Research Interests:
The Kalivas lab studies neuroplasticity underlying the development of addiction to drugs of abuse, as well as the learning and memory deficits associated with impoverished rearing environments. Research is at the level of protein biochemistry, neural circuitry and behavioral modeling. The current focus for both addiction and isolation rearing is in adaptations in excitatory neurotransmission. In collaboration with electrophysiologists in the department (Drs Lavin, Seamans, Woodward) we are elucidating the fundamental role of extracellular glutamate homeostatis in regulating neurotransmission and neuroplasticity. This has led to preclinical and clinical evaluations of specific proteins as targets in treating addiction, including metabotropic glutamate receptors and the cystine-glutamate exchanger.
Brain circuitry underlying addiction: Long-term cellular changes in the glutamate neurons projecting from the prefrontal cortex to the basal ganglia are critical mediators of addictive behaviors. This includes changes in glutamate homeostasis and G-protein signaling, and involves proteins such as Homer, xCT, AGS3 and mGluRs.

Dr. John Woodward
Professor, Dept. of Neurosciences and Dept. of Psychiatry

Phone: 843.792.5225, 843.792.6374 (Lab)
E-Mail: woodward@musc.edu

Research Interests:
Dr. Woodward’s lab is focused on defining the neural sites of action of alcohol and abused inhalants such as toluene and TCE. Alcohol and abused inhalants produce diverse effects on neuronal function by altering the function of different types of ion channels that regulate neuronal excitability. These include voltagedependent channels as well as those gated by neurotransmitters such as glutamate, Ach and ATP. Electrophysiological recording techniques are used to directly measure the function of both recombinant and native channels while site-directed mutagenesis is used to probe for discrete sites of action on the ion channel itself.

My lab website: http://people.musc.edu/~woodward/

Dr. Lawrence Judson Chandler
Associate Professor

Phone: 843.792.5224, 843.792.5159 (Lab)
E-Mail: chandj@musc.edu

Research Interests:
Dr. Chandler’s research program is focused on understanding the fundamental processes that underlie the plasticity of the nervous system. In particular, his laboratory is investigating how the brain changes and adapts in response to environmental influences such as exposure to drugs of abuse and alcohol. It is widely believed that changes in glutamatergic neurotransmission mediate the neuroadaptive processes of addiction and tolerance. Areas of research interest include receptor trafficking and synaptic localization, signal transduction, and dendritic spine dynamics. Techniques being employed include cell culture, molecular and biochemical procedures, confocal and multiphoton imaging, and in vitro electrophysiology.

Dr. Sammanda Ramamoorthy
Associate Professor, Department of Neurosciences

Phone: 843.792.3689, 843.792.9884 (Lab)
E-Mail: rama@musc.edu

Research Interests:
Studies in the Ramamoorthy laboratory are aimed at understanding the contribution of neurotransmitter transporters to CNS function, and more specifically, directed toward understanding the role of monoamines such as dopamine, serotonin and norepinephrine
transporters (DAT, SERT and NET) in normal neurotransmission and in relevance to mental illness, drug abuse, aging and neurodegenerative diseases. The monoamine transporters by clearing the released neurotransmitter back into neuronal terminals and are molecular targets for addictive drugs including cocaine, amphetamines and MDMA (ecstasy) as well as important therapeutic antidepressants.
Since the cloning of the human serotonin transporter, the major goal of the laboratory is to understand thoroughly the molecular basis of serotonin transporter regulation. By combining molecular, immunological and biochemical approaches, continuing studies in the laboratory seek to identify signals and dissecting cis/trans signaling pathways that participate in the dynamic process of transporters regulatory pathways in more detail. For example transporter phosphorylation, trafficking, protein-protein interactions will be studied at the level of transcriptomics, proteomics and lipomics.
The final goal is to relate studies of molecules from cells to native tissues and intact animals and to define the mechanisms of normal and abnormal regulation of these neurotransmitter transporters in normal and pathological neurotransmission. Outcome of these studies will provide macroscopic visions and microscopic details of neurotransmitter transporters in both CNS and PNS in: healthy/normal conditions, mental illness, drug abuse, aging and neurodegenerative diseases. These studies would also open up possibilities for developing new therapeutic strategies towards mental illness, drug abuse and other and neurological diseases.

Research Interests:
The focus in my laboratory is on neuroplasticity, both during early development and aging. In particular, we are studying factors that influence development and aging in neurons, such as neurotrophic factors.

