My research is aimed at understanding the neurobiological basis for individual preferences and how the biology places constraints on the decisions people make -- a field now known as neuroeconomics. To achieve this goal, we use functional MRI to measure the activity in key parts of the brain involved in decision making. We then link these activity traces to various phenotypes of decision making. For example, we have linked the pattern of activity in the striatum with the receipt of unexpected, salient information with the tendency to alter one's behavior. More recently, we have used the timecourse of activity as a proxy for experiential utility, in the process, bridging the gap between experience and choice. Ongoing research projects are developing these methods to probe decision-making in adolescents as well as group decision-making and the influence of peer pressure at the neurobiological level.

My research interests are in the pathogenesis and pathology of neurodegenerative diseases including Parkinson’s and Alzheimer’s disease. More specifically, the interactions between PD/AD-related genetic factors and external stressors, including mitochondrial impairment, oxidative stress, proteasomal inhibition, and their involvement in protein trafficking pathways in neurodegeneration. I am also interested in the organizational changes in the basal ganglia circuitry that occur in Parkinson’s disease including the dopaminergic and glutamatergic pathways.

The Boulis laboratory focuses on the translation of concepts in neural gene transfer and stem cell transplant to the treatment of functional and degenerative disorders of the nervous system. Functional disorders of interest include epilepsy and spasticity as well as the control of aberrant basal ganglion function in movement disorders. Degenerative disorders of interest include Parkinson’s Disease and Amyotrophic Lateral Sclerosis. To treat degenerative disorders, we have explored a variety of anti-apoptotic and growth factor genes. These are screened through in vitro assays prior to testing in transgenic models. A recent manuscript describes neuroprotection through the delivery of the gene for X-Linked Inhibitor of Apoptosis (XIAP)1, Bcl-xL2, and Insulin-like Growth Factor I (IGF-I). Ongoing projects are exploring the application of cervical spinal cord surgery for the injection of adeno-associated viral vectors encoding IGF-I in SOD1 mutant rats.

In the Center for Biomedical Imaging Statistics (CBIS), a major focus of our research is on the development and applications of statistical methods for analyzing brain imaging data. These methods make use of data reflecting brain function, for example, from functional magnetic resonance imaging (fMRI) as well as structural information obtained from diffusion tensor imaging (DTI). Generally, our statistical methods attempt to improve our understanding of human brain function by (1) determining functional linkages between brain regions either at resting state or when performing specific experimental tasks, (2) identifying specific brain regions that drive the performance of a task and evaluating differences in these distributed patterns of task-related activity between subgroups (e.g. between a patient group and healthy control subjects), and (3) addressing various prediction objectives such as predicting neural responses to treatment and predicting clinical psychiatric symptoms (e.g. associated with major depression) based on functional imaging data. Please see http://www.sph.emory.edu/bios/CBIS/ for additional details.

Our lab studies the neural circuit that controls the hearts of medicinal leeches. We record the electrical activity of neurons in this circuit with microelectrodes. Using voltage clamp techniques, we isolate and characterize the individual ionic currents which contribute to this activity. We also study the biophysics of synaptic transmission and the role of background calcium in synaptic plasticity using Ca imaging. To understand how membrane currents and synaptic transmission interact to produce the activity of the circuit, we simulate the ionic currents and cell connectivity with realistic biophysical models. We also use such models in real time simulation to construct hybrid systems between computer and neuron to analyze circuit and neuronal function. We address the general questions of how rhythmic motor patterns are generated and coordinated by networks of interneurons and how these patterns are used to produce the final pattern of activity in motor neurons that produce functionally coordinated movement.

