Polina Anikeeva designs, synthesizes, and fabricates optoelectronic and magnetic devices to advance fundamental understanding and treatment of disorders of the nervous system.

Our group, centered in the MIT Media Lab and McGovern Institute, and jointly affiliated with the MIT Department of Biological Engineering and the MIT Department of Brain and Cognitive Sciences, works on inventing and applying new tools for the analysis and engineering of brain circuits. We have been developing molecules, hardware, and methods to activate, silence, record, and analyze neural activity and circuit signaling, throughout brain circuits. We also work on ways to map the molecular structure of the brain.  We distribute our tools as freely as possible to the scientific community, and also apply them to the systematic analysis of brain computations, aiming to reveal the fundamental mechanisms of brain function, and yielding new, ground-truth therapeutic strategies for neurological and psychiatric disorders. These technologies include expansion microscopy, which enables complex biological systems to be imaged with nanoscale precision; optogenetic tools, which enable the activation and silencing of neural activity with light; robotic methods for directed evolution that are yielding new synthetic biology reagents for dynamic imaging of physiological signals; novel methods of noninvasive focal brain stimulation; and new methods of nanofabrication using shrinking of patterned materials to create nanostructures with ordinary lab equipment.

We use multiple approaches including traditional- and CRISPR-based genome editing, molecular, optogenetic, electrophysiological, and imaging techniques to understand 1) how olfactory stimuli are transformed to behavioral outputs as function of learning and 2) how the immune system modulates neural circuits to shape and guide behavioral outputs.

The development of the vertebrate brain involves a phase of synaptogenesis during which the activity patterns of young neurons mediate a competition that allows only highly effective synapses to survive. These activity-dependent developmental events are responsible for many of the adaptive changes in brain wiring as children mature and it is also likely to be responsible for some of the devastating and permanent behavioral effects of genetically or environmentally caused disruptions in normal early brain activity. The Constantine - Patton laboratory investigates the mechanisms involved in this developmental synaptic plasticity. Specifically, we are trying to dissect the signaling cascades through which synaptic activity determines which young synapses will be withdrawn and which ones will be retained to mediate adult brain function.

The research goal of the DiCarlo laboratory is to understand the mechanisms underlying visual object recognition. Specifically, we seek to understand how sensory input is transformed by the brain from an initial representation (essentially a photograph on the retina), to a new, remarkably powerful form of representation -- one that can support our seemingly effortless ability to solve the computationally difficult problem of object recognition. 

The Fee lab studies how the brain learns and generates complex sequential behaviors, with a focus on the songbird as a model system. Birdsong is a complex behavior that young birds learn from their fathers and it provides an ideal system to study the neural basis of learned behavior. Because the parts of the bird's brain that control song learning are closely related to human circuits that are disrupted in brain disorders such as Parkinson's and Huntington's disease, Fee hopes the lessons learned from birdsong will provide new clues to the causes and possible treatment of these conditions.

The Fiete group works on the mechanisms underlying memory, integration, error correction, and prediction in the brain, at the circuit level. We use theoretical and computational modeling techniques, and perform quantitative data analysis to tackle mechanistic and function-related questions. Our recent efforts fall right at the nexus of dynamics, coding, and function, as we seek to find how each influences the others.

The goal of our lab is to understand principles of brain organization that are consistent across individuals and those that vary across people due to age, personality, and other dimensions of individuality. We study the brain bases of learning, memory, emotion, and motivation, how these develop in children and adolescents, and how these differ in dyslexia, ADHD, autism, depression, and schizophrenia. Our primary methods are brain imaging (functional and structural), and the experimental study of behavior.

Much of our research occurs at the Martinos Imaging Center at the McGovern Institute at MIT, which is affiliated with the Athinoula A. Martinos Center for Biomedical Imaging. The Martinos centers are a collaboration among the Harvard-MIT Division of Health Sciences and Technology (HST), the McGovern Institute for Brain Research, Massachusetts General Hospital, and Harvard Medical School. Our affiliations with these outstanding research institutions promote the opportunity for cutting-edge basic cognitive neuroscience research and translation from basic science to clinical and education application.

The same brain that can construct language, music and mathematics also lets us develop habits of thought and action. These semi-automatic routines free us to think and attend to the world. But the habit system can also be hijacked by disease and drug exposure. The Graybiel Laboratory focuses on the habit system of the brain and our remarkable ability to switch from conscious activity to nearly non-conscious behavior. The goal of this research is to understand how we make and break habits and how the neurobiology of the habit system is helping to advance understanding of human problems ranging from Parkinson’s disease to obsessive-compulsive spectrum disorders and addiction.

