Faculty

Bio

Martha Streng is an Assistant Professor in the Department of Neuroscience. Her work focuses on the encoding of information by populations of cerebellar neurons, how they contribute to healthy behavior, and how they are disrupted in disease states.

Research Summary

While the cerebellum is classically considered a motor control structure, it has ever-emerging roles in extra motor behaviors and neurological disorders. In the case of epilepsy, cerebellar dysfunction could have major implications for patients, as cerebellar alterations predict comorbidities and negative outcomes in patients with epilepsy. A major challenge in cerebellar physiology is that while the cerebellar cortex has a highly conserved, stereotypic cytoarchitecture, with a precise spatial organization of inputs and outputs, we lack a clear understanding of how this spatial organization relates to the specific computations performed by cerebellar neurons. My laboratory utilizes wide-field optical imaging and intersectional approaches for circuit dissection in rodents to characterize cerebellar dynamics at the network level. We are examining how functional networks of cerebellar neurons are engaged during healthy behaviors, such as reaching or locomotion, but also how they are disrupted in disease states like epilepsy. Our ultimate goal is to link the structural composition of the cerebellar cortex with its functional organization and underlying fundamental computations.

Bio

Mark Thomas is a professor of neuroscience and director of the Medical Discovery Team on Addiction, a new research program funded by the state legislature to fuel cross-disciplinary collaborations and discover new treatment options. His research examines how addictive drugs alter the brain and how these changes can lead to compulsive drug use. His lab is now focusing on ways to disrupt addiction relapse.

Research Summary

Neurobiology of drug-induced plasticity and addiction A fundamental question in neuroscience is how the structure and function of the brain is modified by experience. One compelling model of experience-dependent plasticity is behavioral sensitization—a long-lasting increase in the locomotor stimulatory effects of drugs of abuse following repeated exposure. Behavioral sensitization is also a prominent model for the intensification of drug craving that occurs in human addicts. My laboratory seeks to identify the cellular and molecular mechanisms that underlie this form of plasticity, as well as the genetic factors that may predispose an individual to sensitization. We are currently studying two cellular correlates of drug-induced plasticity, long-term depression at glutamatergic synapses in the nucleus accumbens—a key site of action of drugs of abuse in the brain—and the increases in the length of dendrites and the density of dendritic spines that also occur in accumbens neurons. We are using several complementary approaches to determine the relationship that each of these correlates has with behavioral sensitization and with each other: behavioral studies to determine the consequences of drug exposure, the use of transgenic and knockout mice, analysis of dendritic morphology via several staining methods and whole-cell recordings in brain slices to investigate synaptic function. These studies will provide insight into the cellular and molecular mechanisms of an important form of experience-dependent plasticity that may hold some of the clues to drug addiction.

Research Summary

My main research focuses on mechanisms leading to neuronal cell insult and loss in neurodegenerative conditions. I have worked with neuronal cell cultures and mouse models of Alzheimer's disease (AD) and have developed new transgenic mice overexpressing in the brain a protein/enzyme (metalloproteinase-9) which protects against cognitive deficits by rescuing survival signaling pathways in cortical cells isolated from the AD mice. To investigate in depth different mechanisms involved in neuronal cell dysfunction and loss in neurodegenerative conditions, I have developed a cell culture system using neuroblastoma and primary neuronal cells which are exposed to serum from patients with neurocognitive symptoms (patients with Gulf War Illness/GWI, multiple sclerosis/MS, subjects with cognitive decline, etc.), in order to examine serum-mediated adverse effects. These studies include the examination of signaling pathways important for cytoskeletal (Rho, -Rock, -LIM kinase signaling) and mitochondrial integrity (mitochondrial membrane potential), cell membrane integrity, etc. Main survival pathways mediated by growth factor receptors (TrkA, TrkB, IR, etc.) are also examined. The goal is: a) to identify potential pathogens in the serum of patients with neurocognitive symptoms; b) to eventually develop means to interfere with neuronal cell dysfunction and neuronal cell loss by preventing compromise of vital survival pathways for brain cells.

Creative Activity Summary

Neuronal activity underlying behavior is encoded by distinct populations comprising a myriad of excitatory and inhibitory cell classes. These populations not only form local networks in individual brain areas but also act concertedly with neural assemblies in other relevant brain areas via global connections that facilitate interareal communication. In my recent work, I developed a high-throughput protein engineering and voltage screening approach to create a suite of 4 mutually compatible fluorescent voltage indicators for recording neuronal activity at submillisecond precision. Using a novel dual-polarity, dual-color voltage imaging technique, these indicators enable concurrent optical recordings of the spiking dynamics of three distinct excitatory and interneuronal populations in the visual cortex or the hippocampus in running mice. In a parallel study, I used genetically encoded calcium indicators and a synchronized dual microscope system to uncover the concerted spatial and temporal odor patterning in the dorsal and previously inaccessible lateral regions of the olfactory bulb. Collectively, the multipopulation and multiareal recording approaches will empower studies of the interplay between local and global neural circuit dynamics underlying stimulus-guided behavior in awake animals.

