Training Faculty for the PhD in Neuroscience: Charles River Campus (CRC) & Boston University Medical Campus (BUMC)

Carmela Abraham, Ph.D. (Professor, Member of the GPN GEC, Department of Biochemistry (BUMC)) studies the mechanisms of brain aging and the etiology of Alzheimer’s disease (AD). The 40-42 amino acid amyloid beta peptide (Aß) is the major component of plaques that accumulate in the brains of AD patients and are believed to cause irreversible mental deterioration. Formation and clearance of the neurotoxic Aß are major therapeutic targets for the treatment of AD. Aß is a proteolytic fragment of the amyloid precursor protein (APP), a ubiquitously expressed and conserved protein., The Abraham laboratory is conducting a screen to identify inhibitors of APP dimerization, because of its importance for Aß production, and has identified a proteolytic activity involved Aß degradation.  Her laboratory also studies the aging rhesus monkey as a model for normal human brain aging because they develop cognitive impairment with age. To their surprise, they could not detect cortical neuronal loss, but extensive changes in the white matter and particularly in myelin. They attribute these changes that occur with aging to neuroinflammation, a major area of their research interests along with the anti-aging gene Klotho that is markedly reduced in oligodendrocytes.

Helen Barbas, Ph.D. (Professor, Department of Health Sciences, Sargent College, Professor, Department of Anatomy and Neurobiology (CRC/BUMC)) focuses on the organization of the prefrontal cortex and its role in central executive functions in primates. The goal is to investigate prefrontal pathways that interface with both excitatory and inhibitory neurons in cortical and subcortical structures that may provide the basis for the selection of relevant information and suppression of irrelevant information in behavior. Research involves investigation of bidirectional pathways between prefrontal cortices and structures associated with sensory, cognitive, mnemonic and emotional processes in the cortex, the thalamus, and the amygdala.  Experimental approaches include the use of neural tracers to label pathways, combined with histochemical, immunocytochemical and molecular procedures to characterize the postsynaptic site of prefrontal pathways. We use quantitative approaches and imaging to reconstruct in 3D neural circuits at the level of systems and at the synaptic level, and employ multidimensional analyses to reveal patterns and principles of connections.

Michael Baum, Ph.D. (Professor, Department of Biology (CRC)) focuses on the mechanisms controlling the sexual differentiation and adult display of courtship behaviors in mice.  One project uses transgenic mice in which the /Cyp-19 /(aromatase) gene has been disabled to study the role of the sex hormone, estradiol, in the differentiation of female-typical aspects of courtship behavior, including olfactory responses to conspecifics. Another project concerns the interaction between the main and accessory olfactory nervous systems in the control of mate recognition and sexual motivation in male and female mice.  Techniques that used include brain immunocytochemistry to localize neuronal immediate-early gene products, steroid hormone receptors and several neuropeptides; in situ hybridization autoradiography to localize and quantify mRNAs for pheromone receptors in the vomeronasal organ; the quantitative analysis of sexual, scent marking, and olfactory behaviors as well as operant methods for assessing animals’ ability to detect pheromones as well as their sexual partner preferences; and brain infusions of neurotoxins, tract tracers and neuropeptides to study the olfactory mechanisms controlling sociosexual behaviors.

Peter Bergethon, M.D. (Associate Professor, Department of Anatomy and Neurobiology (BUMC)) focuses on discovering the underlying structural organization and biophysical mechanisms in the nervous system that can give rise to creative and intelligent behavior. Several essential questions that his laboratory explores are: 1) what is the fundamental unit of neural computation? 2) What are the mechanisms by which the properties associated with the nervous system, especially creative activity emerge from a system of these essential units? 3) What role does the electrical field play in modulating and modifying the electrochemical properties of the neural computation units. And 4) how do we bioengineer and build a computational system capable of synthetic creative behavior? They use a neurophysics research paradigm called “Intelligence Modeling” to convert complex observed behaviors (molecular, cellular and organism levels) into predictive modeling equations that can be parameterized via a variety of measurements. Techniques used in the laboratory to parameterize the modeling equations include fMRI, cortical near infrared spectroscopy and electroencephalography in humans and animals; computer modeling and bionic simulation; and bioelectrochemical studies of model membranes.

Gene Blatt, Ph.D. (Associate Professor, Department of Anatomy and Neurobiology (BUMC)) directs the Laboratory for Autism Neuroscience Research that is focused on the neuropathological and neurochemical alterations in the brains of individuals with autism. Cerebellar, limbic and cortical regions are investigated using a variety of proven neuroanatomical and neurochemical techniques including autoradiography, in situ hybridization and immunocytochemistry. Their goal is to identify and quantify core neural substrates as biomarkers for the developmental disorder in order to aid in the development of novel pharmacotherapies and to better understand current treatments within subsets of autistic individuals.

J. Krzysztof Blusztajn, Ph.D. (Professor, Department of Pathology (BUMC)) studies the effects of perinatal availability of an essential nutrient, choline, on brain development and aging in experimental animals. This research endeavors to determine why it is that supplementation with choline during critical perinatal periods in rats and mice causes a long-term facilitation of visuospatial memory which persists until old age. To this end they are utilizing biochemical, neuroanatomical, and behavioral techniques in a highly unified experimental design. Their studies to date have focused on the development of the basal forebrain cholinergic system, hippocampal MAPK and CREB signaling, and on the developmental patterns of brain gene expression.  They are also the first to show that choline nutrition in pregnancy alters the epigenome of the brain.

