigm. Response profiles to various activators of the MAP kinase cascade will be assessed to determine if KSR is a general scaffolding molecule or functions only when certain activating signals are given. In addition, long term potentiation from KSR null mice will be investigated to discover the contribution of KSR to mechanisms of synaptic plasticity. Other regulatory elements of the ERK kinase system have been implicated in several mental retardation syndromes. So, not only will this research expand the understanding of normal molecular mechanisms crucial for learning and memory, but it may provide insight into disease states, including mental retardation.