The Cohen Lab develops and applies new tools to study biology. We push the limits of physics and chemistry to make measurements in previously inaccessible regimes. Work in the lab combines optics, protein engineering, chemistry, electrophysiology, simulation, and theory. We work at the levels of individual molecules, single cells, and whole, genetically modified, organisms.

A major focus is toward studying electrical signaling in the nervous system. We developed fluorescent reporters of membrane voltage and associated instrumentation to map electrical activity with high resolution in space and time. We study information processing in the brains of awake, behaving mice and zebrafish. We also work on electrical signaling in other tissues; on mechanical signaling in cells; and on the roles of physical forces in embryonic development.

Optically triggered action potential in a rat hippocampal neuron, mapped at 100,000 frames/s.


Research Areas

Microcircuit

Excitability, synaptic transmission, and microcircuits

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Neuron

Voltage imaging tool development

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Zebrafish heart

Voltage imaging throughout life

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Membrane Mechanics Placeholder

Synthetic electrophysiology and bioelectrical patterning

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Photostick image

Membrane and DNA mechanics

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trapped nanoparticle

Past research projects

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News

Looking for a postdoc

We're looking for a postdoc to help lead an effort to develop tickertape-like protein assemblies for brain-wide neural recording. Desired background, in order of priority: Protein engineering, microscopy and image processing, in vivo neuroscience. If interested, please email cover letter, CV and names of references to Adam Cohen. Here is the full job posting.

Stretching our minds, or at least our neurons (8/2022)

Zheng and Sarah discovered that membrane tension propagates pretty quickly (~20 microns/s) in growing axons. They showed that tension coordinated long-range competition between extension of existing growth cones vs nucleating new branches closer to the soma. Is this a mechanism for mechanical obstacle avoidance in axon guidance?

2P or not 2P (6/2022)

That is the question. Hunter Davis won a Best Poster Prize at the recent conference on Sculpted Light in the Brain.  Congratulations, Hunter!  His poster compared one-photon and two-photon approaches to voltage imaging.

Twinkle, twinkle, little astrocyte! (4/2022)

Moritz Ambruster and Chris Dulla did voltage imaging in astrocytes, now out in Nature Neuroscience. They observed surprisingly localized fluctuations in voltage, modulated by nearby neural activity. Yoav and I helped out on the voltage imaging and interpretation. Congratulations to Moritz, Chris and team!

Lighting up dendrites (3/2022)

Andrew Landau and Bernardo Sabatini did a beautiful study of back-propagating action potentials in L2/3 pyramidal cells, now out in eLife. We chipped in some voltage imaging using Tian's new QuasAr6 voltage indicator, paired with calcium imaging. Congratulations to Pojeong Park (electrophysiology), David Wong-Campos (instrumentation), and Tian He (protein engineering). Great to collaborate with Bernardo and team!

Tales of fish tails (1/2022)

Urs' major paper just came out in Neuron! He combined light-sheet voltage imaging, optogenetic stimulation, and genetic knockout to characterize excitatory spinal neurons in zebrafish swimming in a virtual reality environment. He discovered that a previously uncharacterized population, V3, controls the strength of the swimming tail motions. Read Urs' tale in Neuron.

Polarized views of dendrites (11/2021)

Super (former) undergrad William Bloxham and postdoc Daan Brinks showed that the fluorescence of many protein and dye-based voltage indicators depends on the polarization of the incident light. By aligning the polarization with the transition dipole, you can substantially increase the brightness and signal-to-noise ratio! Read about it in Biophys. J.

Stimulating thoughts on emission (10/2021)

David Wong-Campos and Trey Porto analyzed the pattern of photon emission from a single excited fluorophore undergoing stimulated emission. It turns out to be super subtle and interesting. This paper was for a special issue of J. Phys. Chem., in honor of Adam's thesis advisor, W. E. Moerner. Our findings support the Moerner Lab ethos (with apologies to PW Anderson), Fewer is Different!

Fellowships and prizes galore! (7/2021)

So many awards for the great members of the team:

Light up neurons like a super NovA(rch) (5/2021)

Miao and Daan developed Photoactivated voltage imaging in tissue with an archaerhodopsin-derived reporter, out in Science Advances. When tickled with blue or 2-photon light, the far-red fluorescent reporter gets up to seven-fold brighter. It's called NovArch (get it?). We can now map voltage in dendrites in tissue!

