7. Project Summary/Abstract
Human experience is shaped by our senses, which receive diverse inputs from our
environment. These varied inputs, however, all contribute to a single integrated
representation in our minds of the outside world. Neuroscientists have studied sensory
perception, and the integration different sensory modalities like vision, hearing, and
touch, for decades, but there are still important unanswered questions about how
sensory cells in the brain work, and how the circuits that they form control the flow of
information through the brain. Understanding these networks in detail would expand our
knowledge of the brain in general, and would serve as a starting point for addressing
disorders like autism spectrum disorder, in which sensory systems function abnormally.
In a large part, these functioning sensory circuits have remained mysterious for technical
reasons. Traditional techniques either sample from the whole brain without seeing the
individual neurons or record from a few neurons at a time without seeing the larger
networks. This project addresses this gap using the zebrafish model system by imaging
activity across the entire brain, including the activity of each neuron individually. The first
aim contains a plan to map such brain-wide activity while the brain perceives and
processes visual or auditory information, using a set of novel approaches for sensory
stimulation. Experiments in the second aim will present various visual and auditory
stimuli simultaneously, looking for the ways in which the brain's functioning networks
integrate this information. These data will be used to build mathematical network models
of how the brain processes and integrates vision and hearing. The third aim will shed
light on functional and structural aspects of these sensory neurons, revealing biological
realities that we will use to adjust the purely mathematical models from the prior aims.
The resulting biologically grounded models will set the stage for concrete functional
experiments in the fourth aim, where we will optogenetically activate or silence specific
circuit elements to test the models' predictions.
The overall goal is to describe, for the first time, all of the auditory and visual neurons in
the brain, and to develop and test models for how they receive, process, and integrate
information across sensory modalities.