Elly Nedivi

Candidate Plasticity Genes

Structural Plasticity in Cortical Circuits

Motivated by the large number of CPGs that affect neuronal structure, we have also been collaborating 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. Using this system we have chronically imaged and reconstructed the dendritic trees of neurons in visual cortex of thy1-GFP transgenic mice through surgically implanted cranial windows. Our lab was the first to show unambiguous evidence of dendritic growth and retraction and of branch tip additions in the adult brain. Surprisingly, our data singled out GABAergic interneurons as those capable of structural dynamics, suggesting that circuit rearrangement is restricted by cell type-specific rules.

By combining chronic two-photon microscopy in vivo with classic visual manipulations we showed that experience drives structural remodeling of superficial cortical layer 2/3 interneurons in an input- and circuit-specific manner. Currently we are using in vivo dual color imaging to examine different types of input onto the different excitatory and inhibitory cell types in the cortical circuit, as well as the timing of constructive and destructive events in terms of pre and postsynaptic components.

With Dr. So, we are also developing the use of high-speed microscopy (Multifocus, Multiphoton Microscopy) to aid in imaging large neuronal volumes at synaptic resolution at short time intervals. A large part of the lab is now devoted to imaging-related projects, some associated with characterization of CPG function in vivo, others asking more general questions related to structural plasticity of cortical circuitry.