Jason Bohland, Ph.D. (Assistant Professor, Department of Health Sciences, Sargent College (CRC)) focuses on understanding the structural and functional architecture of neural circuits in the human brain, with emphasis on those that support speech and language processes. The laboratory uses an integrative approach that combines computational, informatics, and experimental brain imaging methods. A key area of focus is in linking the molecular level of organization to the neural systems and behavioral levels through the use of spatiotemporal profiles of gene expression coupled with brain imaging results, with the ultimate goal of better understanding genotype to phenotype relationships in neurodevelopmental disorders. Dr. Bohland is additionally involved in a collaborative experimental and informatics effort to comprehensively map the mesoscale connectivity patterns in the adult mouse brain.

Daniel Bullock, Ph.D. (Professor, Department of Cognitive and Neural Systems (CRC)) Interests of the Bullock lab are focused on the use of integrated computational models of local circuits implicated in reinforcement learning, planning of action sequences (including speech), and motivated decision making. Current models focus on forebrain circuits within or linking: laminar frontal cortex, the striatum and other parts of the basal ganglia, and midbrain dopaminergic areas.  The long-term goal is construction of quantitative models of sufficient accuracy to predict effects of many pharmacological manipulations on decision-making, voluntary behavior, and skill learning.

Jiang-Fan Chen, M.D., Ph.D. (Associate Professor, Departments of Neurology and Pharmacology and Experimental Therapeutics (BUMC)). In the laboratory of molecular pharmacology, Dr. Chen’s research focuses on the neurobiology of adenosine and the A2A adenosine receptor and the role they may play in the development and treatment of neuropsychiatric disorders. Dr. Chen has developed an A2A receptor knockout mouse model and couples this genetic approach with pharmacological manipulation to explore the pathophysiological role of A2A receptors in animal and cellular models of neuropsychiatric disorders. The knowledge derived from these studies may provide the neurobiological basis for rational development of A2A receptor agents as treatment strategies for neuropsychological disorders, ranging from Parkinson’s disease to drug addiction.

James Cherry, Ph.D. (Professor, Department of Psychology (CRC)) uses mouse models to understand the relationship between brain and behavior.  The laboratory uses neuroanatomical, behavioral and electrophysiological techniques to characterize functional differences in the neural circuitry that processes socially relevant odors (pheromones), with the goal of defining the specific roles of the main and accessory olfactory pathways in pheromone detection.  A second research area examines the role of type 4 phosphodiesterases in mechanisms underlying drug addiction and memory.

Dominic A. Ciraulo, M.D. (Professor and Chair, Department of Psychiatry (BUMC)). Dr. Ciraulo’s research interests focus on addiction psychopharmacology. He is the Principal Investigator of the National Institute on Drug Abuse and The BUMC Medication Development for Stimulants Center, and the Principal Investigator on grants from the National Institute on Alcohol Abuse and Alcoholism that study the role of medications and psychosocial therapies in the treatment of alcoholism. His research also examines the relationship between animal and human models for screening of medications to treat addiction. The medication development program incorporates the latest neuroimaging technologies in collaboration with the Brain Imaging Center at Boston University School of Medicine.

Pietro Cottone, Ph.D. (Assistant Professor, Department of Pharmacology and Experimental Therapeutics (BUMC)) is co-director of the Laboratory of Addictive Disorders.  The research  focus of the laboratory is the neurobiological substrates of motivated behaviors including feeding and addiction with the major goal of identifying the biological bases of and potential treatments for obesity and eating disorders. Current studies concern the role of stress in compulsive eating and palatable food dependence. Areas of focused research include the investigation of the neurobiological bases of stress-related disorders such as anxiety and depression. Dr. Cottone’s studies are carried out using environmental and genetic animal models, with behavioral, biochemical, and molecular approaches.

Alice Cronin-Golomb, Ph.D. (Professor, Department of Psychology (CRC)) directs the Vision & Cognition Laboratory whose principal focus is determining the factors that influence visual cognition in normal aging and age-related neurological disease. Her laboratory is identifying the brain bases of high-order cognitive dysfunction in neuropsychological populations, principally Alzheimer’s disease and Parkinson’s disease. Areas of interest in disease states include: (1) The relation between sensory function and cognitive function and (2) Neural circuitry of visuospatial function.  Dr. Cronin-Golomb teaches courses in neuropsychology and in the psychology of aging.

Uri Eden, Ph.D. (Assistant Professor, Department of Mathematics (CRC)) focuses on developing mathematical and statistical methods to analyze neural spiking activity.  He has worked to integrate methodologies related to model identification, statistical inference, signal processing, and stochastic estimation and control, and to expand these methodologies to incorporate point process observation models, making them more appropriate for modeling the dynamics of neural systems observed through spike train data.  His research can be divided into two categories; first, a methodological component, focused on developing a statistical framework for relating neural activity to biological and behavioral signals and developing estimation algorithms, goodness-of-fit analyses, and mathematical theory that can be applied to any neural spiking system; second, an application component, wherein these methods are applied to spiking observations in real neural systems to dynamically model the spiking properties of individual neurons, to characterize how ensembles maintain representations of associated biological and behavioral signals, and to reconstruct these signals in real time.

Howard Eichenbaum, Ph.D. (Professor and Director of the BU Center for Neuroscience, Departments of Psychology and Pharmacology and Experimental Therapeutics (CRC/BUMC)) The hippocampus plays a critical role in memory formation, but our understanding of just what the hippocampus does and how it performs its functions are still issues of considerable controversy. To enhance our knowledge about hippocampal function, the laboratory is pursuing a combination of neuropsychological studies of the nature of memory loss in animals with damage to the hippocampus and related cortical areas, and we are pursuing electrophysiological recording studies that seek to determine how information is represented by the hippocampus and associated cortical areas.

