Research

Elly Nedivi
Principal Investigator

Associate Professor
Departments of Brain and Cognitive Sciences and Biology

Ongoing Research Projects

• Screening the CPG pool
• CPG15
• CPG2
• Interneuron remodeling in the adult brain
• CPGs as molecular probes of visual system development
• Compare a sequence against the CPG database

Synaptic Plasticity
      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'? In the case of both developmental and adult plasticity, there is evidence that correlated neuronal activity induces expression of specific plasticity genes whose protein products then bring about molecular changes in the neurons, strengthening their response to a given stimulus. Our approach to understanding the cellular mechanisms of activity-dependent synaptic plasticity is to identify and characterize participating genes and their protein functions.

Candidate Plasticity Genes
     We have developed a highly sensitive subtractive cloning and differential screening method that has allowed us to identify and isolate a large pool of genes involved in neuronal plasticity (Nature, Nedivi et al. 1993). These 377 candidate plasticity-related genes (CPGs), approximately 210 of them novel, constitute the basis of our studies. The large number of CPGs isolated necessitates their priority ranking for further analysis. We are using various criteria to assess how interesting each CPG is, how closely related it may be to plasticity and whether there are hints as to it function that could aid in its characterization.

Structural plasticity in the adult brain
      Many CPGs are capable of modifying neuronal structure, suggesting that neuronal structure can be modified by activity even in the adult brain. To investigate the molecular mechanisms underlying structural plasticity in the mammalian brain we have collaborated with Dr. So’s group in the Dept. of Mechanical Engineering at MIT to develop a multi-photon microscope for chronic in vivo imaging of neuronal morphology in the intact rodent cerebral cortex. Using this system we have imaged and reconstructed the dendritic trees and axon collaterals of neurons in visual cortex of thy1-EGFP transgenic mice. These transgenic mice express EGFP in a random subset of neurons sparsely distributed within the superficial cortical layers that are optically accessible through surgically implanted cranial windows. The images show an abundance of detail, with the basal and apical dendrites instantly recognizable and spines clearly visible. This enables dendritic branch dynamics in individual neurons to be examined over several months. Consistent with the idea that dendritic structural remodeling is a substrate for adult plasticity, our studies have revealed that even in the absence of peripheral perturbations, dendritic arbors in layer 2/3 neurons of visual cortex undergo rearrangements on a day-to-day basis (Wei et al., 2006). Different morphological classes of neurons show different remodeling dynamics, suggesting that cell-type specific rules influence circuit rearrangement.