We are interested in the genetic and neuroendocrine bases of social behavior. We hope to understand (1) how genes, hormones and the environment interact to modulate brain plasticity, and (2) how inherited genetic changes, such as chromosomal rearrangements, affect neuroendocrine gene expression and function. Our research approach emphasizes evolutionary principles and combines the fields of molecular biology, genetics, neuroendocrinology, animal behavior, and physiological ecology. We collaborate extensively with faculty in the departments of Human Genetics, Psychiatry, and Biology. Techniques include quantitative real-time PCR, molecular cloning, in situ hybridization, immunohistochemistry, and behavioral analysis.

My research focuses on how the hippocampus and associated brain regions participate in the processes that enable our day to day memories. The study of memory benefits greatly from the close homology of the hippocampus across the mammalian taxon, and my lab studies memory by pursuing electrophysiological recordings in rats as they perform memory tasks. In particular, we are interested in the fundamental neurobiological computations arising from the circuitry of the hippocampus and parahippocampal region--the ways in which the anatomy and physiology of the hippocampus enact changes on incoming information and the ways in which this altered information is stored in the brain.

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We study the critical decision processes by which neuronal cells control survival vs. death and differentiation vs. proliferation during cellular development and in more mature stages. We are particularly interested in the roles of nuclear factors in regulating these central processes. In this context, we want to determine how neurons process specific signals, how these signals are relayed to the nucleus by mediators, and how nuclear proteins are modulated in response. Specifically, we are investigating the role and regulatory mechanisms of a transcription factor myocyte enhancer factor 2 (MEF2) of cyclin dependent kinase 5 (Cdk5), a protein that has been implicated in neurodegeneration (Neuron 2003, 38 (1) 33-46). More recently, we have demonstrated that the mechanisms by which Cdk5 negatively regulates MEF2 is a via a phosphorylation-dependent caspase-mediated degradation (Journal of Neuroscience, 2005, accepted)

My research program has as a central theme, the characterization of neural systems mediating mood and emotional behaviors in health and disease, with a primary emphasis on major depression and its recovery. Functional neuroimaging (PET, fMRI) serve as the core methodologies, although all projects are multi-disciplinary (clinical trials, neurophysiology, personality structure, genetics, cognitive neuroscience, functional neurosurgery). The long-term goals of these integrated studies is the improved understanding of clinical algorithms that will discriminate patient subgroups, optimize treatment selection, predict relapse risk, and provide markers of disease vulnerability.

My lab is interested in examining the response of the CNS to injury, with a focus on identifying factors that lead to neuronal death or axonal regenerative failure. We are particularly interested in elucidating the role of one type of glial cell, the reactive astrocyte, since the astrocytic response to injury has been implicated in processes as diverse as neuronal protection versus inhibition of axonal regeneration. Ongoing projects are designed to examine the role of specific injury-induced growth factors and/or cytokines on astrocytic gene expression, particularly those genes involved with energy mobilization or synthesis of axon growth inhibitory molecules. By understanding the astrocytic response to injury, we hope to devise new strategies to enhance neuronal survival and axonal regeneration.

Work in our laboratory examines the relationship among the brain, the neuroendocrine system and the immune system as it relates to neuropsychiatric disorders including depression. Particular emphasis is focused on the impact of cytokines on the brain and behavior and the role of glucocorticoids and their receptors in the regulation of inflammatory responses. Studies in laboratory animals and humans are conducted, including treatment trials of immune-targeted therapies for depression.

Our lab is interested in the role of pesticides (persistent organochlorine insecticides) in the development of Parkinson's disease, with a focus on how these compounds alter the function of the molecules that are responsible for transporting and packaging dopamine. We have recently established novel behavioral methods to assess motor impairment in mouse models of Parkinson's disease. The lab is also interested in the beneficial effects of exercise in neurodegenerative disease, such as Parkinson's.

