The discipline of neuroscience examines nervous system function at numerous levels, incorporating a molecular and cellular viewpoint on the one hand and an integrative systems approach on the other. It is the goal of modern neuroscience research to integrate the two sides of this neurological coin into a consistent continuum, one that blends neurochemistry, developmental neurobiology, neuropharmacology, neurophysiology, neuroanatomy, and behavior neuroscience into a seamless intellectual construct capable of generating novel, testable hypotheses of how these individual disciplines are coordinated to produce the remarkable machine we call the nervous system. The Department of Neuroscience at UConn Health has applied these principles in the development of an equally integrated community of neuroscience investigators, with special strengths in the following areas of research: cellular and molecular, developmental, neuroinflammation and neuroimmunology, neurological disease, neurotransmission, sensory processing, and systems.

 

Cellular and Molecular Research

Molecular Neuroscience aims to understand nervous system function at the level of individual molecules and regulated complexes. Prominent approaches utilize structural biology, genetics, recombinant DNA methodology, biochemistry, chemical biology, proteomics and bioinformatics.

Cellular Neuroscience works at the level of the basic biological unit, the cell. Signal transduction cascades, membrane biogenesis and function, ion channel structure and function and intracellular trafficking of RNA and protein are forefront areas of investigation, often using sophisticated microscopic and imaging techniques. Although both of these disciplines tend by their nature to be reductionist in philosophy, there is a continuing trend to the study of the integrative nature of molecular and cellular events. The Department of Neuroscience at UConn Health has a strong and growing commitment to this approach to neuroscience, as indicated by the research interests of the faculty listed below. In addition, there is pervasive strength in molecular and cellular science in many other departments throughout UConn Health, including the Departments of Genetics and Developmental Biology, Biochemistry, Microbiology, and Psychiatry.

 

 

Developmental Research

Developmental neuroscience seeks to reveal how multipotential progenitor cells differentiate into specialized cell types, in particular neurons and glia; how these cells migrate and interact with each other to form specific nervous tissue structures; how they influence each others fate, and behavior; and how neuronal activity modulate their function.

A) NEURONS

One of our research interests concerns the mechanisms by which neural epithelial cells develop to form the cerebral cortex. Analyses of the sequence of events leading to the mature, carefully positioned neurons offer potential for furthering our understanding of disease mechanisms of developmental pathologies, such as congenital malformations and fetal alcohol syndrome. A particular strength of our faculty is the coordinated study of the development of the synaptic structure and microcircuitry of the auditory system, and of the role of factors in neurodegenerative diseases induced by acoustic overstimulation which aims at unveiling mechanisms that could be manipulated to stimulate neuronal repair and regeneration. Microscopic and molecular methods in cell culture experiments, transgenic mice, and transplantation of cultured neurons into the central nervous system further provide complementary models and a theoretical framework for exploring the cellular basis of critical periods in the differentiation of specific types of neurons and their connections.

B) GLIA

Oligodendrocytes produce the myelin sheath, a multilamellar membrane that envelops axons and is necessary for the salutatory conduction of nerve impulses. The development of oligodendrocytes is regulated by a plethora of environmental interactions, including numerous specific growth factors and cell adhesion molecules. After the oligodendrocyte progenitor becomes committed to a myelinating phenotype, the cell undergoes further regulated maturation leading to the production of the mature myelin membrane. These studies are essential to the development of strategies for enhancing oligodendrocyte production, and myelin repair in patients affected with conditions such as Multiple Sclerosis. Current interests of the faculty emphasize the regulation of oligodendrocyte development by fibroblast growth factor (FGF) and its family of receptors, molecular mechanisms of myelin biogenesis, and signal transduction in both oligodendrocytes and myelin.

Microglia are involved in the immune surveillance of the central nervous system. Current studies seek to expose the interactions of microglia with oligodendrocytes at early stages of development that may be essential in determining the pattern of immune response seen in adults when they are exposed to viral, bacterial, or self-antigen, such as the case may be in Multiple Sclerosis.

Astrocytes perform several functions in the central nervous system, and these functions vary as the brain develops and cell-cell interactions become highly specialized. One area of investigation concerns the mechanism by which astrocytes may signal oligodendrocytes to delineate the axonal territory that is to be myelinated. Astrocytes undergo changes in gene expression in several pathological conditions associated with chronic diseases, infections, or injury. A particular question being asked by our faculty is whether these changes represent a return to an early developmental stage that can contribute to repair of the nervous tissue.

 

 

Neuroinflammation and Neuroimmunology

Faculty in our department are exploring how inflammation in the nervous system contributes to many acute, chronic, immune and degenerative diseases of the nervous system. From studies involving T cell mediated immunity in diseases such as multiple sclerosis, to study of how innate immune cells, including brain resident microglia and infiltrating monocyte/macrophage, contribute to neuropathology in stroke, leukodystrophy or Alzheimer's disease, our faculty are interrogating various molecular and cellular pathways as future treatment strategies to delay, attenuate and possibly prevent neurological diseases.

