Graduate Program Chairperson

M. Flint Beal, Department of Neurology and Neuroscience, Joan and Sanford I. Weill Cornell Medical College, 1300 York Avenue, A-569, New York, NY 10021, 212-746-6575

Graduate Program Director

Stewart Anderson, Department of Psychiatry, Joan and Sanford I. Weill Cornell Medical College, 1300 York Avenue, New York, NY 10021, 212-746-3921. Contact: Alime Lukaj, 212-746-6582, (Fax) 212-746-4879

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Overview of Research Activities

Functional magnetic resonance imaging reveals regions of the human brain that are neurally active during performance of specific tasks. This figure shows a typical functional brain response when the subject performs a bilateral finger/thumb tapping task. The brain areas that are active (yellow) identify motor (anterior lateral), sensory (posterior lateral) and supplementary motor (medial) areas that participate in these hand movements. This new ability to map brain functions opens many new opportunities to investigate and understand the human brain.

Our unifying theme is an abiding interest in the development and function of the nervous system. Members of the Program in Neuroscience study the nervous system with a wide variety of scientific disciplines, including molecular genetics, biochemistry, pharmacology, neuroanatomy, electrophysiology, computational neuroscience, and behavior. They work at the molecular, cellular, and organismal levels, exploring the nervous system in animal systems ranging from insects to rodents to human and non-human primates. The research interests of the program cover the entire range of neuroscience, including the regulation of neural development, neuronal plasticity, control of neurotransmitter synthesis & release, learning, the response of neurons and neural tissue to injury, the regulation of gene expression, endocrine function, vision & other sensory systems, information processing, and behavior. Many members of the program have a special interest in questions that are particularly relevant to human disease, and their research has important implications for topics such as stem cell therapeutics, the regulation of pain, neurodegenerative diseases such as Alzheimer's and Parkinson's disease, neural tumors, stroke, addiction, aging, and neuropsychiatric illneses. The research interests of the faculty can be grouped into six major areas including:

1. neural disease
2. synaptic transmission
3. developmental neurobiology and regeneration
4. vision,
5. cognitive and computational neuroscience
6. neuropharmacology

Note that these divisions are somewhat arbitrary since our faculty collaborate with one another and with other groups across the world - as a result, individual faculty frequently have interests in more than one of these areas.

Newly generated neurons from adult human temporal lobe in phase contrast (A) and after immunostaining for the neuronal protein MAP-2 (B). After loading with the calcium indicator dye fluo-3 (C), depolarization increases fluorescence (D).

Neural Disease

The majority of the faculty in the program have strong interests in human neurological or neuropsychiatric disease. Flint Beal focuses on oxidative damage as a cause and focus of treatment of Huntington's disease, Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Gunnar Gouras studies the cause of synaptic dysfunction in and molecular pathogenesis of Alzheimer's disease. Chenjian Li is using transgenic mouse technology to generate and study better models of Parkinson's and Huntington's disease. Giovanni Manfredi focuses on the involvement of mitochondria in neurodegenerative disease. John Blass is interested in the molecular basis of Alzheimer's disease and neural degeneration. Arthur Cooper is interested in neurotoxicology, amino acid metabolism, and energy production in Alzheimer's disease and during ischemia. Gary Gibson is interested in signal transduction and oxidative processes in the neurodegeneration associated with Alzheimer's Disease, ischemia, and metabolic disease.

A large number of investigators are interested in stroke and protection against ischemic injury. Rajiv Ratan, Director of the Burke/Cornell Medical Research Institute, is examining the transcriptional regulation of protective neuronal responses to oxidative stress. Bruce Volpe and Costantino Iadecola are also interested in neural degeneration after ischemia.

Several laboratories are studying the neurobiology of cancer. Jerry Posner studies the antigenic responses to cancer that induce neural degeneration (para-neoplastic syndromes). Ronald Blasberg uses Positron Emission Tomography (PET) to image brain tumors and to study tumor phenotype. He combines gene transfer technology and imaging of reporter gene expression to elucidate cellular and molecular processes including signal transduction and the expression of therapeutic genes. Anna Kenney is studying the role of Sonic Hedgehog signaling in medulloblastoma, the most common solid tumor in children.

In addition to translational studies on neurologic disease, several of our faculty focus on study of neuropsychiatric illnesses. Some these include depression (Francis Lee, Miklos Toth) addiction (Virginia Pickel, Teresa Milner), schizophrenia (Virginia Pickel and Stewart Anderson), and Attention Deficit Disorder (Teresa Milner, B.J. Casey).

