NYSCF Innovator Collaboration Creates A New Tool for Tracking Brain Activity in Disease Research

The Context: One of the most useful ways for brain researchers to observe the activity of neurons is through a technique called calcium imaging, but current calcium imaging tools often pick up on activity of surrounding cells, ‘contaminating’ the data with unwanted information.

The Study: A new method developed by NYSCF – Robertson Neuroscience Investigator Alumnus Ed Boyden, PhD, of MIT in collaboration with NYSCF – Robertson Neuroscience Investigator Alumna Kay Tye, PhD, of the Salk Institute creates a new molecule that allows accurate calcium imaging at the level of single neurons. The study appears in Neuron.

The Importance: With more accurate measures of how neurons ‘fire’ in the brain, researchers can better understand how this process goes awry in neurological diseases and develop new treatments. 

To study diseases of the brain such as Alzheimer’s or Parkinson’s, scientists need to be able to examine how neurons act — specifically, how they ‘fire’ to communicate with each other.

A new method developed by NYSCF – Robertson Neuroscience Investigator Alumnus Ed Boyden, PhD, of MIT in collaboration with NYSCF – Robertson Neuroscience Investigator Alumna Kay Tye, PhD, of the Salk Institute can more accurately track neural firing, improving research into brain diseases. The study appears in Neuron.

Searching for Calcium Surges

One way scientists track neuron activity is by looking for surges of calcium that occur after a neuron fires.

“Calcium is easy to image, because it goes from a very low concentration inside the cell to a very high concentration when a neuron is active,” Dr. Boyden, the Y. Eva Tan Professor in Neurotechnology and a Professor of Biological Engineering and of Brain and Cognitive Sciences told MIT News. “People are using calcium indicators for monitoring neural activity in many parts of the brain.”

The issue with current calcium-based activity tracking is that the tools for performing it often pick up on crosstalk with surrounding cells, leading to somewhat ‘contaminated’ results. 

An Improved Calcium Sensor

Dr. Boyden’s team created a new molecule that integrates into current procedures for calcium imaging while yielding more accurate results. The molecule, which includes a common calcium indicator called GCaMP joined to a peptide that guides it to a cell of interest, has been termed ‘SomaGCaMP.’ By binding and acting only within the body of a neuron, imaging with SomaGCaMP can exclude signals from surrounding cells.

“Our new indicator makes the signals more accurate. This suggests that the signals that people are measuring with regular GCaMP could include crosstalk,” explained Dr. Boyden. “Now they can get better results.”

The new molecule can be easily integrated into current workflows, giving researchers better results with minimal effort for employing a new procedure.

“It should be very easy to implement, and in fact many groups are already using it,” remarked Dr. Boyden. “They can just use the regular microscopes that they already are using for calcium imaging, but instead of using the regular GCaMP molecule, they can substitute our new version.”

Dr. Tye’s lab validated the use of SomaGCaMP, showing that it did, in fact, decrease collection of unwanted signals in imaging. She looks forward to what it will enable for brain research.

“This is an exciting new technology that will help us conduct more accurate research on a wide range of brain diseases,” she noted. “I was happy to collaborate with Ed, another NYSCF Innovator, on this study, and I think it speaks to the pioneering work being conducted by members of this community.”

Journal Article:

Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator
Or A Shemesh, Changyang Linghu, Kiryl D Piatkevich, Daniel Goodwin, Orhan Tunc Celiker, Howard J Gritton, Michael F Romano, Ruixuan Gao, Chih-Chieh Jay Yu, Hua-An Tseng, Seth Bensusse, Sujatha Narayan, Chao-Tsung Yang, Limor Freifeld, Cody A Siciliano, Ishan Gupta, Joyce Wang, Nikita Pak, Young-Gyu Yoon, Jeremy F P Ullmann, Burcu Guner-Ataman, Habiba Noamany, Zoe R Sheinkopf, Won Min Park, Shoh Asano, Amy E Keating, James S Trimmer, Jacob Reimer, Andreas S Tolias, Mark F Bear, Kay M Tye, Xue Han, Misha B Ahrens, Edward S Boyden. Neuron. 2020. doi: 10.1016/j.neuron.2020.05.029