Research Area: Cellular & Molecular Neuroscience

​synapses, vesicles, electrophysiology, protein complexes, signaling, small molecules, disease-linked genes, dendrites, cell death, brain disorders, neurodevelopment

The neural basis of sensory hypersensitivity

Anne Trafton |

Many people with autism spectrum disorders are highly sensitive to light, noise, and other sensory input. A new study in mice reveals a neural circuit that appears to underlie this hypersensitivity, offering a possible strategy for developing new treatments.

MIT and Brown University neuroscientists found that mice lacking a protein called Shank3, which has been previously linked with autism, were more sensitive to a touch on their whiskers than genetically normal mice. These Shank3-deficient mice also had overactive excitatory neurons in a region of the brain called the somatosensory cortex, which the researchers believe accounts for their over-reactivity.

There are currently no treatments for sensory hypersensitivity, but the researchers believe that uncovering the cellular basis of this sensitivity may help scientists to develop potential treatments.

“We hope our studies can point us to the right direction for the next generation of treatment development,” says Guoping Feng, the James W. and Patricia Poitras Professor of Neuroscience at MIT and a member of MIT’s McGovern Institute for Brain Research.

Feng and Christopher Moore, a professor of neuroscience at Brown University, are the senior authors of the paper, which appears today in Nature Neuroscience. McGovern Institute research scientist Qian Chen and Brown postdoc Christopher Deister are the lead authors of the study.

Too much excitation

The Shank3 protein is important for the function of synapses — connections that allow neurons to communicate with each other. Feng has previously shown that mice lacking the Shank3 gene display many traits associated with autism, including avoidance of social interaction, and compulsive, repetitive behavior.

In the new study, Feng and his colleagues set out to study whether these mice also show sensory hypersensitivity. For mice, one of the most important sources of sensory input is the whiskers, which help them to navigate and to maintain their balance, among other functions.

The researchers developed a way to measure the mice’s sensitivity to slight deflections of their whiskers, and then trained the mutant Shank3 mice and normal (“wild-type”) mice to display behaviors that signaled when they felt a touch to their whiskers. They found that mice that were missing Shank3 accurately reported very slight deflections that were not noticed by the normal mice.

“They are very sensitive to weak sensory input, which barely can be detected by wild-type mice,” Feng says. “That is a direct indication that they have sensory over-reactivity.”

Once they had established that the mutant mice experienced sensory hypersensitivity, the researchers set out to analyze the underlying neural activity. To do that, they used an imaging technique that can measure calcium levels, which indicate neural activity, in specific cell types.

They found that when the mice’s whiskers were touched, excitatory neurons in the somatosensory cortex were overactive. This was somewhat surprising because when Shank3 is missing, synaptic activity should drop. That led the researchers to hypothesize that the root of the problem was low levels of Shank3 in the inhibitory neurons that normally turn down the activity of excitatory neurons. Under that hypothesis, diminishing those inhibitory neurons’ activity would allow excitatory neurons to go unchecked, leading to sensory hypersensitivity.

To test this idea, the researchers genetically engineered mice so that they could turn off Shank3 expression exclusively in inhibitory neurons of the somatosensory cortex. As they had suspected, they found that in these mice, excitatory neurons were overactive, even though those neurons had normal levels of Shank3.

“If you only delete Shank3 in the inhibitory neurons in the somatosensory cortex, and the rest of the brain and the body is normal, you see a similar phenomenon where you have hyperactive excitatory neurons and increased sensory sensitivity in these mice,” Feng says.

Reversing hypersensitivity

The results suggest that reestablishing normal levels of neuron activity could reverse this kind of hypersensitivity, Feng says.

“That gives us a cellular target for how in the future we could potentially modulate the inhibitory neuron activity level, which might be beneficial to correct this sensory abnormality,” he says.

Many other studies in mice have linked defects in inhibitory neurons to neurological disorders, including Fragile X syndrome and Rett syndrome, as well as autism.

“Our study is one of several that provide a direct and causative link between inhibitory defects and sensory abnormality, in this model at least,” Feng says. “It provides further evidence to support inhibitory neuron defects as one of the key mechanisms in models of autism spectrum disorders.”

