Available Rotations

Active Perception Lab, Dr. Martina Poletti

Research in the Active Perception Lab stands at the intersection between visual perception, action and attention. I am interested in the neural and computational mechanisms underlying the control of attention and eye movements, and the establishment of spatial representations in humans. Using psychophysics and new techniques allowing for high resolution gaze localization and precise control of retinal stimulation (Dual Purkinje Image eyetracking, gaze-contingent display control, and retinal imaging), I examine how human oculomotor behavior and attention impact the acquisition and processing of visual information. 

Rotations are available to work on projects studying selective attention and its resolution within the fovea, and how fine control of eye movements enhances high acuity vision. Students rotating in the lab will work closely with other lab members and will take active part in weekly lab meetings.

For more information please contact the Active Perception Lab.

Advanced Retinal Imaging Alliance, Dr. Jesse Schallek

The neural cells that line the back of our eyes are sensitive to light and initiate our ability to see. These cells are among the most metabolically active tissues in the human body and are nourished by a dense network of capillaries that circulate blood to deliver nutrients and remove waste products from these hard-working cells. However, dysfunction of this neural-vascular system associates with a variety of retinal diseases and collectively gives rise to the leading cause of blindness in the developed world.

Our lab investigates blood flow in the living eye by using a specialized camera called an Adaptive Optics Scanning Light Ophthalmoscope (AOSLO) to correct for small imperfections of the optics of the eye. Once corrected, we can image the microscopic integrity of the smallest vessels that are ten-times thinner than a human hair. Additionally, capturing videos of this tissue enables study of the movement of single blood cells flowing within this network. We are developing and applying this cutting-edge technology to study blood flow in the retina in conditions of health and disease.

We are pursuing several projects in this area that include in vivo basic research in models of retinal disease and imaging human patients in the Flaum Eye Institute.

1. Examining the role of blood flow regulation and capillary level neurovascular coupling in the central nervous system
2. Characterizing blood flow at the smallest vascular level to determine what constitutes normal vascular perfusion
3. Imaging aberrant blood flow in patients with a number of vascular diseases of the retina
4. Developing new instrumentation to detect new sensitive biomarkers of retinal disease

For more information please contact the Advanced Retinal Imaging Alliance.

Advanced Retinal Imaging Alliance, Dr. Juliette McGregor

This research examines the role of retinal ganglion cells in the visual perception of primate (human and macaque) and mouse. Although the retina contains more than 17 types of ganglion cells and each type forms a complete mosaic across the retina, little is known about what role each type plays in seeing. ARIA is studying the role of different ganglion cell types using adaptive optics imaging of their calcium response.

We are pursuing several projects in this area in the Flaum Eye Institute.

1. Imaging the physiological activity of retinal ganglion cells with G-CaMP, a calcium indicator.
2. Restoration of vision to blind retina by inserting channel rhodopsin into retinal ganglion cells.
3. Determines how perception can be mediated by light-gated channels used to restore vision to blind subjects.
4. Identification and classification of retinal ganglion cells using response characteristics to chromatic and spatio-temporal stimuli.

For more information please contact the Advanced Retinal Imaging Alliance.

Briggs Lab

In the Briggs laboratory, we are interested in understanding how specific and identified cortical circuits encode information about the visual world. We also examine how attention impacts the way in which visual information is encoded by neurons and circuits. We use a variety of technical approaches including multi-electrode array recordings in alert and behaving animals trained on attention-demanding tasks and combination of multi-electrode array recordings with optogenetics to record and manipulate the activity of select neuronal populations in intact animals. In order to match neurophysiological recordings to identified neurons and circuits, we perform histology and reconstruct the anatomical structure of recorded and labeled neurons.

The following rotation projects are available in my laboratory:

1. Optogenetic manipulation of corticogeniculate neurons in vivo to examine the function of corticogeniculate feedback in visual processing. Project involves surgical injection of virus to drive expression of optogenetic proteins in target neurons followed by neurophysiological recording experiments. Histological processing of tissue is the final experimental step. Data analysis involves spike sorting and generating tuning curves for recorded neurons. Additional data analysis includes morphological reconstruction of labeled neurons.
2. Multi-electrode array recordings in the visual thalamus and primary visual cortex of alert and behaving animals performing attention-demanding tasks. Project involves daily recordings in behaving animals from arrays inserted daily and/or chronically implanted. Data analysis involves spike sorting and analysis of tuning and attentional modulation of recorded neurons. Local field potentials are also recorded in multiple brain structures and signal processing techniques are utilized to analyze amplitude and phase relationships between simultaneously recorded signals.
3. Analysis of large datasets including recordings from the visual thalamus and primary visual cortex across attention conditions, or with and without optogenetic manipulation of corticogeniculate feedback. Data is already collected and uniform analyses are applied to each dataset. Project involves spike sorting and analysis of tuning data as well as analyses of local field potentials for spike-field relationships. Computational modeling of individual neuron or local field potential interactions is also feasible for students with expertise in computer science.
4. Morphological reconstruction of virus-labeled neurons in tissue sections. Data is already collected and uniform reconstruction techniques are applied to gather morphological data from labeled neurons in a variety of brain structures.
    

For more information please contact Dr. Briggs.

Carney Lab

The Carney lab focuses on Auditory Neuroscience, including the encoding and processing of complex sounds in the central nervous system. We use physiological, behavioral, and computational techniques, and study listeners with and without sensorineural hearing loss.

For more information please contact the Carney Lab.