We have primarily focused on trophic factor influence on cholinergic, adrenergic, and dopaminergic pathways in the brain and the neurotrophic factors NGF and GDNF. We are using transplantation of fetal brain tissue and stem cells intracranially and into the anterior chamber of the eye as a means to study connectivity, and also as replacement therapy. More recently, we have also started working on estrogen/testosterone replacement therapy, as well as dietary supplementation with antioxidants and low-cholesterol diets.

The overall goal of the laboratory is to develop treatment strategies for Parkinson's and Alzheimer's disease by using growth factors, hormone replacement, or dietary prevention therapies. We are using a systems approach, studying memory and movement behaviors, and correlating these behavioral data with biochemical and structural correlates in the brain. Recently, we have incorporated a translational research approach, with ongoing studies together with clinical laboratories around our campus and at other aging centers.

Dr. Jakie McGinty
Professor, Department of Neurosciences

Phone: 843.792.9036, 843.792.9481 (Lab)
E-Mail: mcginty@musc.edu

Research Interests:
My research focuses on (1) the effects of drugs of abuse on neurotransmitter release and gene expression in the rat brain and (2) the effects of methamphetamine neurotoxicity in neurotrophic factor knockout mice during aging. Using in vivo microdialysis, my lab has demonstrated that endogenous opioid and muscarinic systems decrease the psychostimulant-induced release of neurotransmitters such as dopamine and glutamate in the striatum. By affecting intracellular kinase cascades in neurons which express dopamine and glutamate receptors, we have demonstrated that psychostimulants change the activity of nuclear transcription factors and the expression of their target genes.
Currently we are using cDNA microarray technology, in situ hybridization, immunoblotting, and immunohistochemistry to characterize changes in gene expression that may signify longterm neuroadaptations in the brain thought to underlie drug addiction and neurotoxicity during aging.

Dr. Gary S. Aston-Jones
Professor, Murray Chair of Excellence in Neuroscience
Director, Carolina Primate Center

Phone: 843.792.1800, 843.792.4423
E-Mail: astong@musc.edu

Research Interests:
Dr. Gary Aston-Jones primary research interests are in the brain neuromodulatory systems, and their roles in cognitive performance, drug abuse, sleep and waking, and affective disorders. He uses a multidisciplinary approach, primarily involving single unit neurophysiology, neuroanatomy and behavioral neuropharmacology in rats and monkeys. He and his colleagues have recently described a role for the brain noradrenergic locus coeruleus system in decision processes, in the circadian regulation of sleep and waking, and in depression. Other of his lab's recent work also reveals a key role for the A1/A2 noradrenergic brain system innervation of the ventral forebrain in the affective response to drug withdrawal, and also indicates an important role of this and related systems in the drug seeking that accompanies protracted opiate withdrawal.

Research Interests:
My research interests relate to the organization and the functional properties of the neural circuitry of the prefrontal cortex, and the pathophysiology of this circuitry in schizophrenia.

An important cognitive feature of higherorganisms is their ability to temporarily structure their behavior and to actively hold in mind information relevant for goal-attainment. This so called “working memory” is closely related to the functions of the prefrontal cortex and its innervation by dopaminergic fibers.

In collaboration with Drs. Seamans and Chandler, I study the network properties that underlie persistent activity required for working memory, using electrophysiological recordings and high-resolution calcium-imaging. I am particularly interested in the role of inhibition in the network provided by GABAergic interneurons, and how this is modulated by dopamine.

A second area of interest is to see how persistent activity is disturbed by drugs of abuse, specifically cocaine.

Research Interests:
Neural substrates of addiction and relapse: Our laboratory has developed animal models of chronic psychostimulant and opiate self-administration to study the role of specific brain nuclei in mediating drug-taking and drug-seeking behavior. A particular focus is the role of corticolimbic function in regulating the learned associations that mediate relapse to compulsive drug abuse.

Sex differences in addiction: This line of research examines sex differences in a model of relapse to cocaine-seeking behavior produced by various stimuli. Further studies are using this model to examine sex differences in the response to possible pharmacotherapies for relapse.

Neural basis of antipsychotic drug effects: This research is directed towards understanding the mechanisms of short- and long-term antipsychotic drug action in the brain. These studies involve administration of a variety of drugs that affect basal ganglia function as measured by changes in neurotransmitter release via intracranial microdialysis.

Dr. Swapan Ray
Associate Professor

Phone: 843.792.7595
E-Mail: raysk@musc.edu

Research Interests:
Programmed cell death in malignant and neurodegenerative diseases, involvement of calpain in spinal cord injury and neurodegenerative diseases.