He now plans to study the timing of when these impairments arise during an animal’s development, which could help to guide the development of possible treatments. There are existing drugs that can turn down excitatory neurons, but these drugs have a sedative effect if used throughout the brain, so more targeted treatments could be a better option, Feng says.

“We don’t have a clear target yet, but we have a clear cellular phenomenon to help guide us,” he says. “We are still far away from developing a treatment, but we’re happy that we have identified defects that point in which direction we should go.”

The research was funded by the Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the Nancy Lurie Marks Family Foundation, the Poitras Center for Psychiatric Disorders Research at the McGovern Institute, the Varanasi Family, R. Buxton, and the National Institutes of Health.

Joshua Sanes awarded the 2020 Scolnick Prize

by Sabbi Lall |

The McGovern Institute announced today that Joshua Sanes is the 2020 recipient of the Edward M. Scolnick Prize in Neuroscience. Sanes is being recognized for his numerous contributions to our understanding of synapse development. It was Sanes who focused the power of molecular genetics toward understanding how synapses are built. He is currently the Jeff C. Tarr Professor of Molecular and Cellular Biology and the Paul J. Finnegan Family Director at the Center for Brain Science at Harvard University.

“We have followed Josh’s work for many years, and the award honors the profound impact he has had on neuroscience” says Robert Desimone, director of the McGovern Institute and the chair of the committee. “His work on synapse development and connectivity is critical to understanding brain disorders, and will also be essential to deciphering the highest functions of the brain.”

Individual neurons are labeled in the hippocampus of the Brainbow mouse. The Sanes lab developed this method, yielding some of the most iconic images in neuroscience. Image: Josh Sanes

While the space between neurons at the synapse is called a cleft, it has a defined structure, and as a postdoctoral fellow and faculty member at Washington University, Sanes studied the extracellular matrix proteins that line this region in the motor system. This work provided a critical entry point to studying synaptic development in the central nervous system and Sanes went on to examine how synapses form with exquisite specificity. In pursuit of understanding interactions in the nervous system, Sanes developed novel cell-marking methods that allow neuronal connectivity to be traced using multi-colored fluorescent markers. This work led to development of the ‘Brainbow’ mouse, yielding some of the most striking and iconic images in recent neuroscience. This line of research has recently leveraged modern sequencing techniques that have even identified an entirely novel cell type in the long-studied retina. The methodologies and findings from the Sanes lab have had a global impact, and deepened our understanding of how neurons find one another and connect.

Sanes becomes the 16th researcher to win the prestigious prize, established in 2004 by Merck to honor Scolnick, who spent 17 years holding the top research post at Merck Research Laboratories. Sanes will deliver the Scolnick Prize lecture at the McGovern Institute on April 27th, 2020 at 4:00pm in the Singleton Auditorium of MIT’s Brain and Cognitive Sciences Complex (Bldg 46-3002), 43 Vassar Street in Cambridge. The event is free and open to the public.

 

Explaining repetitive behavior linked to amphetamine use

by Sabbi Lall |

Repetitive movements such as nail-biting and pacing are very often seen in humans and animals under the influence of habit-forming drugs. Studies at the McGovern Institute have found that these repetitive behaviors may be due to a breakdown in communication between neurons in the striatum – a deep brain region linked to habit and movement, among other functions.

The Graybiel lab has a long-standing interest in habit formation and the effects of addiction on brain circuits related to the striatum, a key part of the basal ganglia. The Graybiel lab previously found remarkably strong correlations between gene expression levels in specific parts of the striatum and exposure to psychomotor stimulants such as amphetamine and cocaine. The longer the exposure to stimulant, the more repetitive behavior in models, and the more brain circuits changed. These findings held across animal models.

The lab has found that if they train animals to develop habits, they can completely block these repetitive behaviors using targeted inhibition or excitation of the circuits. They even could block repetitive movement patterns in a mouse model of obsessive-compulsive disorder (OCD). These experiments mimicked situations in humans in which drugs or anxiety-inducing experiences can lead to habits and repetitive movement patterns—from nail-biting to much more dangerous habitual actions.