William Eldred, Ph.D. (Professor, Member of the GPN GEC, Department of Biology (CRC)) The laboratory studies nitric oxide (NO) that has normal physiological functions in every retinal cell type, and every retinal cell type can potentially make NO.  NO is also involved in many ocular pathologies including diabetic retinopathy and inhibiting NO is often beneficial.  NO signaling is regulated by many factors, both in normal retinal function and pathology, making it desirable to target just the pathological pathways.  Research of the laboratory focuses on how NO can be selectively targeted to decrease the neuronal and vascular pathology in diabetic retinopathy.  They are testing the following two hypotheses. 1) Diabetes increases the retinal levels of adrenomedullin (ADM), which in turn activates neuronal nitric oxide synthase (nNOS) to increase retinal NO production to pathological levels.  These studies provide the first demonstration of the ADM/nNOS/NO signaling pathways in retina and their modulation in the neuronal and vascular pathology in diabetic retinopathy. 2) Neuronal and vascular pathology in diabetic retinopathy share similar molecular pathways and are amenable to similar pharmacological interventions.  Their results will clarify the role of specific NOS isoforms and ADM in diabetic retinopathy and how these pathways can be optimally targeted to treat the pathology.  Upregulation of ADM is also found in proliferative vitreoretinopathy, uveitis, vitreoretinal disorders, primary open angle glaucoma, and retinitis pigmentosa.  A clearer understanding of the ADM/NOS/NO signaling pathways and how they can be manipulated in retina may have broad implications for much ocular pathology.

David H. Farb, Ph.D. (Professor and Chair, Member of the Executive Committee of the BU Center for Neuroscience, Department of Pharmacology and Experimental Therapeutics (BUMC)) focuses on the identification of pharmacological treatments for mental disorders of learning and memory.  His research integrates existing electrophysiological, behavioral, pharmacological, and molecular genetic technologies in a novel systems-level platform for assessing the impact of cognitive enhancers upon fundamental hippocampal systems for pattern separation (encoding), and pattern completion (retrieval) that are believed to be essential for cognition in all mammals, including man. Deficits in aspects of episodic memory dependent on hippocampal function are evident in a variety of mental disorders that have a huge social impact, including schizophrenia, autism, Alzheimer’s Disease, and normal aging. Existing pharmacotherapies for many such conditions are limited and carry substantial risk of adverse effects. High-density electrophysiological recordings in awake behaving rats are being used to identify deficits in hippocampal function that underlie cognitive deficits exhibited by aged animals and animals reared in social isolation, the latter being a model for environmental stress during development. A multidisciplinary approach that includes the techniques of neurophysiology, molecular biology, patch-clamp electrophysiology, cell biology, and molecular neuroanatomy are combined to elucidate the mechanisms and modalities of cognitive enhancers and the discovery of therapeutic treatments for disorders or diseases of the nervous system.

Lindsay A. Farrer, Ph.D. (Professor of Medicine, Neurology, Genetics & Genomics, Epidemiology, & Biostatistics; Chief, Genetics Program (BUMC)). Dr. Farrer’s research investigates genetic risk factors in familial neurodegenerative and other chronic diseases. In collaboration with other laboratories worldwide, his group has localized genes causing rare and common disorders including Alzheimer disease (AD), Wilson disease, Machado-Joseph disease, Waardenburg syndrome, hypertension, sensorineural deafness, and osteoarthritis. In collaboration with researchers at other institutions, Dr. Farrer is conducting a genome scan to search for genes conveying susceptibility to cocaine and opioid dependence among families with multiple affected members.

Christopher Gabel, Ph.D. (Assistant Professor of Physiology & Biophysics and Pharmacology & Experimental Therapeutics)  Dr. Gabel’s research program is focused on the development and application of femtosecond laser surgery and optical neurophysiology to the study of the nervous system of the nematode worm C. elegans. Using tightly focused pulses from an ultrafast laser, Dr. Gebel can ablate regions of biological tissue with submicron precision, making it possible to snip individual nerve fibers within an intact worm (Fig 1). This enables in vivo study of neural regeneration and dissection of neurocircuitry at a new level of resolution. A small transparent body, simple stereotyped nervous system and powerful genetic tools combined to make C. elegans an ideal model organism for this work. Femtosecond laser technology applied to this versatile and tractable system allows Dr. Gabel to tackle fundamental questions in neural regeneration and function.

Timothy Gardner, Ph.D. (Assistant Professor, Department of Biology (CRC)) studies how neural circuits form in the development of animal behavior. We focus on vocal learning in songbirds — a subject that lends itself to quantitative approaches.  How do songbirds memorize the songs of other birds, and how do these memories influence their own vocal learning? Many songbirds sing fairly normally when reared in isolation, but in the right circumstances, they may also imitate external models. Song learning is therefore the result of innate programming that provides a basic outline for song, and an auditory-memory based learning that builds on the innate program. The laboratory is currently investigating the process that builds and maintains the core sequence of the song behavior.  What growth mechanisms form the core structure of song and what are the geometric properties of the resulting circuit? What features of the circuit govern the flexible ordering of song? What homeostatic mechanisms maintain the circuit, and what is the role of spontaneous neural activity in sleep? For genetically identical birds, how would song learning differ? The lab is addressing one or more of these questions through tools including quantitative behavioral experiments and inbreeding, in-vivo imaging, electrophysiology and functional perturbation of neural activity.

Terrell T. Gibbs, Ph.D. (Associate Professor, Member of the GPN GEC, Department of Pharmacology and Experimental Therapeutics (BUMC)) research interests focus on the pharmacology of neurotransmitters and neuromodulators, and on mechanisms of modulation and regulation of neurotransmitter receptor function, including allosteric modulation, up- and down-regulation, desensitization, and tolerance. Current studies concern the acute and chronic effects of modulators of amino acid neurotransmitter receptors, including benzodiazepines, barbiturates, and neuroactive steroids. Computational and electrophysiological methods are used to evaluate thermodynamically plausible models for receptor function. Trainees will participate in the design and execution of pharmacological studies, and will be trained in the use of biochemical and/or electrophysiological techniques for studying receptor function.

