Entry Date:
February 20, 2000

Nedivi Lab Research

Principal Investigator Elly Nedivi

Project Website http://nedivilab.org/


Learning and memory are specific cases of the brain’s ability to modify connections in response to altered input. The property of the brain that allows it to constantly adapt to change is termed plasticity and is a prominent feature not only of learning and memory in the adult, but also of brain development. Connections between neurons (synapses) that are frequently used become stronger, while those that are unstimulated gradually dwindle away. How does activity modify a synapse to make it ‘strong’, or cause the addition and elimination of synaptic connections? In the case of both developmental and adult plasticity, there is evidence that correlated neuronal activity induces expression of specific plasticity genes. The protein products of these genes then act to strengthen connections or locally remodel circuits through new synapse formation and elimination.

The Nedivi lab studies the cellular mechanisms that underlie activity-dependent plasticity in the developing and adult brain through studies of synaptic and neuronal remodeling, identification of the participating genes, and characterizing the cellular functions of the proteins they encode.

After identifying a large number of candidate plasticity genes (CPGs) (Nedivi E. Nature 1993), we focused on several and characterized their very different activities. We have elucidated the neuronal and synaptic function of two previously unknown CPGs, CPG15 and CPG2, and characterized their very different activities, showing that each provides unique insight into diverse aspects of plasticity mechanisms. The CPG pool remains a trove that can be screened for additional genes of interest, many as yet uncharacterized, prioritized according to mechanistic and/or disease relevance. Motivated by the large number of CPGs that affect neuronal structure, we have a long-standing collaboration with Peter So’s lab in the Department of Mechanical Engineering at MIT to develop multi-photon microscopy for large volume, high resolution imaging of dendritic arbor and synaptic structural dynamics in vivo.