My research interest is how various forms of experience alter the structural organization of nerve cell communication. We are pursuing this interest in the amygdala, where we are studying how stress alters the distribution and plasticity of glutamate receptors and key signaling proteins. We are also studying how dopamine depletion alters the signal transduction environment in direct versus indirect pathway striatal medium spiny neurons. Finally, we are studying the action of antipsychotic drugs in different brain regions using PET imaging techniques. These studies will inform our understanding of experience and drug mediate alterations in brain functioning and will be relevant to a wide variety of neuropsychiatric disorders, including PTSD, Parkinson's Disease and Schizophrenia.

Research in the Neigh Laboratory focuses on the role of cerebral vascular compromise in the generation of affective disorders. We place a particular emphasis on periods of increased plasticity and susceptibility to insults such as development (prenatal, postnatal, and puberty) and aging.

Our research focuses on understanding the neurocognitive, social, and adaptive behavioral development of children and young adults with autism spectrum disorders, as well as those with specific genetic disorders, such as 22q11 Deletion Syndrome. We apply both neuropsychological assessment and neuroimaging techniques to identify critical diagnostic and biological markers which may predict short-term and long-term outcomes.

Our lab's interest is in the biology and treatment of the major psychiatric disorders and can be divided into the following main areas: 1) molecular and cellular pharmacology of antidepressant, anxiolytic, and antipsychotic drugs, 2) candidate novel targets for drug development (e.g. neuropeptides), 3) pharmacological characterization of novel radiotracers for neuroimaging, 4) developmental pharmacology as it relates prenatal drug exposure, 5) markers for assessing adequate pharmacotherapy, and 5) pharmacokinetics and bioavailability of drugs in laboratory animals. These research areas utilize an array of molecular, biochemical, physiological and behavioral techniques.

Dr. Pace's laboratory investigates alterations in resting and psychosocial stress-induced inflammatory immune function in participants with current major depression and/or a history of trauma in the formative years of life. Excessive inflammation is hypothesized to result from insufficient glucocorticoid inhibition of inflammatory signaling that occurs subsequent to abnormal corticosteroid receptor function and/or abnormal cortisol release. Routine measures include plasma levels of proinflammatory cytokines and glucocorticoids, activation of inflammatory signaling pathways in circulating immune cells, and in vitro assessments of glucocorticoid sensitivity (determined via proinflammatory endpoints). The lab also investigates the effectiveness of proinflammatory antagonists that target inflammatory signaling pathways (including the nuclear factor-kappa B pathway and mitogen activated protein kinase cascades) to reverse changes in behavior and mood associated with hyperinflammatory states.

We work in the area of pathophysiology and therapeutics of neurodegenerative disorders. Our research is focused in Parkinson's disease and other movement disorders. Current projects are based on electrophysiology and Pharmacology/cellular biology techniques using primate animal models. Physiology studies involve recording of neuronal activity in vivo, and pharmacology studies involve behavioral testing, autoradiography, in situ hybridization, immunohistochemistry, etc.

My research interests center around characterizing retinal defects using electrophysiological and anatomical methods and developing treatments for retinal degenerative diseases. The main projects in the laboratory investigate neuroprotective agents that could slow the progression of retinal degeneration, providing potentially years of improved visual function. Such treatments include electrical stimulation produced by retinal prosthetics and anti-apoptotic agents. In addition, we are investigating how defects in retinal pathways and the visual environment influence refractive development.

My lab is dedicated to understanding comparative aspects of social cognition. We use computerized tasks, behavioral observations, eye-tracking and neuroimaging to study face perception, facial expression categorization and emotional processing in chimpanzees, rhesus monkeys and humans of various ages.

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The work in my laboratory examines the cellular and molecular mechanisms by which viral infections and immune activation can lead to neuropathological and psychiatric abnormalities across the lifespan. Our work is cross-disciplinary, combining neuroimmunology and pre-clinical pharmacology with translational (human) research. Much of our research focuses on pregnancy and brain development. We collaborate with obstetricians, psychiatrists, psychologists, and epidemiologists to investigate gene-environment interactions and causative pathways in schizophrenia, autism, and depression. Our long-term goal is to discover biomarkers and potential drug targets for these neuropsychiatric illnesses.

