Abstract
Subthalamic nucleus (STN) is the main source of feed-forward excitation in the basal ganglia and a main target of therapeutic deep brain stimulation in movement disorders. Alleviation of motor symptoms during STN stimulation can be accompanied by deterioration of abilities to quickly choose between conflicting alternatives. Cortical afferents to the subthalamic region (ST), comprising STN and zona incerta (ZI), include projections from the medial prefrontal cortex (mPFC), yet little is known about prefrontal-subthalamic coordination and its relevance for decision-making. Here we combined electrophysiological recordings with optogenetic manipulations of projections from mPFC to ST in mice as they performed a spatial working memory task (T-maze) or explored an elevated plus maze (anxiety test). We found that gamma oscillations (30–70 Hz) are coordinated between mPFC and ST at theta (5–10 Hz) and, less efficiently, at sub-theta (2–5 Hz) frequencies. An optogenetic detuning of the theta/gamma cross-frequency coupling between the regions into sub-theta range impaired performance in the T-maze, yet did not affect anxiety-related behaviors in the elevated plus maze. Both detuning and inhibition of the mPFC-ST pathway led to repeated incorrect choices in the T-maze. These effects were not associated with changes of anxiety and motor activity measures. Our findings suggest that action selection in a cognitively demanding task crucially involves theta rhythmic coordination of gamma oscillatory signaling in the prefrontal-subthalamic pathway.
Highlights
Subthalamic nucleus (STN) is the main source of feed-forward excitation in the basal ganglia and a main target of therapeutic deep brain stimulation in movement disorders
Confocal imaging revealed distinct bundles of medial prefrontal cortex (mPFC)-originating fibres leaving the cerebral peduncle close to the ventromedial part of STN and the adjacent parasubthalamic nucleus, and arborizing in these regions and dorsally in zona incerta (ZI) (Fig. 1A). These findings are in line with previous reports of mPFC efferents to STN established using chemical tracers in primates and rats[24] and to ZI, using retrograde viral tracing in mice[25]
We studied the coordination of network oscillations in mPFC and subthalamic region (ST) using local field potential (LFP) recordings, while implanted mice were trained in the delayed non-matching-to-place (T-maze) paradigm
Summary
Subthalamic nucleus (STN) is the main source of feed-forward excitation in the basal ganglia and a main target of therapeutic deep brain stimulation in movement disorders. An optogenetic detuning of the theta/ gamma cross-frequency coupling between the regions into sub-theta range impaired performance in the T-maze, yet did not affect anxiety-related behaviors in the elevated plus maze. Both detuning and inhibition of the mPFC-ST pathway led to repeated incorrect choices in the T-maze. Studies in rodents and primates showed the role of basal ganglia in action selection via encoding and modulation of action outcomes in the striatum and globus pallidus[1,2] These regions are interconnected with the subthalamic nucleus[2], stimulation of which in Parkinson’s disease patients can impair rapid decision-making[3]. Optogenetic manipulations opposing theta/ gamma PAC in the mPFC-ST pathway differentially affected decision-making in T- and elevated plus mazes
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