Ann Graybiel (right) at work in the lab with research scientist Jill Crittenden. Photo: Justin Knight

Why would these circuits exist in the brain if they so often produce “bad” habits and destructive behaviors, as seen in compulsive use of drugs such as opioids or even marijuana? One answer is that we have to be flexible and ready to switch our behavior if something dangerous occurs in the environment. Habits and addictions are, in a way, the extreme pushing of this flexible system in the other direction, toward the rigid and repetitive.

“One important clue is that for many of these habits and repetitive and addictive behaviors, the person isn’t even aware that they are doing the same thing again and again. And if they are not aware, they can’t control themselves and stop,” explains Ann Graybiel, an Institute Professor at MIT. “It is as though the ‘rational brain’ has great difficulty in controlling the ‘habit circuits’ of the brain.” Understanding loss of communication is a central theme in much of the Graybiel lab’s work.

Graybiel, who is also a founding member of the McGovern Institute, is now trying to understand the underlying circuits at the cellular level. The lab is examining the individual components of the striatal circuits linked to selecting actions and motivating movement, circuits that seem to be directly controlled by drugs of abuse.

In groundbreaking early work, Graybiel discovered that the striatum has distinct compartments, striosomes and matrix. These regions are spatially and functionally distinct and separately connect, through striatal projection neurons (SPNs), to motor-control centers or to neurons that release dopamine, a neurotransmitter linked to all drugs of abuse. It is in these components that Graybiel and colleagues have more recently found strong effects of drugs. Indeed opposite changes in gene expression in the striosome SPNs versus the matrix SPNs, raises the possibility that an imbalance in gene regulation leads to abnormally inflexible behaviors caused by drug use.

“It was known that cholinergic interneurons tend to reside along the borders of the two striatal compartments, but whether this cell type mediates communication between the compartments was unknown,” explains first author Jill Crittenden, a research scientist in the Graybiel lab. “We wanted to know whether cholinergic signaling to the two compartments is disrupted by drugs that induce abnormally repetitive behaviors.”

Amphetamine drives gene transcription in striosomes. The top panel shows striosomes (red) are disticnt from matrix (green). Amphetamine treatment activates lead to markers of activation (the immediate early gene c-Fos, red in 2 lower panels) in drug-treated animals (bottom panel), but not controls (middle panel). Image: Jill Crittenden

It was known that cholinergic interneurons are activated by important environmental cues and promote flexible rather than repetitive behavior, how this is related to interaction with SPNs in the striatum was unclear. “Using high-resolution microscopy,” explains Crittenden, “we could see for the first time that cholinergic interneurons send many connections to both striosome and matrix SPNs, well-placed to coordinate signaling directly across the two striatal compartments that appear otherwise isolated.”

Using a technique known as optogenetics, the Graybiel group stimulated mouse cholinergic interneurons and monitored the effects on striatal SPNs in brain tissue. They found that stimulating the interneurons inhibited the ongoing signaling activity that was induced by current injection in matrix and striatal SPNs. However, when examining the brains of animals on high doses of amphetamine and that were displaying repetitive behavior, stimulating the relevant interneurons failed to interrupt evoked activity in SPNs.

Using an inhibitor, the authors were able to show that these neural pathways depend on the nicotinic acetylcholine receptor. Inhibiting this cell-surface signaling receptor had a similar effect to drug intoxication on intercommunication among striatal neurons. Since break down of cholinergic interneuron signaling across striosome and matrix compartments under drug intoxication may reduce behavioral flexibility and cue responsiveness, the work suggests one mechanism for how drugs of abuse hijack action-selection systems of the brain and drive pathological habit-formation.

The Graybiel lab is excited that they can now manipulate these behaviors by manipulating very particular circuits components in the habit circuits. Most recently they have discovered that they can even fully block the effects of stress by manipulating cellular components of these circuits. They now hope to dive deep into these circuits to find out the mystery of how to control them.