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Our lab studies the molecular and cellular mechanisms underlying the morphogenesis of the mammalian auditory organ, the organ of Corti. In particular, we are interested at how cells at particular location of the developing inner ear are singled out to become the precursors of the sensory epithelium, withdraw from cell cycle, and subsequently differentiate into a given cell type of the organ of Corti, and how the differentiation process is coupled to the establishment of the polarity of the sensory epithelium

My research focuses on the molecular pathogenic mechanisms of Parkinson’s disease (PD). We are using molecular, cellular, proteomic, and biochemical approaches to delineate the molecular pathways by which the mutations in familial PD proteins DJ-1, Parkin, and PINK1 lead to neurodegeneration and to identify additional proteins and new pathways involved in PD pathogenesis (J. Biol. Chem. 279: 8506-8515; J. Comp. Neurol. 500: 585-599; PLoS Biology: 5: e172.). By using a redox proteomic approach, we are characterizing protein targets of oxidative damage in idiopathic PD brains and investigating the gene-environment interactions in PD pathogenesis (J. Biol. Chem. 281: 10816-10824). We are also studying the role of ubiquitination and aggresome formation in PD pathogenesis (J. Cell Biol. 178: 1025-1038). Our goal is to use the mechanistic insights gained from these studies for developing new intervention strategies to treat PD.

Our lab is interested in molecular mechanisms of acid-base regulation in the brain and kidney. In particular, we focus on the sodium/bicarbonate transporters that move Na+ and HCO3 ions across the cell membrane. These transporters not only regulate the acid-base balance in the cell or tissue, but they can also modulate distinct cell physiology such as neuronal activity, fluid secretion or reproduction. We are interested in how the transporters affect acid-base homeostasis of the cell, how they work at the molecular level, and how they are regulated.

The long term goals of this research are to examine the role of normal and abnormal visual experience on the development of neural circuits mediating binocular alignment and binocular coordination of eye movements. We plan to use an approach based on structural imaging of extraocular muscle, behavioral experiments to examine control of eye movements with particular emphasis on control of torsion, neurophysiological experiments to examine the calibration of sensory and motor structure in the brain and biomechanical modeling of extraocular musculature simulating experimental data to help us intvestigate these important questions that relate to strabismus in particular and the developing brain in general.

My lab studies the neurobiology of learning and memory using the fear-potentiated startle reflex in rats, mice, monkeys and humans. Another focus is the effects of stress on behavior with special emphasis on neuropeptides, neurotransmitters and second messenger systems in the extended amygdala.

The work in our lab involves the development of real-time, dynamical models of neuronal systems and on the interfacing of those models to living neuronal tissue. This research is focused in three primary areas: neuromorphic engineering, neural interfacing technology, and hybrid neural microsystems.

Glutamate receptors mediate the vast majority of excitatory synaptic transmission in the brain. A major research effort in my lab is focused on regulation of glutamate receptor-mediated synaptic transmission in the brain by the co-activation of selected G-protein coupled receptors. A second research emphasis involves the use of microarray and associated technologies to identify novel targets and pathways involved in the basic cellular and molecular mechanisms of epilepsy. These research interests converge and have highlighted a role for cyclooxygenase-2 (COX2) signaling pathways in the cognitive deficits, impaired synaptic inhibition, and neurodegeneration caused by seizures. We are currently seeking the prostaglandin receptors responsible for each of these effects; we will then employ a chemical biology approach to develop novel small molecule modulators of these receptors in an effort to interrupt the development of epilepsy. As a whole our work integrates information from a variety of experimental strategies to contribute to a better understanding of epilepsy, with broad implications for other brain disorders including stroke and schizophrenia.

The main interest in my laboratory is enhancing functional recovery following injury to the peripheral nervous system. Peripheral nerve injuries are common clinically but functional recovery from them is rare. Following nerve injury, denervated muscles are deprived of neural control and sensory feedback regulating muscle function is lost. In addition, synaptic inputs onto spinal motoneurons are withdrawn. The slow growth of regenerating axons and the slow reformation of synapses, both in the periphery and in the CNS, are the reasons given for poor functional outcomes. We have found that exercise or electrical stimulation enhances the growth of regenerating axons. Using a combination of transgenic and knockout mice we are investigating the roles played by the neurotrophins BDNF and NT-4/5 in that enhancement, as well as in the reformation of synapses at both neuromuscular junctions and spinal motoneurons. Using chronic electrophysiologic recordings in rats, we are evaluating the effects of exercise or electrical stimulation on functional recovery following peripheral nerve injury.

The research projects in my laboratory investigate the molecular basis of the cell-to-cell communication which regulates the development, maintenance, regeneration, and plasticity of the vertebrate nervous system. In particular, we are focusing on understanding the biological activities of the neuregulin family of "growth and differentiation" (or "trophic") factors.