Cerebrovascular and Neurocognitive Research Group - Busza Lab

A multidisciplinary group of clinical and bench researchers has been formed at the University of Rochester Medical Center (URMC) to study cerebrovascular disease. The Cerebrovascular and Neurocognitive Research Group (CNRG), which consists of faculty from Neurology,   Neurosurgery, Electrical and Computer Engineering, Microbiology and Immunology, and Vascular Biology will leverage advanced brain imaging technologies to investigate a number of diseases, including stroke, cerebral small vessel disease (CSVD), and vascular dementia. 

Significant scientific advances in cerebrovascular and related neurocognitive disorders require an infrastructure that facilitates collaborations among clinicians, clinical and basic scientists. CNRG will become a catalyst for innovative research in cerebrovascular and related neurocognitive disorders, providing the link between basic research and clinical trials. 

These efforts are being supported in part by a new $2.7 million grant from the National Institute of Mental Health, to study how chronic inflammation drives cerebrovascular disease and disrupts the structure and connections between different parts of the brain.

My particular interests are in stroke rehabilitation.

For more information please contact Dr. Busza

Chemosensation and Social Learning Lab - Meeks Lab

The goal of the Meeks Lab is to better understand the mechanisms by which nonvolatile olfactory cues, including pheromones, guide animal social and reproductive behaviors. The neural pathway that detects and processes this information is called the accessory olfactory system, or AOS. This system begins in the nose in a small blind-ended tube called the vomeronasal organ (VNO), which sends information from the periphery into the first AOS neural circuit – the accessory olfactory bulb (AOB). 

For more information please contact Dr. Meeks.

Cognitive Neurophysiology Lab, Dr. John Foxe

We’re interested in understanding how the brain processes input from our sense organs. We have a particular interest in how conditions and disorders with genetic and neurological components affect sensory perception and sense-related cognition. To date, researchers in our lab have published articles related to Autism Spectrum Disorder, Dyslexia, Multiple Sclerosis, Schizophrenia, addiction, ADHD, and Rett Syndrome, to name a few.

We utilize a variety of techniques including electroencephalography, electrocorticography, functional magnetic resonance imaging, and transgenic murine models to study the characteristics of these diseases and how they are manifested in the brain. Our mission is to identify and understand the physiology of the fundamental deficits behind these syndromes and to connect these deficiencies to common genetic, physiological, and behavioral traits. Furthering our knowledge of these diseases has allowed us to develop clinical trials to ameliorate these deficits and measure that progress.

For more information please contact the CNLRochester website.

Crane Lab

A current focus in the laboratory are how multi-sensory stimuli (visual, vestibular, and proprioceptive) are used to determine orientation and heading in humans. The laboratory uses a hexapod motion platform and psychophysics techniques to examine these issues in controls and those with relevant pathology.

For more information please contact the Crane Lab.

Computational Neuroscience of Audition Lab, Dr. Norman-Haignere

Our lab studies the neural and computational mechanisms of hearing. Everyday hearing - understanding a sentence, recognizing a voice, or picking out the melody of a song - is a feat of biological engineering. Machine hearing systems are just beginning to catch up to their biological counterparts and still lag behind them in many respects. The long-term goal of the lab is to understand and model the neural computations that underlie human hearing, and to use these insights to improve machine systems and aid in the treatment of sensory deficits. Our lab focuses on measuring human brain responses using functional MRI as well as intracranial recordings from patients undergoing electrode implantation as a part of their clinical care. We also collaborate with animal physiology labs to understand how the human brain differs from other species, as well as address questions that are difficult to answer using human neuroscience methods alone.

For more information please contact the CNA Lab.

DeAngelis Lab

Neural Basis of Depth Perception

A rotation is available to work on a project related to the cortical mechanisms of 3D vision (depth perception). This may involve understanding how single neurons and populations of neurons represent 3D surface structure from binocular disparity, how neurons combine visual and extra-retinal signals to compute depth from motion parallax, as well as how disparity and motion parallax cues are integrated in the brain.

Relevant methods/skills: animal psychophysics (behavioral training), single and multi-neuron electrophysiological recording, computational modelling, computer programming.

For more information please contact the DeAngelis Lab.

Dragony Fu Lab

Our laboratory investigates the cellular roles of nucleic acid modification enzymes in biological processes ranging from neurodevelopment to the cellular stress response. In particular, we focus on discovering the targets and functions of two classes of enzymes: the SAM-dependent methyltransferases and the iron-dependent AlkB dioxygenases. To study the diverse processes modulated by these enzymes, we use an integrated biochemical, molecular and genetic approach in mammalian tissue culture systems as well as mouse knockout models. Through this approach, we have discovered novel targets and functions for enzymes involved in DNA repair, RNA modification and regulated cell death. The pathways and mechanisms identified through our studies provide critical insight into multiple aspects of human health and disease, including anti-cancer chemotherapy, degenerative disorders and aging.

For more information please contact the Dragony Fu Lab.

Fogaça Lab

Research in the Fogaça lab focuses on understanding the molecular basis of behaviors relevant to stress and the actions of fast antidepressant and anxiolytic drugs, aiming to identify specific circuits, neuronal subpopulations and synaptic mechanisms involved in these responses. Because currently available antidepressants have serious limitations for treating Major Depressive Disorder (MDD), including low response rates, a significant number of treatment resistant patients, and a time-lag before there is a therapeutic response, the lab is interested in exploring new pharmacological strategies to treat MDD, including compounds that target the glutamatergic and/or the GABAergic systems in the brain, such as ketamine, ketamine-like drugs and GABA receptor modulators. To this goal, we combine molecular neuropharmacology, genetic approaches and circuit-level studies of neurobiological systems to investigate how specific subpopulations of GABAergic (notably somatostatin and parvalbumin interneurons) and glutamatergic neurons crosstalk to modulate excitation and inhibition network dynamics that lead to phenotypes relevant to stress disorders and to the actions of fast antidepressants.

