Circuit and neurotransmitter mechanisms underlying neural and behavioral variabil

University Of California, San Francisco, San Francisco CA

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Abstract

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