Mark Schnitzer Principal Investigator

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Mark Schnitzer is Assistant Professor of Biology and Applied Physics and is an Investigator of the Howard Hughes Medical Institute. His research concerns the innovation of novel optical imaging technologies and their use in the pursuit of understanding neural circuits. The Schnitzer lab has invented two forms of fiber-optic imaging, one- and two-photon fluorescence microendoscopy, which enable minimally invasive imaging of cells in deep brain tissues. The lab is further developing microendoscopy technology, studying how experience or environment alters neuronal properties, and exploring two different clinical applications. The group has also developed two complementary approaches to imaging neuronal and astrocytic dynamics in awake behaving animals. Much research focuses on cerebellum-dependent forms of motor learning. By combining imaging, electrophysiological, behavioral, and computational approaches, the lab seeks to understand cerebellar dynamics underlying learning, memory, and forgetting. Further work in the lab concerns neural circuitry in other mammalian brain areas such as hippocampus and neocortex, as well as the neural circuitry of Drosophila.

After completing postdoctoral research in neuroscience at Stanford and Genentech, Inc., I worked as a scientist and scientific manager at Entelos, Inc., working closely with both biologists and engineers to build computer based models of disease, including asthma and other inflammatory diseases. I have returned to Stanford to apply principles of scientific management to the work in the Schnitzer lab, where innovation of new brain imaging modalities involves detailed planning and coordination between several personnel with distinct areas of expertise. I also help coordinate our relationships with scientific corporations seeking to translate our inventions into the marketplace.

Juergen Jung Operations Director

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 My early work in the Schnitzer lab concerned the invention of both one- and two-photon fluorescence microendoscopy. Now, as Operations Director I am coordinating multiple aspects of our internal research program and our interactions with industry. I continue to engage in research on microendoscopy and have recently focused on the creation of a microendoscope for imaging the human cochlea, in collaboration with Joan Savall.

I support the laboratory through a variety of research activities involving histology, circuit tracing, genotyping, husbandry, and surgery. My collaborators include Robert Barretto, Lynn Sun, and Axel Nimmerjahn.

My research career began in medical robotics in the Department of Mechanical Engineering in KULeuven, Belgium. Subsequently, I was an Assistant Professor of Machine Theory at the University of Navarra and a Researcher in the Applied Mechanics Department at CEIT, Spain. I am now a visiting scholar at Stanford and have joined Prof. Schnitzer's laboratory to focus on the development of custom actuators to enhance surgeons’s use of our cochlear microendoscope. This project is a collaboration with Juergen Jung and Dr. Nikolas Blevins, a surgical otologist in Stanford’s Dept. of Otolaryngology.

The hippocampus is a brain structure central for encoding of declarative memory, consolidation of long-term memory and recalling of stored memory. To date, because of its location the hippocampal formation has been inaccessible for in vivo imaging studies. My interest is in using our lab's in vivo microendoscopy imaging techniques to study the mechanisms by which memory is encoded and retrieved both at the cellular and at the network levels.

My research focuses on the analysis of Drosophila foraging strategies, with the aim of identify their neurocomputational basis. Upon detecting attractive odors, suggesting the presence of a close-by food source, flies very efficiently track down that source. In order to obtain a detailed psychophysical description of flies' odor-tracking strategies, we are currently working on implementing machine-vision based tracking of fly trajectories during foraging. I am also interested in imaging the neural dynamics underlying these ecologically relevant computations.

Axel Nimmerjahn Postdoctoral Scholar

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In addition to neurons, the brain contains three major types of glial cells. Among these, the role of astrocytes, including Bergmann glia (BG) in the cerebellum, has remained enigmatic. In recent years, astrocytes have been shown to have some surprising functions, including control of synapse formation and function. Furthermore, both synaptic and structural plasticity processes thought to underlie learning and memory in the brain involve astrocytes. To study the potential role of BG cells in cerebellum-dependent motor learning I will monitor neuronal and BG network function in live mammalian subjects using two-photon fluorescence imaging of cellular calcium dynamics. By using transgenic mice I will examine how selective BG gene interference perturbs neuron-glia network processing as well as the acquisition and expression of learned behavior.

