A biophysical model of striatal microcircuits suggests gamma and beta oscillations interleaved at delta/theta frequencies 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 β (*15-30 Hz) and low γ (*40-60 Hz), and a state involving θ (*4-8 Hz) and high γ (*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 β oscillations, we show that networks of striatal fast-spiking interneurons (FSIs) are capable of generating δ/θ (ie, 2 to 6 Hz) and γ rhythms. Under simulated low dopaminergic tone our model FSI network produces low γ band oscillations, while under high dopaminergic tone the FSI network produces high γ band activity nested within a δ/θ oscillation. SPN networks produce β rhythms in both conditions, but under high dopaminergic tone, this β oscillation is interrupted by δ/θ-periodic bursts of γ-frequency FSI inhibition. Thus, in the high dopamine state, packets of FSI γ and SPN β alternate at a δ/θ 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 γ-rhythmic inhibition enables switching between β-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.

Interactions Between Motor Thalamic Field Potentials and Single-Unit Spiking Are Correlated With Behavior in Rats

“…However, locally-referenced electrodes have also detected similar cross-frequency coupling in the striatum and the subthalamic nucleus (López-Azcárate et al, 2013 ). Striatal origins for delta, beta, and gamma oscillations have also been proposed (Chartove et al, 2020 ), and subthalamic nucleus-globus pallidus, pars externa connections are implicated in generating beta oscillations (Tachibana et al, 2011 ; Mirzaei et al, 2017 ). Finally, modeling studies suggest that focal synaptic input to nonlaminar subcortical structures (e.g., striatum and thalamus) can generate measurable LFPs (Tanaka and Nakamura, 2019 ).…”

Deep brain stimulation in the subthalamic nucleus for Parkinson’s disease can restore dynamics of striatal networks

“…We modeled DBS in STN as a combination of these two aspects: DBS suppresses STN somatic activity, thereby suppressing the beta activity in STN, and replaces it with HFS at the level of STN axons. Our simulations show that HFS of the STN-FSI pathway fully restores striatal network dynamics including a reduction of beta and, most surprisingly, the re-expression of gamma and theta, striatal rhythms previously thought to be dependent on high levels of DA [22,[35][36][37]. Moreover, our models suggest that the gamma/theta and beta dynamics can be modulated by cortical input during DBS, rather than by DA, thus allowing an alternative mechanism to DA modulation during task performance.…”

“…The question we seek to answer is how striatal network level dynamics are restored, through DBS in STN, despite persisting cellular level disruptions due to loss of DA. To answer this question, building on established computational models of striatum [13,22], we explore network activity associated with a previously understudied but direct connection from STN to striatum [23][24][25][26][27][28]. Recent research shows that the direct STN to striatum pathway projects strongly and almost exclusively to striatal fast spiking interneurons (FSIs) [28].…”

Two Players in the Field: Hierarchical Model of Interaction between the Dopamine and Acetylcholine Signaling Systems in the Striatum

“…These rhythmic changes can be described based on their rates. Striatal microcircuits potentially generate rhythms [ 81 ], and striatal projection neurons and fast-spiking interneurons are capable of generating oscillations. The level of dopaminergic tone determines the rates of oscillations [ 81 ].…”

“…Striatal microcircuits potentially generate rhythms [ 81 ], and striatal projection neurons and fast-spiking interneurons are capable of generating oscillations. The level of dopaminergic tone determines the rates of oscillations [ 81 ]. As the striatum is one of the brain structures involved in locomotor control, it is possible to deduce that it would be involved in biological rhythms connected to motor activity, locomotion, or addiction (drug/reward seeking).…”