The faculty in Cellular and Molecular Neuroscience at Cornell come from eight departments and graduate fields. While some of the faculty study detailed mechanisms of molecular action in neurons (structure-function studies in channels and receptors, signal transduction pathways in development), the majority integrate cellular and molecular studies into a multi-level neuroethological analysis of the mechanisms of behavior and its modulation. The focus is on neuronal mechanisms in networks that drive different behaviors, from sensory perception to locomotion. Graduate students receive training in state-of-the-art techniques in electrophysiology, optogenetics, molecular biology, neuroanatomy and functional behavioral analysis to show how molecular and cellular mechanisms are integrated into adaptive animal behavior.
Research areas: Cell and molecular Organisms used: Manduca sexta, drosophila Research interests: The long-term goal of the research in our laboratory is to determine the neural basis of behavioral ontogeny using the moth Manduca sexta, and the fly Drosophila melanogaster as model systems. Both of these insects go through a complete metamorphosis from a larva to an adult through the developmentally interesting pupal stage. Along with the dramatic changes in body morphology metamorphosis also results in the in shift in the behaviors repertoire of these insects. Our goal is to understand the neural correlates that accompany these changes in behavior. We exploit Manduca's large and easily accessible nervous system allowing us to examine the role of extrinsic cues (e.g. hormones; cell-cell interactions) and in the regulation of postembryonic development of the CNS. Currently, we are examining the role of a set of hormones in regulating the motor patterns during Manduca's molt cycles. We also exploit the genetic tools offered by Drosophila in our research program to learn more about cellular and molecular basis of postembryonic neurogenesis. We recently completed a screen for Drosophila mutants that disrupted the pattern of postembryonic neurogenesis. The genetic and molecular analysis of these mutants should provide new insights into the factors involved in the regulation of postembryonic neurogenesis.
Research areas: Cell and molecular, physiology Techniques used: Molecular biology, physiology, pharmacology and biophysics to tackle these problems Organisms used: Rodents Research interests:Primary sensory neurons encode environmental stimuli into electric signals. This task usually initiates with activation of modality-specific receptors that express in distinctive populations of nerve fibers. Many of the receptors involved in this transduction process are TRP family ion channels. The specificity of transduction channels to respond exclusively to a particular category of physical or chemical stimuli enables neurons to distinguish different environmental cues, even when the final outputs are universally a train of action potential spikes. Besides the modality specificity, transduction channels must generate the signal quantitatively matching the stimulus intensity in order to faithfully represent the environmental information. Modulation of transduction channels thus provides a powerful strategy to modify our subjective perception of the external world. We are interested in understanding the molecular basis of these modulations and their biomedical relevance.
Research areas: Cell and molecular, physiology Techniques used: Molecular biology, physiology, pharmacology and biophysics to tackle these problems Organisms used: Rodents Research interests:At its most basic, our work studies how the chemical reactions of biology are organized within the cellular boundaries. Biological organization is both spatial (cellular architecture), and temporal (cellular dynamics). We are interested in how cellular organization is maintained and harnessed by the animal to generate distinct physiological outputs, and how changes in intracellular organization underlie pathophysiological conditions.
Research areas: Cardio-vasculor system Techniques: Functional genomics Research interests:Professor Davisson’s research focuses on the basic mechanisms of function, control, and signaling in the cardiovascular system in health and disease. Her investigations employ the interdisciplinary approach of “functional genomics,” a new endeavor at the interface of classical physiology and molecular genetics. Understanding the molecular mechanisms underlying hypertension, heart failure, and the pregnancy-induced cardiovascular syndrome pre-eclampsia are the main focuses of her research efforts. She has published numerous original research and review articles and book chapters and has given invited presentations throughout the United States as well as in South America, Europe, and Asia.
Research areas: Cell and molecular, gene expresssion Techniques: Electrophysiology, molecular and genetics Organisms used: Drosophila
Research interests: How are behaviors generated? This question remains a very challenging one. However, genetic model organisms can provide essential tools with which to probe different behaviors. The Deitcher laboratory is using the genetic and transgenic tools of Drosophila melanogaster to uncover the molecular mechanisms that underlie normal and abnormal behaviors. Our laboratory is also collaborating with the Bass lab in the study of communication and hearing in fish and with the Levitan lab on neuropeptide mobility and secretion.
Approximately 50 million people worldwide suffer from epilepsy. While there are many different types of seizures, uncontrolled neural activity is shared by all forms of epilepsy. A class of Drosophila mutants, known as bang-sensitives, reproduces many aspects of the human disease. My laboratory has conducted screens to identify enhancers and suppressors of these bang-sensitives in order to identify pathways that regulate neuronal activity. Our hope is that the genes we identify in Drosophila will lead to the development of new drugs to treat the human disease.