Lee Goldstein, M.D., Ph.D. (Associate Professor, Departments of Psychiatry, Neurology, Ophthalmology, Pathology and Laboratory Medicine, & Biomedical Engineering (BUMC/CRC)) is focused on understanding the role of abnormal protein aggregation in chronic degenerative disorders of aging. The work in his laboratory concentrates on Alzheimer’s disease, age-related cataracts, and other common diseases of aging that involve pathogenic protein aggregation. His team recently discovered the first evidence of Alzheimer’s disease-associated amyloid pathology outside the brain as well as a new transcription factor that plays a crucial role in cellular differentiation within the lens and brain. He and his laboratory are developing a laser-based diagnostic technology that will hopefully detect Alzheimer’s disease years before the first symptoms emerge.

Stephen Grossberg, Ph.D. (Professor, Department of Cognitive Neural Systems (CRC)) develops brain models of vision and visual object recognition; audition, speech, and language; development; attentive learning and memory; cognitive information processing; reinforcement learning and motivation; cognitive-emotional interactions; navigation; sensory-motor control and robotics; and mental disorders. These models involve many parts of the brain, ranging from perception to action, and multiple levels of brain organization, ranging from individual spikes and their synchronization to cognition. He also collaborates in experimental projects to test predictions of his models, carrys out analyses of the mathematical dynamics of neural systems, and transfers biological neural models to applications in neuromorphic engineering and technology.

Frank Guenther, Ph.D. (Professor, Associate Director GPN, Departments of Speech, Language, and Hearing Sciences and Cognitive and Neural Systems (CRC)) combines theoretical modeling with behavioral and neuroimaging experiments to characterize the neural computations underlying speech and language. He is also involved in the development of speech prostheses that utilize brain-computer interfaces to restore synthetic speech to paralyzed individuals.  The primary goal of the lab is to develop, test, and refine a computational modeling framework that addresses the neural processes underlying speech. This theoretical framework is applied to communication disorders and the design of neural prosthetics in collaborative projects with other labs within and outside of Boston University.

Xue Han, Ph.D. (Assistant Professor, Departments of Biomedical Engineering, Pharmacology and Experimental Therapeutics (CRC/BUMC)) Brain disorders represent the biggest unmet medical need, with many disorders being untreatable, and most treatments presenting serious side effects. The Han laboratory is discovering design principles for novel neuromodulation therapies. They invent and apply a variety of genetic, molecular, pharmacological, optical, and electrical tools to correct neural circuits that go awry within the brain. As an example, they have pioneered several technologies for silencing specific cells in the brain using pulses of light. They have also recently participated in the first pre-clinical testing of a novel neurotechnology, optical neural modulation. Using these novel neurotechnologies and classical ones such as deep brain stimulation (DBS), they modulate the function of neural circuits to establish causal links between neural dynamics and behavioral phenomena (e.g., movement, attention, memory, and decision making). One of their current interests is the investigation of how neural synchrony arises within and across brain regions, and how synchronous activity contributes to normal cognition and pathology.

David Harris, M.D., Ph.D. (Professor and Chair, Department of Biochemistry (BUMC)) The Harris laboratory studies prion diseases, including Creutzfeldt-Jakob disease and kuru, that are fatal neurodegenerative disorders now of great medical importance because of the emergence of “mad cow disease” in Europe and the U.S., and its likely transmission to human beings. These diseases are also of enormous scientific interest because they involve an entirely novel mechanism of biological information transfer: they result from a change in the conformation of an endogenous membrane glycoprotein (PrPC) that converts it into a pathogenic isoform (PrPSc) that is infectious in the complete absence of nucleic acid.  To address this field, the laboratory utilizes several experimental systems including yeast, cultured mammalian cells, and transgenic mice.  They employ a wide range of techniques, including cell labeling, protein chemistry, light and electron microscopy, proteomics, DNA microarray analysis, mouse genetics, neuropathology, and animal bioassays.

Michael Hasselmo, Ph.D. (Professor, Department of Psychology (CRC)) Research in the Hasselmo laboratory is concerned with the cortical dynamics of memory-guided behavior, including effects of neuromodulatory receptors and the role of theta rhythm oscillations in cortical function. Neurophysiological techniques are used to analyze intrinsic and synaptic properties of cortical circuits in the rat, and to explore the effects of modulators on these properties. Computational modeling is used to link this physiological data to memory-guided behavior.  Experiments using multiple single-unit recording in behavioral tasks are designed to test predictions of the computational models. Areas of focused research include episodic memory function and theta rhythm dynamics in the entorhinal cortex, prefrontal cortex and hippocampal formation. Research addresses physiological effects relevant to Alzheimer’s disease, schizophrenia and depression.

Tarik Haydar, Ph.D. (Associate Professor, Department of Anatomy and Neurobiology  (BUMC)) The Haydar Laboratory of Neural Development and Intellectual Disorders uses a molecular neuroscience approach to study mammalian brain development, specifically focusing on the neural stem cells and precursors in the neocortex and hippocampus. The lab also investigates the cellular and genetic mechanisms of developmental disorders including those underlying mental retardation in Down syndrome using state of the art techniques such as in utero electroporation, in vivo genetic fate mapping and cell ablation.