Get the voltage imaging wiggles (4/2021)

Super-undergrad Michael Xie led a multi-lab effort to develop a data analysis pipeline for High-fidelity estimates of spikes and subthreshold waveforms from 1-photon voltage imaging in vivo, out in Cell Reports. Great collaboration with labs of Liam Paninski and Karel Svoboda! This pipeline distinguishes real subthreshold events from out-of-focus crosstalk and other optical artifacts.

Welcome Maddie! (4/2021)

Madeleine Howell officially joins the lab! Maddie will be working on optomechanical imaging systems to probe microscale mechanical properties of cells and tissues. Welcome, aboard, Maddie!

MOSAIC: Multiplexed optical sensors in arrayed islands of cells (8/2020)

Kit developed a technique to record from > 20 fluorescent reporters simultaneously, monitoring how many different metabolites and signaling molecules respond to physiological perturbations. Powerful new tool, out in Nature Communications. Great collaboration with Emil Hansson!

MOSAIC 

Lateral inhibition in cortical L1 (1/2020)

Linlin used Optopatch and an inhibitory version, i-Optopatch, to dissect the role of lateral inhibition in sensory processing cortical Layer 1. Check out the paper in Cell. Great collaboration with Anne Takesian and Ed Boyden labs.

Bioelectrical domain walls (1/2020)

Harry discovered that homogeneous tissues can spontaneously break spatial symmetry to form bioelectrical domain walls. Check out the paper in Nature Physics. Great collaboration with Olivier Pourquie and lab.

Jiggling like Jello (11/2019)

Zheng and Adam wrote a review about cell membrane mechanics Do cell membranes flow like honey or jiggle like jello? Here's some food for thought, just out in BioEssays. See also the video abstract:

All-optical electrophysiology in behaving mice (4/2019)

Yoav's epic project to develop optical electrophysiology in awake, behaving mice just came out in Nature! Voltage imaging of spikes and subthreshold events reveal interesting hippocampal dynamics associated with locomotion.

All-optical neurophysiology in brain slices (4/2019)

Sami and Vicente combined Hadamard microscopy with a new blue-shifted channelrhodopsin and a red-shifted, nuclear-localized Ca++ indicator for ultrawide-field all-optical neurophysiology in brain slices. Find out how your favorite drug acts, brain wide! Published in Journal of Neuroscience. Cover Story!

High-speed Hadamard Microscopy (1/2019)

Vicente and Carlos developed a beautiful imaging technique that combines structured illumination with Hadamard sequences and compressed sensing. See their paper on Compressed Hadamard Imaging in J. Phys. D. Using one-photon illumination, they achieved high-speed optically sectioned imaging in tissue. Come for the math, stay for the images!

Cells and gels in Cell (11/2018)

Zheng's paper on cell membrane mechanics just came out in Cell. He showed that tension in the cell membrane is highly localized, and propagates slowly and diffusively. This is counter to the widely held view of the cell membrane as a freely flowing liquid: think Jello, not honey!

Artificial arrhythmias (10/2018)

Harry's paper on the geometry-dependent transition between regular spiking and arrhythmia in spiking HEK cells was the cover story in Cell Systems. He showed that even in a very simple excitable cell type, the spiking dynamics are sensitive to the overall tissue geometry through long-range electrotonic coupling. This is a challenge for using human stem cell-derived cardiomyocytes for disease modeling or cardiotoxicity screening. Be still, my beating heart!

synOptopatch in Nature Methods (10/2018)

Linlin's paper on an all-optical assay for synaptic transmission just came out in Nature Methods! She also showed that ketamine induces disinhibition by primarily blocking excitatory-to-inhibitory synapses. Bravo, Linlin!

Poster children (7/2018)

Two labmembers won 'Best Poster' awards at separate conferences this summer. Congratulations to Zheng for winning at the FASEB conference on Molecular Biophysics of Membranes. Congratulations to Yoav for winning at the Gordon Research Conference on Optogenetics and Imaging. Hooray!

Cell membranes resist flow (5/2018)

Zheng's paper is on the bioRxiv! Cell membranes are more like Jello than maple syrup. This was a surprise to us--maybe to you too!

All-optical electrophysiology in awake, behaving, mice (3/2018)

Yoav's paper is on the bioRxiv! This heroic piece of work combines new voltage indicators, new microscopes, new mice, and new software. Great team effort! All to see how the hippocampus represents locomotion.

Archive

Contact:

tel: (617) 496-9466
email: cohen@chemistry.harvard.edu
Office: Mallinckrodt 115

 

Harvard University
12 Oxford Street
Cambridge, MA 02138

Administrator: Tracey Schaal

tel: (617) 496-8233
email: schaal@chemistry.harvard.edu