For more information please contact the Fogaça Lab.

Fudge lab

Our research is focused on microcircuits through the amygdala, as a way to understand the amygdala diverse roles in emotional processing. For example, the amygdala is involved in danger detection, which in humans depends on social cues. One project would involve mapping inputs from salience networks versus social cognition networks in prefrontal cortex to examine topographic relationships and interactions in amygdala subregions.

For more information please contact the Fudge Lab.

Goldman lab

The Center for Translational Neuromedicine is comprised of two divisions, which are respectively led by Drs. Steve Goldman and Maiken Nedergaard. The Goldman lab comprises the Division of Cell & Gene Therapy, whose affiliation is with Rochester’s Department of Neurology. The lab investigates the cellular and molecular bases for stem and progenitor cell-based repair of the central nervous system, with a focus on progenitor cell-based treatments of both the neurodegenerative and myelin diseases. We are also engaged in studies of the biology of primary brain tumors, given our observations of progenitor dysregulation in gliomagenesis. In addition, we are investigating the genesis, modeling and potential treatment of neuropsychiatric diseases, given the high incidence of glial pathology and likely progenitor cell contributions to these disorders.

The principal projects in the lab, and the faculty assigned to each:

• Biology of adult neurogenesis: Endogenous progenitors for the treatment of Huntington’s disease; Abdellatif Benraiss, Assistant Professor
• Biology of adult neurogenesis: Avian modeling and molecular regulation of neuronal recruitment; Robert Agate, Assistant Professor
• Biology of gliogenesis: Differential transcriptional and pathway regulation of glial progenitor cells of the fetal and adult human CNS, during de- and remyelination; Su Wang, Associate Professor
• Phenotype-specified instruction of human iPSC and ES cell-derived neural progenitors for transplantation and disease modeling; Su Wang, Associate Professor
• Biology of gliomagenesis: Tumor stem cells of the CNS, and their genesis from glial progenitors; Romane Auvergne, Assistant Professor
• Glial progenitor-based therapy in myelin disease: pediatric leukodystrophies and multiple sclerosis; Martha Windrem, Assistant Professor; Joana Osorio, Senior Instructor
• Use of human glial chimeric mice to study human glial-specific disease, with focus on human gliotrophic viruses; Yoichi Kondo, Assistant Professor
• Use of human glial chimeric mice to study disease-specific contributions of human glia to both neurologic and neuropsychiatric disorders, using patient-specific hiPSCs; Martha Windrem, Assistant Professor; Su Wang, Associate Professor

For more information please contact the Goldman lab.

Gomez-Ramirez lab

To generate stable representations of hand-held objects, our brain recruits high-level cognitive functions that dynamically interact with low-level sensori-motor neural representations. Our lab studies the neural dynamics along this cognitive-sensori-motor axis using a multi-species (rodents, non-human primates, and humans) and multi-method approach (high-density electrophysiology, optogenetics, and neural imaging). Trainees in my lab will have the opportunity to learn a combination of experimental techniques (e.g., 1- or 2-photon imaging coupled with optogenetics or single-unit recordings) to study the neural dynamics of different functional populations underlying haptics in animals performing active tactile discrimination tasks.

For more information please contact the Haptic Perception lab.

Haber Lab

The goal of the Haber lab is to understand the prefrontal-basal ganglia circuits associated with reward and decision-making in and changes associated with disease. A rotation project would include charting pathways from a prefrontal area, developing a 3-D model of those connections and testing how well diffusion imaging tractography replicates them.

For more information please contact the Haber Lab.

Hablitz Lab

My lab investigates the interaction between circadian timing and fluid movement between the brain and the body. Recently, we have shown that cerebrospinal fluid redistributes between the glymphatic system, the waste clearance system of the brain, and the lymph nodes in the periphery based on an endogenous, circadian (~24h) rhythm. Rotation students have the opportunity to contribute to projects investigating the genetic underpinnings of circadian timing in regulation of glymphatic function, how rhythms in glymphatic function could impact stroke pathology, whether chronotherapy can be used to treat chronic pain, and, finally, whether the brain-wide fluid movement within the glymphatic system may entrain the brain to the environment. Our lab uses a combination of live animal surgery, in vivo macroscopic and 2-photon imaging, ex vivo tissue analysis, and confocal imaging to ask how the body times itself to the 24h world, and how disruptions in this evolutionarily conserved timing process contribute to diseases such as stroke, pain, Alzheimer’s disease, and more.

For more information please contact the Dr. Hablitz.

Henry Lab

A rotation is available to study the consequences of cochlear neurodegeneration on auditory processing and perception of complex sounds. Of ~35,000 neurons present in each cochlea at birth, 1000-2000 are lost per decade due to normal aging and exposure to loud sound. Our lab uses behavioral operant conditioning experiments in an avian model species to characterize the effects of cochlear neurodegeneration on behavioral sensitivity to complex sounds. We also use neural recordings from the central auditory system to identify the changes in central processing that underlie deficits in auditory perception.

For more information please contact Dr. Henry.

