Alcohol Research Training in Neurosciences (ARTN)
From Genes to Behavior
The Department of Neurosciences at the University of New Mexico Health Sciences Center contains an established group of investigators whose research focuses on various aspects of alcoholism. In August of 2003, the National Institutes of Health awarded the University of New Mexico a $600,000 grant to support an Alcohol Research Training in Neurosciences (ARTN) program. The award provides financial support for four graduate students per year working on various problems in alcohol research.

The overall goal of the ARTN Program is to provide Ph.D and M.D./Ph.D students with multipdisciplinary training in neuroscience, thus preparing them for a career in alcohol research. The program aims to provide students with a broad base of neurobiological concepts and methodological approaches for solving problems related to alcoholism.


Active research programs exist in several areas, including:

1) Fetal Alcohol Spectrum Disorders (FASD)
2) Alcohol craving, dependence, tolerance and withdrawal
3) Interactions between alcohol, stress, and hormones
4) Effects of alcohol on cognitive processes
5) Development of treatments for alcoholism and FASD

Opportunities are available for training in:

1) functional genomics and proteomics
2) molecular biology and biochemistry
3) electrophysiology
4) behavioral analyses
5) neuropharmacology

 

 


CORE FACULTY AND RESEARCH INTERESTS
The Core Faculty of the training program consists of six investigators studying various aspects of the neurobiologic effects of alcohol:



Andrea M. Allan, Ph.D., (Associate Professor, Department of Neurosciences)

In recent years, research in Dr. Allan's laboratory has primarily focused on the neurochemical mechanisms involved in alcohol and drug reward responding, impulse control and fetal alcohol exposure deficits. Previously, she characterized a mouse over-expressing the serotonin 5HT 3 receptor in the brain; these animals have decreased ethanol self administration and lower levels of anxiety. Concomitantly, Dr. Allan has been investigating the role of fetal alcohol exposure in the regulation and initiation of impulsive behavior, learning and memory, depression, anxiety and stress responding. Fetal alcohol exposure increases depressive and impulsive behaviors in the adult mice. There were also significant reductions in performance on several cognitive tasks in the adult offspring of alcohol drinking mothers. Research in her laboratory has found that there is reduced neurogenesis and lower levels of brain-derived neurotrophic factor associated with fetal alcohol exposure. Dr. Allan is investigating epigenetic changes that may underlie these changes. Techniques employed are related to basic and behavioral pharmacology, enzyme kinetics, genetics, behavior, learning and memory and biochemistry of receptors.

Selected Publications:

 

Kevin K. Caldwell, Ph.D., (Associate Professor, Department of Neurosciences)

An area of ongoing research in Dr. Caldwell’s laboratory is the study of signal transduction systems that are required for learning and memory and their roles in cognitive dysfunction resulting from prenatal exposure to ethanol. These studies aim to test the hypothesis that errors in the integration of cellular signaling are important components of the neurochemical imbalances that underlie the cognitive and behavioral abnormalities associated with fetal alcohol exposure. Results from these studies will facilitate the development of rational strategies for the treatment of alcohol-induced learning disorders in humans. In addition, Dr. Caldwell’s laboratory has recently initiated studies aimed at uncovering mechanisms linking prenatal ethanol exposure and various psychiatric disorders, with a focus on depression and post-traumatic stress disorder (PTSD). Currently, he is studying the effects of prenatal ethanol exposure on the expression of brain-derived neurotrophic factor levels in the hippocampal formation and frontal cortex to determine their role in the etiology of FASD-associated depression and PTSD.

Selected Publications

Lee Anna Cunningham, Ph.D., (Professor, Department of Neurosciences)

Dr. Cunningham’s research interests are in mechanisms of cell death and repair in the adult CNS. Current research in her laboratory is focused on neurogenesis in the adult mammalian brain in mouse models of stroke and prenatal alcohol exposure. Using both in vitro and in vivo models of ischemic injury, Dr. Cunningham’s laboratory is investigating the contribution of neuronal stem cells to revascularization and repair processes following stroke. Together with the alcohol research group at UNM, Dr. Cunningham is also studying the effects of moderate prenatal alcohol exposure on neurogenic responses in the adult hippocampus. In particular, she has been investigating the effect of fetal alcohol exposure on the neurogenic response to an enriched environment in adult mice. .

