A biophysical model of striatal microcircuits suggests theta-rhythmically interleaved gamma and beta oscillations mediate periodicity in motor control

Abstract

Striatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. Local field potential recordings in rodent striatum show dopamine- and reward-dependent transitions between two states: a "spontaneous" state involving {beta} (~15-30 Hz) and low{gamma} (~40-60 Hz), and a state involving{theta} (~4-8 Hz) and high{gamma} (~60-100 Hz) in response to dopaminergic agonism and reward. The mechanisms underlying these rhythmic dynamics, their interactions, and their functional consequences are not well understood. In this paper, we propose a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of these rhythms, as well as their modulation by dopamine. Building on previous modeling and experimental work suggesting that striatal projection neurons (SPNs) are capable of generating {beta} oscillations, we show that networks of striatal fast-spiking interneurons (FSIs) are capable of generating{delta} /{theta} (ie, 2 to 6 Hz) and{gamma} rhythms. Under simulated low dopaminergic tone our model FSI network produces low{gamma} band oscillations, while under high dopaminergic tone the FSI network produces high{gamma} band activity nested within a{delta} /{theta} oscillation. SPN networks produce {beta} rhythms in both conditions, but under high dopaminergic tone, this {beta} oscillation is interrupted by{delta} /{theta}-periodic bursts of{gamma} -frequency FSI inhibition. Thus, in the high dopamine state, packets of FSI{gamma} and SPN {beta} alternate at a{delta} /{theta} timescale. In addition to a mechanistic explanation for previously observed rhythmic interactions and transitions, our model suggests a hypothesis as to how the relationship between dopamine and rhythmicity impacts motor function. We hypothesize that high dopamine-induced periodic FSI{gamma} -rhythmic inhibition enables switching between {beta}-rhythmic SPN cell assemblies representing the currently active motor program, and thus that dopamine facilitates movement in part by allowing for rapid, periodic shifts in motor program execution. Author summaryStriatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. The mechanisms underlying these rhythmic dynamics, their interactions, and their functional consequences are not well understood. In this paper, we propose a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of striatal rhythms, as well as their modulation by dopamine. Our model suggests a hypothesis as to how the relationship between dopamine and rhythmicity impacts the function of the motor system, enabling rapid, periodic shifts in motor program execution.