Holt Lab

Many sensory systems are endowed with efferent feedback mechanisms that can modulate their primary input to the brain. That is, incoming information from a peripheral detector is delivered to a way station within the CNS which then modifies the output from that same detector. Everyday examples include the pupillary reflex to bright light entering the eyes, the contraction of middle ear muscles to loud sounds, or the recruitment of additional muscle fibers when first lifting a heavy object. Here, the function of the efferent loop is presumably to optimize or tune each sensory modality to its stimulus. Sensory information regarding the position and movement of the head are encoded by the vestibular system, which begins as a number of small detectors located within the inner ear.

Taking a reductionistic approach, my lab is addressing the function of the vestibular efferent system from three vantage points:

1. Identifying the receptor mechanisms by which different efferent responses are generated during activation of their pathways
2. Characterizing how these efferent receptor mechanisms modulate afferent response properties by pairing afferent recordings during vestibular stimulation with activation of efferent pathways
3. Identification of efferent discharge patterns with direct, in vivo recordings from vestibular efferent neurons.

For more information please contact the Holt Lab.

Hunter Lab

The ability to image individual cells at the back the living eye can provide important structural and functional information about the visual processes in healthy and diseased eyes. Our research focuses on developing cutting edge techniques to non-invasively interrogate retinal cells. We are employing non-linear fluorescence imaging to see the regeneration of photopigment in retinal photoreceptors, to image otherwise transparent ganglion cells, and to understand the metabolic response of the retina to visual stimuli. These studies are currently underway in animal models and in the future, will be extended to animal models of disease and to humans. In addition, we are studying ex vivo models to better understand our in vivo imaging results. Students will have the opportunity to participate in these adaptive optics retinal imaging experiments from start to finish.

For more information please contact the Hunter Lab.

Huxlin Lab

Broadly, research across my labs is focused on better understanding how the damaged, adult visual system can repair itself. What kind of plasticity is the damaged visual system capable of? What are the principles governing such processes? Can they be recruited to recover function? Two projects are available for student rotations:

Project 1: Using visual retraining to recovery vision after stroke and other forms of brain damage

Psychophysical techniques are used to both measure and retrain visual performance following damage to the primary visual cortex, which induces blindness over a large portion of the peripheral visual field. In addition to behavioral characterization of the properties of the recovery that can be attained with different training paradigms, we are interested in using attentional and other manipulations (e.g. transcranial magnetic stimulation, pharmacology) to enhance the recovery potential of the damaged visual system. Functional MRI is also used to study how the remaining cortical circuitry is altered by damage and subsequently, by training. It is hoped that this body of work will not only improve our understanding of the plasticity inherent in brain-damaged individuals with vision loss, but will ultimately improve how we treat this underserved patient population clinically.

Project 2: Factors controlling nerve regeneration after corneal injury

The eye is the sensory input to the entire visual system and it relies on a transparent and properly-shaped cornea. If the cornea is damaged, this impairs all of vision. Corneal nerves code discomfort and pain in response to mechanical stimulation, temperature change and/or chemical stimulation. They are critical for the health of the cornea, and for protecting the rest of the eye from outside elements. Disease, infection and ocular surgery can all damage corneal nerves, with long-term consequences in terms of pain, dry eye, recurrent erosions, opacity and even blindness. Yet, there are no effective therapies in clinical practice for treating nerve dysfunction in the context of corneal wounds. Our research employs a cat model of corneal wound healing after photorefractive keratectomy (a form of laser refractive surgery) and a combination of in vivo and in vitro approaches to study the basic cellular and molecular mechanisms controlling adult corneal nerve regeneration post-injury. The proposed, systematic characterization of nerve regeneration and its underlying molecular substrates during wound healing are critical for the development of new therapeutic strategies to treat corneal wounds, with an eye to promoting optimal nerve regeneration and ensuring long-term health of the ocular surface.

For more information please contact the Huxlin Lab.

Johnson Lab

The overall focus of our lab is on the molecular mechanisms of neurodegeneration. In particular we have two primary areas of research. The first area is on the role of the protein tau in Alzheimer’s disease as well as other neurodegenerative conditions with tau pathology. The second area of interest is on the role of the protein transglutaminase 2 (TG2) in mediating the survival of neural cells subsequent to stroke or physical injury to the nervous system.

In the context of the research interests of our lab the following are possible rotation projects:

1. examining the mechanisms that facilitate tau clearance from neurons
2. elucidating the specific transcriptional signaling pathways that regulate tau
3. identifying the mechanisms by which TG2 protects neurons from ischemic stress
4. understanding the role of TG2 in astrocyte function and survival

For more information please contact the Johnson Lab.

Keane Lab

The Keane lab studies behavioral psychophysics and functional neuroimaging to investigate the visual basis of psychosis.

Our brains are faced with the formidable challenge of having to parse and make sense of a kaleidoscope of incoming visual information. Healthy people segment scenes effortlessly but people with psychosis exhibit specific impairments linked to diagnosis, symptom severity, premorbid functioning, and age of onset. A major goal of the lab is to harness tools of behavioral psychophysics and functional neuroimaging to understand the neural and information processes that underlie visual object perception, both in healthy and psychotic populations.

For more information please contact the Keane Lab.

Kiernan Lab

The overall focus of the Kiernan laboratory is to understand the molecular development of sensory systems, particularly the inner ear and eye.  Uncovering molecules involved in important cell fate decisions represents a promising avenue for developing cell regeneration or cell replacement strategies to treat deafness and anterior segment dysgenesis (ASD).  Our lab uses advanced mouse genetics approaches to perturb gene function, including generating and analyzing conditional knockouts, Cre/loxP cell lineage analysis, and overexpression approaches using both tamoxifen-inducible and tet-inducible approaches.  Rotation projects could include confocal analysis of sensory hair cells, embryonic analysis, hearing testing measuring auditory brainstem responses, clinical eye exams in mice for ASD phenotypes, immunohistochemistry, and lineage tracing using mice engineered to express fluorescent proteins.

