2007 — 2009 |
Triplett, Jason |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
The Role of Ephrins in Topographic Mappin of the Visual System @ University of California Santa Cruz
[unreadable] DESCRIPTION (provided by applicant): The long-term objective of our research is to elucidate the mechanisms of precise neuronal targeting during development of the central nervous system (CNS): Specifically, we hope to gain an understanding of the molecular mechanisms underlying the phenomenon of topographic mapping in the visual system. In the pursuit of this goal, we will learn a great deal about neuronal development, which will prove useful in the understanding of both developmental and degenerative neuronal disorders. We will investigate the role of the cell surface ligands ephrin-As and their receptors, EphAs, in the precise topographic mapping of the visual system. We hypothesize that regulation of EphA/ephrin-A interactions are important for proper neuronal targeting. To test this we have developed two specific aims. In Aim 1, we will develop conditional knockout mouse models to delete ephrin-As specifically from the retina, midbrain, or cortex of developing mice. By specifically deleting ephrin-As, we will distinguish between three proposed models for the role of ephrins in neuronal targeting. In Specific Aim 2, we will determine the role of ephrin-As in the integration of sensory information in the brain. Detection, processing, and integration of multiple sensory inputs are necessary for survival. We will test the hypothesis that ephrin-As play an important role in ensuring that visual and somatosensory information are in register in the mouse superior colliculus using axon tracing methods in ephrin-A knockout models. Understanding the role of ephrins in this process will lead to insights into the integration of sensory information in 'higher' cortical areas responsible for attention, planning, and personality. In this study, we propose to use genetic mouse models to achieve a better understanding of the precise development of the visual system and CMS. Understanding this process will have broad impact in the treatment of developmental neurological disorders, such as generalized seizures, attention deficit hyperactivity disorder, and autism, as well as degenerative disorders, such as macular degeneration, Alzheimer's disease, and Parkinson's disease. [unreadable] [unreadable] [unreadable] [unreadable]
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0.915 |
2015 — 2019 |
Triplett, Jason |
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. |
Mechanisms of Synaptic Specificity in Visual Circuits @ Children's Research Institute
? DESCRIPTION (provided by applicant): Integrating sensory information is critical for detection of salient stimuli and direction of appropriate responses, a necessary survival behavior. Disruptions in specific aspects of sensory processing and integration are hallmark features of several neurodevelopmental disorders, underscoring the importance of precise sensory circuit formation. Despite this, the mechanisms by which such synaptic specificity is established in integrative centers remains poorly understood, precluding the development of effective therapies. To fill this gap in knowledge, we will investigate the mechanisms by which sensory circuits are established in the superior colliculus (SC), a critical center where multiple modalitis of sensory information are integrated. Specifically, we will focus on the developmental mechanisms of precise visual connections in the SC, which integrates input from retinal ganglion cells (RGCs) and Layer 5 (L5) neurons of the primary visual cortex (V1) during normal development and how these process are disrupted in neurodevelopmental disorders. First, we will use a combination of in vivo electrophysiology, cutting-edge neuronal tracing, and molecular analysis in a unique knock-in mouse model to determine the mechanisms by which distinct subtypes of L5 V1 neurons integrate into the appropriate subcircuit. Second, we will use a combination of in vivo electrophysiology and axon tracing paradigms in conditional knockout mouse models to dissect the mechanisms by which alignment of visual spatial maps is achieved. Finally, we will use a combination of in vivo electrophysiology, axon tracing and molecular analysis in a mouse model of FXS to determine the specific neural sensory processing deficits and which processes are disrupted to give rise to these deficits. Taken together, the proposed experiments will elucidate novel mechanisms by which precise connectivity and function are established in visual centers in development and neurodevelopmental disorders. Our results will provide critical insights necessary for the design of effective therapeutic strategies to treat these disorders.
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0.816 |