Efficient control of multiple effector muscles in a changing body and environment requires concerted and adjustable activity in populations of neurons. The Schnitzer lab has developed new techniques for imaging the activity of tens of identified neurons simultaneously, with single-cell resolution, in behaving rodents. My research focuses on applying these tools to further our understanding of the network mechanisms by which the cerebellum contributes to the learning and execution of coordinated motor outputs.

I obtained my doctorate from the Byer group at Stanford University in the area of high power lasers and nonlinear optics. I joined the Schnitzer group in January 2009 and am currently working on the Massively Parallel Brain Imaging project with Eric Ho, Eric Cocker, Tony Zhang, and Georg Dietzl.

The hippocampus contains different types of neurons that act in concert to enable learning and memory. In my research I am applying transgenic mouse tools and novel microendoscopy-based imaging techniques to investigate how experience affects structural and functional interactions between different types of hippocampal cells in vivo.

Robert Barretto Graduate Student

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I am interested in using in vivo two-photon fluorescence microscopy to visualize neuronal dynamics in the cerebellum. I am particularly interested in studying cerebellar circuit dynamics related to classical conditioning. I hope to further our understanding of how an animal analyzes available sensory information, and determines the salient information warranting a conditioned response.

My current projects are focused on the development of fluorescence microendoscopy approaches to imaging cellular level activity in freely moving rodents. This research involves a combination of applied optics and behavioral and circuits neuroscience. In these pursuits I am collaborating with Axel Nimmerjahn, and Eric Cocker.

My main research interests lie in the designing of mechatronic devices in the sub-areas of medical devices and robotics. I am currently working with Laurie Burns, Juergen Jung, and others in the lab on the design and implementation of a miniature device for imaging in the brains of awake-behaving mice.

I am interested in the interface between physics, mathematics, and the biological sciences. I am currently studying large-scale cerebellar networks and, in collaboration with the lab of Thomas Clandinin, motion detection in flies. As a theoretical scientist, I hope that by combining ideas and techniques from theoretical physics, neuroscience, statistics, and computer science, new insights can be developed into these beautiful and complex phenomena.

My primary interest lies in extending the capabilities of fluorescence imaging techniques such as exploring new ways to image faster and deeper.

My graduate research combines imaging, genetic manipulation, and analysis of behavior to assay computation and information flow in the cerebellar cortex.

Lynn Sun Graduate Student

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My current research aims to combine and utilize molecular biology, behavioral neuroscience and biophysical techniques towards the study of cerebellar circuits. At present, I have developed and am developing lentivirus and pseudorabies vectors to deliver genetically encodable optical probes to the neurons of live rodents. These viral vectors will be used in a collaborative project with Juergen Jung to assess structural changes in neurons and neuronal as the animal undergoes various physiological/behavioral events. In addition, I am also constructing viral vectors for the expression of calcium sensors with which I hope to gain an insight into the calcium signaling patterns of neurons and how these patterns may change as neurons are exposed to different electrical or behavioral stimuli. In both cases, imaging will be done using in vivo microendoscopy or microscopy approaches developed by the Schnitzer group.

I'm interested in the neural computations underlying motor learning and motor control, and will study these phenomena using a variety of techniques.

Dan Wetmore Graduate Student

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My research interests are focused on understanding the brain at a systems-level—to attempt to decode the patterns of communication between populations of cells and to integrate this knowledge with mechanisms of behavior. In collaboration with Devin Kehl, I am developing a mouse model of eyeblink conditioning, a cerebellar-dependant form of associative learning. Together with Todd Anderson, we will study the physiology of cerebellar neurons that are responsible for specific features of this behavior, such as acquisition, savings, and extinction. Electrophysiology in both anesthetized and awake, behaving animals will map these features to cerebellar regions and cell types. In addition, future imaging experiments offer promise for investigating sub-cellular processes involved in learning. In parallel with these in vivo experiments, I am collaborating with Eran Mukamel on computer simulations of cerebellar biophysics and circuit properties.

In order to understand neural codes, we require new tools for probing and watching neural circuitry in vivo. I am pursuing studies of cerebellar control of motor behavior by developing and using in vivo imaging techniques. My work draws on my substantial background in physics and computation and more recent interests in neuroscience. I collaborate with Laurie Burns, Daniel Wetmore, and Eric Cocker.

My work focuses on the mechatronic and optomechanical challenges involved in the massively parallel brain imaging project (MPBI), as well as in the design of the lab’s tiny, portable microscopes in the 1-3 gram range.