For more information please contact the Kiernan Lab.

Lalor Lab

The neuroscience of how humans perceive and engage with the world around them is still not well understood. In the Lalor lab for Computational Cognitive Neurophysiology, we use quantitative models to interrogate electroencephalographic data (EEG) from human participants as they engage in naturalistic experimental paradigms. Experiments involve acquiring EEG signals to natural stimuli while subjects perform a variety of tasks. EEG data are analysed using custom written MATLAB software and open source toolboxes. Rotation students can engage with projects through the development of novel stimuli and experimental paradigms; EEG data collection; analysis or reanalysis of existing data sets; and the development of new computational models for understanding human perception.

For more information please contact the Lalor Lab.

Libby Lab

The Libby laboratory studies neurodegenerative conditions of the eye.  We are particularly interested in diseases where axonal injury is an important aspect of the neuronal degeneration process, such as in glaucoma.  Rotation projects are available on projects examining axonal injury signaling, axonal degeneration pathways, and somal degeneration pathways.  There are also projects available to examine the importance of endothelin signaling in glaucomatous neurodegeneration.

For more information please contact the Libby Lab.

MacLean Lab

Our research focuses on how the functional properties of ligand-gated ion channels arise from their structure and how these properties enable their physiological roles. We focus on ionotropic Glutamate Receptors (iGluRs) and Acid Sensing Ion Channels (ASICs).

Glutamate is the main excitatory neurotransmitter in the mammalian central nervous system and the actions of this neurotransmitter are carried out, primarily, by iGluRs. In the last decade we have learned that certain iGluRs are accompanied by a variety of auxiliary proteins that alter trafficking and function and have brain region specific expression. In principle, therapeutic drugs which bind to interfaces between specific auxiliary proteins and iGluRs could impart brain region specificity and hence reduce side effects. We are pursuing this possibility and a rotation project is available to investigate structure-function relationships between specific iGluRs (AMPA receptors) and auxiliary proteins using patch clamp, unnatural amino acids and biochemical techniques.

For years Acid Sensing Ion Channels were thought to be nothing more than extracellular acid alarms. However, recently ASICs were found to contribute to excitatory postsynaptic currents in the amygdala, nucleus accumbens and calyx of held. We have found that the timecourse of ASIC currents under such circumstances are exquisitely sensitive to small pH changes. ASIC currents at pH 7.2 decay more then 30 fold slower than at 7.6. We suspect this unique feature of ASIC gating may underlie this channel’s importance in fear-related learning and substance abuse. A rotation project is available to develop and refine existing ASIC channels lacking this gating feature using patch clamp, molecular modeling and molecular biological techniques.

For more information please contact Dr. MacLean.

Majewska Lab

The Majewska lab studies the mechanisms governing synaptic plasticity. We use the visual cortex of adolescent mice as a model. We are most interested in the interplay of glia and neurons during plasticity, and the molecular signaling pathways that mediate neuroglial interactions. We are also interested in the role that arousal plays in the functions of glia and neurons during plasticity. Rotation projects may involve in vivo two-photon imaging of microglia, astrocytes and/or neurons, use of transgenic mouse models, immunohistochemistry, confocal imaging and image analysis, proteomic or genomic approaches.

For more information please contact the Majewska Lab.

Mayer-Pröschel Lab

Project 1

The overall goal of this project is to determine the impact of infection with a human-specific virus, human herpes simplex virus 6 (HHV6), on the repair function of human oligodendrocyte progenitor cells (hOPCs) in the context of demyelination and myelin repair. The student will be involved in the in vitro and in vivo analyses of human latent infected glial progenitor cells in respect to cell division, differentiation and migration in vitro. To examine the impact of latent HHV6 infection on myelination and cell migration in vivo, infected cells will be transplanted into a demyelinating mouse model and the capacity of infected cells to participate in oligodendrocyte generation and myelination will be studied.. The project involves cell culture techniques, Immunofluorescent cell labeling, in vitro migration assays, stereotactic transplantation of cells into animals, generation and characterization of tissue section using confocal microscopy.

Project 2

Our studies on the genetic disease Ataxia Telangiectasia (AT) demonstrated that mutation of the ATM gene in cerebellar astrogliarenders astrocytes defective in their ability to protect neurons from cell death. The defect seems to be in a downregulation of xCT, the major cysteine antiporter in astrocytes. The project is focused on analyzing the link between loss of ATM function and downregulation of xCT. Our preliminary data suggest a possible pathway that is inappropriately activated. The student will generate an antisense probes to a number of candidates we have identified, which will then be transfected into mutant ATM astrocytes and the impact of pathway inhibition will be analyzed. The project involves primary cell culture techniques, construction of antisense probes and expression of constructs in cells. The student will also perform western blot and redox analyses to examine the function of manipulated astrocytes.

Project 3

The project is conducted in collaboration with the Noble lab and is focused on analysis of the role of redox biology in lymphomas that arise in AT animals with a 100% penetrance. The student will be involved in analysis of a new cancer model for AT lymphomas, drug screening experiments to identify novel therapeutic approaches, and analysis of novel therapeutic approaches in other cancers. The project involves cell cultures analyses, automated adherent cell microscopy and tumor cell analysis in vivo.