My lab utilizes mass spectrometry for identifying proteins and their modifications such as phosphorylation and ubiquitination. Neurodegenerative Diseases - we are interested in mapping and profiling proteins and their modifications in the aggregates from patients and animal models, combining with tools in molecular biology, cell biology, and genetics, we will explore the function of these proteins and their modifications in the development of these devastating diseases. These studies may provide strategies for diagnosis and therapeutic intervention.

New Neuroscience Technologies for Studying Learning in Vitro. We are merging software, hardware, and wetware in a new paradigm for neurobiology research, "Embodied Cultured Networks." It brings together top-down (cognitive, behavioral, ethological) and bottom-up cellular, molecular) approaches to studying the brain. We are applying Multi-electrode array culture dishes, 2-photon time-lapse microscopy, and High-speed imaging of neural activity to study cultured networks of hundreds or thousands of mammalian neurons. We are especially interested distributed activity patterns and information processing in these cultured networks. We give them a body, either simulated or robotic, and an environment in which to behave. We developed a real-time feedback system for 2-way communication between a computer and a cultured neural network. In collaboration with Dr. Robert Gross in Neurosurgery, we are using our closed-loop stimulation and recording technology to develop methods for treating epilepsy with electrical stimulation.

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One of our major goals is to identify the evolutionary specializations of the human brain, which we do by comparing humans to chimpanzees and to other nonhuman primates. We want to understand the extent to which evolutionary expansion of the human brain was accompanied by the addition of new areas or by the enlargement and internal reorganization of existing areas. To this end, we carry out comparative studies of cortical organization using immunocytochemistry and other techiniques that are useful for mapping cortical areas and investigating the laminar and cellular organization of cortex. Recently, we have begun to employ genomics techniques to identify genes that are differentially expressed in human brains, followed by in situ hybridization and immunocytochemical studies to demonstrate where the genes identified by genomics are expressed in the nervous system.

I study the signal processing and homeostatic regulation in small neural networks with a combination of computational ex experimental approaches. Current research projects include the computational exploration of homeostatic regulatory mechanisms in neural circuits, the construction, visualization and analysis of high-dimensional model datasets, and the investigation of synchronization in networks of neural oscillators with hybrid techniques.

My lab investigates the cellular and neurophysiological mechanisms underlying emotional aspects of cognition, with an emphasis on the role of the extended amygdala in fear conditioning and extinction and its role in stress reactivity and anxiety-like behavior. Multiple techniques are employed to examine the functional and neurochemical connectivity of the amygdala and related structures in an attempt to create a functional map of the intrinsic circuitry, and to determine how sensory information gains affective weight within this structure. These methods range from molecular biology, through in vitro whole-cell patch clamp recording from visually identified neurons, to in vivo multiunit recording from freely moving rats. By understanding how sensory information is processed in the extended amygdala our ultimate objective is to shed light on the cellular processes that may contribute to the development of mood disorders such as depression, generalized anxiety disorder, panic disorder, and post traumatic stress disorder.

The goal of my laboratory is to create a program which utilizes the enormous power of molecular biology to approach difficult and important questions in systems neuroscience. I use genes known to be involved in synaptic plasticity to examine plasticity in the amygdala and regions which connect with it during the consolidation phase of fear memory formation. I am also initiating a program to create transgenic animal models for visualizing the amygdala neurons, some of its sensory inputs and the neuromodulatory projections which together mediate some of the important behavioral responses of fear and stress. These models will create novel and powerful tools to begin to address systems level neuroscience questions at genetic, molecular and cellular levels in combination with electrophysiological and neuroimaging approaches to neural circuitry.

The research in my laboratory uses MRI, fMRI and PET imaging to explore the neural basis of human social cognition and to compare the brains of living primates to glean insights into human brain evolution

Our laboratory seeks to discover the molecular, cell, and brain systems underlying various aspects of normal and pathological sleep/wake behaviors with an eye on improving recognition and treatment for common sleep disorders. Bench research is driven by 'bedside' clinical observations, therefore ensuring that our efforts translate to the human condition. A principal focus is on Restless Leg Syndrome (RLS) and associated comorbidities (e.g., cardiovascular and psychoaffective disorders) given our discovery in 2007 of the major genetic basis for this common disorder. We are also deeply committed to deciphering the biological basis for maintaining proper alertness throughout the day. We employ anatomical, physiological, and pharmacological techniques in genetically engineered mice, rats, and non-human primates, and complementary investigations in humans. Molecular biological tools are being incorporated into our repertoire informed by ours and deCODE Genetics (Reykjavik, Iceland) collaborative efforts to mine the human genome for the genetic basis for sleep and its disorders.

