RT Journal Article
SR Electronic
T1 A biophysical model of striatal microcircuits suggests <em>θ</em>-rhythmically interleaved <em>γ</em> and <em>β</em> oscillations mediate periodicity in motor control
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 725416
DO 10.1101/725416
A1 Julia A. K. Chartove
A1 Michelle M. McCarthy
A1 Benjamin R. Pittman-Polletta
A1 Nancy J. Kopell
YR 2019
UL http://biorxiv.org/content/early/2019/08/09/725416.abstract
AB 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 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 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 β oscillations, we show that networks of striatal fast-spiking interneurons (FSIs) are capable of generating θ and γ 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 γ band activity nested within a θ oscillation. SPN networks produce β rhythms in both conditions, but under high DAergic tone, this β oscillation is interrupted by θ-periodic bursts of γ-frequency FSI inhibition. Thus, in the high DA state, packets of FSI γ and SPN β alternate at a 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 DA and rhythmicity impacts motor function. We hypothesize that high DA-induced periodic FSI γ-rhythmic inhibition enables switching between β-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.Author summary Striatal 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 DA. Our model suggests a hypothesis as to how the relationship between DA and rhythmicity impacts the function of the motor system, enabling rapid, periodic shifts in motor program execution.