For more information please contact the Mayer-Pröschel Lab.

Merigan Lab

The project will involve in vivo high resolution imaging of monkey or mouse retina. The particular project can be discussed with the student and could involve such issues as; in vivo measures of the response of identified retinal ganglion cells, restoring visual responses to blinded ganglion cells with channelrhodopsin, etc.

For more information please contact the Merigan Lab.

Mitchell Lab

An understanding of information processing at the level of cortical circuits remains a key challenge for understanding the brain and how the dysfunction of its circuits contributes to human mental disease. It has long been appreciated that internal brain states, such as selective attention, can profoundly modulate our perception. For example, when an observer focuses their attention toward a single object, such as a friend at a crowded party, it can lead to an almost complete filtering of the background. My research focuses on the role that internal brain states, such as selective attention, play in modulating sensory processing. I have forged a new direction in research developing the smaller New World primate, the marmoset (Callithrix Jacchus), to study active visual perception and attention. The marmoset provides several advantages as a model organism for these studies. First, the marmoset’s visual and oculomotor system is highly similar to that of larger primates and humans. Second, the recent development of transgenic lines in this species has opened many new opportunities for biomedical research. Last, due to their smooth lissencephalic brain, all of the visual and oculomotor areas lie accessible at the cortical surface of the marmoset, facilitating the use of modern recording methods with planar and laminar arrays. In recent work I have established the necessary techniques for visual behavior and neurophysiology in this species. This opens new opportunities to study visual perception and attention in cortical circuits at much greater precision.

For more information please contact Dr. Mitchell.

Nedergaard Lab

A rotation project could involve imaging of astrocytic calcium signaling in awake behaving mice to establish how astrocytes modulate the activity of glutamatergic synapses. Another project would be to validation of our transcriptome of human astrocytes using immunohistochemistry and molecular tools to manipulate gene expression in cultured human astrocytes. However, the lab are engaged in other lines of work mapping various aspects of astrocytic functions in health and disease.

For more information please contact the Nedergaard Lab.

Noble Lab

In general, our work follows the path of making novel discoveries, deriving the general principles that follow from these discoveries, and then applying this work to the understanding and treatment of challenging neurological diseases. The current major projects in the laboratory, for which rotations are available, are focused on cancer and on diseases of lysosomal dysfunction.

Our cancer work is focused on the development of new therapies that are more effective, cause less damage to the central nervous system (and are generally selective for cancer cells over normal cells) and that are suitable for rapid clinical transition. Glioblastoma and breast cancer have been our starting models, but we also are applying the principles discovered in this work to multiple other cancers. After pioneering the study of the biological foundations for the adverse effects of systemic chemotherapy on the CNS, we now are starting to publish our studies on protective strategies, and with our work on therapies moving along at a rapid clip.

In both areas, students who join the laboratory learn cellular and molecular biology, stem cell biology, the integration of metabolic regulation with cell signaling, drug discovery and both in vitro and in vivo analyses.

For more information please contact the Noble Lab.

Padmanabhan Lab

My primary research interests are to understand how patterns of neuronal activity encode for sensory stimuli and how this activity ultimately guides behavior. Using electrophysiology, imaging, and computational methods, I address these questions both in in vivo murine models, and well as in vitro cultures of human induced-Pluripotent Stem Cell (iPSC) derived neurons. I look forward to working with students who are interested in quantitative and computational approaches to neuroscience, including those with experimental interests in electrophysiology, behavior and imaging and those with theoretical interests in dynamics and information processing and look forward to taking rotation students in the Fall of 2016.

Project 1: The Role of Feedback Circuits in Shaping Sensory Perception

We have recently identified a direct feedback connection from the ventral CA1 region of the hippocampus to the main olfactory bulb 2 synapses from where olfactory information is first detected. Ventral CA1 is involved in encoding memory and learning, reward, social information and anxiety. The direct connections between these “higher order” representations and primary sensory regions suggest that sensory perception at the earliest stages may be modified and shaped by existing experience. How this occurs, what this means for the perception of odors, and ultimately how this affects behavior remains an open question.

Rotation Project 1a
Students interested in stress, anxiety and behavior will combine existing behavioral paradigms (an odor paired with a foot shock for instance) with novel viral tracing methods and imaging to identify CA1 feedback cells involved in encoding aversive experiences. Students working on this project will receive training in behavior, viral tracing methods, imaging, and image processing techniques.

Rotation Project 1b
Students interested in understanding how CA1 projections shape olfactory perception will develop the skills to perform in vivo multi-unit recordings in the main olfactory bulb coupled with optogenetic control of feedback projections. Students working on this project will receive training in in vivo electrophysiology, analysis of neural activity, and optogenetic methods.

Project 2: Analysis of the Dynamics of Large Scale Neural Networks

We have collected multi-unit electrophysiology recordings from large networks of neurons both in vitro and in vivo including from neurons reprogrammed from patient populations. These spontaneous activity recordings reflect the internal dynamics of neuronal networks, and reveal important links between properties of network architecture and the dynamic evolution of patterns of neuronal activity. What remains unknown is how the dynamics of networks are connected to the architecture of those networks, and how these two features are altered in neurological and psychiatric disorders like schizophrenia.

Rotation Project 2a
Students interested in statistical methods for data analysis, analyzing networks of neurons, and computational approaches to neuroscience will have the chance to quantify and classify patterns of activity from large scale neural networks. Students working on this project will receive training in data analysis and methods for analyzing patterns of neuronal activity using information theory.

