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

Striatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. Local field potential (LFP) recordings in rodent striatum show dopamine- (DA-) 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 DAergic 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 DA. 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 theta and gamma rhythms. Our model consists of three interconnected populations of single or double compartment Hodgkin-Huxley neurons: a feedforward network of FSIs exhibits a D-type potassium current as well as DA-modulated gap junctional and inhibitory connectivity, and two networks of SPNs exhibit an M-type potassium current and express either excitatory D1 or inhibitory D2 DA receptors. Under simulated low DAergic tone the FSI network produces low γ band oscillations, while under high DAergic tone the FSI network produces high gamma band activity nested within a theta oscillation. SPN networks produce beta rhythms in both conditions, but under high DAergic tone, this beta oscillation is interrupted by theta-periodic bursts of gamma-frequency FSI inhibition. Thus, in the high DA state, packets of FSI gamma and SPN beta alternate at a 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 DA and rhythmicity impacts motor function. We hypothesize that high DA-induced periodic FSI gamma-rhythmic inhibition enables switching between beta-rhythmic SPN cell assemblies representing the currently active motor program, and thus that DA facilitates movement by allowing for rapid, periodic shifts in motor program execution.