Research Summary

Research in the Vulchanova lab is focused on mechanisms underlying persistent pain. Our long-term goal is to contribute to the development of novel non-addictive chronic pain treatments. We are interested in elucidating the spinal circuits that mediate pain signaling, and in the discovery of novel signaling pathways involved in the development and maintenance of chronic pain. We are employing cutting-edge circuit-tracing, functional imaging, and transcriptomic approaches to investigate the organization of spinal pain circuits, and to quantify the contribution of novel signaling mediators (VGF-derived peptides) to chronic pain.

Research Summary

Brainstem control of spinal function: methods of fluorescence microscopy Almost everything we do and every sensation we perceive appears to be under the control of the brain. However, the mechanism by which this control is exerted is unclear. Our laboratory is interested in how the brainstem -- in particular, the serotonergic neurons of the lower brainstem -- controls the function of neurons in the spinal cord. Some, but not all, serotonergic neurons of the lower brainstem also contain other neurotransmitters -- chiefly, neuropeptides. We have examined the projections of these different types of serotonergic cells and found that there were distinct patterns of innervation: the cells containing neuropeptides predominantly innervated motor regions and the cells not containing neuropeptides innervated sensory regions. These differences suggest that these different types of serotonergic neurons have different functions. We are also localizing different types of serotonergic receptor to determine if different types of spinal neurons employ different receptors, i.e. if there is a functional organization at the level of receptors. The techniques that we employ include sophisticated types of optical microscopy, specifically, confocal microscopy, which allows tissue to be stained with several different fluorescent labels and "optically sectioned." In addition to our studies of receptor localization we combine molecular biological methods such as in situ hybridization with fluorescent neuronal labeling. Our research has required us to engineer several novel microscopic methods and doing so has been part of the job of this work. 

Research Summary

Neurotransmission of Pain Dr. Wilcox and colleagues are engaged in research into the spinal neurotransmission of pain and mechanisms underlying hyperalgesia, analgesia and analgesic tolerance. Studies of both excitatory and inhibitory neurotransmission in the rodent spinal cord apply behavioral, electrophysiological (both in vivo and in vitro),immunocytochemical and molecular techniques. Behavioral experiments define biologically relevant interactions, which are then examined at the cellular and molecular level using the more reductionist approaches. A key feature of research projects in this laboratory is open collaboration with laboratories located both here and at other universities. One major thrust of these investigations examines neurotransmitters thought to mediate major components of excitatory neurotransmission from primary afferent sensory fibers to secondary projection neurons in spinal cord dorsal horn: the excitatory amino acids (EAAs) like glutamate and the neurokinins like substance P. Intense or prolonged excitatory transmission via both these pathways is thought to evoke long term synaptic plasticity and excitotoxicity, which may underlie the development of some chronic pain states. A second major focus of work in the laboratory is the characterization of several inhibitory neurotransmitters and their receptors which together modulate this excitation. The neurotransmitters, enkephalin, serotonin and noradrenaline, inhibit various components of the incoming excitatory pain message in the dorsal horn via a number of inhibitory receptor subtypes. We are characterizing the interactions between these receptor subtypes and localizing them using transgenic mice, antisense oligonucleotides and immunocytochemical techniques. Finally, Dr. Wilcox facilitates access for Neuroscience students to high performance computing laboratories on campus - The Laboratory for Computational Science & Engineering and The Minnesota Supercomputer Institute (MSI). High performance computers and visualization are now finding applications in biological imaging, macromolecular modeling and neuronal simulation. A recent neuroscience graduate student developed a new method to optimize correspondence between neuronal simulations and experimental structure-function data.

Bio

Dr. Jan Zimmermann is an Assistant Professor in the Department of Neuroscience and the Center for Magnetic Resonance Research. His lab studies how the brain represents and constructs subjective value and how that signal is used to guide decision making. The lab is particularly interested in how the brain adaptively changes its coding strategy to encode statistical regularities within a changing environment. Using electrophysiology, ultra high field MRI and computational modeling the lab tries to understand how changes in reward encoding sensitivity could relate to a propensity for drug addiction.

Research Summary

The primary research goal of our laboratory is to better understand decision making. Making a choice, independent of it being a complex decision about your retirement allocations or which flavor of ice-cream to pick, is the normative consequence of any behavior that is observable.To understand this process, we combine a multitude of tools that allow us to study neural function of non human primates associated to decision making. We combine single cell electrophysiology, computational modeling of neural responses as well as careful behavioral analysis and ultra high field functional magnetic resonance imaging to figure out how organisms adaptively use their finite neural coding capacity to make choices.