 

Neurological Disease Research

NEURODEGENERATION

Many of the degenerative diseases & acute neurological injuries of the nervous system take a huge toll on their sufferers and on society. Most of these diseases involve the premature death of nerve cells leading to loss of cognitive function (e.g., Alzheimer's disease, Stroke, Huntington's), paralysis (Stroke, ALS, spinal muscular atrophy), and blindness (traumatic injury, glaucoma and macular degeneration). Various molecular pathways for initiation and possible prevention of these defects are under active investigation by members of this department.

Neurotransmission Research

A key feature of neurons is that they receive inputs, often conduct action potentials to another site, and then transmit to another cell. Neurotransmission involves the synthesis, storage and release of chemical messengers (transmitters) into extracellular space; the reception of information from the neurotransmitters at the target cell; and then transduction of that signal into another set of biochemical and voltage changes. A set of neurons working together is called a network. Experimental systems include whole animals, neurons and endocrine cells grown in tissue culture, transgenic mice, Drosophila, and other lower creatures.

Transmitters come in several types: conventional, such as acetylcholine and norepinephrine; neuropeptides, such as cholecystokinin and neuropeptide Y; and others, such as gases and ATP. Acetylcholine is the molecule that killed so many people during nerve gas attacks in World War I. The nerve gases blocked the normal inactivation of acetylcholine, and acetylcholine is the transmitter whose biological punch is messed up in muscular dystrophy and in the key neurons lost in early Alzheimer's disease. Norepinephrine stabilizes blood pressure when you stand up, and the precursor of norepinephrine (dopamine) is the molecule lacking in Parkinson's disease. Cholecystokinin is a major peptide transmitter in the brain, and cholecystokinin imbalances underlie panic disorder. Neuropeptide Y contracts your pupil and causes long-lasting contractions of blood vessels in the brain. The department has experts in many of these areas, focusing on the synthesis, storage, release and regulation of transmitters. The studies of regulation of neurotransmitter metabolism now have progressed to include molecular modeling as part of experimental design.

Transduction of nervous signals falls into a couple of broad categories: ionic signals (currents and voltage changes) and biochemical events. The target cells for transmitters can respond by changing their membrane potentials up or down, by changing the rate of production or levels of "second messengers," and by other means. The department has active research concerning a number of second messenger systems. In addition, intracellular signaling among the far-flung parts of neurons is also a hot area of much interest in the department. Networks are a unique attribute of the nervous system and to a lesser extent the endocrine system. Networks are studied by recording the properties and responses of many individual neurons simultaneously in order to discern how their synaptic properties may be modified such that, as a coordinated group, they are able to store and transmit information.

Sensory Processing Research

BINAURAL HEARING

The study of binaural hearing concerns how and how well the ear and brain process information that arrives at two ears. In real-world settings, the information that arrives at the ears differs in terms of its timing and in terms of its intensity. It is these interaural differences that allow for the localization of sounds in space and for the detection and discrimination of signals in noisy backgrounds (e.g., speech in a background of noise). Several aspects of binaural hearing are the focus of research within the Department of Neuroscience. These range from the anatomical and physiological underpinnings of binaural processing to behavioral, or psychoacoustic measures in humans.

HEARING DIAGNOSTICS

Vibrations are generated by the normal hearing mechanism as part of its processing of sounds that impinge on the eardrum. That is, the ear makes sounds of its own. The measurement of these otoacoustic emissions can serve as a powerful diagnostic tool for evaluating the health, status, and function of the inner ear and the auditory system. Electrophysiological measurements offer another noninvasive means of evaluating the status of the hearing mechanisms. These are made by measuring electrical potentials at the scalp that occur in response to sounds. Within the Department of Neuroscience, investigators are involved in the development, refinement, and utilization of diagnostic techniques based on the measurement of hearing diagnostics.

Systems Research

CELLULAR BASIS OF SENSORY INFORMATION PROCESSING

Sound, light, tactile, and chemical stimuli are translated into neural signals. The brain must process this information using neurons, neural networks, and synapses and ultimately create what we recognize as a sensory experience. The study of this underlying machinery is the heart of the cellular basis of information processing. Within the Department of Neuroscience are laboratories that study the cellular basis of sound localization, neural networks, neurotransmitters, synapse formation, and employ anatomical and electrophysiological methods both in vivo and in vitro.

Systems neuroscience follows the pathways of information flow within the central nervous system, attempts to define the kinds of processing occurring there, and uses this information to help explain behavioral functions. Investigators work to understand sensory and perceptual systems and motor control. Research groups are asking how axonal systems develop, how they respond to damage, and how they change as a result of alterations in internal, chemical, and sensory environmental conditions.