“We hope that by pinpointing these circuit elements—which seem to have overlapping effects on habit formation, addiction and stress, we help to guide the development of better therapies for addiction,” explains Graybiel. “We hope to learn about what the use of drugs does to brain circuits with both short term use and long term use. This is an urgent need.”

Single neurons can encode distinct landmarks

by Sabbi Lall |

The organization of many neurons wired together in a complex circuit gives the brain its ability to perform powerful calculations. Work from the Harnett lab recently showed that even single neurons can process more information than previously thought, representing distinct variables at the subcellular level during behavior.

McGovern Investigator Mark Harnett and postdoc Jakob Voigts conducted an extremely delicate and intricate imaging experiment on different parts of the same neuron in the mouse retinosplenial cortex during 2-D navigation. Their set up allowed 2-photon imaging of neuronal sub-compartments during free 2-D navigation with head rotation, the latter being important to follow neural activity during naturalistic, complex behavior.

Recording computation by subcompartments in neurons.

 

In the work, published recently in Neuron, the authors used Ca2+-imaging to show that the soma in a single neuron was consistently active when mice were at particular landmarks as they navigated in an arena. The dendrites (tree-like antennas that receive input from other neurons) of exactly the same neuron were robustly active independent of the soma at distinct positions and orientations in the arena. This strongly suggests that the dendrites encode distinct information compared to their parent soma, in this case spatial variables during navigation, laying the foundation for studying sub-cellular processes during complex behaviors.

 

Two CRISPR scientists on the future of gene editing

by Sabbi Lall |

As part of our Ask the Brain series, Martin Wienisch and Jonathan Wilde of the Feng lab look into the crystal ball to predict the future of CRISPR tech.

_____

Where will CRISPR be in five years?

Jonathan: We’ll definitely have more efficient, more precise, and safer editing tools. An immediate impact on human health may be closer than we think through more nutritious and resilient crops. Also, I think we will have more viable tools available for repairing disease-causing mutations in the brain, which is something that the field is really lacking right now.

Martin: And we can use these technologies with new disease models to help us understand brain disorders such as Huntington’s disease.

Jonathan: There are also incredible tools being discovered in nature: exotic CRISPR systems from newly discovered bacteria and viruses. We could use these to attack disease-causing bacteria.

Martin: We would then be using CRISPR systems for the reason they evolved. Also improved gene drives, CRISPR-systems that can wipe out disease-carrying organisms such as mosquitoes, could impact human health in that time frame.

What will move gene therapy forward?

Martin: A breakthrough on delivery. That’s when therapy will exponentially move forward. Therapy will be tailored to different diseases and disorders, depending on relevant cell types or the location of mutations for example.

Jonathan: Also panning biodiversity even faster: we’ve only looked at one small part of the tree of life for tools. Sequencing and computational advances can help: a future where we collect and analyze genomes in the wild using portable sequencers and laptops can only quicken the pace of new discoveries.

_____

Do you have a question for The Brain? Ask it here.

McGovern scientists named STAT Wunderkinds

by Sabbi Lall |

McGovern researchers Sam Rodriques and Jonathan Strecker have been named to the class of 2019 STAT wunderkinds. This group of 22 researchers was selected from a national pool of hundreds of nominees, and aims to recognize trail-blazing scientists that are on the cusp of launching their careers but not yet fully independent.

“We were thrilled to receive this news,” said Robert Desimone, director of the McGovern Institute. “It’s great to see the remarkable progress being made by young scientists in McGovern labs be recognized in this way.”

Finding context

Sam Rodriques works in Ed Boyden’s lab at the McGovern Institute, where he develops new technologies that enable researchers to understand the behaviors of cells within their native spatial and temporal context.

“Psychiatric disease is a huge problem, but only a handful of first-in-class drugs for psychiatric diseases approved since the 1960s,” explains Rodriques, also affiliated with the MIT Media Lab and Broad Institute. “Coming up with novel cures is going to require new ways to generate hypotheses about the biological processes that underpin disease.”

