Anatomy & Neurobiology Faculty
Mark Moss, Ph.D., Chairman
Research focus on the neurobiology of learning and memory in non-human primate models, particularly with respect to aging and age-related disease. 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.
Research explores the neuropsychological sequelae of human brain damage. Since the early 1970s, her research has been supported by grants from the Medical Research Service of the VA, and from the US Department of Health and Human Services. Her recent publications are on the cognitive and emotional changes that result from chronic alcoholism, as well as on the behavioral consequences of brain damage in patients with other disorders of the central nervous system. 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.
Research interests are focused on the neurochemistry and neuropathology of autism, affecting the development of limbic, cortical and cerebellar systems. Specific focus is on major neurotransmitter systems including the GABAergic, glutamatergic and serotonergic systems. Techniques utilized in these projects include immunocytochemistry, histochemistry, in vitro on the slide ligand binding to receptors, computer assisted densitometic analysis, stereology, and in situ hybridization via collaborative studies.
Patsy B. Cipolloni, M.D.
The long-term interest is in the functional synaptic organization of the cerebral cortex. The current ongoing projects are the analyses of the organization of the frontoparietal opercular cortices in the primate; the synaptic organization of various classes of pyramidal projection neurons of the cat neocortex; the areal, laminar, cellular and subcellular distributions of four classes of muscarinic receptors in the cortex and the synaptic organization of physiologically characterized and intracellularly labeled neurons of the neocortex.
We use cellular and molecular techniques to study mammalian forebrain development, specifically focusing on the neural stem cells and precursors in the neocortex and hippocampus. By delivering DNA and RNA constructs directly into the neural stem cells in their intact environment, we investigate the gene expression and cellular movements responsible for proper formation of the forebrain. The lab also investigates the cellular and genetic mechanisms of developmental disorders including those underlying mental retardation in Down syndrome.
Research is focused on two different topics, the biology of pulmonary small-granule neuroendocrine cells and factors influencing the differentiation of macrophages, and is being investigated by physiological, cell- and molecular biological, and morphometric methods. Work on mechanisms regulating peptide secretion by the endocrine cells has shown that their response resemble those of the carotid bodies. Recently, attention also has been devoted to the effects of steroid sex hormones on vaginal tissue structure and (patho) physiology.
Dr. Joseph conducts research on neurocognitive development in children with autism. The focus of his research is on brain maturational processes as they relate to cognitive and behavioral functioning, particularly in the domains of social perception (face and gaze processing) and attention (orienting and search). To study these questions, he and his colleagues use magnetic resonance brain imaging and computerized tests that measure behavioral reaction time, eye-movement behavior, and psychophysiological response to visual stimuli.
Major areas of research interest are: (1) The effect of nutritional deprivation on the anatomical development of the rodent brain, (2) the anatomical organization of aging changes in the human and monkey brain, and (3) the anatomical changes in the brain of infantile autism, Rett’s syndrome and other developmental disorders. The major techniques used are whole brain serial sectioning, cell counting with stereology, and immuno-cytochemistry.
Dr. Killiany’s research has focused on exploring the relationship between brain structure and cognition. Studies have focused on identifying the morphological changes that take place in the brain during aging and disease processes in order to gain insights into the mechanisms behind the specific cognitive changes that characterize these processes. Initial studies focused on the determining specific structure/function relationships during development in the memory system of the non-human primate as a model for human development. More recent studies have focused on the processes of normal aging and cerebrovascular disease. In this work part of the focus has been on characterizing the cognitive changes taking place in non-human primate models. In addition, Magnetic Resonance Imaging (MRI) studies were added in order to assess volumetric changes in the brains of healthy elderly and cognitively impaired subjects. The focus of research continues to evolve to include functional techniques such as fMRI (functional magnetic resonance images), SPECT (single photon emission computerized tomography) and PET (Position Emission Tomography) scanning in order to study the brain in vivo. A primary focus of Dr. Killiany’s research most recently has been aimed at exploring the value of MRI in predicting which subjects will develop cognitive decline of Alzheimer’s disease and which will remain cognitively stable. Ongoing studies are also focused on identifying changes in the brain of gulf war veterans.
The general focus of our research is normal aging and Alzheimer’s disease. We use whole-cell patch-clamp and intracellular filling techniques to examine the electrophysiological and morphological properties of identified neurons in in vitro slices of the monkey and mouse neocortex. Electrophysiological properties of interest include action potential firing patterns and the underlying ionic currents responsible for generating specific patterns, as well as glutamatergic and GABAergic synaptic response properties. With regard to morphological properties, we are interested in detailed dendritic architecture and dendritic spine morphology and distribution. Both morphological and electrophysiological data from single neurons are incorporated into computational models in collaboration with theoretical mathematicians at Mt. Sinai School of Medicine.