 

Selected Publications

 

Nora I. Perrone-Bizzozero, Ph.D. (Professor, Department of Neurosciences, ARTN Co-Director)

Dr. Perrone-Bizzozero’s program involves studies on the post-transcriptional control of neuronal gene expression during normal nervous system development and in neurodevelopmental disorders, particularly in an animal model for fetal alcohol exposure. She is interested in defining how fetal alcohol exposure affects the levels of GAP-43, BDNF, the K +-Cl - co-transporter 2, and other neuronal proteins both during development and during learning and memory mechanisms. More recently, she has turned her attention to the effects of ethanol on the mature cerebellum. This work is being done by a UNM-ARTN trainee (Vibhati Kulkarny). In the future, she is planning on performing studies on the effect of ethanol on cerebellar development in collaboration with Dr. Valenzuela. She is also studying the molecular and cellular alterations in the brains of control and alcoholic patients with schizophrenia. Throughout these studies, Dr. Perrone-Bizzozero’s group employs a variety of molecular, cellular and in vivo techniques, ranging from RT-PCR and DNA microaarray studies to in situ hybridization and immunocytochemistry in animals exposed to different behavioral paradigms.

Selected Publications:

 

Daniel D. Savage II, Ph.D. (Regents Professor and Chair, Department of Neurosciences)

Dr. Savage has sustained NIAAA funding throughout most of his twenty-three-year career as an independent investigator. Using a rat model of prenatal ethanol exposure, his laboratory was the first to observe that the consumption of moderate quantities of ethanol during pregnancy can cause persistent neurochemical changes in specific brain regions involved in memory consolidation. The alterations in ionotropic and metabotropic glutamate receptors caused by prenatal ethanol exposure decrease activity-dependent enhancement of synaptic communication between neurons leading to functional deficits in these brain regions. These changes may contribute to the learning disabilities observed in children whose mothers drank during pregnancy. More recently, Dr. Savage has appied his moderate exposure paradigm in two novel translational research endeavors: 1) Preclinical screening of therapeutic interventions for fetal ethanol-induced behavioral deficits and, 2) as a system for developing novel diagnostic approaches for identifying offspring with functional brain damage which may occur in the absence of the physical birth defects that may be associated with FASD. In addition, his work has begun to span from basic to clinical science with preliminary investigations combining neuropsychological assessment and functional neuroimaging of adolescents with FASD.

Selected Publications:

 

C. Fernando Valenzuela, M.D., Ph.D., (Associate Professor, Department of Neurosciences, ARTN Co-Director)

Dr. Valenzuela’s long term research interests are the actions of ethanol on neurotransmitter-gated ion channel function and synaptic transmission with particular emphasis on its actions during development. His team recently discovered that ethanol modulates glutamatergic transmission in an age-dependent manner in the CA3 hippocampal region. Specifically, AMPA but not NMDA receptors are sensitive to ethanol in slices from neonatal rats (i.e., a period equivalent to the third trimester of human pregnancy) Another important area of research interest in his laboratory is the mechanism of action of neurosteroids and the role of these agents in FASD. Fetal alcohol exposure produces a dramatic elevation of neurosteroid levels and premature activation of silent synapses, which could explain some of the synapse maturation abnormalities that characterize FASD. Another line of research concerns the effects of ethanol on neuronal oscillations in the immature brain. These oscillations contribute to activity-dependent modulation of neuronal growth and synaptogenesis. It was found that ethanol alters the normal pattern of this developmental oscillatory network activity and the mechanism of this effect is being characterized. His team is also studying the effects of alcohol on the function of mature cerebellar neuronal circuits. Data suggest that ethanol depresses synaptic transmission and plasticity in the mature cerebellar cortex by presynaptically modulating neurotransmitter release as well as regulating postsynaptic neurotransmitter receptors at major synapses within the basic circuit unit. Several techniques are used in parallel in his laboratory for these studies, including patch-clamp electrophysiological recordings from brain slices, immunohistochemical-confocal microscopy, fluorescence in-situ hybridization, Ca 2+ imaging and biochemical techniques.