For more information please contact Dr. Padmanabhan.

Portman Lab

Research interests in the Portman lab center around understanding sex differences in the nervous system: how does sex regulate neural gene expression, circuit structure and function, and behavior? Because these mechanisms are likely to be conserved across the animal kingdom, we are exploring these questions using the relatively simple and highly tractable model system C. elegans. Several rotation projects are currently available and can be specifically tailored to the interests and goals of individual students. Rotation projects could involve molecular biology and gene expression analysis, the study of behavior in wild-type and mutant animals, or the use of fluorescent synaptic markers to examine sex differences in neural connectivity.

For more information please contact the Portman Lab.

Pröschel Lab

Our lab utilizes a wide variety of techniques to manipulate neural cell populations in vitro, and to measure the effect of cell therapeutic interventions in animal models of CNS disease. Besides the commonplace molecular methods (QPCR, Western blot, cloning, lentiviral gene delivery, etc.), we have specialized protocols for the isolation and culture of different neural cell populations, including fetal and post-natal neurons, glial precursors, neural stem cells and inducible pluripotent stem cells (iPSCs) and hESCs. Chemically defined culture conditions are used to grow cells, and induce the directed differentiation of precursors. These in vitro methods allowing us to study the behavior and functions of these cells in culture, and to generate specific cell populations for transplantation into the injured CNS. For this purpose we use several different injury models, in particular rodent models of spinal cord injury, and Parkinsonian neurodegeneration. Functional readouts include common tests of motor skills (Foot placement, forepaw usage, gaitscan, grip strength, pellet reaching), as well as sensory assays (Hargraves, von Frey) and electrophysiological measures (EEG, MEP, SSEP). Post-mortem analysis uses immunhistology and stereological analysis of tissue sections. Because of the large number of techniques, students and post-docs are strongly encouraged to collaborate. However, to ensure a firm grasp of experimental design, and a sound foundation in methodological experience, PhD students are expected to master all the methodologies required to address their specific project needs, ranging from cloning to in vivo work. Projects available to rotation students can include any of these methods, typically however do not involve surgical procedures. All rotation students will be expected to give a brief presentation at the start and end of their rotation. The first presentation is intended to introduce them and their project to the lab. This ensures students have understood the theoretical background of their project and that they can quickly integrate into the lab. The second presentation will take place at the end of the rotation and will include data presentation and discussion.

For more information please visit the Pröschel lab.

Rochester Environment and Child Health Laboratory - Jusko Lab

As an environmental epidemiologist, Dr. Jusko's research interests concern the environmental causes of human disease. Within this broad area, Dr. Jusko's research primarily focuses on how environmental chemicals contribute to adverse immunological development over the entire lifespan. He is interested in the immune system as both a disease outcome (e.g., asthma, lowered vaccine response, development of autoimmunity), and as a mechanism of susceptibility for other disease outcomes, such as neurobehavioral development.

For more information please contact Jusko Lab.

Romanski Lab

Studies in my laboratory are aimed at understanding how neurons in the prefrontal cortex combine auditory and visual information such as facial gestures and vocal sounds during communication. We use electrophysiology, anatomical, and behavioral methods to understand the organization and functions of the primate prefrontal cortex.

For more information please contact the Romanski Lab.

Schieber Lab

We study control of arm and hand movements from the motor and premotor cortex by recording neural activity through implanted microelectrode arrays simultaneously with electromyographic activity and kinematics.

For more information please contact the Schieber Lab.

Singh Lab

The overall objective of our laboratory is to understand the molecular mechanism(s) of specific retinal and neurodegenerative diseases with the goal of developing pharmacological therapies.

The current projects in the laboratory utilize patient-derived human induced pluripotent stem cells (hiPSCs) for:

• Studying the role of individual cell layer and intercellular interaction in retinal physiology and disease development
• Delineating the disease mechanism(s) of retinal and neurodegenerative disease(s) including Batten disease and age-related macular degeneration
• Elucidating the role of gene-environment interaction in the pathophysiology of macular degeneration

For more information please contact the Singh Lab.

The Science of Neuro-Glia Interaction - Nathan Smith Lab

Projects in my laboratory focus on “Neuro-Glia” interactions. My research will explore the understudied and novel mechanisms by which neuromodulators mediate the interactions between neurons, astrocytes, and microglia in both normal and disease states. By studying how neuromodulators mediate the unique interactions between these three cell types, we will elucidate their coordinated functions in the normal, healthy brain and how disruptions of neuronal-glial crosstalk will contribute to disease processes such as ADHD, depression, and epilepsy. To that end, we hope these studies will provide valuable insight on the role of glia in pathophysiology, which is under-recognized in developmental disorders, with the hope of revealing pathways suitable for manipulation to alter disease progression in the central nervous system. To accomplish these goals, we employ a combination of transgenic animals, electrophysiology, pharmacology, behavioral assays, and 2-Photon Ca²⁺ imaging in acute slices and awake behaving animals.

For more information please contact Dr. Smith

Snyder Lab

The visual world contains more information than our brains can handle. My research is focused on the computational mechanisms that enable the brain to process goal-relevant visual information and to block out distractions. This involves studying how information is represented and manipulated at the level of small populations of neurons in cerebral cortex, as well as how the activity of multiple cortical areas is coordinated at a brain-wide level. The overarching goal of this research program is to develop interventions that improve our ability to successfully navigate the visual world.

For more information please contact Adam Snyder.