My lab studies neurobiological systems that control stress physiology and emotion regulation in nonhuman primates. I am particularly interested on the developmental effects of early adverse experiences on stress neuroendocrine systems, emotion regulation and related neurobiological substrates of primates. The long-term research goals are (1) to identify the neural substrates affected and the time course of events, as well as the genetic factors that increase vulnerability to those experiences and (2) to understand the molecular and cellular mechanisms by which early adversity increases vulnerability to psychopathology and pathophysiology.

Our group is interested in understanding how our brains adapt and what happens when neurons in the brain die or perform abnormally. The remarkable adaptability of the brains in all animals relies crucially on the lifelong ability of individual neurons to change in response to specific stimuli. It is this Neuronal Plasticity (as it applies to Learning, Neurodegeneration or Sleep) that forms the research focus of our group. The favored model organism for our studies is Drosophila, or the fruit fly, which, though surprising to some, shows a remarkable range of “complex behaviors” as it navigates through life. What makes this a truly advantageous model organism, however, is the vast array of genetic tools at the disposal of the experimental biologist and the ability to assay plasticity at multiple levels of complexity, all the way from genes to circuits to behavior.

Our research interests are Tactile perception, its neural basis and its alteration in neurological disorders. Neural plasticity in the tactile system. Cross-modal interactions between tactile and visual systems. Visual attention and its neural basis. Neurological rehabilitation with special reference to stroke and blindness.

The main research interest of my laboratory is to understand the pathophysiology of Parkinson's disease and characterize changes in the synaptic plasticity of the basal ganglia in normal and pathological conditions. To achieve these goals, we have developed a collaborative, interdisciplinary research program that uses in vitro and in vivo anatomical, electrophysiological and pharmacological approaches to study the functional organization of the basal ganglia in normal nonhuman primates and in animal models of Parkinson's disease. This work is complemented with behavioral studies of novel surgical and pharmacologic therapies for Parkinson's disease in nonhuman primates.

My laboratory focuses on the factors regulating the survival and differentiation of the enteric nervous system and how it is altered in diseases associated with altered gastrointestinal motility such as diabetes.

We are a translational laboratory studying the role of neurosteroids, especially progesterone and its metabolites, in recovery of function after traumatic brain injury and stroke. We are highly interdisciplinary and work from the laboratory bench, using the latest cell culture, molecular biological and immunocytochemical techniques, to the patient's bedside, where we combine our efforts with medical colleagues in emergency medicine, neurology, radiology, pediatrics and neuro-ophthalmology to examine how different kinds of brain injuries can be repaired at the morphological and functional levels. Working closely with local and national clinical colleagues in emergency medicine, we are currently testing progesterone in traumatically brain-injured patients to reduce mortality and enhance functional recovery.

How do we move so elegantly through unpredictable and dynamic environments? In my lab, we study balance control and locomotion in humans and animals to understand the organization of neural mechanisms underlying motor behaviors in general. Using a novel combination of engineering and neurophysiology techniques, and an interplay of experimental and computational studies, we are studying sensorimotor processes underlying muscle coordination in both heath and disease. Our work integrates ideas from neuroscience, biomechanics, robotics, rehabilitation, physiology, psychology, and cognitive science, addressing how neural circuits, musculoskeletal properties, adaptive process, and perception shape how we move.

My laboratory studies the basic mechanisms underlying the function and regulation of ligand gated ion channels involved in excitatory synaptic transmission. Our goal is to use this information to understand normal brain functions that involve synaptic transmission such as learning and memory. In addition, information about regulation of the ion channels involved in excitatory synaptic transmission may provide insight into the neuropathology of epilepsy and stroke.