Rodriques also works on several technologies within the Boyden lab, including preserving spatial information in molecular mapping technologies, finding ways of following neural connectivity in the brain, and Implosion Fabrication, or “Imp Fab.” This nanofabrication technology allows objects to be evenly shrunk to the nanoscale and has a wide range of potential applications, including building new miniature devices for examining neural function.

“I was very surprised, not expecting it at all!” explains Rodriques when asked about becoming a STAT Wunderkind, “I’m sure that all of the hundreds of applicants are very accomplished scientists, and so to be chosen like this is really an honor.”

New tools for gene editing

Jonathan Strecker is currently a postdoc working in Feng Zhang’s lab, and associated with both the McGovern Institute and Broad Institute. While CRISPR-Cas9 continues to have a profound effect and huge potential for research and biomedical, and agricultural applications, the ability to move entire genes into specific target locations remained out reach.

“Genome editing with CRISPR-Cas enzymes typically involves cutting and disrupting genes, or making certain base edits,” explains Strecker, “however, inserting large pieces of DNA is still hard to accomplish.”

As a postdoctoral researcher in the lab of CRISPR pioneer Feng Zhang, Strecker led research that showed how large sequences could be inserted into a genome at a given location.

“Nature often has interesting solutions to these problems and we were fortunate to identify and characterize a remarkable CRISPR system from cyanobacteria that functions as a programmable transposase.”

Importantly, the system he discovered, called CAST, doesn’t require cellular machinery to insert DNA. This is important as it means that CAST could work in many cell types, including those that have stopped dividing such as neurons, something that is being pursued.

By finding new sources of inspiration, be it nature or art, both Rodriques and Strecker join a stellar line up of young investigators being recognized for creativity and innovation.

 

Brain region linked to altered social interactions in autism model

by Sabbi Lall |

Although psychiatric disorders can be linked to particular genes, the brain regions and mechanisms underlying particular disorders are not well-understood. Mutations or deletions of the SHANK3 gene are strongly associated with autism spectrum disorder (ASD) and a related rare disorder called Phelan-McDermid syndrome. Mice with SHANK3 mutations also display some of the traits associated with autism, including avoidance of social interactions, but the brain regions responsible for this behavior have not been identified.

A new study by neuroscientists at MIT and colleagues in China provides clues to the neural circuits underlying social deficits associated with ASD. The paper, published in Nature Neuroscience, found that structural and functional impairments in the anterior cingulate cortex (ACC) of SHANK3 mutant mice are linked to altered social interactions.

“Neurobiological mechanisms of social deficits are very complex and involve many brain regions, even in a mouse model,” explains Guoping Feng, the James W. and Patricia T. Poitras Professor at MIT and one of the senior authors of the study. “These findings add another piece of the puzzle to mapping the neural circuits responsible for this social deficit in ASD models.”

The Nature Neuroscience paper is the result of a collaboration between Feng, who is also an investigator at MIT’s McGovern Institute and a senior scientist in the Broad Institute’s Stanley Center for Psychiatric Research, and Wenting Wang and Shengxi Wu at the Fourth Military Medical University, Xi’an, China.

A number of brain regions have been implicated in social interactions, including the prefrontal cortex (PFC) and its projections to brain regions including the nucleus accumbens and habenula, but these studies failed to definitively link the PFC to altered social interactions seen in SHANK3 knockout mice.

In the new study, the authors instead focused on the ACC, a brain region noted for its role in social functions in humans and animal models. The ACC is also known to play a role in fundamental cognitive processes, including cost-benefit calculation, motivation, and decision making.

In mice lacking SHANK3, the researchers found structural and functional disruptions at the synapses, or connections, between excitatory neurons in the ACC. The researchers went on to show that the loss of SHANK3 in excitatory ACC neurons alone was enough to disrupt communication between these neurons and led to unusually reduced activity of these neurons during behavioral tasks reflecting social interaction.

Having implicated these ACC neurons in social preferences and interactions in SHANK3 knockout mice, the authors then tested whether activating these same neurons could rescue these behaviors. Using optogenetics and specfic drugs, the researchers activated the ACC neurons and found improved social behavior in the SHANK3 mutant mice.