In addition, we collaborate with other investigators at BUSM who utilize molecular biological (single cell PCR and microarray) and electronmicroscopic (ultrastructural analysis) techniques to examine cells from which we record. Overall goals include: 1) to examine the individual and network properties of neocortical 3 pyramidal cells in the prefrontal cortex; 2) to determine the effects of normal aging on these properties in behaviorally characterized rhesus monkeys, and 3) to determine the effects of amyloid deposition and tauopathy (hallmarks of Alzheimer’s disease) on these properties in transgenic mouse models of Alzheimer’s disease.
Research interests focused on the physiology of sleep, specifically on the influence of drugs of abuse on the circadian system. The effects of cocaine on young and old zebrafish were analyzed to determine the immediate effects of drugs of abuse on circadian rhythms, as well as monitoring age dependent changes in the circadian process.
Dr. Moore is an Assistant Professor in the department of Anatomy and Neurobiology and Director of the graduate program in Forensic Anthropology. She teaches courses in anatomy, neurobiology and forensic anthropology. She is a co-investigator on research projects funded by the National Institutes of Health that investigate the effects of age and age-related disease on the brain and the Principal Investigator on a project developing a non-human primate model of stroke and recovery. She has recently completed training courses with the Federal Bureau of Investigation in Human Remains Recovery and Crime Scene Management and Evidence Collection.
Deepak N. Pandya, M.D.
Major research efforts are directed to study cerebral cortical architecture of human and monkey. Studies also have carried out cortical connectional in monkey using retro- and anterograde tracer techniques. These studies have provided underlying principals of cortical organization. These principals follow the dual origin of cerebral cortex. Current studies deals with comparative architectonics of parieto-temporal areas in human and monkey. Investigations also are being done on the detailed organization of white matter pathways of the cerebral cortex. Other research efforts are also focused on connections of prefrontal and preoccipital regions in monkey. Research is aimed to provide more refined understanding of cortical connections. This in turn can lead to better understanding of cortical disorders and provide framework for further studies using behavioral and physiological approaches.
Dr. Pessina is pursuing research related to the return of motor function after cortical injury in a primate model. The current project includes developing test measures and evaluation methods to objectively assess primate hand function after cortical lesion. These data are correlated with electrophysiological findings and histological observations to determine the extent of cortical plasticity after acute injury. Dr. Pessina also continues clinical work in the area of upper extremity rehabilitation at Massachusetts General Hospital and her clinical research addresses functional outcomes after hand injury. In addition, in an effort to continually evaluate and improve the educational process, Dr.Pessina is investigating innovative teaching methods and their effectiveness with both medical and dental students.
Alan Peters, Ph.D.
Studies are being carried out on the cerebral hemispheres of the non-human primate central nervous system to assess the effects of normal aging on its neurons, neuroglial and systems of myelinated nerve fibers. These studies involve the use of electron and light microscopy, confocal microscopy, quantitative counting methods and immunocytochemistry. The qualitative and quantitative results obtained are carefully examined to determine if there are correlations between increasing age and the cognitive status of the animals, or both of these factors. The basic point of these studies is to try to ascertain which of the many structures affected by normal aging are critical in determining the cognitive status of animals, and if any factors are more critical than others.
My research interests focus 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. To accomplish this, the laboratory employs multidisciplinary methods to investigate these issues in animal models. These methods include combinations of behavioral, neurohistochemical, neurophysiological, neuroanatomical, and neurosurgical techniques to study these cognitive functions. We use a non-human primate model of normal aging and of cerebrovascular disease as well as a model of cortical stroke and of other brain lesions. In addition, a rat model of prenatal malnutrition is studied to identify the basis of the effect of this prenatal insult on the brain. Following behavioral characterization using a large array of behavioral testing methods, specific methods for neurobiological analysis of the pertinent brain changes include MRI and PET scans, standard histology, quantitative neuroanatomy using modern stereological methods, immunocytochemistry, enzyme histochemistry, and on the slide receptor autoradiography. In addition we have collaborations adapting methods of statistical physics to assess spatial relationships of the microcolumnar structure of the cortex and utilize in vivo and in vitro neurophysiological methods to assess the function of individual neurons and to follow this up with single cell gene expression analyses. More recent efforts include the use of methods of statistical physics to model and characterize spatial relationships of neurons in the cortex, especially as they form microcolumns, and the correlated use of diffusion MRI to characterize spatial features of axon pathways and neurons in the cortex.
Dr. Rushmore studies the unique contributions of cerebral and subcortical brain regions to functional activity in connected brain structures, and the link between neural activity in discrete cortical regions and specific behaviors. His work focuses on the posterior parietal cortex and the neurobiology underlying the neurological syndrome of visuospatial neglect. He is also interested in the capacity of the brain to undergo adaptive or maladaptive change following damage or reversible deactivation of cerebral cortical areas.