We are investigating a novel mechanism to explain the development of hypoxia and pseudopalisading necrosis in glioblastoma based on vaso-occlusive and regression events; mechanisms that are relevant to angiogenesis and more aggressive tumor growth. To target the hypoxic fraction of tumors that is a major physiological inducer of angiogenesis and tumor progression as well as an important cause for chemo- and radio-resistance we developed two novel lines of therapeutic agents. These include oncolytic adenoviruses that restrictively replicate in and lyse hypoxic/HIF-1 expressing cells as well as natural product-like small molecules that inhibit Hypoxia Inducible Factor-1 (HIF-1), a transcription factor that activates hypoxia-responsive genes such as those encoding the Vascular Endothelial Growth Factor and glycolytic enzymes. Our aim is to now combine these novel agents with the anti-tumor properties of angiogenesis inhibitors towards clinical testing.

Psychotic disorders involve an abnormality in central nervous system functioning. Our research program is concerned with shedding light on the nature and origins of this abnormality, its interaction with adolescent neuromaturational processes, and the role of environmental stressors in triggering psychotic episodes. We are studying the developmental precusors of psychosis in order to identify premorbid manifestations of dysfunction, including neurohormonal and genetic factors. Research on stress hormones and their effects on cognitive functions and brain structural and functional characteristics is also being conducted.

Our lab works on developing more representative transgenic models of Alzheimer's disease; clarifying the mechanisms whereby amyloid proteins form pathogenic assemblies in vivo; and the role of aging in the development of neurodegenerative diseases. Areas of particular interest include the seeded induction of proteopathy in the brain, somatic cell gene transfer, and evaluating the efficacy and safety of therapeutic immunization for Alzheimer's disease in animal models.

We investigate the role of neuroendocrine systems on the development and expression of sexual and sex-related behavior in nonhuman primates. Our work uses intact stable social groups of monkeys to investigate the effect that manipulating hormonal conditions prenatally, eripubertally, and in adulthood have on the expression of sex-typed behavior. Current work focuses on the 1) development of sex differences in cognition and behavior; 2) Model systems for hormonal replacement therapy in women; 3) Human cognitive sex differences. Additional interests are in human sexual behavior and neural sexual differentiation.

Our laboratory seeks to understand the genetic basis of neuropsychiatric disease. A longstanding interest is in inherited cognitive deficiencies, such as fragile X syndrome and autism. For fragile X, the field has matured from our initial cloning of the responsible gene to now conducting drug screens and clinical investigations. For autism we are still searching for responsible genes, but now using cutting edge technologies made available through the genome project. Similarly, we have two large studies underway examining genomic variation (both in sequence and in structure) seeking genetic contributions to schizophrenia and bipolar disorder predisposition using case/control as well as family-based approaches.

Research in my lab focuses on the mechanism of cell death after ischemic stroke and novel treatment of CNS disorders including ischemic and traumatic brain injuries. The major focus of my research is stem cell transplantation therapy for ischemic stroke.

My lab combines genetically engineered mice with altered noradrenergic signaling and pharmacological tools to explore the influence of norepinephrine on behavior, physiology, and neurochemistry. Specific areas of interest include drug addiction, Alzheimer's and Parkinson's disease, epilepsy, depression, and hibernation.

My laboratory provides a wide range of training opportunities in the area of fundamental behavioral neuroscience. The laboratory utilizes behavioral, biochemical, electrophysiological, and immunological techniques to explore the relationship between brain, physiology, and behavior. A major area of interest is the construction of animal (rodent) models of abnormal behavior and the exploration of physiological processes underlying abnormal behavior by using these models. Another major focus of the laboratory is on the interaction between brain and the immune system focusing on how behavioral factors influence peripheral immune responses, and how immune products such as cytokines, influence brain and behavior.

The development of neural circuits requires a progressive series of synaptic decisions that determine whether the network behaves appropriately, or alternatively leads to developmental disorders (autism and childhood epilepsy/seizure). We study a recently identified form of synaptic plasticity that homeostatically regulates the levels of network activity, and provides a guiding principle for the normal maturation of synaptic connections in these nascent circuits. We examine the underlying mechanisms of this plasticity using electrophysiological, molecular, optical, and immunocytochemical techniques.

