We are continually in motion. This self-motion is sensed by the vestibular system, which contributes to an impressive range of brain functions, from the most automatic reflexes to spatial perception and motor coordination. The objective of Dr. Cullen's lab's research program is to understand the mechanisms by which self-motion (vestibular) information is encoded and then integrated with signals from other modalities to ensure accurate perception and control of gaze and posture. Our studies investigate the sensorimotor transformations required for the control of movement, by tracing the coding of vestibular stimuli from peripheral afferents, to behaviorally-contingent responses in central pathways, to the readout of accurate perception and behavior. Our experimental approach is multidisciplinary and includes a combination of behavioral, neurophysiological and computational approaches in alert behaving non-human primates and mice. Funding for the laboratory has been and is provided by the Canadian Institutes for Health Research (CIHR), The National Institutes of Health (NIH), the National Sciences and Engineering Research Council of Canada (NSERC), FQRNT / FQRSC (Quebec).

How do brain dynamics give rise to our sensory experience of the world? The O'Connor lab works to answer this question by taking advantage of the fact that key architectural features of the mammalian brain are similar across species. This allows us to leverage the power of mouse genetics to monitor and manipulate genetically and functionally defined brain circuits during perception. We train mice to perform simple perceptual tasks. By using quantitative behavior, optogenetic and chemical-genetic gain- and loss-of-function perturbations, in vivo two-photon imaging, and electrophysiology, we assemble a description of the relationship between neural circuit function and perception. We work in the mouse tactile system to capitalize on an accessible mammalian circuit with a precise mapping between the sensory periphery and multiple brain areas. Our mission is to reveal the neural circuit foundations of sensory perception; to provide a framework to understand how circuit dysfunction causes mental and behavioral aspects of neuropsychiatric illness; and to help others fulfill creative potential and contribute to human knowledge.

The neuroimaging and Modulation Laboratory (NIMLAB) investigates neural correlates of cognition and behavior using neuroimaging methods such as functional magnetic resonance imaging (fMRI) and neuromodulation techniques such as transcranial magnetic stimulation (TMS). We are looking in depth at the contributions of the cerebellum and cerebro-cerebellar circuits to cognition; the effects of chronic heavy alcohol consumption on cognition and brain activation underlying cognitive function; how aging in humans affects neural systems that are important for associative learning and stimulus awareness; and the integration of transcranial magnetic stimulation with functional MRI.

The studies of the Functional Neurosurgery Lab currently test whether neural activity related to the experimental vigilance and conditioned expectation toward pain can be described by interrelated networks in the brain. These two psychological dimensions play an important role in chronic pain syndromes, but their neuroscience is poorly understood. Our studies of spike trains and LFPs utilize an anatomically focused platform with high temporal resolution, which complements fMRI studies surveying the whole brain at lower resolution. This platform to analyze the oscillatory power of structures in the brain, and functional connections (interactions and synchrony and causal interactions) between these structures based upon signals recorded directly from the waking human brain during surgery for epilepsy and movement disorders, e.g. tremor. Our studies have demonstrated that behaviors related to vigilance and expectation are related to electrical signals from the cortex and subcortical structures. These projects are based upon the combined expertise of Dr. Nathan Crone in recordings and clinical management of the patients studied; Dr. Anna Korzeniewska in the analyses of signals recorded from the brain; Drs. Claudia Campbell, Luana Colloca and Rick Gracely in the clinical psychology and cognitive neurology of the expectation of pain and chronic pain; Dr. Joel Greenspan in quantitative sensory testing; and Dr. Martin Lindquist in the statistical techniques. Dr. Lenz has conducted studies of this type for more than thirty years with continuous NIH funding.

Led by Stephen Wegener, Ph.D, this research group focuses on projects that have the potential to improve function and quality of life and reduce disability following injury or illness. These projects include research on cognitive, behavioral, psychological and health care system factors that affect outcomes following injury.

The Caterina lab is focused on dissecting mechanisms underlying acute and chronic pain sensation. We use a wide range of approaches, including mouse genetics, imaging, electrophysiology, behavior, cell culture, biochemistry and neuroanatomy to tease apart the molecular and cellular contributors to pathological pain sensation. A few of the current projects in the lab focus on defining the roles of specific subpopulations of neuronal and non-neuronal cells to pain sensation, defining the role of RNA binding proteins in the development and maintenance of neuropathic pain, and understanding how rare skin diseases known as palmoplantar keratodermas lead to severe pain in the hands and feet.

The Wolfgang Laboratory is interested in understanding the metabolic properties of neurons and glia at a mechanistic level in situ. Some of the most interesting, enigmatic and understudied cells in metabolic biochemistry are those of the nervous system. Defects in these pathways can lead to devastating neurological disease. Conversely, altering the metabolic properties of the nervous system can have surprisingly beneficial effects on the progression of some diseases. However, the mechanisms of these interactions are largely unknown. We use biochemical and molecular genetic techniques to study the molecular mechanisms that the nervous system uses to sense and respond to metabolic cues. We seek to understand the neurometabolic regulation of behavior and physiology in obesity, diabetes and neurological disease. Current areas of study include deconstructing neurometabolic pathways to understand the biochemistry of the nervous system and how these metabolic pathways impact animal behavior and physiology, metabolic heterogeneity and the evolution of metabolic adaptation.

The Robinson Lab studies the way in which mechanical stress guide and direct the behavior of cells, including when they are part of tissues, organs and organ systems.

The research conducted in the Mumm Lab (Dept. of Ophthalmology, Wilmer Eye Institute) is focused on understanding how neural circuits are formed, how they function, and how they can be regenerated, to develop new therapies for retinal regeneration. Toward that end, we investigate the development, function, and regeneration of disease-relevant neurons and neural circuits responsible for vision. An emphasis is placed on translating what can be learned in regenerative model systems to develop novel therapies for stimulating dormant regenerative capacities in humans, Therefore, we apply what we learn from a naturally regenerative species, the zebrafish, toward the development of novel therapies for restoring visual function to patients. We place an emphasis on unique perspectives zebrafish afford to biological studies, such as in vivo time-lapse imaging of cellular behaviors and cell-cell interactions, and high-throughput chemical and genetic screening. We have pioneered several technologies to support this work including multicolor imaging of neural circuit formation, a selective cell ablation methodology, and a quantitative high-throughput phenotypic screening platform. Together, these approaches are providing novel insights into how the degeneration and regeneration of discrete retinal cell types is controlled.

The Marshall Shuler Laboratory aims to understand the means by which brain reward systems convey reward value, expectancy, quality, probability and utility, and the rules by which such activity is used to affect synaptic weight within brain networks to encode stimulus-action associations. We use an interdisciplinary approach combining multisite recordings of neural activity, targeted pharmacological manipulation, viral-mediated gene transfer and behavior to study the neural mechanisms of reward-based interval learning in the primary visual cortex.