In order for insects to grow larger and develop, they need to shed their old cuticle. The process of ecdysis involves stereotyped rhythmic muscle contractions that free the larva from the old cuticle. Ecdysis is initiated after a series of neuropeptide hormones are released in the proper sequence. We are studying when these neuropeptides are secreted using a GFP-tagged neuropeptide. We are also using RNAi to perturb the neuropeptide signaling process necessary for this behavior. Through both approaches we will dissect the sequence of events that lead to this simple behavior.
Drosophila males court females with a courtship song. Like many animals, this communication is important for mating success. What neurons are involved in this complex behavior? What genes regulate this process? We are investigating which genes are involved in generating the courtship song. We have found a transcription factor that affects the ability of males to produce the song. We are investigating how this transcription factor is involved in the network of neurons that produce the song. Publications
Research areas: Motor control, neuronal networks, hindbrain, spinal cord, sleep, spinal injury and regeneration. Techniques used:Behavioral studies, studies of fluorescently labeled neurons and proteins in living fish, imaging of neuronal activity in live animals, and electrophysiological studies. Organisms used: Zebrafish Research interests: Our lab: 1) studies how movements are produced by the brain and spinal cord of vertebrates; 2) explores strategies to restore function after spinal injury; and 3) studies the events that occur in the nervous system during sleep. We mostly use zebrafish as a model system because they allow us to combine genetic and optical methods with more conventional physiological approaches to attack the problems of interest to us.
Research areas: Cellular and Molecular Neuroscience, neural networks, central pattern generators, computational, motor networks, spinal cord Techniques: Electrophysiology, in vitro, imaging, immunocytochemistry, molecular biology, modeling. Organisms used: Rodents Research interests: We study the cellular and synaptic interactions of neural networks for simple behaviors. We focus on Central Pattern Generators, which organize rhythmic movements such as locomotion and respiration. Our current focus is on the mouse spinal locomotor CPG. We have three major projects: 1) Identify the interneurons that are components of the locomotor CPG, and their synaptic interconnections, using transgenic mice expressing fluorescent and other markers; 2) Study how neuromodulators such as serotonin modify the properties of the CPG neurons and connections, to allow flexibility in the motor pattern the network generates; 3) Study the consequences of spinal cord injury on network interneurons and their synapses, which undergo homeostatic changes following the loss of descending synaptic inputs from the brain. Our work is primarily electrophysiological and immunocytochemical; we collaborate with mathematicians to generate and study models of network function.
Research areas: Cell and molecular, physiology. Techniques used: Patch clamp, imaging, stem cells Research interests:The Kotlikoff laboratory focuses on the molecular processes underlying excitation-contraction coupling and rhythmicity in cardiac and smooth muscle cells and the processes underlying muscle development. A major goal of the laboratory is to understand processes of intercellular communication and the generation of spontaneous electrical activity. Techniques used to study these processes include gene targeting, development of in vivo imaging methods using genetically targeted cell sensors, embryonic stem cell engraftment, patch clamp measurements of ion channel function, and in vivo imaging. Current projects in the laboratory include the study of the development of electrical activity in the embryonic heart, the use of embryonic cardiomyocytes and embryonic stem cells to alter electrical rhythm disturbances that occur after cardiac injury, the basis of spontaneous rhythm in smooth muscle tissues, and the development of genetically encoded sensors of cell signaling.
Research areas: Cell and molecular, development, genetics Techniques used: Mouse mutants, laser microdissection, single-cell RNA amplification, microarrays, tissue culture models Organisms used: Rodents Research interests:The Lin lab studies the development and degeneration of the nervous system using the mouse olfactory system as a model. During development, billions of neurons must form connections with their appropriate partners in order to form a functional nervous system. How is this remarkable process of axon guidance and target recognition accomplished? Once neurons are born, they are exposed to a variety of environmental insults that must be properly dealt with to avoid degeneration. Neurodegenerative disorders, such as Alzheimer’s disease, are thought to arise in part due to a failure to deal with this increased stress. The olfactory system represents an excellent system in which to study both processes.
Research areas: Biophysics; exocytosis; mechanisms of vesicle fusion and transmitter release. Techniques used: Patch clamp technique, amperometry using a carbon fiber electrode Organisms used: Rodents Research interests: The mechanisms of exocytosis and endocytosis represent one of the most exciting topics in cell biology. The process of regulated exocytosis is responsible for release of neurotransmitters and neuropeptides by nerve terminals and endocrine cells, release of enzymes or cytotoxic proteins by granulocytes, release of histamine and other mediators by mast cells, as well as several other secretory processes. During exocytosis the membrane of secretory granules fuses with the plasma membrane of the cell, allowing the secretory granules to release their contents through the fusion pore. Although biochemical studies revealed a set of proteins that are somehow involved, the mechanisms of fusion are still obscure. Functional studies of the fusion processes have revealed details of the dynamics of the fusion events and the combination of functional and biochemical techniques will be central to further elucidate the mechanism of exocytosis. We use a combination of molecular, biophysical and computational approaches to elucidate the molecular mechanisms of vesicle-plasma membrane tethering, fusion and transmitter release.