Angela Ho, Ph.D. (Assistant Professor, Department of Biology (CRC))  The focus of the Ho lab’s research is to study cellular and molecular pathways involved in Alzheimer’s pathogenesis.  They examine Alzheimer’s related proteins by integrating mouse genetics with biochemical and cell biological approaches to address the physiological function and pathological processes that lead to neurodegeneration in the AD brain.  One of the pathological hallmarks of AD is the formation of extracellular neuritic plaques containing deposits of 40-43 amino acid amyloid peptides that are derived from the parent amyloid precursor protein (APP).  To date, the normal biological function of the APP gene family remains unclear.  They are investigating the role of the APP gene family in development, specifically on synaptic function and learning, and more importantly, their native function in the adult brain.  The second interest of the lab focuses on an essential family of neuronal adaptor proteins named Mint/X11s that have been implicated in coupling synaptic functions to the regulation of amyloidogenic processing of APP.

Tsuneya Ikezu, M.D., Ph.D. (Professor of Pharmacology & Experimental Therapeutics and Neurology (BUMC))  The Ikezu Laboratory of Molecular NeuroTherapeutics primarily focuses on Neuroimmunology and how the innate immune-related molecules in the central nervous system (CNS) influences the pathology and progression of select neurodegenerative disorders e.g. Alzheimer’s Disease (AD). The lab also investigates pharmacological means to suppress the innate immune response in the CNS with the goal of enhancing neuronal protection and minimizing collateral damage from an activated immune response in the CNS. Specifically they are investigating the role of the signaling cytokine IL-4/10/CD200 and its potential anti-inflammatory/neuroprotective role between microglia and both neurons and astrocytes during active CNS inflammation. Further, they are exploring IL-4/10/CD200 as a potential therapeutic in chronic inflammatory states within the CNS, such as seen in Alzheimer’s disease, to minimize neuronal cell loss.  A second focus of the Ikezu lab is the investigation of tau-tubulin kinases (TTBK1 and 2) and their role in hyper-phosporylating tau protein leading to the formation of tau and alpha-synuclein tangles within neurons, a key pathology observed in AD, Amyotrophic lateral sclerosis (ALS)/Lou Gehrig’s Disease, Spinocerebellar Ataxia, and Frontotemporal Dementia (FTD).

Angela L. Jefferson, M.D. (Associate Professor, Departments of Neurology and Medicine (Geriatrics) (BUMC)) Dr. Jefferson’s primary research interests are focused on elucidating unrecognized vascular risk factors for accelerating abnormal cognitive aging, including mild cognitive impairment and Alzheimer’s disease. These interests include examining relations between cardiac function and brain aging, the clinical and cognitive correlates of white matter disease, and neurogenetics of vascular disease and mild cognitive impairment. Dr. Jefferson is also interested in the identification and quantification of early higher-order functional decline in mild cognitive impairment and pre-clinical dementia.

Kathleen Kantak, Ph.D. (Professor, Member of the GPN GEC, Department of Psychology (CRC)) uses animal models to conduct translational research related to drug addiction, attention deficit hyperactivity disorder and their co-morbidity. Using intravenous drug self-administration procedures in rats, they investigate how multiple memory systems regulate drug-seeking and drug-taking behavior as well as how drug exposure influences the neurocognitive functioning of multiple memory systems. In addition, they investigate how cognitive-enhancing therapeutics may be useful to facilitate extinction learning for drug-conditioned cues and attenuate drug relapse. Other studies focus on evaluating the frontostriatal and medial temporal lobe neurocognitive deficits in rats with an ADHD phenotype and their response to medications as well as comorbidity between ADHD and vulnerability to drug addiction. In the context of all this research, Kantak collaborates with other investigators to conduct image analysis or to understand the neurochemical and molecular correlates of these disorders and their treatment.

Gary Kaplan, M.D. (Professor, Departments of Psychiatry and Pharmacology and Experimental Therapeutics (BUMC)) Addiction can be conceptualized as a progressive phenomenon initiated and maintained by the conditioned rewarding effects of drugs of abuse. As a result of neural plasticity in motivational and cognitive circuits, exposure to drug cues previously can evoke drug craving and seeking responses and that can reinstate drug taking. Our research examines the effects of gamma-aminobutyric acid- (GABA) type B and N-methyl-D-aspartate receptor receptor agents on the acquisition and expression of opiate and cocaine reward, self-administration, their extinction, and reacquisition. Such research defines the mechanisms related to drug relapse and defines novel therapeutic targets of interest for clinical studies. We utilize state-of-the-art methods in behavioral neuroscience, neuroanatomy, and neurochemistry to study these signaling pathways and circuitry in addiction and PTSD.

Nancy Kopell, Ph.D. (Professor, Member of the GPN GEC & Computational Neuroscience Curriculum Committee, Department of Mathematics (CRC), National Academy of Sciences) is interested in the dynamics of cortical electrical activity associated with sensory processing, cognition and motor control.  This broad area includes 1) the physiological and anatomical bases of the multiple rhythms measured in EEG, MEG and invasive paradigms; 2) the relationships between those rhythms and cognitive function; 3) how pathologies in those rhythms relate to cognitive and motor symptoms in neurological diseases.  Dr. Kopell is the currently co-director of the Center for BioDynamics (CBD) in the College of Engineering at Boston University. This multidisciplinary, interdepartmental center aims to train undergraduates, graduates, and postdoctoral fellows in leading techniques from dynamical systems theory and its applications to biology and engineering.

Conan Kornetsky, Ph.D. (Professor, Departments of Psychiatry and Pharmacology and Experimental Therapeutics (BUMC)) Dr. Kornetsky is internationally recognized as one of the early pioneers in the field of drug abuse.  He has carried out experiments on the role of the brain reward system in the reinforcing effects of abused substances, including alcohol, opioids and psychostimulants. Currently, his laboratory is pursuing research on the interaction of the brain reward and pain systems.  His latest discovery suggests that there may be an endogenous antagonist for the activity of endorphins that remains to be identified.  The research of graduate students in this laboratory continue to study the mechanisms involved in the rewarding actions of abused substances using the following techniques and procedures: stereotaxic surgery for implanting intercerebral stimulating electrodes and/or cannulae directly into specific brain sites, the use of psychophysical methods for determining thresholds for various types of intracerebral electrical stimulation (e.g., appetitive, aversive), the use of an intravenous drug self-administration model in rats, the use of the quantitative 2-[14C] deoxyglucose method for determining cerebral metabolic rates of glucose in specific brain areas., and the evaluation of brain-stimulation reward in knockout mice models.

