# Cortical Intra‐Layer Hypersynchronization in Levodopa‐Induced Dyskinesia Mouse Model

## TL;DR

The study finds that dyskinesia in Parkinson's disease mice is linked to unusual synchronization of neurons in the motor cortex.

## Contribution

The novel finding is cortical intra-layer hypersynchronization in LID, previously unobserved in Parkinson's disease models.

## Key findings

- LID is associated with increased intra-layer hypersynchronization in the motor cortex.
- Inter-layer cross-correlation between M1 and the striatum is elevated in LID compared to PD.
- These changes in functional connectivity are absent in wild-type mice receiving l-dopa.

## Abstract

Levodopa (l‐dopa)‐induced dyskinesia (LID) is a common and difficult complication in Parkinson's disease (PD) patients. It may result from hyperactivation of the primary motor cortex (M1) due to hypoactivation of the basal ganglia (BG) output nuclei. Electrophysiological evidences are sparse, mainly due to technological limitations related to the poor ability to simultaneously acquire data from many neurons of the different involved regions. We exploited the Neuropixels technology to overcome these obstacles.

Extracellular Neuropixels recordings were acquired from awake head‐restrained mice in wild‐type (WT), parkinsonian, and LID conditions. Activity was recorded from M1 and the motor striatum simultaneously and compared for each mouse in four conditions: control (WT with and without l‐dopa), hemiparkinsonian (6‐hydroxydopamine model), and LID states.

Neural firing rates in M1 were decreased in PD and increased in LID as expected. Focusing on the quiet periods, the firing rates between the different conditions were similar. LID was associated with cortical intra‐layer hypersynchronization, a phenomenon not previously described. The overall synchrony was significantly increased between neurons of Layers 2, 3, and 5 in M1 in LID compared to PD state. Inter‐layer cross‐correlation was increased in LID, compared to PD state, between Layer 5 of M1 and the striatum. These changes in functional connectivity were absent in WT mice receiving l‐dopa.

Our single‐cell recordings from thousands of neurons provide insight into cortical network changes in LID. We found that LID is associated with intra‐layer hypersynchronization of neurons within the motor cortex, which may be an intrinsic network feature within the cortico–BG loop.

Using Neuropixels technology, we obtained single‐cell data from thousands of neurons in the motor cortex and striatum of mice at different stages: WT, parkinsonian, and dyskinetic (LID). We found that LID is associated with intra‐layer hypersynchronization within the motor cortex, which may be an intrinsic network feature within the cortico–BG loop.