Synaptic Transmission

The study of signaling among neurons and between neurons and other cells lies at the heart of neural functioning, so nearly all laboratories have an interest in this area; but several of our faculty focus strongly on the action of neurotransmitters and their receptors. Neil Harrison studies receptors for the inhibitory neurotransmitter GABA, their mechanisms of activation and modulation by endogenous modulators and drugs. Regulation of the rate of neurotransmitter release is a key regulator of information processing in the nervous system. Tim Ryan uuses optical techniques to study the fundamental mechanism of neurotransmitter release. Understanding signaling among neural cells is greatly facilitated by understanding the connections among nerve cells at the anatomical level, an approach used by many members of the program. Notably, Virginia Pickel is targeting opioid and catecholamine receptors and neurotransmitter transporters in basal ganglia, and their implications for reward and addiction. Teresa Milner is elucidating receptor selectivity of the transmitter components of the septohippocampal pathway that underlies learning and memory.

Developmental Neurobiology and Regeneration

Lorenz Studer studies neuronal stem cells and their potential for transplant and regeneration, for example in Parkinson's Disease. Stewart Anderson investigates the origins and fates of cortical interneurons. Betsy Ross studies neuronal migration together with the genetics of brain development and neural birth defects. John Wagner studies the role of peptide growth factors in the visual system. Barbara Hempstead studies the role of neurotrophin receptors in the development of the neural crest and the retina, and Francis Lee examines neurotrophin function in mouse forebrain. Urs Rutishauser investigates cell-cell interaction in the nervous system with a special interest in the role of neural cell adhesion molecules (NCAMs) and polysialic acid on neural migration and axon guidance. Bernice Grafstein studies axonal transport and regeneration as well as the development of the pia-arachnoid, which helps provide an appropriate environment for neural development. Dimitar Nikolov studies structure and function of axon guidance molecules, including ephrins, netrins, and semaphorins and their receptors. Ching-Hwa Sung studies the growth cone motility and synaptogenesis during neuronal development.

Cognitive and Computational Neuroscience

We have several labs studying brain function on the levels of imaging, multiunit recordings, and computer modeling. B.J. Casey, Director of the Sackler Institute for Developmental Biology, uses functional and structural magnetic resonance imaging to study the development of cognitive and affect regulation and its disruption in developmental disabilities. This work is heavily grounded in animal models. Bruce McCandliss uses high density electrical recording and fMRI to study the development of attention and language. This work has led to the development of behavioral interventions for children with learning disabilities.

Keith Purpura is interested in how attention influences cortical processing and how neural assemblies can represent the external world and influence behavioral tasks. Jonathan Victor studies signal processing and information coding in the nervous system. Daniel Gardner combines neurophysiology and artificial intelligence to elucidate the principles used to form neural networks.

Neuropharmacology

Charles Inturrisi and Gavril Pasternak are interested in the neuropharmacology of the opiates and their receptors. Many faculty are interested in drug abuse and the use of opiates for the control of pain. These efforts are supported by a training grant that is directed by Charles Inturrisi, which also supports several students. Ronald Blasberg uses PET to image opioid receptors, while Virginia Pickel and Teresa Milner study the localization of opiate peptides and their receptors at the ultrastructural level. Charles Inturrisi and Gavril Pasternak focus on the molecular basis of opiate receptor function, tolerance, and dependence. Xin-Yun Huang studies the ways GTP binding proteins and tyrosine phosphorylation are involved in transmitter signaling. Miklos Toth introduces germ line mutations into serotonin receptors to study their function. Lonny Levin is interested in signal transduction by adenylyl cyclase in axonal guidance and neuronal survival via a novel soluble adenylyl cyclase. Samie Jaffrey is conducting research on the function of protein synthesis in axons, and on the regulation of axonal growth cone signaling by microRNAs.

Since the ultimate purpose of the nervous system is to regulate behavior, several members of the program are attempting to determine the structural and biochemical basis of behavior. Miklos Toth uses genetic approaches to generate animal models of disease. His primary interest is the serotonergic system, which is associated with anxiety disorders, obsessive compulsive behavior, and aggressiveness in humans. He is also studying a transgenic model of epileptic seizure. Francis Lee examines how mutations in brain derived neurotrophic factor impact responsiveness to antidepressants in a rodent model of anxiety and depression. James Gibbs is interested in the regulation of feeding behavior, including its regulation by neuroendocrine function, neuropeptides, and dietary fat.

Vision

The visual system is a premier system to study sensory processing in both the retina and the brain. Members of the Dyson Vision Institute, directed by Enriqué Rodriguez-Boulan have a special interest in this area. Work in vision research is supported by an NIH training grant, which provides support for several students. Ching-Hwa Sung is interested in the molecular mechanism underlying the protein targeting and polarity establishment of mammalian visual cells and its relationship to retinal dystrophy. Enriqué Rodriguez-Boulan and Silvia Finneman focus on the cell biology of the retina, on how the retinal pigment epithelium promotes photoreceptor survival and how its dysfunction causes retinal degeneration. Jonathan Victor is interested in processing of visual information in both the retina and the cortex. Keith Purpura is interested in communication among the cortical areas involved in processing visual information.

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