Research interests emcompass PET and SPECT radiotracer development of heart, brain and oncology agents with an emphasis on the design and evaluation of radiolabeled fatty acids for in vivo study of regional fatty acid metabolism in heart disorders, cocaine analogs for in vivo study of the dopamine, serotonin, and norepinephrine reuptake sites in neurodegenerative disease, psychiatric and addictive disorders, heterocyclic spiperone analogs for in vivo mapping of D2 dopamine recpetors in psychiatric disorders, peripheral benzodiazepine receptor ligands for imaging peripheral vascular disease and mappping of intracranial tumors, carbohydrates for in vivo study of regional glucose metabolism in heart disorders, brain disorders, and cancer, and alicyclic and branched chain amino acids for in vivo mapping of intracranial ans systemic tumors.

Our laboratory focuses on determining mechanisms of selective neuronal vulnerability in neurodegenerative diseases. Using behavioral analyses, global assessment of gene expression, live-cell imaging, and assays of cellular metabolism and toxicity, we are attempting to determine pathogenic mechanisms of neuron death and dysfunction in Parkinson’s disease. This includes analysis of the enteric nervous system as one of the earliest sites of neuronal dysfunction in PD.

The goal of my laboratory is to develop novel surgical therapies utilizing cell and/or gene therapy, or electrical stimulation, for ameliorating neurological diseases: 1) Axon guidance molecules in the development and reconstruction of the nigrostriatal pathway. We have been examining the role of semaphorins and their receptors in the developing and adult nigrostriatal pathway. 2) The role of RhoGTPase in mediating the inhibitory effects of the adult CNS on neural reconstruction. RhoGTPases mediate inhibitory effects of a range of molecules, including semaphorins, on regenerating neurons. To counteract these effects, we have produced a lentiviral vector encoding C3 transferase which catalytically inhibits RhoA, and shown that it markedly increases outgrowth of axons from a variety of cells including neural stem cells derived neurons. 3) The role of microglia in neurotoxin-induced degeneration of the nigrostriatal pathway. Towards developing novel therapy for neuroprotection in Parkinson's disease and other degenerative conditions, we have been examining the role of microglial activation after treatment of young and old rats. We are currently embarking on examining the role of RhoGTPases in mediating the microglial-inhibitory effects of neuroprotective peptides. 4) Closed-loop multi-microelectrode recording and microstimulation in focal epilepsy in the rat. In collaboration with Steve Potter, we are examining whether a novel microrecording and stimulation algorithm is capable of blocking the onset of propagation of epileptic seizures in rat models of epilepsy 5) Deep brain stimulation (DBS) in Parkinson's disease, Dystonia, Tourette's Syndrome, Epilepsy and Depression. In collaboration with Emory neurologists, experimental protocols are underway to examine STN vs. GPi DBS in PD.

We study the mechanisms of signal transduction by neurotransmitter and hormone receptors. Our typical approach is to first uncover receptor interactions with either intracellular proteins or other receptors, and then elucidate the physiological consequences of these interactions in a variety of functional studies. Understanding the mechanisms of signal transduction by neurotransmitter and hormone receptors is of paramount clinical importance, since such receptors are common targets for therapeutic pharmaceuticals in the treatment of many neuropsychiatric conditions.

We have been studying C1 channels, which play an important role in neuro-degenerative diseases. Knockout of C1C-2, C1C-3 and C1C-7 in mice all produce post-natal degeneration of specific parts of the nervous system. I am particularly interested in bestrophin, a C1 channel that produces retinal (macular) degeneration.

We seek to understand how neuromodulatory transmitters (serotonin, dopamine, and nor-adrenaline) modify sensorimotor integration in the mammalian CNS. We use predominantly electrophysiological approaches to study the role of these transmitters and their dysfunction after spinal cord injury, and in association with Restless Legs Syndrome (RLS), pain, and locomotion.

