A central goal of neuroscience is to understand how patterns of neural activity in the brain control behavior. In principle, neurons can encode information via their firing rates, the precise timing of their spikes, or both. However, nearly all prior studies of motor systems have relied exclusively on spike rates to investigate how the brain controls behavior. We recently demonstrated that in songbird vocal motor cortex, spike timing – down to millisecond-scale differences in spike patterning – is far more informative about upcoming behavior than is spike rate. Although this suggests that variations in cortical spike timing could modulate behavior, it is unknown whether precise cortical spike timing drives a similarly precise code downstream in motor neurons and muscle tissue, or indeed whether variations in motor neuron spike timing are capable of modifying behavior. The proposed experiments will combine innovative behavioral, physiological, and computational techniques to understand how the nervous system uses precisely timed patterns of electrical activity to regulate the acoustics of vocal output in songbirds. Our long-term goal is to understand how spiking activity in the brain controls behavior. The objective of this proposal is to determine which properties of motor spiking drive variations in behavior in control of vocalizations in songbirds. Our central hypothesis is that the brain controls behavior by precisely (down to a precision of a few milliseconds) modulating spike timing. This hypothesis will be tested in three specific Aims. In Aim 1, we will use a newly developed electrode system to study spiking activity from muscle tissue (i.e., the spikes of individual motor units, each of which consists muscle fibers innervated by a single motor neuron) in vocalizing songbirds to determine the timescale of neuromuscular control. In Aim 2, we will use innovative in vivo, in vitro, and ex vivo techniques to determine whether spike-timing differences observed in muscle fibers affect motor output. In Aim 3, we will examine how precise firing patterns are coordinated across multiple muscles. All three Aims will tightly integrate experimental studies and computational analyses to identify specific spike timing patterns that most strongly influence behavior and to generate and test hypotheses about the biomechanical bases of precise motor control. The rationale for these studies is that they will upend long-held notions that cortical motor control is based solely on spike rate codes and establish a broadly applicable framework for analyzing timing-based spike codes both within and beyond the motor system. Furthermore, our findings and techniques may significantly contribute to the improvement of neural prosthetic devices by showing how decoding algorithms might make use of spike timing in addition to the rate information commonly used in current approaches.

This research will use the songbird vocal control system to increase our understanding of how the brain uses precisely timed electrical signals to control behavior. Such an understanding can be used to improve the lives of patients suffering from motor production disorders caused by neurological diseases or trauma.