We are interested in understanding the function of the basal ganglia in the normal state and in movement disorders such as Parkinson's disease or dyskinesias. These experiments will help to develop new rational treatments for these diseases that can then be used in humans. For these studies we are using a combination of electrophysiologic, biochemical and anatomical methods.

Our lab uses both rodent and monkey models to understand how social variables affect a number of neuroendocrine systems and, thus,  the regulation of behavior.  Our studies in nonhuman primates are directed at understanding the neuroendocrine and metabolic mechanisms that produce stress-induced infertility.  Using the ethnologically valid stressor of social subordination characteristic of macaque societies, we studying how corticotropin releasing hormone (CRH) disrupts reproduction and whether this is meditated by specific metabolic signals.  This model allows allows us to study how social stressors change diet preference and food consumption as a means to understand the adverse consequences of stress induced obesity.   Parallel studies in rodents are using a viral vector that over expresses CRH in selected brain regions to determine the pathways by which this neuropeptide  disrupts reproduction and steroid-induced socio-sexual behavior.

My primary interests involve instrumented learning of motor control in human subjects. As part of that learning we are now engaged in examining associations between cortical reorganization and functional improvements among individuals who have sustained a cerebrovascular accident as they are forced to use the impaired upper extremity while the better upper limb is immobilized. Cortical reorganization is assessed using transcranial magnetic stimulation (TMS) and functional MRI. We also assess kinetic changes in upper limb use during efforts to manipulation the environment. We have started a series of studies using TMS to create upper extremity muscle maps in able-bodied humans as a basis for ascertaining motor cortical plasticity following interventions designed to enhance motor control. Another focus of this laboratory involves examining postural control and gait in older adults who undergo novel treatment interventions, such as Tai Chi, which are designed to reduce or delay fall events. Last, we continue to study morphological and physiological aspects of multi-joint muscles to further comprehend their kinesiological significance.

The focus of my research is on the pathophysiology of neuroinjury and the development of early interventions and treatments. My current research focus is to determine if the administration of neurosteroids are effective in mediating neuroprotection and neurorepair after traumatic brain injury (TBI). Our research demonstrates the progesterone and allopregnanolone reduce cerebral edema, loss of neurons, inflammatory cytokine production, lipid peroxidation, and improve behavioral outcome after experimental TBI.

My lab investigates the molecular and neuroendocrine mechanisms by which neuropeptides and neuropeptide receptors regulate social behaviors. We use a range of techniques ranging from transgenics, viral vector gene transfer, and promoter analysis to examine the mechanisms underlying social behaviors such as affiliation, pair bonding and social recognition in rodents.

Research in my lab focuses on the ionic mechanism of cell death in ischemic and traumatic injuries. We also investigate the mechanism of stem cell differentiation and potential stem cell transplantation therapy for CNS and PNS disorders.

Precisely-wired neuronal circuitry underlies the proper and complex functions of the nervous system. We investigate the molecular and cellular mechanisms underlying a variety of developmental events that lead to the construction of the complex nervous system. Our current focus is on the signal transduction and cytoskeletal mechanisms underlying neuronal migration, axon growth and guidance, and synaptic plasticity. Our goal is to not only provide a mechanistic understanding of these crucial developmental events, but also gain substantial knowledge on the molecular and cellular basis of wiring defects associated with brain abnormality, degeneration, and mental illness. It is our hope that these basic studies will build the foundation for developing potential strategies and treatments to promote regeneration and repair of damaged neuronal circuitry after neural injuries and degeneration.

Our research program is focused on identifying the brain structures important for memory and delineating how these structures separately and in combination contribute to memory function. Our work in animals currently includes monkeys and rats, and the behavioral tests we use to assess memory in our experimental animals are based in large part on our experience with testing human amnesic patients. We use a variety of memory tasks, brain imaging, conditioning paradigms, and naturalistic behaviors, and more recently have been developing the use of reversible lesions to study both declarative memory (mediated by the temporal lobe) and nondeclartive memory (mediated by brain regions outside the temporal lobe). Additionally, we study emotional behavior and its link to memory function in humans and animals.