Mark Kramer, Ph.D. (Assistant Professor, Department of Mathematics (CRC)) focuses his research on topics in mathematical neuroscience, with particular emphasis on neural rhythms, dynamical systems, data analysis, and brain disease.  The work is highly interdisciplinary, involving mathematicians, statisticians, neuroscientists and clinical collaborators.  He is especially interested in the quantitative analysis of electrophysiological data, and understanding the biophysical mechanisms that produce the dynamic neural activity observed.  His current clinical work focuses on analyzing multivariate data and identifying the mechanisms that support the pathological brain activity characteristic of epilepsy.

Susan E. Leeman, Ph.D. (Professor, Department of Pharmacology and Experimental Therapeutics (BUMC)) Dr. Leeman’s work focuses on the two peptides, substance P (SP) and neurotensin, which were isolated and chemically defined in her laboratory and lead to her membership in the National Academy of Sciences. Projects that are currently underway include: 1. the role of glycosylation of the NK1 receptor on its signal transduction pathways, 2. the roles of SP in several models of inflammation in the gastrointestinal tract, including post-surgical cell adhesion formation, and the effect of non-peptide SP antagonists. 3. the role of LITAF, a newly described transcription factor participating in TNF alpha synthesis in macrophages obtained from inflamed colonic tissue.

Jen-Wei Lin, Ph.D. (Professor, Departments of Biology and Pharmacology and Experimental Therapeutics (CRC/BUMC)) focuses on cellular and molecular mechanisms of neurotransmitter secretion Neurotransmitter secretion is a complicated process that involves ion channel gating and secretion steps. In addition, the mobilization and recycling of synaptic vesicles are needed to maintain the function of a synapse and to contribute to synaptic plasticity. Ultimately, an understanding of the secretory events means that one can establish a kinetic scheme for this multi-step process and identify molecules responsible for each step. Therefore, a combined electrophysiological and molecular approach is used in the Wei-Lin laboratory to investigate these questions.

Jennifer Luebke, Ph.D. (Associate Professor, Department of Anatomy and Neurobiology (BUMC)) employs whole-cell patch-clamp and intracellular filling techniques to examine the electrophysiological and morphological properties of neurons in in vitro slices of monkey and mouse neocortex. Research is focused on action potential firing patterns (and underlying ionic currents), glutamatergic and GABAergic synaptic response properties and detailed dendritic architecture. Data from single neurons are incorporated into computational models in collaboration with mathematicians at Mt. Sinai School of Medicine. In addition, collaborations are ongoing with investigators at BUSM who use molecular biological (single cell PCR and microarray) and electron microscopic (ultrastructural analysis) techniques to examine cells from which recordings are obtained. Overall goals include: 1) to examine the individual and network properties of cells in the prefrontal cortex; 2) to determine the effects of normal aging on these properties in the rhesus monkey, and; 3) to determine the effects of amyloid and tau on these properties in transgenic mouse models of Alzheimer’s disease.

Hengye Man, Ph.D. (Assistant Professor, Departments of Biology and Pharmacology and Experimental Therapeutics (CRC/BUMC)) is interested in the mechanisms in the expression of synaptic plasticity.  Since most of synaptic transmission is mediated by glutamatergic AMPA receptors, the studies have been focused on regulation of AMPA receptor expression, turnover and synaptic localization as well as synaptogenesis.  The questions they address include: What molecules and signaling pathways determine AMPAR synaptic localization? How does neuronal activity regulate AMPA receptor trafficking and expression? How does the neuron maintain a specific amount of total receptors? How are receptors degraded and what regulates the rate of turnover? Using cultured cortical and hippocampal neurons and brain slices, we study receptor trafficking and synaptic transmission by employing a wide range of techniques including immunocytochemistry, confocal/fluorescence microscopy, live-imaging, biochemistry (western blotting, immunoprecipitation), and electrophysiology (patch clamp recording).

Ennio Mingolla, Ph.D. (Professor, Department of Cognitive and Neural Systems (CRC), Professor of Psychology, Director, CELEST, Center of Excellence for Learning in Education, Science, and Technology) works on development and empirical testing of neural network models of visual perception, notably the segmentation, grouping, and contour formation processes of early and middle vision in primates, and on the transition of these models to technological applications.

Mark Moss, Ph.D. (Professor and Chairman, Member of the Executive Committee of the BU Center for Neuroscience, Department of Anatomy and Neurobiology (BUMC)) studies the neurobiological basis of successful and unsuccessful aging, with particular respect to memory and executive functions.  Specific interests include (1) the interaction of the prefrontal cortices with the medial temporal lobe limbic system in cognition; (2) the separate and combined effects of age and hypertension on cognition and integrity of the blood-brain barrier in a non-human primate model of hypertensive cerebrovascular disease and (3) parallel studies in normal aged humans and patients with MCI and Alzheimer’s disease. Techniques include automated behavioral assessment, functional and structural MR imaging, and an array of immunocytochemical and related anatomical-morphological techniques.

David Mountain, Ph.D. (Professor, Department of Biomedical Engineering (CRC)) Dr. Mountain’s research centers around the experimental and theoretical  studies of hearing function, including: cochlear biomechanics, otoacoustic emissions, auditory processing of complex sounds, and auditory evoked potentials. Professor Mountain also engages in studies designed to predict the impact of anthropogenic sound sources on marine mammals.  Dr. Mountain is a member of the Auditory Biophysics and Simulation Laboratory in the Boston University Hearing Research Center.  Auditory information processing; sensory biophysics; computer simulation; biomedical electronics; biomedical signal processing; environmental engineering.