Our laboratory studies how the biophysical features of individual neurons endow neural circuits with powerful processing capabilities, ultimately facilitating the complex computations required to drive adaptive behavior.  A principal focus of our work is the role of dendrites, the elaborate tree-like structures where neurons receive the vast majority of afferent input.  The spatial arrangement of synaptic contacts on dendrites and the interaction of various biophysical mechanisms enable complex integration of synaptic inputs – our hypothesis is that circuit-level computations are built out of these fundamental operations.

BIOPHYSICS & SINGLE-CELL COMPUTATION

The morphological features and local ion channel mechanisms in specific dendritic compartments strongly influence how neurons integrate their inputs.  We combine brain slice electrophysiology, two-photon imaging, and biophysical modeling to investigate the rules and mechanisms supporting different forms of input-output processing across mammalian species.  

NEURONAL COMPUTATION IN THE BEHAVING ANIMAL

How do biophysical mechanisms influence circuit-level computation during behavior?  To address this question, we combine 2-photon imaging and multi-unit electrophysiological recording techniques with novel rodent behavioral paradigms to measure the activity of neuronal populations including subcellular compartments.  This allows us to evaluate the engagement of dendritic mechanisms as a function of circuit dynamics during complex behaviors.  These experiments are complemented by detailed anatomical and single-cell physiological investigations in brain slices.

HEAD-DIRECTION COMPUTATIONS

Head direction is critical for efficient navigation and provides an experimentally tractable system with which to study multimodal integration in neural circuits.  We use state-of-the-art chronic tetrode implants to record HD activity while mice perform goal-directed navigation in darkness and reorient to visual landmarks.  These experiments are combined with anatomical, physiological, and optogenetic techniques, as well as novel behavioral and computational methods, to dissect the cellular and circuit architecture of head direction representations.

The contribution of the oculomotor system to the acquisition and maintenance of visually guided behavior is being examined in cats. Surgical immobilization of an eye in dark-reared kittens precludes development of guidance when the paralyzed eye is provided exposure in light. Light-reared animals retain visual guidance following eye immobilization surgery. Similarly, when proprioception from ocular musculature is surgically interrupted in dark-reared kittens, they fail to acquire visually guided behaviors when later exposed in light. The findings imply that both visually elicited eye movements and proprioception from the extraocular muscles are essential to acquisition of visually guided behaviors, while their role is reduced following this development.

Hogan's research in the Newman Laboratory emphasizes forceful interaction between the motor control systems of humans and machines (i.e., robots). Recent work pioneered therapeutic neurobotics to promote recovery after brain injury. It provides durable benefits even for chronic-phase stroke survivors, suggesting that with appropriate stimulation neural plasticity may be harnessed even long after injury. Devices to address balance, gait and abnormal lower-limb motor synergies, both in animals and humans, are in development or beginning trials.

A new generation of brain scanning methods will combine the specificity of cellular neuroimaging with the noninvasiveness and coverage of functional magnetic resonance imaging. The Jasanoff Laboratory is developing molecular strategies to help achieve this. We work on the chemistry and biochemistry of novel neuroimaging agents, and our overall goal is to apply the new agents for high-resolution analyses of the neural mechanisms of simple behavior in animals.

The Kanwisher lab investigates the functional organization of the brain as a window into the architecture of the human mind. In the past, our lab has discovered a number of cortical regions that are stunningly specialized for specific cognitive tasks such as the perception of faces, places, bodies, and words. Current work is attempting to better characterize the function of each of these regions, to test long-standing but unresolved claims of other cortical specializations (e.g., for language), and to search for new unpredicted specializations using novel clustering methods (in collaboration with Polina Golland). More generally, we want to know which mental functions get their own specialized piece of cortical territory and why we have cortical regions specialized for some mental functions, but apparently not others.

Research in the Littleton lab is aimed at characterizing the mechanisms by which neurons form synaptic connections, how synapses transmit information, and how synapses change during learning and memory. The lab combines molecular biology, protein biochemistry, electrophysiology and neuroimaging approaches with Drosophila genetics to address these questions. Given defects in synaptic connectivity and function contribute to neurodevelopmental diseases like autism, and loss of synapses is a major feature of neurodegenerative diseases like Alzheimer’s and Parkinson’s, work in the lab also provides critical insights into how diverse neurological diseases damage or disrupt synaptic function. The lab uses the fruitfly Drosophila as a model system for these studies. Despite the dramatic differences in complexity between Drosophila and humans, the molecular components of the synapse and the functional mechanisms they govern appear remarkably similar. Drosophila provides key advantages for this work, as neuronal development is very rapid and can be interrogated with genetic and imaging technologies that can’t be employed in humans. The lab has developed several technologies and toolkits that allow visualization of synapse formation and function in living animals. Using these new transgenic tools to visualize single active zone exocytosis, the lab is characterizing how synapses work, how they undergo plasticity, and how they contribute to both evoked and spontaneous fusion. In addition, the lab is defining the molecular machines that regulate both evoked and spontaneous synaptic transmission, as well as synaptic plasticity.

