From Genetics to Behavior, the Dynamics and Mechanisms of Adult Neurogenesis in a Sensorimotor Circuit

Abstract

The most defining attribute of the nervous system is that it shows extensive plasticity of structure and function that allows animals to adjust their behavior, physiology, and morphology to changes in their environment. One example of such plastic changes is the seasonal changes in the neural circuit responsible for singing behavior in song birds. The songbird neural circuit is comprised of the sensorimotor nucleus HVC and its target, the robust nucleus of the arcopallium (RA). Neuronal number in the HVC of adult song bird Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelli) changes seasonally with around 25%, or nearly 68,000, neurons being born and dying each breeding and nonbreeding season, respectively. White-crowned sparrow singing behavior also changes with season such that during breeding season birds produce more songs of high stereotypy. Resultantly, the avian song control system provides a unique model that allows us to investigate the basic natural processes, regulatory mechanisms, and behavioral results of neuronal birth and addition in the adult brain, or adult neurogenesis. Within this dissertation, I document the natural dynamics between new neuronal addition and mature neuronal death within and between breeding and nonbreeding seasons. I demonstrate that neuronal death and the resulting inflammatory response are both necessary and sufficient for increased production of new neurons and that neural activity is necessary and sufficient for the addition of the newly generated neurons into the song control neural circuit. Finally, I examine the genetic regulatory networks coordinating the multitude of processes and modulatory mechanisms of adult neurogenesis in the avian brain. Together, these studies uncover the basic cellular and genetic dynamics in addition to key regulatory mechanisms guiding successful incorporation and survival of adult-born neurons in functional neural circuits. Understanding the processes and mechanisms described herein is critical both for our basic understanding of adult neurogenesis and neural plasticity and for exploiting the clinical potential of neuronal replacement to repair damage associated with injury and neurodegenerative diseases.