Browsing by Subject "Vocalization, Animal"
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Item Cell Type-Specific Roles of FoxP Transcription Factors in Vocalization and Cognition(2019-07-23) Co, Marissa; Tsai, Peter; Konopka, Genevieve; Johnson, Jane E.; Roberts, ToddMutations of the forkhead domain transcription factors FOXP2 and FOXP1 are highly associated with neurodevelopmental disorders affecting speech and language. Across vertebrate species, their conserved expression patterns in the developing and adult brain predict important functions in neural circuits mediating vocalization and sensorimotor learning. Their known gene targets regulate neuronal development, activity, and plasticity, and animal models of FoxP2 and FoxP1 function have linked some of these molecular functions with neurophysiological and behavioral phenotypes. Still, much remains unknown about molecular networks in the brain driven by these transcription factors, especially in specific regions and cell types. During my dissertation work, I sought to elucidate FoxP2 and FoxP1 functions in cortical, striatal, and cerebellar neurons in mice and zebra finches. This approach of combining comparative genomics with functional studies of salient genes has proven a powerful method for understanding higher cognitive functions such as language (Chapter Two). By characterizing mice lacking cortical Foxp2, I identified its roles in dopamine signaling, interneuron development, and cognitive behavior, but surprisingly not in vocalization (Chapter Three). I further studied the interaction between FoxP2 and its cortical binding partner TBR1, and I found synergistic gene regulation by these transcription factors in neural cells (Chapter Four). I contributed to identification of roles for cortico-hippocampal FoxP1 in cortical development and vocalization (Chapter Five), as well as roles for cerebellar FoxP2 in Purkinje cell morphology, vocalization, and gross motor function (Chapter Six). Finally, I generated tools and datasets to further our understanding of corticostriatal functions of FoxP2 and FoxP1 in vocal learning zebra finches (Chapter Seven). In light of these studies, I discuss their implications for understanding human disorders affecting speech and language, and I impart further hypotheses and recommendations for continuing their study (Chapter Eight). Together, these findings contribute to our knowledge of conserved roles for FoxP2 and FoxP1 in vocal behavior and cognition.Item Finding the Engram: A Pathway for Song Memory in Zebra Finches(2019-07-01) Zhao, Wenchan; Xu, Wei; Meeks, Julian P.; Cooper, Brenton; Elmquist, Joel; Roberts, ToddFinding memory traces, also called engrams, has been a major goal in the neuroscience field for decades. Although episodic memory -- the memory of autobiographical events -- is known to rely on the hippocampus for its formation, procedural memory -- the memory of motor skills -- does not require hippocampus and the exact nature and mechanism of it has remained largely unknown. Vocal learning is a form of procedural learning of a sequence of vocal movements from a social model, a rare trait detected in only few animal species including songbirds and humans. The learning of vocal production is guided by the retention of the memory of the social model's vocal behavior. In this dissertation, I used song learning in zebra finches as the animal model to study the neural basis of song memory. I used a newly developed spatiotemporally specific optogenetic method combined with neuron population-specific genetic lesion to target a neural pathway of zebra finches and examined its role in song memory. Through this series of experiments, I showed that 1) imposing artificial activity in this pathway results in birds singing songs with temporal structure conforming to the imposed activity, suggesting a mechanism for encoding the temporal structure of song; 2) imposing activity paired with live bird tutoring cause the birds to learn only from the imposed activity, but not from the live bird tutor, suggesting this pathway is either able to override other pathways for acquiring song memory, or a non-redundant pathway for encoding the temporal structure of song; 3) genetic lesioning of cells in this pathway precludes birds from learning from a tutor, but does not affect song learning if birds received tutoring before lesioning, suggesting this pathway is necessary for acquiring song memory and that memory transmitted via this pathway is not stored within but downstream of it. This study is the first case showing artificial activity imposed in a neural pathway implants memories that subsequently guide the learning of a motor skill. In Part I of this dissertation, I introduce memory and strategies that can be used to find engram, song learning of zebra finches and previous work in search of the engram of song memory and discuss the rationale of my design of experiments. In Part II, I present in three separate chapters experiments I conducted to examine of the role of a neural pathway of zebra finches in song memory.Item Transitioning Between Preparatory and Precisely Sequenced Neuronal Activity in Production of a Skilled Motor Behavior(2019-06-18) Daliparthi, Vamsi Krishna; Pfeiffer, Brad E.; Meeks, Julian P.; Li, Wen-Hong; Fiolka, Reto; Roberts, ToddPrecise neural sequences are associated with the production of well-learned skilled behaviors. Yet, how neural sequences arise in the brain remains unclear. In songbirds, premotor projection neurons in the cortical song nucleus HVC are necessary for producing learned song and exhibit precise sequential activity during singing. Using cell-type specific calcium imaging we identify populations of HVC premotor neurons associated with the beginning and ending of singing-related neural sequences. We characterize neurons that bookend singing-related sequences and neuronal populations that transition from sparse preparatory activity prior to song to precise neural sequences during singing. Recordings from downstream premotor neurons or the respiratory system suggest that pre-song activity may be involved in motor preparation to sing. These findings reveal population mechanisms associated with moving from non-vocal to vocal behavioral states and suggest that precise neural sequences begin and end as part of orchestrated activity across functionally diverse populations of cortical premotor neurons.