Marlene Oscar-Berman, Ph.D. (Professor, Member of the GPN GEC, Departments of Anatomy and Neurobiology, Psychiatry, and Neurology (BUMC)) explores the brain and behavioral consequences of human neurological disorders.  Her recent publications are on the cognitive and emotional changes that result from chronic alcoholism, as well as on brain structural changes that are apparent in regions involved in cognitive and emotional functioning. Dr. Berman also has studied the behavioral consequences of brain damage in patients with other disorders of the central nervous system.  Additionally, her work on brain asymmetries addresses questions concerning the different roles of the two cerebral hemispheres in processing, understanding, and responding to visual information having emotional and non-emotional content.  Dr. Berman is the recipient of numerous awards, including a Fulbright award and a Senior Scientist and Mentorship award from the National Institute on Alcohol Abuse and Alcoholism in the National Institutes of Health.

Jason Ritt, Ph.D. (Assistant Professor, Biomedical Engineering) Dr. Ritt’s research concentrates on how organisms gather and use information from their environment, through processes of active sensing and sensory decision making.  Current projects employ electrophysiological, behavioral, optogenetic and theoretical methods applied to the rodent whisker system, a highly refined tactile sensory system.  Experiments combine multi-electrode recording of brain activity; high speed videography of behavior and development of automated image analysis algorithms; and optical stimulation of specific cell types (e.g., excitatory vs. inhibitory neurons) using genetically targeted expression of light sensitive ion channels.  Parallel modeling uses tools from dynamical systems, control theory and decision theory. Augmenting experiments with model-driven, real-time feedback forms a basis for development of brain machine interfaces, with an emphasis on sensory neural prosthetics, in addition to providing state of the art tools to address basic questions of neural function.

Douglas Rosene, Ph.D. (Professor, Member of the GPN GEC, Course Director for GPN, Department of Anatomy and Neurobiology (BUMC)) The research of Dr. Rosene focuses on identifying the neurobiological basis of learning and memory and related higher cognitive functions in the normal brain and the basis of disruption of these processes in various neurodegenerative diseases and forms of neurological damage. The laboratory employs multidisciplinary methods to investigate these issues in the rhesus monkey model of cognitive function. Methods include combinations of behavioral, neurohistochemical, neurophysiological, neuroanatomical, neurosurgical, and MRI techniques. Investigations supported by the Program Project that he directs, seeks to identify the neurobiological basis of age-related impairments in learning, memory and executive function in the rhesus monkey model of normal aging. Results of these investigations have demonstrated that cortical neurons are not lost in normal aging as conventional wisdom held but instead the main changes are in the subcortical white matter of the forebrain. Parallel studies are focused on neurodegenerative disease, cerebrovascular disease and traumatic brain injury, and in collaboration with Dr. H. Eugene Stanley in the Physics Dept at BU the development of novel ways to quantify the microcolumnar structure of cerebral cortex using methods from statistical physics.

Michele Rucci, Ph.D. (Associate Professor, Departments of Psychology and Biomedical Engineering (CRC)) directs The Active Perception Lab that focuses on active perception in biological and artificial systems. Experimental and theoretical approaches are combined to examine motor influences on perceptual performance and on the encoding of sensory information in the brain. Robots replicating the sensory-motor strategies of various species are studied in an effort to develop efficient machine perception systems. Research in the Active Perception Laboratory has raised specific hypotheses regarding the influences of eye movements during visual development and in the neural encoding of visual information. This research has also demonstrated the involvement of fixational eye movements in fine spatial vision, produced a new system for experimental studies of visual neuroscience, and led to the development of robots directly controlled by models of the brain.

Shelley Russek, Ph.D. (Professor and Director of GPN, Department of Pharmacology and Experimental Therapeutics (BUMC)).  The research of Dr. Russek focuses on the role of BDNF in brain plasticity of neural networks and in multiple neurologic and neuropsychiatric disorders, such as anxiety, epilepsy, autism, depression and schizophrenia.  It is clear that BDNF plays a crucial role in organizing the response of the genome to dynamic changes in the extracellular environment that enable brain plasticity and it has emerged as one of the most important signaling molecules of diverse intracellular programs that maintain a healthy balance of excitation and inhibition in the brain. How BDNF transcriptionally controls the pool of important proteins that are the substrate of this balance in vivo, increasing as well as decreasing the number and kind of key proteins and enzymes, is not understood and is a major question of the Russek laboratory. How BDNF controlled gene networks in individual neurons may impact the dynamics of a neural circuit, such as the brain reward pathway, is also a major question of her research that employs a variety of techniques in molecular, cellular, and systems neuroscience.

Valentina Sabino, Ph.D. (Assistant Professor, Department of Pharmacology and Experimental Therapeutics (BUMC)) is co-director of the Laboratory of Addictive Disorders. Dr. Sabino is currently researching the neurobiology of addiction and stress-related disorders.  Studies on addiction aim to understand the neurobiological substrates of alcohol abuse and dependence, by exploring the role of central neurochemical systems in excessive alcohol drinking. She is working toward the development of new therapeutic agents to alleviate alcohol addiction.  Animal models for excessive drinking are studied in order to identify compounds for potential clinical development.  Research is also conducted on the neurobiology of stress-related disorders such as anxiety and depression. The laboratory uses environmental and genetic animal models of disease, with a multidisciplinary approach to understand the neurobiology of psychiatric disorders and to develop novel therapies.

