Understanding how the brain functions is one of the most ambitious current scientific goals. This challenge will only be accomplish by a multidisciplinary approach involving genetics, molecular biology, optics, ethology, neurobiology and mathematics and using tractable model systems. The zebrafish larva is a transparent genetically tractable small vertebrate, ideal for the combination state-of-the- art imaging techniques (e.g. two-photon scanning microscopy, single-plane illumination microscopy, spatial light modulator microscopy and lightfield microscopy), bioluminiscence and optogenetics to monitor and manipulate neuronal activity from single specific neurons up to the entire brain, in an intact behaving organism. Furthermore, the zebrafish model offers large and increasing collection of mutant and transgenic lines modelling human brain diseases. With these advantages in hand, the zebrafish larva became in the recent years, a novel animal model to study neuronal circuits and behaviour, taking us closer than ever before to understand how the brain controls behaviour.

Understanding how the brain functions is one of the most ambitious current scientific goals. This challenge will only be accomplish by a multidisciplinary approach involving genetics, molecular biology, optics, ethology, neurobiology and mathematics and using tractable model systems. The zebrafish larva is a transparent genetically tractable small vertebrate, ideal for the combination state-of-the- art imaging techniques (e.g. two-photon scanning microscopy, single-plane illumination microscopy, spatial light modulator microscopy and lightfield microscopy), bioluminiscence and optogenetics to monitor and manipulate neuronal activity from single specific neurons up to the entire brain, in an intact behaving organism. Furthermore, the zebrafish model offers large and increasing collection of mutant and transgenic lines modelling human brain diseases. With these advantages in hand, the zebrafish larva became in the recent years, a novel animal model to study neuronal circuits and behaviour, taking us closer than ever before to understand how the brain controls behaviour.

Experience influences how we perceive the world, how we interact with our environment, and how we develop. In fact, almost all animals can modify their behavior as a result of experience. Psychologists have long distinguished between different forms of learning and memory, and later determined that they are encoded in distinct brain areas. Neuroscientists dating back to Santiago Ramón y Cajal suggested that learning and memory might be encoded as changes in synaptic connections between neurons, but it wasn't until the second half of the 20th century that experimental evidence corroborated this idea. Specific firing patterns of neurons during learning results in strengthening or weakening of synapses, and morphological modifications that can lead to long lasting changes in neural circuits. The molecular mechanisms that drive these changes are remarkably conserved across vertebrates. However, understanding how synaptic plasticity is integrated at a network level remains a big challenge in neuroscience. Relatively few studies have focused on how neural circuits encode changes in behavior in a natural context. In this dissertation I present two such examples using calcium imaging and optogenetic techniques in larval zebrafish. First, in collaboration with others, I studied neural activity that drives the onset of the very first behavior of the fish, tail coiling. We characterized the transition of spontaneous activity in the spinal cord from a sporadic, uncorrelated state, to a regular and synchronized state. We determined that this transition occurred through coalescence of local microcircuits, and that inhibiting the early sporadic activity impaired normal development of the central pattern generator network. Second, I studied how experience of prey affects hunting behavior and underlying neural activity. I developed a paradigm to assess the effect of prior hunting on prey capture behavior and showed that experienced fish initiate more captures than their naïve counterparts. I next established that experience does not affect the ability of the fish to see prey. Rather, experience increases the probability that activity in visual areas will evoke a capture initiation. This is accomplished by increasing the impact of information transfer from visual to motor areas, possibly due to increased activity in forebrain areas for experienced fish.

The complexity of the animal brain begs for simple tools that will assist scientists attempting to unravel the beautifully entangled mess. I begin by describing an experimental strategy for indentifying the components of neural circuits that control innate behaviors. My approach emphasizes the role of behavior analysis and the insights offered by neuroethology. While describing the neuroethological strategy, I will introduce the larval zebrafish and tools that I have developed to study the neural basis of innate visual behavior. The second chapter reports an implementation of the strategy that successfully revealed components of the circuit underlying the zebrafish optomotor reflex. We discovered distinct subsets of spinal projection neurons that were responsible for directing the swims and turns that constitute an important visual response to whole-field motion. The success of this study relied on the ability to record behavior-related neural activity in a restrained zebrafish, but this was found to be difficult for other visual behaviors. The third chapter addresses this problem by describing a novel technique to monitor neural activity in an unrestrained, behaving zebrafish. Employing the bioluminescent calcium reporter, Aequorin, we were able to detect the activity of Hypocretin neurons in freely swimming zebrafish. The success of this technique will allow an extensive survey of how identified populations of neurons collectively choreograph the complex behavior patterns of a developing vertebrate.

Handbook of Sleep Research, Volume 30, provides a comprehensive review of the current status of the neuroscience of sleep research. It begins with an overview of the neural, hormonal and genetic mechanisms of sleep and wake regulation before outlining the various proposed functions of sleep and the role it plays in plasticity, and in learning and memory. Finally, the book discusses disorders of sleep and waking, covering both lifestyle factors that cause disrupted sleep and psychiatric and neurological conditions that contribute to disorders. Emphasizes a comparative and multidisciplinary approach to the topic of sleep Covers the neurobiology and physiology of sleep stages, mechanisms of waking, and dreaming Discusses in detail the proposed functions of sleep, from health and rest, to memory consolidation and synaptic plasticity Examines the current state of research in mammalian and non-mammalian species, ranging from primates to invertebrates

Essential Fish Biology provides an introductory overview of the functional biology of fish and how this may be affected by the widely contrasting habitat conditions within the aquatic environment. It describes the recent advances in comparative animal physiology which have greatly influenced our understanding of fish function as well as generating questions that have yet to be resolved. Fish taxa represent the largest number of vertebrates, with over 25,000 extant species. However, much of our knowledge, apart from taxonomy and habitat descriptions, has been based on relatively few of them , usually those which live in fresh water and/or are of commercial interest. Unfortunately there has also been a tendency to base our interpretation of fish physiology on that of mammalian systems, as well as to rely on a few type species of fish. This accessible textbook will redress the balance by using examples of fish from a wide range of species and habitats, emphasizing diversity as well as recognizing shared attributes with other vertebrates.

Comprehensive Toxicology, Third Edition, Fifteen Volume Set discusses chemical effects on biological systems, with a focus on understanding the mechanisms by which chemicals induce adverse health effects. Organized by organ system, this comprehensive reference work addresses the toxicological effects of chemicals on the immune system, the hematopoietic system, cardiovascular system, respiratory system, hepatic toxicology, renal toxicology, gastrointestinal toxicology, reproductive and endocrine toxicology, neuro and behavioral toxicology, developmental toxicology and carcinogenesis, also including critical sections that cover the general principles of toxicology, cellular and molecular toxicology, biotransformation and toxicology testing and evaluation. Each section is examined in state-of-the-art chapters written by domain experts, providing key information to support the investigations of researchers across the medical, veterinary, food, environment and chemical research industries, and national and international regulatory agencies. Thoroughly revised and expanded to 15 volumes that include the latest advances in research, and uniquely organized by organ system for ease of reference and diagnosis, this new edition is an essential reference for researchers of toxicology. Organized to cover both the fundamental principles of toxicology and unique aspects of major organ systems Thoroughly revised to include the latest advances in the toxicological effects of chemicals on the immune system Features additional coverage throughout and a new volume on toxicology of the hematopoietic system Presents in-depth, comprehensive coverage from an international author base of domain experts