Grant: Discovery Grants Program - Individual

Memory, which refers to the ability of organisms to integrate, encode, store, and recall information, is a fundamental and adaptive process that defines experience, and is encoded by changes in the strength of connections between brain cells at highly-specialized sites of communication called synapses. Most excitatory synapses are housed within small protrusions emanating from dendrites called dendritic spines. Changes in both structure of dendritic spines and the molecular composition of synapses, termed synaptic plasticity, are thought to serve as the neurobiological basis of learning and memory formation. Many of the underlying events that regulate synaptic plasticity show a striking similarity to processes that occur during neural development, and it is a long-standing hypothesis that the molecular mechanisms responsible for neural development may also contribute to plasticity events related to learning and memory in the adult nervous system. Guidance cue proteins are highly-conserved proteins that were first described helping to direct axonal migration and synaptic connections during embryonic development, but recent work has suggested that they may play a role in shaping synaptic transmission in the adult brain. Semaphorins are a family of membrane-bound and secreted chemorepulsive guidance cues that were first described as key molecules involved in repulsive cellular responses through actions on the actin cytoskeleton. The secreted guidance cue semaphorin 3A (Sema3A) continues to be expressed in the adult hippocampus, a brain structure involved in learning and spatial memory formation, yet little is known regarding its physiological function. The research program proposed here will investigate the role of Sema3A in synaptic transmission and plasticity underlying spatial memory formation in the adult hippocampus by addressing the following aims: i) Examine the effect of Sema3A on cellular morphology and synaptic transmission in excitatory neurons in the adult hippocampus, ii) Assess the contribution of Sema3A to classic activity-dependent forms of synaptic plasticity, and iii) Determine the contribution of Sema3A in spatial memory function. In summary, this research program will highlight how instructive guidance cues important during development continue to play key roles in shaping synaptic transmission in the adult brain through effects on both the structure and molecular composition of synapses.