Researchers in the Adam Sapirstein Lab focus on the roles played by phospholipases A2 and their... lipid metabolites in brain injury. Using in vivo and in vitro models of stroke and excitotoxicity, the team is examining the roles of the cytosolic, Group V, and Group X PLA2s as well as the function of PLA2s in cerebrovascular regulation. Investigators have discovered that cPLA2 is necessary for the early electrophysiologic changes that happen in hippocampal CA1 neurons after exposure to N-methyl-d-aspartate (NMDA). This finding has critical ramifications in terms of the possible uses of selective cPLA2 inhibitors after acute neurologic injuries. view more

The Brown Lab is focused on the function of the cerebral cortex in the brain, which underlies o...ur ability to interact with our environment through sensory perception and voluntary movement. Our research takes a bottom-up approach to understanding how the circuits of this massively interconnected network of neurons are functionally organized, and how dysfunction in these circuits contributes to neurodegenerative diseases like amyotrophic lateral sclerosis and neuropsychiatric disorders, including autism and schizophrenia. By combining electrophysiological and optogenetic approaches with anatomical and genetic techniques for identifying cell populations and pathways, the Brown Lab is defining the synaptic interactions among different classes of cortical neurons and determining how long-range and local inputs are integrated within cortical circuits. In amyotrophic lateral sclerosis, corticospinal and spinal motor neurons progressively degenerate. The Brown Lab is examining how abnormal activity within cortical circuits contributes to the selective degeneration of corticospinal motor neurons in an effort to identify new mechanisms for treating this disease. Abnormalities in the organization of cortical circuits and synapses have been identified in genetic and anatomical studies of neuropsychiatric disease. We are interested in the impact these abnormalities have on cortical processing and their contribution to the disordered cognition typical of autism and schizophrenia. view more

The Christopher Potter Lab functions at an intersection between systems and cellular neuroscien...ce. We are interested in how neurons and circuits function in the brain to achieve a common goal (olfaction), but we also develop, utilize and build tools (molecular and genetic) that allow us to directly alter neuronal functions in a living organism. The specific focus of my laboratory is to understand how the insect brain receives, interprets, and responds to odors. Insects rely on their sense of smell for all major life choices, from foraging to mating, from choosing where to lay eggs to avoiding predators and dangers. We are interested in understanding at the neuronal level how odors regulate these behaviors. Our long-term aim is to apply this knowledge to better control insects that pose a threat to human health. Our general approach towards achieving this goal is to develop and employ new genetic methods that enable unprecedented control over neural circuits in both the model organism Drosophila melanogaster and human malaria vector Anopheles gambiae. view more

The Cochlear Neurotransmission Group studies the generation and propagation of neural signals i...n the inner ear. Our laboratories use biophysical, electrophysiological, molecular biological and histological methods to determine fundamental molecular mechanisms by which neurotransmitters are released from primary sensory cells ('hair cells') to excite second order neurons carrying information to the brain. We apply these same techniques to study inhibitory feedback produced by brain neurons that project to and regulate the sensitivity of the cochlea.
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The Dong Laboratory has identified many genes specifically expressed in primary sensory neurons... in dorsal root ganglia (DRG). Our lab uses multiple approaches, including molecular biology, mouse genetics, mouse behavior and electrophysiology, to study the function of these genes in pain and itch sensation. Other research in the lab examines the molecular mechanism of how skin mast cells sensitize sensory nerves under inflammatory states. view more

The Bergles Laboratory studies synaptic physiology, with an emphasis on glutamate transporters ...and glial involvement in neuronal signaling. We are interested in understanding the mechanisms by which neurons and glial cells interact to support normal communication in the nervous system. The lab studies glutamate transport physiology and function. Because glutamate transporters play a critical role in glutamate homeostasis, understanding the transporters' function is relevant to numerous neurological ailments, including stroke, epilepsy, and neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). Other research in the laboratory focuses on signaling between neurons and glial cells at synapses. Understanding how neurons and cells communicate, may lead to new approaches for stimulating re-myelination following injury or disease. Additional research in the lab examines how a unique form of glia-to-neuron signaling in the cochlea influences auditory system development, whether defects in cell communication lead to certain hereditary forms of hearing impairment, and if similar mechanisms are related to sound-induced tinnitus. view more

The Fuchs Laboratory uses cellular electrophysiology, immunolabeling and electron microscopy to... study synaptic connections between sensory hair cells and neurons in the cochlea. One effort focuses on an unusual cholinergic receptor that mediates efferent inhibition of hair cells, driving discovery of the molecular mechanisms, and offering a target for protection against acoustic trauma. A second topic concerns the small number of unmyelinated "type II" afferent neurons whose synaptic connectivity and response properties argue for a role as the pathway for noxious (too loud) sound. Our studies are motivated by curiosity about fundamental mechanisms, and to provide a foundation for understanding cochlear pathogenesis. view more

Human induced pluripotent stem cells (hiPSCs) provide unprecedented opportunities for cell repl...acement approaches, disease modeling and drug discovery in a patient-specific manner. The Gabsang Lee Lab focuses on the neural crest lineage and skeletal muscle tissue, in terms of their fate-determination processes as well as relevant genetic disorders.

Previously, we studied a human genetic disorder (familial dysautonomia, or FD) with hiPSCs and found that FD-specific neural crest cells have low levels of genes needed to make autonomous neurons--the ones needed for the "fight-or-flight" response. In an effort to discover novel drugs, we performed high-throughput screening with a compound library using FD patient-derived neural crest cells.

We recently established a direct conversion methodology, turning patient fibroblasts into "induced neural crest (iNC)" that also exhibit disease-related phenotypes, just as the FD-hiPSC-derived neural crest. We're extending our research to the neural crest's neighboring cells, somite. Using multiple genetic reporter systems, we identified sufficient cues for directing hiPSCs into somite stage, followed by skeletal muscle lineages. This novel approach can straightforwardly apply to muscular dystrophies, resulting in expandable myoblasts in a patient-specific manner.
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Research in the Glowatzki Lab focuses on the auditory system, with a particular focus on synapt...ic transmission in the inner ear.

Our lab is using dendritic patch clamp recordings to examine mechanisms of synaptic transmission at this first, critical synapse in the auditory pathway. With this technique, we can diagnose the molecular mechanisms of transmitter release at uniquely high resolution (this is the sole input to each afferent neuron), and relate them directly to the rich knowledge base of auditory signaling by single afferent neurons.

We study pre- and post-synaptic mechanisms that determine auditory nerve fiber properties. This approach will help to study general principles of synaptic transmission and specifically to identify the molecular substrates for inherited auditory neuropathies and other cochlear dysfunctions.

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