DOI: 10.25549/usctheses-c40-335848
title: Cortical circuits for vocal learning and microtubule dynamics in neural development

description: Our remarkable ability to perceive, interact with and remember the world around us is a reflection of the complex networks of cells comprising our nervous system. The basic unit of the nervous system is a neuron, composed of a cell body and a number of processes called neurites in immature neurons. In mature neurons, these processes have become dendrites, which collect information, and axons, which send information from the cell body to a downstream partner. To accomplish highly sophisticated tasks like walking, talking, or playing the piano, individual neurons are ordered into precisely arranged circuits which integrate and analyze sensory information relevant for that specific task, select and produce motor behaviors, and modify synaptic connections during learning. ❧ Developing precisely organized circuits requires individual growing axons to use a flexible tip structure called a growth cone to follow specific paths through the immature nervous system as they elongate and eventually form synapses onto specific targets. Growth cones are steered by a combination of external guidance cues and internal molecular mechanisms, and may split to extend into multiple regions. Eventually, growth cones reach their destination and form a synapse where they can pass information to their downstream partner—either another neuron or a responsive tissue, like muscle fiber. Additional refinement of axonal branching, stability and synaptic strength can occur later in development, during critical periods of learning, or throughout life. ❧ Connections established during development and learning determine a neuron's function: for example, a neuron which receives multiple inputs from a variety of sensory receptors could function as an information integrator, while a neuron with branching axons can efficiently coordinate downstream partners by sending identical information to multiple places. Entire pathways through successive brain regions can also be arranged to maintain a specific organization—for example, medial regions may project to downstream medial regions, while lateral regions project to lateral regions. Because neurons are often arranged into maps according to their properties, maintaining the organization of axonal projections between brain areas throughout a circuit can preserve the organization of information processed in successive brain areas. Information carried along parallel pathways can then be integrated at a point of convergence, where signals can be added together, compared, evaluated, or modified before the information is sent forward. ❧ This dissertation addresses two central questions about neural circuits: how are neural circuits organized to mediate specific functions, and what molecular mechanisms regulate neurite growth during development? In the following sections in this chapter, I review the current literature about neural circuitry mediating vocal learning in songbirds and insights into how the structural organization of a circuit enables this complex developmental behavior. I also review current literature about molecular mechanisms which regulate the growth of neurons during development. In chapter 2, I describe my work using a systems-level investigation into the organization of songbird neural circuits that enable multimodal vocal learning and inter-hemispheric coordination. In chapters 3 and 4, I describe my work developing and using a novel method for quantifying microtubule dynamics within growing neurons to investigate a molecular mechanism for regulating neurite branching during development.