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High-probability grants
According to our matching algorithm, Alan J. Nighorn is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2000 — 2004 |
Nighorn, Alan J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Regulation of Cgmp in the Manduca Sexta Olfactory System
DESCRIPTION: (Adapted from the Investigator's Abstract) The intracellular messenger cGMP is important for a wide variety of functions. It is generated by the enzyme guanylyl cyclase (GC). GCs exist in multiple forms and are classified as being either receptor (membrane associated) or soluble. Increases in the level of cGMP through the activation of GCs is thought to be important for the regulation of many different pathways with pathophysiological significance, including migraine, impotence, and asthma. cGMP is also involved in neuronal plasticity including LTP and LTD, adaptation at the level of the olfactory receptor neurons, and visual signal transduction among others. This application proposes to investigate the role of cGMP in the nervous system by examining the mechanisms of cGMP regulation in the olfactory system of Manduca sexta, an experimentally favorable model system in which the anatomy and electrophysiology are well studied. The studies described in this proposal will have significance for the understanding of the function of cGMP in the olfactory system, in the nervous system in general, and finally in any system in which cGMP plays a role in mediating cellular communication and function. The PI proposes to address the regulation of guanylyl cyclases in the olfactory system of Manduca sexta by answering the following questions as specific aims: (1) Which neurons in the antennal lobe can and do respond to NO? Nitric oxide (NO) is a potent stimulator of soluble GCs. (2) What is the function of the NO/sGC system in the antennal lobe? This specific aim examines the effects of pharmacological manipulation of the NO/sGC for either behavioral or electrophysiological outputs of the antennal lobe. (3) How is the activity of the function of the novel GC, MsGC-1, regulated in the olfactory system of Manduca sexta? MsGC-1 is a new type of GC whose expression pattern suggests that it plays an important role in the mediation of cGMP in the olfactory system. (4) What other GCs are expressed in the olfactory system of Manduca sexta? The PI has evidence of at least four more GCs expressed in the olfactory system. The PI proposes to clone these and examine their roles in mediating cGMP levels in the olfactory system.
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1 |
2006 — 2010 |
Nighorn, Alan J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Nitric Oxide Signaling in a Model Olfactory System
[unreadable] DESCRIPTION (provided by applicant): Nitric oxide (NO) is a small, gaseous free radical molecule that can mediate cellular signaling that is critical for the proper functioning of the vascular, immune and nervous systems. Within the nervous system, its ability to cross cell membranes and mediate communication between cells in the absence of specialized synaptic machinery gives it a power and flexibility not possible for conventional neurotransmitters. High levels of nitric oxide synthase (the enzyme that generates NO) expression has led to the hypothesis that NO mediates and/or modulates signaling within the primary olfactory neuropil. This idea has been strengthened by the observation that the hallmark spheroidal structures within the primary olfactory neuropil could be ideal to regulate the diffusion of a small molecule such as NO. This proposal takes advantage of the relative simplicity, but parallel organization of an insect olfactory system to investigate the function of NO signaling within the primary olfactory neuropil. We will investigate the production, diffusion, and function of NO within the olfactory system. This will be done by applying the talents of a group of expert researchers to complete the following three specific aims: (1) Characterize odor-induced NO production and diffusion within the AL. (2) Characterize the functional roles of NO signaling in AL neurons. (3) Characterize the behavioral consequences of interfering with NO signaling in the AL. The successful completion of these specific aims will result in a very detailed understanding of the role of NO in the function of this model olfactory system. This understanding will yield insight into the function of this important signaling system in other organisms including humans. In addition, these insights will likely serve as the basis for other experiments designed to examine the role of this very important signaling molecule both in other olfactory systems and in the nervous system in general. [unreadable] [unreadable] [unreadable]
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1 |
2007 |
Nighorn, Alan J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Aminergic Modulation Underlying Olfactory Plasticity
DESCRIPTION (provided by applicant): Primary sensory neuropils perform the initial decomposition of complex sensory signals in the environment. Beyond this basic function, sensory circuits also must discriminate perceptual objects under a wide range of different ambient conditions, including situations that may involve the formation of learned associations with other sensory cues. We need a more thorough understanding of how sensory networks are modulated by inputs from other brain regions in order to gain better insight into the mechanisms that help stabilize internal perceptual states in the brain. A deeper analysis of sensory-circuit plasticity is crucial for the development of more effective therapies for sensory brain disorders and treatments for the aberrant sensations that often accompany mental illness. Using the olfactory system of an experimentally favorable model, Manduca Sexta, we now have evidence that a learning-based reorganization of odor-evoked network responses takes place in the antennal lobe, the structural and functional analog of the mammalian olfactory bulb. What mechanisms underlie this unexpected network plasticity in the pdmary olfactory center? In order to understand the nature of this modulation, research must be focused on the structural and functional organization of the olfactory circuits that exhibit these changes, and more must be learned about the complex interplay among multiple neurotransmitter systems that helps to reshape the spatiotemporal representations of olfactory stimuli with experience. In Manduca, four candidate amine transmitters have been localized to separate neurons in the glomeruli of the antennal lobe, making this an ideal system to examine the modulatory roles of biogenic amines in olfactory-information coding. This project will build on a strong foundation of experience with this experimentally-favorable model and will seek to characterize the regulatory roles of aminergic modulation in reshaping odor representations during olfactory conditioning. We will employ a strongly multidisciplinary approach, combining single-unit and neural-ensemble recording & anatomy with neuropharmacology and behavioral bioassays to study the roles of amines in regulating the formation, storage, and recall of offactory memories during the conditioning process. Our understanding of the functional meaning of plasticity in early olfactory processing is still rudimentary, and the proposed studies aim to test the hypothesis that centrifugal aminergic modulation plays a key role in olfactory plasticity and the regulation of adaptive behavior.
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1 |