Areas of Neuroscience Research

The research programs of the faculty of The Neuroscience Institute are diverse, representing most areas of modern neuroscience research. Within the program are several strong areas of research focus, where in many instances basic scientists and clinical investigators interact to investigate the mechanisms of diseases of the nervous system. The participating faculty have organized these areas into eight research focus groups, within which there is considerable intellectual interaction and collaborative research. The groups include Neurological and Neurodegenerative Disorders, Neuro-oncology, Excitable Properties of Neurons, Sensory Information Processing, Vision and Retina, Neurogenetics, Development and Evolution, Mental and Addictive Disorders, Neural Cell Signaling, as well as Other Research Interests.

Neurological diseases include disorders of the nervous system arising from nervous system malfunction or degeneration. Among these are the movement disorders (which include Parkinson’s disease, essential tremor, Huntington’s disease, dystonia, myoclonus, Tourette’s syndrome, paroxysmal dyskinesias, drug-induced dyskinesias, restless legs syndrome, spinocerebellar ataxias, spasticity, multiple system atrophy, and progressive supranuclear palsy), dementing diseases (notably Alzheimer’s), primary motor diseases (such as amyotrophic lateral sclerosis and multiple sclerosis), and diseases of neurotransmission abnormality (such as epilepsy). The integration of genetic, cellular, and physiological information will be required to unravel the pathophysiology of each disorder and improve therapeutics. Due to aging of our population, movement disorders and dementing diseases will place an enormous and ever increasing financial burden on society. Investigations carried out by this group of scientists will play an important role in the breakthroughs needed to understand and treat these diseases. Current areas of focus include: cellular and network physiology of basal ganglia oscillations in the context of Parkinson’s disease, neurobiology of neuronal dysfunction and death in Huntington’s disease, and molecular biology of synaptogenesis in dystonia. Faculty are also studying the potential protective effects of hypothermia on cerebral ischemic insults, pathophysiology of Alzheimer’s disease, and molecular mimicry in immune-mediated neurological disease.

Primary brain tumors and tumors metastatic to the central nervous system are relatively common and associated with tremendous morbidity and mortality. The most prevalent form of adult primary central nervous system tumors is collectively referred to as glioma, and the most common and devastating glioma is glioblastoma multiforme. Despite dramatic improvements in neural imaging and neurosurgical techniques, the prognosis for high-grade gliomas has not improved significantly over the last 40 years. Clearly new therapies are needed to overcome the obstacles to treating brain tumors. The focus of the adult neuro-oncology group is to combine large-scale gene expression analysis of patients with brain tumors with cell and molecular studies of cell lines, tissues, and animal models of brain cancer. Research is directed towards the identification of genes associated with central nervous system tumors, understanding the mechanism by which genes affect intra- and extracellular tumor behavior, and the development of therapies that target these genes.

Behavior, mental processes and physiological homeostasis are all a function of neuronal activity in the nervous system. This activity can be encoded by membrane polarity or in the rates and patterns of neuronal action potentials. Information is passed among neurons through synaptic transmission. Whether a neuron fires at any given moment is determined by the interaction of intrinsic membrane properties with synaptic inputs. Research in this group focuses on these properties from several viewpoints. At the molecular level, studies determine the genetic capacity for producing proteins related to specific ion channels and neurotransmitter receptors. Expression patterns of the proteins in classes of neurons impart a unique signature of ion channels and receptors. Electrophysiological recordings can reveal the properties of ionic currents underlying particular patterns of firing, the modulation of these currents by neurotransmitters, the precise properties of synaptic input, and the plasticity of neuronal activity. At a more global level, neuronal activity can be studied within an intact neuronal network and correlated with behavior. The common goal of this group is to understand how and why neuronal activity occurs in both normal tissue and in neurological disorders.

Sensory systems extract information from the environment and provide the nervous system an interface with the outside world. Understanding the way in which this information is represented in neuronal activity is the focus of this research group. To understand sensory processing, we need to address the genetic basis of sensory function, the coding of information by individual sensory neurons at several levels of the nervous system, from peripheral receptors to cerebral cortex, and the role of the environment in shaping the responsiveness of these neurons through mechanisms of neuronal plasticity. Interactions between somatosensory and motor cortices, the effects of early alcohol exposure on sensory and motor processing, the control over gustatory information processing by descending influences from limbic forebrain, the genetics of taste processing, the processing of nociceptive (pain) information, and synaptic processing in the olfactory bulb are all areas of research addressed by this group.