Dr. Leonard L. Howell has an established research program in behavioral neuropharmacology with a focus on central nervous system stimulants and the development of medications to treat stimulant addiction. The program is multidisciplinary and integrates operant-conditioning techniques to study behavior and drug use, in vivo microdialysis to characterize brain neurochemistry, and functional brain imaging. Ongoing studies investigate in nonhuman primate models the neurochemical mechanisms that mediate drug effects on behavior. Recent efforts have focused on drug-induced changes in brain neurochemistry with in vivo microdialysis in behaving monkeys trained to self-administer cocaine. In addition, Dr. Howell serves as Director of PET Imaging at the Yerkes Neuroimaging Core Facility. His neuroimaging program includes drug receptor occupancy, pharmacokinetics, brain metabolism and functional magnet resonance imaging (fMRI) in awake, behaving monkeys. The long-range objective is to develop a unique, multidisciplinary research program in substance abuse that effectively integrates behavior, neurochemistry and functional brain imaging in nonhuman primates.

The research in our lab lies in the development of biomedical imaging techniques, particularly those based on magnetic resonance imaging (MRI), and their application to the understanding of anatomy, function and physiology of brain in its normal state and diseased state. Specifically, we are focusing on functional MRI and diffusion tensor imaging and interested in furthering and using these techniques for understanding how brain works at a system level. Current projects include improvement of image acquisition and processing methods, investigation of underlying biophysics and physiology of imaging measurements, and elucidation of neurobiological underpinning of neuropsychiatric and neurodegenerative disorders.

Research in my laboratory focuses on circadian clocks and neuromodulators that regulate neuronal plasticity. Most studies utilize the retina as an experimental model, as it contains circadian oscillators that regulates the release of two neuromodulators – melatonin and dopamine – that fine-tune synaptic mechanisms controlling dark adaptation and light adaptation and many aspects of circadian retinal physiology. Expression of circadian clock genes and their effectors are studied using cellular, molecular and genetic approaches.

We combine electrophysiological recordings and detailed compartmental modelling to examine how neurons in the basal ganglia and in the cerebellum process their inputs. In particular we are interested in the functional role of inhibitory inputs and the role of active neural properties in network processing. We also apply these concepts to investigate the mechanisms underlying the clinical effects of deep brain stimulation using multisite recordings in anesthetized rodents.

I am interested in investigating the rules by which cellular architecture is choreographed during two aspects of development: the mitotic cell division and post-mitotic neuronal differentiation. We have focused on microtubules, which play a crucial role in both of these processes. To understand diverse microtubule behavior during these biological processes, we first analyzed the genes that encode subunit proteins tubulins which assemble to form microtubules. We are now analyzing how different tubulin protein subunits contribute to different behavior of microtubules during neuronal morphogenesis. The approach we are taking combines genetics, molecular cell biology, biochemistry, and structural biology.

The ongoing grant-funded research within my group focuses on the use of in vivo molecular and functional brain imaging in human and nonhuman primates to explore molecular and neural processing models of normal and abnormal behavior. A current research emphasis relates to defining the neural processing correlates of hallmark diagnostic features of drug addiction - deficits in impulse control and pathological motivational states for drug abuse. My group also uses similar technology applications in exploring the relatedness of genetic polymorphisms of individual differences in neural processing related to encoded proteins. As an example, my group is currently exploring the impact of variable number of tandem repeats (VNTR) polymorphism in the dopamine transporter gene on in vivo dopamine transporter availability and dopamine-related neural processing elicited by tasks or medications. My group also is involved in neuroimaging applications to exploring the neural processing related to complex social behaviors such as preference choice, morality and ethics, decision-making, and emotional memory.

A major focus of my research program is the behavioral pharmacology of cocaine and related psychomotor stimulants in nonhuman primates. One of our major goals is to study the pharmacokinetics and harmacodynamics of cocaine and its checmial analogs and to relate these properties to their reinforcing effectiveness. We are also interested in how different neurotransmitters in the brain modulate the effects of drugs of abuse. We are involved in developing medications for reducing drug use in humans. We use operant conditioning techniques in vivo microdialysis with HPLC, and neuroimaging to determine the neuropharmacology of cocaine and related compounds in nonhuman primates.

Our general interests include the structure and function of the brain, and particulary the deficits that occur in neuropsychiatric disease. There is an emphasis on neurotransmitter systems and their involvement in brain function. A recent focus has been on molecular and cellular mechanisms of drug addiction, and particularly on novel genes associated with the addiction process. Current topics of research include CART peptides, development of medications for drug addicts, and a study of novel genes involved in the addiction process.

