Circuit and neurotransmitter mechanisms underlying neural and behavioral variabil

点击翻译按钮获取中文摘要

In songbirds, a discrete neural circuit is devoted to the learning and production of a stereotyped vocal motor behavior, song, providing a useful model for studying brain mechanisms of behavior, with strong relevance to human speech learning. In particular, a specialized 'cortical'-basal ganglia circuit known as the anterior forebrain pathway (AFP) is crucial for song learning and plasticity throughout life. Recent evidence from our lab and others has revealed that the AFP provides a source of variability potentially important for learning to the motor circuit. In addition, we have found that the outflow nucleus of the AFP, 'LMAN', switches from bursty, highly variable firing when birds sing alone, to more reproducible firing when birds sing to a female, suggesting that social cues could be important in the control of variability. The two social states of LMAN activity are associated with high and low variability song, respectively. Here we propose to further investigate the function of AFP variability by examining and then manipulating the circuit and neurotransmitter mechanisms that give rise to it. We will record chronically from cells in the basal ganglia inputs to LMAN as well as from LMAN neurons, to study where the social context-dependent variability of firing emerges and how it travels across this circuit. We will also measure how correlated LMAN firing is across neurons, to assess how variability may be 'read out' to the motor pathways, and how it relates to behavior (Aim 1). We will then alter the levels of the neuromodulators norepinephrine (NE) and dopamine (DA) both in adults (Aim 2) and in juveniles in late sensorimotor learning (Aim 3), and examine the effects on AFP activity and on song, to test the hypothesis that these neurotransmitters regulate neural and consequently behavioral variability. The song system provides a tractable model for studying the mechanisms by which social and other environmental cues act on the nervous system and ultimately affect behavioral output, both normally and in disease. Understanding these mechanisms has the potential to provide insights into the many neuropsychiatric disorders that have their locus in cortical-basal ganglia circuits.