“Next, we are planning to explore brain regions downstream of the ACC that modulate social behavior in normal mice and models of autism,” explains Wenting Wang, co-corresponding author on the study. “This will help us to better understand the neural mechanisms of social behavior, as well as social deficits in neurodevelopmental disorders.”

Previous clinical studies reported that anatomical structures in the ACC were altered and/or dysfunctional in people with ASD, an initial indication that the findings from SHANK3 mice may also hold true in these individuals.

The research was funded, in part, by the Natural Science Foundation of China. Guoping Feng was supported by NIMH grant no. MH097104, the  Poitras Center for Psychiatric Disorders Research at the McGovern Institute at MIT, and the Hock E. Tan and K. Lisa Yang Center for Autism Research at the McGovern Institute at MIT.

Ed Boyden wins premier Royal Society honor

by Sabbi Lall |

Edward S. Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT, has been awarded the 2019 Croonian Medal and Lecture by the Royal Society. Twenty-four medals and awards are announced by the Royal Society each year, honoring exceptional researchers who are making outstanding contributions to science.

“The Royal Society gives an array of medals and awards to scientists who have done exceptional, ground-breaking work,” explained Sir Venki Ramakrishnan, President of the Royal Society. “This year, it is again a pleasure to see these awards bestowed on scientists who have made such distinguished and far-reaching contributions in their fields. I congratulate and thank them for their efforts.”

Boyden wins the medal and lecture in recognition of his research that is expanding our understanding of the brain. This includes his critical role in the development of optogenetics, a technique for controlling brain activity with light, and his invention of expansion microscopy. Croonian Medal laureates include notable luminaries of science and neurobiology.

“It is a great honor to be selected to receive this medal, especially
since it was also given to people such as Santiago Ramon y Cajal, the
founder of modern neuroscience,” says Boyden. “This award reflects the great work of many fantastic students, postdocs, and collaborators who I’ve had the privilege to work with over the years.”

The award includes an invitation to deliver the premier British lecture in the biological sciences, given annually at the Royal Society in London. At the lecture, the winner is awarded a medal and a gift of £10,000. This announcement comes shortly after Boyden was co-awarded the Warren Alpert Prize for his role in developing optogenetics.

History of the Croonian Medal and Lecture

William Croone, pictured, envisioned an annual lecture that is the premier biological sciences medal and lecture at the Royal Society
William Croone, FRS Photo credit: Royal College of Physicians, London

The lectureship was conceived by William Croone FRS, one of the original Fellows of the Society based in London. Among the papers left on his death in 1684 were plans to endow two lectureships, one at the Royal Society and the other at the Royal College of Physicians. His widow later bequeathed the means to carry out the scheme. The lecture series began in 1738.

 

 

Ed Boyden holds the titles of Investigator, McGovern Institute; Y. Eva Tan Professor in Neurotechnology at MIT; Leader, Synthetic Neurobiology Group, MIT Media Lab; Professor, Biological Engineering, Brain and Cognitive Sciences, MIT Media Lab; Co-Director, MIT Center for Neurobiological Engineering; Member, MIT Center for Environmental Health Sciences, Computational and Systems Biology Initiative, and Koch Institute.

Ed Boyden receives 2019 Warren Alpert Prize

by Sabbi Lall |

The 2019 Warren Alpert Foundation Prize has been awarded to four scientists, including Ed Boyden, for pioneering work that launched the field of optogenetics, a technique that uses light-sensitive channels and pumps to control the activity of neurons in the brain with a flick of a switch. He receives the prize alongside Karl Deisseroth, Peter Hegemann, and Gero Miesenböck, as outlined by The Warren Alpert Foundation in their announcement.

Harnessing light and genetics, the approach illuminates and modulates the activity of neurons, enables study of brain function and behavior, and helps reveal activity patterns that can overcome brain diseases.

Boyden’s work was key to envisioning and developing optogenetics, now a core method in neuroscience. The method allows brain circuits linked to complex behavioral processes, such as those involved in decision-making, feeding, and sleep, to be unraveled in genetic models. It is also helping to elucidate the mechanisms underlying neuropsychiatric disorders, and has the potential to inspire new strategies to overcome brain disorders.