Research areas: Cell and molecular Techniques used:Patch clamp, two-electrode voltage clamp, extracellular recording, quantitative real-time PCR, genetic engineering in mice, behavioral analysis. Organisms used: Rodents Research interests: We are interested in how and why specific ion channels contribute to 1) rapid information processing in the nervous system, and 2) experience-dependent plasticity in processing and behavior. We have focused on BK (Big calcium-activated K channels) in adrenaline-secreting chromaffin cells of the adrenal gland, where we have described stress- and steroid hormone-related regulation of transcription of the main pore-forming channel gene (Slo) and its Beta subunits, regulation of alternative splicing of Slo, and immediate effects of steroid hormones on channel function. Complementing neuroendocrine and behavioral experiments, we have used a comparative approach, as well, finding robust differences between species, genetic strains, sexes, and developmental stages.
Research areas: Cellular and molecular biology, NMDA channels Techniques used: Cell cultures, whole cell voltage clamp, molecular techniques Organisms used: Rodents Research interests: Members of my laboratory are studying excitatory amino acid (EAA) or "glutamate" activated receptor-channels in the vertebrate central nervous system. The principal approach to these investigations involves recordings of EAA activated receptor-channels in mammalian brain neurons in primary culture and recombinant receptor-channels expressed in mammalian cell lines. Single channel recordings are employed to analyze basic biophysical parameters of receptor channel function. Whole cell voltage-clamp recordings are also combined with single cell molecular biology methods in an effort to ascertain the likely subunit compositions of pharmacologically and biophysically distinct receptor-channel subtypes observed in cerebellar granule neurons.
Research areas: Molecular neurobiology and biophysics; neurotransmitter receptors and signal transduction. Techniques used: Organisms used: Research interests:Our research interests center on the structure and function of proteins involved in signal transduction. These include two important membrane proteins (nicotinic acetylcholine receptors and glutamate receptors) and an intracellular GTP binding protein (Cdc42Hs). Nicotinic acetylcholine and glutamate receptors are large membrane-bound proteins which mediate the flow of ions from the exterior to the interior of a cell following an interaction with a small organic molecule (i.e.,an agonist). Acetylcholine receptors are important neurotransmitter receptors in skeletal muscle, the peripheral nervous system, and the central nervous system; glutamate receptors are the primary excitatory neurotransmitter receptors in the vertebrate central nervous system. Cdc42Hs is a soluble protein involved in signaling pathways related to the structure of cytoskeleton.
Research areas: Systems and computational neuroscience; cognitive neuroscience; motivation and reward; learning and memory; psychiatric disease models. Techniques: Optogenetics, awake behaving neurophysiology, patch clamp electrophysiology, behavior, imaging, molecular biology, pharmacology, immunohistochemistry, computational modeling and analysis. Organisms used: Rodents Research interests: Our lab investigates the neural circuitry underlying complex cognition and behavior, with a focus on circuits mediating reward, motivation, and learning and memory. We study these systems with both an observational and causal approach, combining monitoring and decoding of neural activity with optical control of genetically and topologically defined circuit elements. We are interested in both normal circuit function and dysfunction in psychiatric disease models. Systems of particular interest include the prefrontal cortex and its communication with neuromodulatory and limbic regions. Publications
Research areas: Molecular neurobiology and biophysics; neurotransmitter receptors and signal transduction. Techniques used: Molecular Biology Organisms used: Research interests: My general research interest is in the modulation of receptor properties by neurotransmitters and drugs. Currently we are studying the mechanisms of modulation of the nicotinic cholinergic receptor by its neurotransmitter acetylcholine and by the neuropeptide substance P. Nicotinic receptor responsiveness is regulated by acetylcholine and other cholinergic agonists via desensitization. In fact there are several desensitization processes each of which occurs on a different time scale, ranging from milliseconds to several minutes. Nicotinic receptor responsiveness also appears to be regulated physiologically by substance P, an eleven amino acid peptide that inhibits nicotinic receptor activation. One reason we have focused on both of these modulatory mechanisms is that they appear to be interrelated since at least part of the inhibition by substance P seems to be mediated by an increase in the rate and extent of desensitization.