I have been an Anatomist and Neuroscientist for approximately 30 years. My PhD was concerned with the organization of the reciprocal connections between the prefrontal cortex and the thalamus. After receiving my degree in 1988 I spent three years as an NIH funded post-doctoral student studying the properties of the visual cortex in the lab of Dr. Bertram Payne. I was a founding member of the Boston University Alzheimer’s Disease Core Center and served as the database manager for three years. Over the last 10 years I have worked as a neurophysiologist, sleep scientist and stereologist. Most recently, I became the Associate Director of the Program in Forensic Anthropology where my interests remain in osteology, anatomy and taphonomy.
The laboratory focuses on the functional anatomy of the basal ganglia in normal animals and in experimental models of Parkinson’s disease. Another complementary focus is on the organization and regulation of GABA neurons. One current specific objective is to study the plasticity of GABA-mediated signaling in the basal ganglia and the basis of 1- DOPA-induced dyskinesias in rodent models of Parkinson’s disease. The research involves behavioral analyzes of motor activity, measurements of gene expression by in situ hybridization histochemistry and computerized quantitative image analysis techniques, measurements of protein expression by immunohistochemistry and western- blotting and measurements of small neurotransmitter molecules by in vivo microdialysis combined with HPLC.
I am interested in societal and behavioral dynamics. At the cognitive level this involves understanding how people’s preferences are ascribed and how they make sense of the world around them. This can include such things as how individuals follow groups or institutions in their decision-making practices. To test these types of behaviors requires an understanding of how individuals respond to stimuli and how this stimulus is processed. This process, known as the cybernetic sequence elucidates step-by-step actions from the input of the stimuli through how belief systems are structured. Controlled experiments are a means to uncover how these various process actions occur, what their limits are, and how other external influences may affect these process actions. In real world applications of this research we are exploring how individuals respond under healthcare emergency management and crisis situations.
The general goal of my laboratory is to investigate the reasons for having functional segregation in the cerebral cortex, and learn how the brain uses its functional architecture to help small collections of neurons to solve computational problems. Model systems range from squirrel to human, and include optical imaging, single unit recording, psychophysics and MR techniques. Some current projects include; 1) examining the functional segregation of face and landscape processing in early visual areas, 2) delineating functional maps in parietal cortex using fMRI, 3) investigating the nature of extrastriate cortical regions in non-human mammals and their relation to visual processing and 4) investigating the contribution of oscillatory activity in basal ganglia to modifying cortical response in normal and Parkinson’s disease patients.
Dr. Vaughan is not currently engaged in laboratory research; current interests focus on questions involving teaching and education, especially as related to medical education. Research expertise focused on the effects of advancing age on the nervous system, specifically motor systems. Studies examined the effects of age on the ability of motor neurons to regenerate axons following injury and involved light and electron microscopy, in both morphological, cytochemical and immunocytochemical analyses. Research interests and consultation continue in areas involving the histological aspects of biomedical studies.
Research interests are focused on the neuropathology of autism and its relationship to the timing of this developmental disorder. Using immunocytochemistry and standard histological staining techniques, the cerebellar organization as well as the relative density of several neuronal subpopulations in the autistic cerebellum are examined. The study of cerebral cortical organization, using immunohistochemistry, is also being pursued. Based on the known timing and sequence of CNS developmental events, our data has been useful in gaining greater insight into the timing of the pathology in the autistic brain.
The research is focused on the role of the circadian system in sleep, aging and effects of drugs of abuse, as well as age-dependent changes in the circadian processes. Two animals models are used, the zebrafish and rhesus monkeys. The methodological approaches include assessment of locomotor activity (image analysis techniques), cognitive functions (performance tests and classic conditioning), polysomnography (in primates only), measurements of intracellular messengers in brain tissue, evaluation of gene expression using real-time RT-PCR, radioimmunoassay and ELISA techniques.
The retina, which is part of the central nervous system, is an outstanding model to investigate fundamental aspects of nervous system function due to its accessibility and to the ability to precisely control its natural (visual) input. The primary focus of our laboratory is the microcircuitry and dendritic properties that enable particular retinal interneurons to encode directional and motion information. We have shown that individual dendrites of these ‘starburst amacrine cells’ express distinct combinations of channels, receptors and transporters within different functional compartments of these dendrites and also likely release their neurotransmitters GABA and acetylcholine via distinct mechanisms. Therefore, under the umbrella of our studies directed toward understanding visual system function, we are actively investigating new aspects of the functional toolbox available to neurons throughout the central nervous system and how these properties relate to normal and pathological neuronal function. Toward this end, we utilize a variety of intracellular filling, immunohistochemical, confocal and electron microscopy techniques as well as targeted synaptic silencing using neurotoxins.
Research interests include various topics related to the neurobiology of education, including the neurobiological underpinnings of adult learning and changes in perception as individuals grow from naïve learners to experts. Dr. Zumwalt uses adult learning theory to examine teaching techniques and document their efficacy in improving students’ retention of knowledge in the long-term. Dr. Zumwalt is also interested in clinical anatomy projects that advance clinicians’ understanding of anatomy with the goal of improving procedures such as surgical approaches, radiation treatments and other clinical interventions.