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Spontaneous Activity and Intrinsic Photosensitivity in the Developing Zebrafish Spinal Cord

Abstract

The process of perception is one of the most complicated and compelling biological phenomena, capable of inspiring thousands of years of philosophers, physicians, and scientists. One of these researchers, Walter Freeman of Berkeley once stated, “The brain reaches out into the environment and sees something which is then interpreted according to its own past experiences. First you look, then you see.” While the neural computations involved in “seeing” may not be understood for many years to come, we have made much progress in understanding how the brain “looks” into its environment. And by studying animal behavior, we can hope to infer some understanding of the cells that transform these sensory inputs into motor outputs. Working with simple neural circuits—be they in model organisms or at early stages in development—the problem seems more tractable, yet new findings can shift our understanding of perception in unexpected ways.

In this thesis, I present research on motor circuits of the embryonic zebrafish spinal cord. These spinal neurons directly drive the earliest muscle contractions in the fish and are a great model for understanding how activity begins in a nervous system. In the course of these studies, we discovered that the activity within this circuit is strongly inhibited by environmental light at an age before vision and before the spinal cord is connected to brain circuitry. Not all photoreceptors are for sight and there are many examples of deep brain photoreception in invertebrates and basal vertebrates, usually driving circadian and seasonal behaviors. Our finding in zebrafish is surprising due to the direct photodetection by motor neurons in the spinal cord, the developmentally early appearance of this photosensitivity, the possible role for primary cilia in sensing light, and the acute affect on behavior. Additionally, by manipulating spontaneous activity within this circuit, we see effects on the development of neural activity in spinal interneurons. These results change how we think about motor circuits and development. No longer are motor neurons simply passive relay cells, we now can see them as sensory inputs. No longer is development in the spinal cord governed solely by genetic programs, but activity dependent processes can be regulated by the outside world. The existence of this category of nonvisual photoreceptor across taxa indicates a new way for the brain to “reach out into the environment.” Discovering whether and how it alters our perception of the world will hopefully be a focus of future research.

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