Professor Rafael Yuste is awarded $13 million to lead an interdisciplinary effort to study how neurons work

Dr. Rafael Yuste and his research team at Columbia have 13 million dollars and 5 years to change how we think about neurons. The Yuste lab was awarded the NIH’s prestigious RM1 grant to lead a team of six labs—at Columbia, Harvard, MIT, NYU, Stanford, and Hebrew University— in an effort to rediscover the dendrite, the part of the neuron that receives and integrates connections from other neurons.  The goal of the project is to look at dendrites from six new angles, with each lab taking an angle that will be compiled under the guidance of Dr. Yuste to create, as he terms it, a “Rosetta Stone” of the dendrite, a complete view of how the dendrite works from the perspective of multiple scientific disciplines. 

Their project focuses on understanding the function of dendrites, those branch-like structures that protrude from the neuron. Dendrites are covered in tiny bumps, called spines, that receive synaptic contacts from other neurons and send it along the dendrite back to the cell body of the neuron. Dr. Yuste explains, “The neuron is like a tree. The dendrites are the branches. Just like a branch is covered with leaves, the dendrite is covered with spines.” For decades, research scientists have focused on these spines and their synapses, and on how changes in synapses could underlie learning and plasticity. The traditional view was that dendrites were mere cables that brought the synaptic currents to the soma of the cells. Then, new technology enabled in vivo imaging of voltage, recording the activity of dendrites in a live animal. 

A former postdoctoral fellow in the Yuste lab, Dr. Victor Cornejo, performed these types of imaging experiments in vivo and realized that the activation of individual spines, and synapses, goes unnoticed by the neuron in a live animal. This raised the question: how do neurons actually receive information? Dr. Cornejo and Dr. Yuste discovered that, instead of just spines being activated, an entire dendritic branch needed to be stimulated in order to make a neuron fire in a live animal. If the dendrite didn’t fire, the neuron didn’t fire.  Dendrites are not just passive cables, but rather they play an important role in the neuron. This work moved the focus from the synapses to the dendrite. Dr. Yuste’s lab published their findings in Science, which has inspired researchers to consider a new question: what is the role of dendrites in neuronal function? 

With NIH funding, over the next five years, Dr. Rafael Yuste, Dr. Michael Lin, Dr. Jeff Lichtman, Dr. Eli Nevidi, Dr. Jayeeta Basu, and Dr. Idan Segev are seeking to answer this question. The Yuste lab is using a novel technology they developed that Dr. Yuste has termed “playing the piano.” Using the holographic two photon microscope they developed, Dr. Yuste and his team are able to use lasers to precisely activate dendritic spines in neurons in the mouse cortex. Just like playing notes in a specific pattern produces a recognizable pop song, activating neurons in a specific pattern produces recognizable behaviors in alive and awake mice. In this way, the Yuste lab will be able link spine and dendrite activation to neural circuit activation and the resulting animal behavior. Concurrently, The Lichtman lab at Harvard is using an electron microscope to obtain high-resolution images of the dendrite’s structure, while the Nevidi lab at MIT maps all the receptors and ion channels in the dendrite. The Lin lab at Stanford is engineering new proteins to better measure voltage changes in dendrites, and the Basu lab at NYU is investigating the basic biophysical properties of dendrites. The Segev lab at Hebrew University is then taking all of the results and using them to build a computational model of the dendrite. In five years, the research team hopes to have answered the question of what dendrites are doing in neuronal function. “We promise the NIH we will deliver a ‘Rosetta Stone’ dataset so that everyone in the world can have the data and use it to understand how these dendrites are working,” says Dr. Yuste. 

The dataset that Dr. Yuste and his colleagues plan to provide is poised to reframe how scientists think about the connections among neurons and open a new field of inquiry for researchers investigating novel therapeutics to neuropsychiatric conditions. “We are going to carefully examine a potential new foundation of neuroscience,” says Dr. Yuste, “and this has repercussions everywhere in the field of neurodevelopment diseases and disorders that have been shown to affect spines and synapses, but no one has looked at how they affect dendrites.”