We rely primarily on our sight to guide us through the world. Our eyes provide the major sensory input to the brain, accounting for one-third of the sensory axons entering the human nervous system. Understanding the normal function of the eye and the way this process is affected by disease is the primary interest of this group. Researchers are addressing the normal development of the eye as well as the genetic basis of function and disease. The current program reflects a comprehensive and synergistic approach to important fundamental questions of eye genetics and development and the application of this new strategy to the treatment of disease. These investigators seek to understand normal and abnormal ocular development and how genes control these events. There is an active program in the application of molecular techniques to the modulation of retinal cell growth and cellular responses to injury using gene therapy. Current areas of focus include prevention and treatment of eye diseases and disorders, eye genetics in development and childhood diseases, retinal degenerative diseases, anterior segment disorders, response of the retina and optic nerve to injury, and genetic control of eye development. The primary goal of the vision and retina research group is to provide a framework for effective communications between research laboratories effecting eventually the translation of basic research to clinical applications.

This group is interested in gaining a deeper understanding of the origins of the impressive structural and functional complexity, diversity, and plasticity of the nervous system. Experimental and technical expertise of this group is broad, ranging from genetic and molecular analysis of the early stages of central and peripheral nervous system development to sophisticated functional assays of neuronal plasticity in response to environmental manipulations. The group is highly collaborative and includes a significant contingent of neuroscientists from St. Jude Children's Research Hospital (primarily the Departments of Developmental Neurobiology and Genetics). Current research tends to rely heavily on genetically defined lines of rodents. Topics of research interest include: control of cell cycling and cell death in the brain, control of axon outgrowth and neurotrophic interactions during neural development, the formation, elimination and stabilization of synapses, functional maturation and environmental/drug sensitivity of the developing nervous system, genetics of disease vulnerability and outcome, and mechanisms of cell migration in the developing brain.

Mental and addictive disorders are due to changes in normal brain function. This research group collaboratively explores changes in brain function that might explain mental disorders, such as depression and addiction, and drug-induced changes in brain function that may be responsible for relieving mental disorders or producing addiction. Research is currently being conducted using both in vivo and in vitro models. Molecular, cellular, neuroanatomical, neurophysiological, neurochemical, morphological and behavioral approaches are all being used to study the neuroscience of mental and addictive disorders. Research efforts are currently focused on depression and antidepressants and drugs of abuse, including cocaine, amphetamine, nicotine, ethanol and toluene. Several collaborative efforts currently exist within the group, including studies on drug effects on ion channels, drug-neuroreceptor adaptations, developmental neuroplasticity and interactions between stress and drugs.

The function, growth and survival of neural cells are regulated by extracellular and intracellular signals. One example is the release of neurotransmitter from a presynaptic neuron, which is sensed by the post synaptic neuron via receptors that recognize specific neurotransmitter molecules. This information is relayed to the cell’s interior by a series of elaborate and interdependent signaling intermediates and results in a change in the cell in response to its environment. This diverse group of researchers is investigating those processes that are collectively referred to as signal transduction using neural or neural-derived cell systems. Indeed, most drugs that are currently used in the management of neurological disorders, such as ADHD, depression, schizophrenia, Parkinson’s disease and others, exert their effects on signaling components. The goal of this group is to understand the involvement of signal transduction in both the normal functioning of neural cells and those pathological changes that are manifested in neurological disorders. Current areas of emphasis include: G-protein-coupled receptor signaling and regulation, growth factor receptor signaling, apoptosis, cellular migration, and mechanisms of neuronal injury and repair.

In addition to these collaborative research groups, there are several other research areas represented within the neuroscience faculty. These areas include clinical studies on neurotrauma and regeneration, cerebrovascular disease and stroke, spinal cord injury and repair, the physiology and pharmacology of the hypothalamus and its neuroendocrine regulation, cellular and molecular regulation of the autonomic nervous system and its impact on the vascular tree, the structure, physiology and neurotransmitters of basal forebrain structures involved in Alzheimer’s disease and epilepsy, the physiology, biochemistry, and pharmacology of the brainstem and its control of cardiovascular function, sleep, cerebral circulation and metabolism, the biochemical analysis of peptides, and brain modeling.