Telias Lab

We are interested in understanding how disease affects the interplay between gene expression, protein function and neuronal activity. For example, in retinal degeneration the death of the photoreceptors in the outer retina results in the appearance of a type of maladaptive plasticity in the surviving inner retinal neurons, especially in the retinal ganglion cells, the neurons that funnel all retinal information into the brain. This corrupted form of plasticity degrades residual vision and prevents meaningful vision restoration. Similarly, in the autism-causing disorder known as Fragile X Syndrome, the absence of the gene FMR1 and its encoded protein FMRP, result in uncontrollable idiopathic spontaneous hyperactivity that corrupts brain circuits, from the hippocampus to the prefrontal cortex. FMRP is an RNA binding protein regulating translation of hundreds of proteins, and its developmentally regulated silencing affects neurogenesis and synaptogenesis in the embryo as well as synaptic plasticity in the adult. Overall, our efforts are to understand how the two-way feedback regulation between neuronal activity and gene expression breaks down in disease, and whether it can be rescued. 

To study all these, we use a combination of molecular biology (gene expression, gene manipulation, protein labeling, fluorescent reporters); electrophysiology and imaging (multi-electrode arrays, single-cell patch-clamp, calcium imaging, neuronal morphology reconstruction), and behavioral assays (operant-conditioning, fear-conditioning, innate behavior). We work in-vitro with immortalized cell lines (HEK cells) and human embryonic/ induced pluripotent stem cells (hESCs, hiPSCs); in-vivo with mice and rats; and ex-vivo (when available) with human or primate biopsies.

Rotation projects available at the Telias Lab:

1. Pharmacological and genetic manipulation of retinoic acid receptor expression and activity in cell cultures and in mouse retina. The project involves working with cell cultures and mice, using several methods including imaging of fluorescent dies and reporters, RNA and protein extraction, RNA-seq, WB and co-IP.
2. Manipulation of P2X7 phosphorylation in dissociated retinal cells and in cell cultures, and correlation to downstream transcription factor activation. Methods are similar to #1.
3. FACS-sorting of in-vitro and in-vivo cell samples labeled with custom-built fluorescent reporters, followed by RNA-seq and bioinformatics analysis. This project involves developing the skills necessary for intraocular injections in living animals.
4. Genetic engineering of an anti-RAR and anti-P2X7 silencing therapy in mice.
5. Building and testing a new behavioral paradigm for innate light avoidance assay in mice.

* Projects 1-4 all involve fluorescent imaging and extracellular recordings performed using a state-of-the-art two-photon microscope and multielectrode array (MEA).

For more information please contact Dr. Telias.

Tivarus Lab

Our research focuses on clinical applications of advanced neuroimaging techniques such as functional MRI (fMRI), MR Spectroscopy (MRS), Diffusion Tensor Imaging (DTI), morphometry, Arterial Spin Labeling (ASL) and Dynamic Susceptibility Contrast (DSC). We have been using these techniques to study patients with brain tumors, epilepsy, Alzheimer’s disease, HIV associated neurocognitive impairment, multiple sclerosis.

• Pre-surgical brain mapping using Functional MRI (fMRI)
• Clinical applications of fMRI, Magnetic Resonance Spectroscopy (MRS), Diffusion Tensor Imaging (DTI) and Perfusion (Arterial Spin Labeling-ASL and Dynamic Susceptibility Contrast-DSC)
• Functional connectivity in the brain using resting state fMRI
• Measurements of cerebrovascular reactivity using BOLD fMRI and ASL

For more information please contact the Tivarus Lab.

White Lab

Hearing Restoration

• ERBB2/3 Activation after Cochlear Damage.
  We are conducting investigations into the timing, delivery, and sequelae of ERBB2/3 activation after cochlear damage. Preliminary data indicates that the genetic activation of ERBB2/3 in supporting cells may improve hearing outcomes after noise damage. These experiments are funded by our NIH R01, and by internal grants through the Schmitt Foundation and UR Ventures.

For more information please contact the White Lab.

Wynne Center for Family Research - Tom O'Connor Lab

The missions of the Wynne Center for Family Research are to conduct clinical research to understand how family and relationship processes influence behavioral and biological bases of mental and physical health; to provide clinical research training for all levels in research skills and activities needed to conduct high-quality and relevant clinical research; and to disseminate clinical research findings to inform clinical practice and public knowledge.

For more information please contact Dr. O'Connor.

Xia Lab

My lab studies the phosphorylation mechanism of synaptic plasticity in anxiety, learning and memory, and other experience-dependent brain functions. We use biochemistry, imaging, electrophysiology, transgenic mice and behavioral assays to address our question. More details about our lab can be found on our website. Below is a list of potential rotation projects available in our lab:

• Set up BRET/FRET assay to screen small molecule inhibitor of protein phosphatase-1 inhibitor-2 (PP1 I-2)
• Test the prediction that I-2 positively regulates PP1 function via facilitating PP1 binding to its scaffolding proteins
• Determine the effect of HUMAN PP1b point mutation on synaptic plasticity and memory formation in both primary neurons and a transgenic knock-in mice model
• Study the functional role of nuclear inhibitor of PP1 (NIPP1) in synaptic transmission, plasticity and memory formation
• To determine the signaling and molecular mechanisms of protein phosphatase-1 inhibitor -2 (PP1 I-2) in promoting escalated anxiety in alcohol dependent rats
• Making conditional I-2 KO mice to study the function of I-2 in different brain regions (hippocampus, striatum, amygdala etc) and cell types (pyramidal vs GABAergic neurons)

For more information please contact the Xia Lab.