Research Interests:
Dr. Sambamurti’s research program is focused on mechanisms of neurodegeneration that ultimately result in the slow decline associated with aging as well as in a number of diseases such as Alzheimer's disease (AD), macular degeneration (AMD) and Parkinson's disease (PD). These diseases are characterized by the failure of the protein maintenance mechanisms resulting in their deposition.

For example, in AD a small peptide of 42-residues_Amyloid beta (Ab) is deposited extracellularly as senile plaques and cerebrovascular amyloid and a microtubule-associated protein, tau, is deposited within affected neurons as neurofibrillary tangles. Ab is also deposited in extracellular deposits called drusen that characterize the neurodegeneration associated with AMD. Although aggregates of Ab are somewhat neurotoxic in vitro, mice that deposit Ab do not show neuronal loss suggesting that the mechanisms of neurodegeneration may be complex.

We are currently, studying APP processing and function to ultimately dissect out the processes and pathways that lead to neuronal dysfunction and death in AD and AMD. Our studies use cellular and animal models to characterize the metabolic pathways of APP and related proteins, understand the function of these proteins and determine the protein interactions and localization changes associated with normal and abnormal functioning of neuronal cells.

Dr. Catalin V. Buhusi
PhD, Duke University, 1999

Associate Professor, Dept. Neurosciences, MUSC
Office Location: 410C Basic Science Bldg., MUSC Campus
Phone: 843-792-4494
Email: buhusi@musc.edu

Research Interests: Behavioral and Computational Neuroscience
The aim of my research program is to provide a more complete understanding of the role of the dopaminergic system in normal and abnormal adaptive behavior by using methods from behavioral-, systems-, and computational neuroscience. Experimental work involves the use of rodent models to manipulate, visualize, and examine various aspects of the involvement of the dopaminergic system in normal and abnormal behavior.  Current work includes behavioral studies, pharmacological manipulations, and multiple electrode recordings in behaving mice and rats. I also use computational models that integrate the growing body of data relative to the role of the dopamine system in learning, memory, and attention. My research is relevant to psychopathology ranging from Mental Retardation, to Schizophrenia and Parkinson’s Disease. My lab has an excellent history of undergraduate participation in this research, including honors theses, poster presentations at national scientific meetings, and publications in international scientific journals.

Selected Undergraduate-Author Publications (* = undergraduate student):
*Aziz D. Evidence for scalar timing in C57BL/6 mice (2007). Honors Thesis. Duke University, Durham, NC.
*Houkal J, Buhusi M, Schachner M, Maness P, Buhusi, CV (2005). Impaired memory for time in mice lacking the CHL1 cell adhesion molecule. The Proceedings and Abstracts of the Annual Meeting of the Eastern Psychological Association, vol. 76, p. 54.
*Chu R, Buhusi MC, Schachner M, Maness PF, Buhusi CV (2005). Impaired working memory on a spatial learning task in mice deficient in the CHL1 cell adhesion molecule. Program No. 996.16. 2005 Abstract Viewer / Itinerary Planner. Washington, DC: Society for Neuroscience. Online. 
Buhusi CV, *Perera D, Meck WH (2005). Memory for timing visual and auditory signals in albino and pigmented rats. Journal of Experimental Psychology: Animal Behavior Processes, 31, 18-30.

Dr. Mona C. Buhusi
PhD, Medical University of Iasi, Romania, 1999

Assistant Professor, Dept. Neurosciences, MUSC
Office Location: 416 Basic Science Building, MUSC Campus
Phone : 843.792.4527
E-Mail : buhusim@musc.edu

Research Interests:
Brain function relies on the precise wiring of neurons during embryonic development, when newly generated neurons migrate to their appropriate location, extend axons and form synapses onto their targets.  My research aims at (a) identifying the specific sets of guidance cues along individual pathways, able to direct one particular group of axons to the corresponding target neurons, (b) understanding how the complex interactions between diverse axonal membrane proteins and their ligands result in specific cellular decisions along the path, and (c) understanding how anomalies in neuronal connectivity relate to human neuropsychopathology.  To achieve these goals, my research involves techniques from molecular biology, protein biochemistry, neuronal cell culture, neuronal tracing, histological and immuno-staining, conventional and laser confocal microscopy on fixed and live specimens, and the construction and analysis of animal models. This research is amenable to undergraduates interested in neuroscience.

Research Interests:
Dr. Holden's professional career has been primarily devoted to the study of neurodevelopmental disabilities presenting from the prenatal period through young adulthood. He has directed and participated in multiple clinical outcome studies, as well as authored numerous peer-reviewed articles on epilepsy, neurodevelopment, pediatrics, and neuroradiology.