A fundamental aspect of neuronal biology is the establishment of synaptic connections and their experience-dependent modification throughout life. Thus, synaptic plasticity, a process that allows neurons to re-adjust their connectivity in an activity-dependent manner, is essential in the establishment and maturation of functional neuronal circuits during development and is thought to be one of the cellular bases for learning and memory.
In hippocampus, early synaptic connections onto pyramidal cells are transformed into dendritic spines with a complex array of scaffolding proteins, signaling molecules, protein receptors, and ion channels, which cluster and form the postsynaptic density. These glutamatergic synapses are established and can be modified by activity. Interestingly, the ability to modify synapses is itself plastic and depends on experience. Thus, as the animal age, synaptic plasticity decreases in several brain regions particularly in cortex. The NMDA-type Glutamate Receptor is critical for these activity-dependent processes that create, reorganize and refine connections, and allow changes in the strength of individual synapses.
Using molecular and cellular techniques, along with advanced imaging and electrophysiology, we try to understand the molecular and cellular mechanisms that a) trigger synapse formation and stabilize them, and b) control the level of synaptic plasticity at different developmental stages of the animal.
Funding: UW Royalty Research Fund, NARSAD, NIH-NINDS