“It is truly an honor to be included among the extremely distinguished list of winners of the Alpert Award,” says Boyden, the Y. Eva Tan Professor in Neurotechnology at the McGovern Institute, MIT. “To me personally, it is exciting to see the relatively new field of neurotechnology recognized. The brain implements our thoughts and feelings. It makes us who we are. This mysteries and challenge requires new technologies to make the brain understandable and repairable. It is a great honor that our technology of optogenetics is being thus recognized.”

While they were students, Boyden, and fellow awardee Karl Deisseroth, brainstormed about how microbial opsins could be used to mediate optical control of neural activity. In mid-2004, the pair collaborated to show that microbial opsins can be used to optically control neural activity. Upon launching his lab at MIT, Boyden’s team developed the first optogenetic silencing tool, the first effective optogenetic silencing in live mammals, noninvasive optogenetic silencing, and single-cell optogenetic control.

“The discoveries made by this year’s four honorees have fundamentally changed the landscape of neuroscience,” said George Q. Daley, dean of Harvard Medical School. “Their work has enabled scientists to see, understand and manipulate neurons, providing the foundation for understanding the ultimate enigma—the human brain.”

Beyond optogenetics, Boyden has pioneered transformative technologies that image, record, and manipulate complex systems, including expansion microscopy, robotic patch clamping, and even shrinking objects to the nanoscale. He was elected this year to the ranks of the National Academy of Sciences, and selected as an HHMI Investigator. Boyden has received numerous awards for this work, including the 2018 Gairdner International Prize and the 2016 Breakthrough Prize in Life Sciences.

The Warren Alpert Foundation, in association with Harvard Medical School, honors scientists whose work has improved the understanding, prevention, treatment or cure of human disease. Prize recipients are selected by the foundation’s scientific advisory board, which is composed of distinguished biomedical scientists and chaired by the dean of Harvard Medical School. The honorees will share a $500,000 prize and will be recognized at a daylong symposium on Oct. 3 at Harvard Medical School.

Ed Boyden holds the titles of Investigator, McGovern Institute; Y. Eva Tan Professor in Neurotechnology at MIT; Leader, Synthetic Neurobiology Group, Media Lab; Associate Professor, Biological Engineering, Brain and Cognitive Sciences, Media Lab; Co-Director, MIT Center for Neurobiological Engineering; Member, MIT Center for Environmental Health Sciences, Computational and Systems Biology Initiative, and Koch Institute.

Mark Harnett receives a 2019 McKnight Scholar Award

Anne Trafton |

McGovern Institute investigator Mark Harnett is one of six young researchers selected to receive a prestigious 2019 McKnight Scholar Award. The award supports his research “studying how dendrites, the antenna-like input structures of neurons, contribute to computation in neural networks.”

Harnett examines the biophysical properties of single neurons, ultimately aiming to understand how these relate to the complex computations that underlie behavior. His lab was the first to examine the biophysical properties of human dendrites. The Harnett lab found that human neurons have distinct properties, including increased dendritic compartmentalization that could allow more complex computations within single neurons. His lab recently discovered that such dendritic computations are not rare, or confined to specific behaviors, but are a widespread and general feature of neuronal activity.

“As a young investigator, it is hard to prioritize so many exciting directions and ideas,” explains Harnett. “I really want to thank the McKnight Foundation, both for the support, but also for the hard work the award committee puts into carefully thinking about and giving feedback on proposals. It means a lot to get this type of endorsement from a seriously committed and distinguished committee, and their support gives even stronger impetus to pursue this research direction.”

The McKnight Foundation has supported neuroscience research since 1977, and provides three prominent awards, with the Scholar award aimed at supporting young scientists, and drawing applications from the strongest young neuroscience faculty across the US. William L. McKnight (1887-1979) was an early leader of the 3M Company and had a personal interest in memory and brain diseases. The McKnight Foundation was established with this focus in mind, and the Scholar Award provides $75,000 per year for three years to support cutting edge neuroscience research.