Melatonin modulation of the olfacto-retinal centrifugal visual pathway
Abstract
The objective of this proposal is to elucidate the mechanisms and roles of pineal melatonin modulation on olfacto-visual centrifugal multisensory integration in the regulation of visual system functions in zebrafish and computer simulations. Tasking to achieve the objectives of this proposal center on two major approaches: Aim 1: The proposer plans to determine the expression of melatonin receptors in the centrifugal visual pathway and examine the role of melatonin released from the pineal gland on the olfactoretinal pathway. 1) Using in situ hybridization and single-cell RT-PCR techniques, proposer plans to determine if melatonin receptors are expressed on the olfactory bulb terminal is neurons that project to the retina in zebra fish. The experiments will be performed in transgenic Tg(GnRH3::GFP) zebrafish, in which the terminalis neurons can be identified by the expression of transgene tagged GFP. 2) The role of melatonin on terminal is neuron activity will be assessed by pharmacologically inhibiting melatonin prior to recordings. Terminalis firing rates will be measured electrophysiologically at multiple time points in the day and night. 3) Proposer also plans to determine the effect of melatonin on olfacto-retinal centrifugal visual modulation by measuring the light threshold that evokes retinal ganglion cell spikes at different times in the day and night in response to olfactory stimulation in double-transgenic Tg(Gnat2-gal4/UAS-nsfB::mCherry) and Tg(GnRH3::GFP) animals treated with metronidazole Treatment with metronidazole le selective destroys pineal photoreceptor cells, thereby diminishes melatonin production from the pineal gland. Aim 2: Based on the results obtained from animal studies, the proposer plans to create neural computational models that represent multi-organ sensory integration and predict the consequence of sensory integration in visual behavior modulation. 1) Sensory coding will be explored by developing a computational extreme value theory-based model of multi-organ sensory integration in zebra fish for biologically-inspired unsupervised feature learning, in analogy to sparse coding approaches in zebrafish. 2) A computational framework for sensory integration will l also be built and based on a full computational framework grounded in statistical models to support sensory integration. This will facilitate simulations of the retinal circuits, and extend to a general-purpose tool for integrating arbitrary sensory input in a machine learning context, yielding a powerful computational fusion capability. 3) Demonstration of neural fidelity will be assessed by model optimization in conjunction with retinal circuit responses observed in a behaving animal for a given stimulus set.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 12, 2017
- Source ID
- W911NF1610316
Entities
People
- Lei Li
Organizations
- Army Contracting Command
- United States Army
- University of Notre Dame