My research is driven by the goal of understanding basic pathogenic mechanisms in Alzheimer's disease (AD). Specific topics of interest include: regulation of amyloid precursor protein (APP) processing through control of intracellular trafficking, analysis of the role of the apolipoprotein (ApoE) receptor LR11 in amyloidogenesis, modulation of APP processing by muscarinic receptor activity, and characterization of new genes involved in AD and neurodegeneration. These questions are being addressed in a variety of cellular and animal models, using plasmid transfections, viral gene transfer, and siRNA techniques combined with biochemical and cell biological analytic methods.

The primary aim of my research is to clarify the functional significance of neuronal Ca2+ binding proteins (NCBPs) in the nervous system. Our initial focus is on how CaBP1 and CaM differentially modulate Ca2+ channels. Current projects include: (1) Defining the molecular mechanisms that distingush Ca2+ channel modulation by CaM and CaBP1. (2) Comparing the regulation of Ca2+ channels by CaBP1 splice variants; (3) Identifying the cellular and subcellular colocalization patterns of Ca2+ channels and CaBP1 in the brain; and (4) Analyzing the effect of phosphorylation and other modulatory influences on the interaction of CaBP1 with Ca2+ channels. In addition, we are characterizing the nteractions of NCBPs with other ion channels and how these interactions may affeect neuronal excitability.

Determining the principals underlying neuron computation within the context of the control of movement. Cellular neurophysiology, to determine how the whole cell behavior arises from their constituent sub-cellular structures in neurons and motoneurons.Computer modeling of neurons, developing advanced methods for automatically tuning neuronal models and for examining and validating the model's behavior.

Dr. Levey investigates Alzheimer's and Parkinson's diseases. One focus is on cholinergic receptors which are potential sites of action for new therapies, and include identification of the functions of receptor subtypes, delineating new signaling pathways, and determining the intracellular trafficking mechanisms. Another major focus is to identify new genes linked to these neurodegenerative diseases, including a collaboration with deCODE Genetics in Iceland. To help determine the functional relevance and pathological or therapeutic significance of candidate gene products, the laboratory combines molecular, immunological, and neuroanatomical techniques in studies of the expression and regulation of the proteins expressed in cell culture model systems as well as in brains of experimental animals and humans affected by neurodegenerative diseases.

My laboratory studies the molecular basis of neurotransmitter release and pathogenic mechanisms of neurodegenerative disorders, such as Parkinson's, Alzheimer's, and Huntington's diseases. A current major focus of our work is to delineate the molecular pathways by which mutations in familial Parkinson's disease proteins ( -synuclein, parkin, DJ-1, and UCH-L1) lead to neurodegeneration and identify additional molecular players in the pathogenic pathways. We are also studying regulation mechanisms of vesicular trafficking and investigating the role of abnormal vesicular trafficking and protein ubiquitination in the pathogenesis of Parkinson's, Alzheimer's, and Huntington's diseases. Our research uses a combination of molecular biological, biochemical, cell biological, proteomic, and molecular genetic approaches, including targeted gene disruption.

The major interest of our laboratory is to elucidate the molecular mechanisms by which misfolded proteins mediate selective neurodegeneration. We focus on inherited neurodegenerative diseases, such as Huntington’s disease, which are caused by the expansion of a polyglutamine domain in proteins associated with various diseases. We are using a combination of molecular neurobiology, biochemistry, cell biology, and transgenic mouse approaches to address how polyglutamine expansion in ubiquitous proteins selectively induces late-onset neurodegeneration. Understanding this issue will also help elucidate the pathogenesis of other age-dependent neurodegenerative disorders such as Alzheimer’s and Parkinson’ diseases.

The primary aim of my lab is to understand how ion channels and receptors contribute to the transduction and homeostasis on the cochlea. The transduction process in the cochlea which turns the mechanical vibration into impulses in the auditory nerve, and homeostasis mechanisms which maintain special fluid and ionic balances in the inner ear, both require the concerted actions of many types of ion channels/receptors in the cell membrane. We use multidisciplinary approaches, including eletrophysiological and optical recording, to understand roles of important ion channels critically involved the normal function of the cochlea.