Barbara Shinn-Cunningham, Ph.D. (Professor, Member of the GPN GEC, Department of Biomedical Engineering (CRC)) Shinn-Cunningham is the Director of the Auditory Neuroscience Laboratory in the Boston University Hearing Research Center, housed in the Department of Cognitive and Neural Systems. Projects in the Auditory Neuroscience Laboratory explore how we perceive sound sources in ordinary listening environments that contain multiple, competing sources, echoes, and reverberation. They are investigating how auditory attention and the perceptual organization of sound influences perception, how the brain encodes features of sound important for perception (including spatial auditory cues), the role of multimodal interactions in perception, and development of physiologically based computational models of auditory processing. A variety of methods are employed, including psychophysics, modeling, EEG, acoustical measurement, and single-unit recording.

Jean-Jacques R. Soghomonian, Ph.D. (Associate Professor, Department of Anatomy and Neurobiology (BUMC)) The laboratory focuses on the functional and chemical neuroanatomy of the basal ganglia and the cerebral cortex in normal animals and in experimental models of Parkinson disease. Current objectives are to study the plasticity of GABA-mediated signaling in the basal ganglia and cerebral cortex and the mechanisms involved in motor and cognitive disorders in Parkinson disease in a 6-hydroxydopamine-rodent model of Parkinson’s disease and on human brains.  The research involves behavioral and biochemical/molecular approaches including analysis of gene expression by in situ hybridization histochemistry and computerized quantitative image analysis, immunohistochemistry, western-blotting and in vivo microdialysis combined with HPLC.

David Somers, Ph.D. (Associate Professor, Department of Psychology (CRC)) heads the Perceptual Neuroimaging Laboratory that investigates the neural and cognitive representations and mechanisms of perception, attention, and perceptual short-term memory in humans using functional magnetic resonance imaging, computational modeling and psychophysics.  In addition to the primary focus on vision, collaborative work investigates tactile and auditory processing. Functional MRI studies focus on within-subject data analysis that permits the functional segregation of small cerebral cortical areas that are often obscured in across-subject analysis.  Recently, they identified and characterized two new visuotopic areas in human posterior parietal cortex using these methods.

H. Eugene Stanley, Ph.D. (Professor, Departments of Physics, Physiology, Chemistry and Biomedical Engineering (CRC/MED)) is a member of the National Academy of Sciences and a University Professor of Boston University.  Dr. Stanley works in collaboration with students and colleagues attempting to understand puzzles of interdisciplinary science. His main current focus is trying to understand the anomalous behavior of liquid water in bulk, nanoconfined, and biological environments. He has also worked on a range of other topics in complex systems, such as quantifying correlations among the constituents of the Alzheimer brain, and quantifying fluctuations in noncoding and coding DNA sequences, and interbeat intervals of the healthy and diseased heart. He was awarded the 2002 Memory Ride Prize for research on Alzheimer’s disease, and IBM awarded Boston University a one million dollar computer to continue that research in new directions.

Chantal Stern, Ph.D. (Professor, Department of Psychology (CRC)) is a core faculty member of the Conte Center for Memory and Brain, a member of the NSF CELEST Science of Learning Center, and a faculty member at the Martinos Center for Biomedical Imaging at the Massachusetts General Hospital. She also serves as an internal advisory board member for the Boston University Alzheimer’s Disease Center.  Her students are trained in basic fMRI research methodology, and in addition are trained either to link their fMRI work to animal and computational models (integration with Hasselmo and Eichenbaum labs) or to link their studies with clinical population studies (Alzheimer’s disease, Parkinson’s disease, HIV dementia, eating disorders). Chantal Stern has been instrumental in providing fMRI training to postdocs and graduate students that were initially trained in other research methodologies, including students and postdocs initially trained in ERP methods; optical animal imaging methods, animal lesion and electrophysiological methods, clinical neuropsychology methods, and structural and morphometric imaging method.

Helen Tager-Flusberg, Ph.D. (Professor, Departments of Psychology (CRC) & Anatomy and Neurobiology (BUMC)) is the Director of the Lab of Developmental Cognitive Neuroscience at Boston University/BU School of Medicine.  For the past three decades she has investigated the cognitive architecture that characterizes children with different neurodevelopmental disorders, including autism spectrum disorders, Williams syndrome, specific language impairment and other genetically-based disorders, with a particular focus on language and social cognition.  Her work emphasizes the integral connection between typical and atypical development exploring how data from children with neurodevelopmental disorders may illuminate theoretical issues of normal development.

Lucia Vaina, M.D., Ph.D. (Professor, Department of Biomedical Engineering (CRC)) The adult brain constantly adapts to changes in stimuli, and this plasticity is manifest not only as learning and memory but also as dynamic changes in information transmission and processing. The goal of research in the Brain and  Vision Research Laboratory is to understand the mechanisms mediating human visual perception in healthy and damaged human brain,  long-term plasticity and short-term dynamics in networks of the  adult normal and damaged (from stroke) cortex by using interactively multimodal imaging (fMRI, MEG, DTI), psychophysics, and biologically constrained computational modeling. An additional facet of our research is translational, conducted hand in hand with several neurologists and psychiatrist clinicians, that investigates multisensory processing for facilitating behavior and recovery in stroke patients.

Benjamin Wolozin, M.D., Ph.D. (Professor of Pharmacology and Experimental Therapeutics (BUMC)) is interested in the pathophysiology of neurodegenerative diseases focusing on the biology of proteins that accumulate as aggregates or regulate aggregation.  For Parkinson’s disease they study alpha-synuclein and LRRK2.  For work on amyotrophic lateral sclerosis they study TDP-43.  Alzheimer research focuses on beta-amyloid, cholesterol and SORL1.  The approaches used include cell and molecular biology, signal transduction, neurotoxicity, apoptosis and neuroprotection.  Models include C. elegans, cell lines, primary neuronal cultures and pathological human tissues.