Inbal Israely, PhD
- Assistant Professor of Pathology and Cell Biology
Dr. Israely received her BSc degree in Molecular Biology at the University of California, San Diego, in 1996. After working for a short while in the field of eukaryotic gene expression, she wanted to understand how the regulation of single proteins could lead to changes in brain function. She began her graduate studies at the University of California, Los Angeles, in the laboratory of Dr. Xin Liu and in collaboration with Dr. Alcino Silva, to study the role of a neural specific adhesion protein in cognitive function. After completing her PhD in 2004, Dr. Israely joined Susumu Tonegawa's lab at MIT, where, using two-photon imaging and glutamate uncaging, she examined long lasting changes at individual synapses upon activity. In 2009, she moved to Portugal to start her own group in the Champalimaud Neuroscience Program.
In the lab, we are interested in understanding how activity can lead to specific structural changes which may be important for learning, and how such changes affect connectivity within neural circuits. While information can be stored over our entire lifespan, it is unclear how it is physically encoded and how the fidelity of connections is maintained. A guiding principle is that neuronal structure and function are intimately linked, and we aim to determine how this relationship allows our brains to learn and remember. The focus of the lab is on single neurons, even single spines, to understand the cellular mechanisms that are important for structural plasticity and learning. Does activity arriving at one or multiple inputs become encoded in the same way? Are some forms of activity more efficacious than others, and do they lead to long lasting changes of spines? We can understand this by tracking the outputs of synaptic plasticity in real-time, since individual spines physically change in size as they change in efficacy. We use 2-photon microscopy to stimulate living spines (through the activation of caged glutamate), and then visualize structural changes (both in size and shape) in response to this stimulation. We also monitor electrophysiological responses of the neuron and image calcium signals using genetically encoded sensors. By delivering diverse activity patterns to individual synapses or to groups of synapses, we shed light on single input encoding as well as on interactions between them, such as cooperation and competition. The latter can serve as mechanisms for clustering spines and may determine how neuronal connectivity is shaped. This is of particular interest as several neurodevelopmental disorders are characterized by abnormal spine morphologies and distributions, and have a high incidence of autism, highlighting the link between structure and cognitive function. We use animal models of such disorders to probe for common principles of neuronal dysfunction. Thus, by combining molecular and genetic tools together with imaging and electrophysiological methodologies, we study how information is physically stored in the brain. Through this approach, we hope to learn how neurons process information in a state of health, as well as to unravel what can go wrong during disease.
UNDERSTANDING HOW ACTIVITY DRIVES DIVERSE SPINE STRUCTURAL INTERACTIONS (Federal Gov)
Mar 1 2020 - Jan 31 2025
CLINICAL AND TRANSLATIONAL SCIENCE AWARD (Federal Gov)
Jul 1 2016 - May 31 2021
Ramiro-Cortés Y, Hobbiss AF, Israely I. (2013) Synaptic competition in structural plasticity and cognitive function Philos. Trans. R. Soc. Lond., B, Biol. Sci. 369 (1633), 20130157 (doi:10.1098/rstb.2013.0157).
Yazmín Ramiro-Cortés, Inbal Israely (2013) Long Lasting Protein Synthesis- and Activity-Dependent Spine Shrinkage and Elimination after Synaptic Depression PLoS ONE 88 (8) (doi:e71155. doi:10.1371/journal.pone.0071155).
Govindarajan A, Israely I, Huang SY, Tonegawa S (2011) The dendritic branch is the preferred integrative unit for protein synthesis-dependent LTP. Neuron 69 (1), 132-146 (doi:10.1016/j.neuron.2010.12.008).
Arikkath J, Peng IF, Ng YG, Israely I, Liu X, Ullian EM, Reichardt LF (2009) Delta-catenin regulates spine and synapse morphogenesis and function in hippocampal neurons during development. J. Neurosci. 29 (17), 5435-42 (doi:10.1523/JNEUROSCI.0835-09.2009).
Arikkath J, Israely I, Tao Y, Mei L, Liu X, Reichardt LF (2008) Erbin controls dendritic morphogenesis by regulating localization of delta-catenin. J. Neurosci. 28 (28), 7047-56 (doi:10.1523/JNEUROSCI.0451-08.2008).
Kosik KS, Donahue CP, Israely I, Liu X, Ochiishi T (2005) Delta-catenin at the synaptic-adherens junction. Trends Cell Biol. 15 (3), 172-8 (doi:10.1016/j.tcb.2005.01.004).
Israely I, Costa RM, Xie CW, Silva AJ, Kosik K, and Liu X (2004) Deletion of the neuron-specific protein delta-catenin leads to severe cognitive and synaptic dysfunction. Curr. Biol. 14 (18), 1657-63 (doi:10.1016/j.cub.2004.08.065).