Selected Publications:



In addition, collaborative training opportunities exist with several other investigators at the University of New Mexico.

Faculty

Department

Expertise

M. C. Wilson, Ph.D.

Neurosciences

Molecular genetics. DNA microarray technology.  Role of SNAP-25 in synaptic neurotransmitter release.
L. D. Partridge, Ph.D. Neurosciences

Electrophysiology of synaptic function. Presynaptic actions of neurosteroids; effects of fetal ethanol exposure on these actions.

C.W. Shuttleworth, Ph.D.

Neurosciences

High-resolution digital Ca2+ imaging coupled with single cell electrophysiology in acute slice preparations. Regulation of Ca2+ signaling and excitotoxicity.

L. Saland, Ph.D.

Neurosciences

Light, confocal and electron microscopy, receptor autoradiography, radioimmunoassay, and in situ hybridization. Effects of chronic ethanol exposure on opiate receptor expression reward pathways.

Derek Hamilton, Ph.D.

Psychology
and
Neurosciences		 Effects of prenatal ethanol exposure on social behavior, experience, and learning in relation to structural plasticity and experience-dependent gene expression in frontal cortex.

Kent Hutchison, Ph.D.

Psychology
and
Neurosciences		 Mechanisms that underlie substance abuse and dependence (e.g., craving and drug reinforcement), to examine individual difference variables, behavioral and pharmacological treatments that may moderate these mechanisms with the intention of reducing substance use.

M. Johnson, M.D.

Neurology and Neurosciences

Preparation of neuronal and glial cell cultures. Immunocytochemical techniques. Effects of prenatal ethanol on development of neuronal and glial cells.

Piyadasa Kodituwakku, Ph.D.

Pediatrics Defining the behavioral phenotype of children with fetal alcohol spectrum disorder (FASD) in the US , South Africa , and Italy . Studies aimed at investigating executive control functioning, attention, memory, language, and motor functioning in children with FASD.

Phillip May, Ph.D.

Sociology and Family & Community Medicine Epidemiology and prevention of suicidal behavior, adult alcoholism, fetal alcohol syndrome, injury, and child abuse and neglect.

Barbara McCrady, Ph.D.

Department of Psychology Development and evaluation of cost-effective behavioral treatments for substance use disorders, with particular emphasis on family-involved approaches, including mutual-help groups (such as A.A.), technology transfer, and services for women.

C. Tesche, Ph.D.

Psychology and Neurosciences

Magnetoencephalography of the human brain. Hippocampal and cerebellar activation during working memory tasks; Fetal Alcohol Syndrome

Steven Verney, Ph.D.

Psychology Information processing efficiency using information processing tasks and psychophysiological ( pupillary and eye-tracking measures) in fetal alcohol spectrum disorder.

Xinyu Zhao, Ph.D.

Neurosciences Molecular and cellular pathways that regulate neurogenesis and neuronal maturation with the goal of applying this knowledge in treating neurological diseases (including fetal alcohol spectrum disorder).

Vincent Clark, Ph.D.

Psychology and Neurosciences

Functional magnetic resonance imaging and magnetoencephalography in substance abusing patient populations

O. Bizzozero, Ph.D.

Cell Biology and Physiology

Protein biochemistry. Proteomics. Biochemistry of myelin


Academic Training
Students enroll in required and selected courses in the Biomedical Sciences Graduate Program and the Neurosciences Division; additional information can be found at (http://www.unm.edu/~neurohsc/grad.htm). In addition, students enroll in specialized courses (e.g., Neurobiology of Alcoholism, Developmental Neurotoxocology) and the Department of Neurosciences seminar series.

Contact Information
Support is available for Ph.D. and M.D./Ph.D. students. Students must be U.S. citizens or permanent resident, and must meet the requirements for the Biomedical Sciences Graduate Program at the University of New Mexico. For more information and details of application procedures, please contact Dr. Fernando Valenzuela (FValenzuela@salud.unm.edu).