Browsing by Author "Washbourne, Philip"

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    The Social Brain of Zebrafish
    (University of Oregon, 2020-02-27) Stednitz, Sarah; Washbourne, Philip
    Social behavior is arguably one of the most complex forms of behavior exhibited by animals. It requires active attention to dynamic multisnsory cues, recall of past experiences, and the generation of situationally appropriate responses. Given the swath of different cognitive systems required, it is unsurprising that social behavior is disrupted in many neurological disorders. Autism spectrum disorders (ASD) are particularly notable, as social impairment is a required diagnostic criteria. Efforts using animal models to both understand the etiology and improve behavioral outcomes for human ASD patients are complicated by the difficulty of replicating the genetic environmental causes. Similarly, measuring deficits in complex behaviors like social interaction is challenging and their neuroanatomical correlates are not yet fully described. To address these issues, I utilized the highly social and genetically tractable zebrafish (Danio rerio) as a model system. I developed a novel assay that shows social engagement requires a behavioral visual stimulus provided by another socially-engaged fish. I demonstrated that both pharmacological manipulation of dopaminergic systems and ablation of a portion of the ventral telencephalon produce predictable deficits in social behavior. Our results also provide evidence that an as yet uncharacterized population of cholinergic neurons in the ventral forebrain are critical for social interactions in zebrafish. This region corresponds to mammalian forebrain regions implicated in social behavior, suggesting an evolutionarily conserved population of cells may drive social orienting in zebrafish and mammals. Further, I identified the time points in early development when specific social behaviors are first observed, suggesting a progressive acquisition of increasingly complex social behaviors over a rapid timescale. This highly variable and early stage in development represents an opportunity to further understand how genetic and environmental factors affect the assembly of the neural circuits underlying complex behaviors.
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    Transcriptional profiling of multi-transmitter neurons in the zebrafish forebrain
    (University of Oregon, 2021-09-13) Ncube, Denver; Washbourne, Philip
    Neurotransmitter phenotype is the hallmark of neuronal identity. Neurons are classified based on the neurotransmitters they release. At the inception of the discipline of neuroscience was a fascination with the structure of neurons and morphology of brain tissue. The pioneering work of Santiago Ramon y Cajal (1852-1934) and Henreich Wilhelm Waldeyer(1836-1921) ushered in the famous Neuron Doctrine, which posited that neurons are not only structural units of the nervous system but as trophic, functional, and genetic units. Deciphering the neurotransmitter identity of neurons has been a principal reference point for making interpretations of their function during specific behaviors. In addition, there is a wealth of evidence which shows that neurons can synthesize and release multiple neurotransmitters. However, the development of such neurons and the factors that drive their development has been largely unexplored. Researchers have often narrowed their investigations to establishing the presence of a single neurotransmitter. Mapping these neurons across the vertebrate phyla has not received nearly enough attention though this is conceivably important in understanding common phylogenetic traits. In addition, it is unknown if multi-transmitter neurons attain this identity in a sequential manner or they develop different neurotransmitters at the same time. To address these questions, I utilized the zebrafish (Danio rerio) as a model system, I characterized a transgenically defined population of multi-transmitter neurons in the zebrafish forebrain. These neurons which are important in social orienting behavior, synthesize both Acetylcholine and GABA and this study was the first to establish this. My work demonstrates that for this cluster of neurons, the neurotransmitters are co-expressed from the first day of development, and this co-expression persists till adulthood. Further, I identified a constellation of specific marker genes expressed by these neurons, which together with three LIM Homeobox Transcription factor genes enables us to map similar neurons in other vertebrates with great accuracy. I also tested a novel hypothesis on specification of these multi-transmitter neurons by LIM homeobox transcription factor genes. In conclusion, the comprehensive characterization contained this work presents a great platform to tease apart fundamental questions on the impact of different perturbations on the development of neurons.