Dopamine depletion selectively disrupts interactions between striatal neuron subtypes and LFP oscillations

Dopamine degeneration in Parkinson's disease (PD) dysregulates the striatal neural network and causes motor deficits. However, it is unclear how altered striatal circuits relate to dopamine-acetylcholine chemical imbalance and abnormal local field potential (LFP) oscillations observed in PD. We perform a multimodal analysis of the dorsal striatum using cell-type-specific calcium imaging and LFP recording. We reveal that dopamine depletion selectively enhances LFP beta oscillations during impaired locomotion, supporting beta oscillations as a biomarker for PD. We further demonstrate that dynamic cholinergic interneuron activity during locomotion remains unaltered, even though cholinergic tone is implicated in PD. Instead, dysfunctional striatal output arises from elevated coordination within striatal output neurons, which is accompanied by reduced locomotor encoding of parvalbumin interneurons and transient pathological LFP high-gamma oscillations. These results identify a pathological striatal circuit state following dopamine depletion where distinct striatal neuron subtypes are selectively coordinated with LFP oscillations during locomotion. [Display omitted] •Dopamine loss selectively enhances LFP beta oscillations during impaired locomotion•6-OHDA injury reduces locomotor encoding ability of PV interneurons and SPNs•Elevated coordination within SPN network after dopamine loss inhibits movement•Dopamine loss leads to pathological LFP high-gamma oscillations during SPN activation Zemel et al. demonstrate that dopamine loss disrupts striatal neural network and enhances local field potential beta oscillations during impaired locomotion. Specifically, striatal projecting neuron activation is abnormally coordinated and accompanied by pathological high-gamma oscillations. While parvalbumin interneurons reduce locomotor encoding, cholinergic interneurons strengthen their interactions with projecting neurons.