CV

SPEAKER AT:

Elly Nedivi, Ph.D. Ph.D, MIT, Cambridge, USA

Elly Nedivi is a Professor in the Department of Brain and Cognitive Sciences at MIT, with a joint appointment in the Department of Biology. She is also a member of the Picower Institute for Learning and Memory. Dr. Nedivi received her Ph.D. in Neuroscience from Stanford University Medical School and completed her postdoctoral training at The Weizmann Institute in Israel. In 1998, after two years at Cold Spring Harbor Laboratory in New York, she joined the faculty of the Department of Brain and Cognitive Sciences and the Picower Institute for Learning and Memory at MIT.The Nedivi lab studies the cellular mechanisms that underlie activity-dependent plasticity in the developing and adult brain through studies of neuronal structural dynamics, identification of the participating genes, and characterization of the proteins they encode. Following a screen for activity-regulated genes and isolation of a large number of candidate-plasticity genes (CPGs), part of the lab is devoted to elucidating the neuronal and synaptic function of two previously unknown CPGs, CPG15 and CPG2, and characterized their very different activities. CPG15 is a novel growth factor that plays a dual role in the nervous system, acting as a survival factor for cortical progenitors and later as a growth and differentiation factor. CPG2 is a large intracellular adaptor protein localized to the postsynaptic endocytic zone of excitatory synapses, and a critical component of the endocytic pathway mediating glutamate receptor internalization. Recently, we have returned to the CPG pool for identification of additional genes of interest.

Motivated by the large number of CPGs that affect neuronal structure, in collaboration with Peter So’s lab in the Department of Mechanical Engineering at MIT we have developed multi-photon microscopy for large volume, high resolution imaging of dendritic arbor and synaptic structural dynamics in vivo. We were 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. 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. Recently, we have also developed methods for labeling and chronic monitoring of excitatory and inhibitory synapses across entire neuronal arbors in the mouse visual cortex in vivo.

CV

SPEAKER AT:

Lose your inhibition: Learn more

Elly Nedivi, Ph.D. Ph.D, MIT, Cambridge, USA

The Picower Institute for Learning & Memory, Dept. of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139

The role of inhibition within the cortical circuit has recently gained prominence as it has become clear that the balance of excitation/inhibition is critical to proper brain development as well as for cognitive function. Indeed, many mental and neuropsychiatric diseases have been linked to deficits in inhibitory function. Yet our understanding of how inhibitory connectivity is modified by experience and how that relates to the excitatory network is minimal. We previously showed that dendrites of inhibitory interneurons in the adult visual cortex remodel on a day-to-day basis and that experience can drive the structural remodeling of interneuron dendrites and axons in an input- and circuit-specific manner.

A major obstacle to visualizing the synaptic correlates of inhibitory arbor remodeling, as well as how it may be coordinated with remodeling of excitatory inputs, has been the inability to visualize inhibitory synapses in vivo. Recently, we developed high-resolution two-color multiphoton microscopy to simultaneously monitor both inhibitory synapse and dendritic spine remodeling across the entire dendritic arbor of cortical L2/3 pyramidal neurons in vivo during normal and altered sensory experience. This has allowed us to address, for the first time, fundamental questions about the interplay between excitatory and inhibitory synaptic transmission during normal adult brain function as well as experience-dependent plasticity. Our findings suggest that inhibitory interneuron restructuring during experience-dependent plasticity results in an initial disinhibition of excitiatory cortical circuits that is permissive to rewiring of local circuits.