The Miller Laboratory uses experimental and theoretical approaches to study the neural basis of cognition. We investigate how categories, concepts, and rules are learned, mental flexibility, how attention is focused, and, more generally, how the brain coordinates goal-directed thought and action.

The overall goal of research in the Potter lab is to understand the very rapid processes involved in perceiving, comprehending, and remembering meaningful material such as words, sentences, or pictures. We've discovered that the meaning of a pictured scene or written word is understood in a fraction of a second, much faster than the time required for stabilizing even a brief memory of that stimulus -- unless the stimulus fits into the viewer's current mental context, like a word that is part of a sentence. To study these processes we use rapid serial visual presentation (RSVP) of words or pictures to mimic continuous reading or viewing. Our research subjects either look for particular targets in these sequences or are tested afterward to assess memory.

Fruit flies can learn. They can identify a specific chemical odor that they have experienced with electric shock and avoid it. Moreover, they can remember to avoid it for several days. The Quinn lab is investigating the molecular mechanisms underlying learning acquisition and memory storage by inducing and selecting single-gene mutations that affect learning or memory, and by engineering transgenic fly strains that disrupt these processes.

The Saxe lab studies Theory of Mind as a case study in the deeper and broader question: how does the brain - an electrical and biological machine - construct abstract thoughts? We use functional neuroimaging, behavioural studies with kids and adults, patient studies, and transcranial magnetic stimulation to study abstract representations in the human brain. In addition to Theory of Mind, our recent research investigates brain development, moral reasoning, causal reasoning, and language. We are interested in students or post-docs with backgrounds in philosophy, computer science, or systems neuroscience, in addition to psychology and cognitive neuroscience.

Current research in the Schneider lab involves axon regeneration in the central nervous system with functional recovery; special topics in human neuropsychology and perception; studies of the brains of sea mammals.

Professor Slotine is the Director of the Nonlinear Systems Laboratory which studies general mathematical principles of nonlinear system stability, adaptation, and learning, and how they apply to robots and to models of biological control. The lab is particularly interested in how stability and performance constraints shape system architecture, representation, and algorithms in robots, and in whether similar constraints may in some cases lead to similar mechanisms in biological systems. Tools from nonlinear control, such as sliding variables, wave variables, and contraction theory also suggest a number of simple models of physiological motor control, which may help understand the specific roles of hierarchies, motor primitives, and nerve transmission delays.

The Tenenbaum laboratory studies the computational basis of human learning and inference. Through a combination of mathematical modeling, computer simulation, and behavioral experiments, we try to uncover the logic behind our everyday inductive leaps: constructing perceptual representations, separating “style” and “content” in perception, learning concepts and words, judging similarity or representativeness, inferring causal connections, noticing coincidences, predicting the future.

The primary goal of the Tsai laboratory is to elucidate the pathological mechanisms underlying neurological disorders affecting learning and memory. The major research areas include brain aging and Alzheimer’s disease. We are taking a multidisciplinary approach to investigate the molecular, cellular, and circuit basis of  neurodegenerative disorders.

The Wexler ab/Normal Language Lab seeks to understand the nature of the computational system of human language in its many guises. We study most aspects of linguistic structure, including syntax, semantics, pragmatics and morphology. In pursuing these goals, we take as our primary linguistic data abnormal language, by which we mean nothing more than any system of language that seems to differ from standard adult language for biological reasons, including lack of maturation, difficulties in learning, and genetic variation.

Xu Laboratory is interested in how neurons respond to external stimuli and induce changes in their neuronal properties that eventually lead to the encoding of the information in the neural circuit. This type of activity-dependent long lasting changes is generally called neural plasticity. One form of neural plasticity, the long-lasting changes in synaptic strength, synaptic plasticity is thought to be the cellular substrate for learning and memory. Membrane excitability and intracellular environment respond to incoming neural activity and fluctuate at different temporal domains with potentially different spatial constraints. These fluctuations can influence the induction and expression of synaptic plasticity.