DOI: 10.5281/zenodo.10733845
title: Data from: Sensory-Behavioral Deficits in Parkinson's Disease: Insights from a 6-OHDA Mouse Model

description: Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the striatum, predominantly associated with motor symptoms. However, non-motor deficits, particularly sensory symptoms, often precede motor manifestations, offering a potential early diagnostic window. The impact of non-motor deficits on sensation behavior and the underlying mechanisms remains poorly understood. In this study, we examined changes in tactile sensation within a Parkinsonian state by employing a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) to deplete striatal dopamine (DA). Leveraging the conserved mouse whisker system as a model for tactile-sensory stimulation, we conducted psychophysical experiments to assess sensory-driven behavioral performance during a tactile detection task in both the healthy and Parkinson-like states. Our findings reveal that DA depletion induces pronounced alterations in tactile sensation behavior, extending beyond expected motor impairments. We observed diverse behavioral deficits, spanning detection performance, task engagement, and reward accumulation, among lesioned individuals. While subjects with extreme DA depletion consistently showed severe sensory behavioral deficits, others with substantial DA depletion displayed minimal changes in sensory behavior performance. Moreover, some exhibited moderate degradation of behavioral performance, likely stemming from sensory signaling loss rather than motor impairment. The implementation of a sensory detection task is a promising approach to quantify the extent of impairments associated with DA depletion in the animal model. This facilitates the exploration of early non-motor deficits in PD, emphasizing the importance of incorporating sensory assessments in understanding the diverse spectrum of PD symptoms.
description: Usage notesIn order to access the data and computer code that support the findings of this study, all files can be downloaded from Zenodo. Files are compressed ZIP files (Windows 11) and need to be saved and extracted before access.

The main dataset contains behavioral readouts (licks and whisker stimulation) in a Go-No-go detection task. For behavior data, psychometric curves were measured in repeated daily sessions (1-2 sessions per day) for a minimum of six days. The psychometric curve was measured for all animals using a constant stimuli method entailing the presentation of repeated stimulus blocks containing multiple stimulus amplitudes (A = [0, 2, 4, 8, 16]°). Stimuli were presented with equal probability (uniform distribution, P = 0.2) after a variable time interval of 6-8s in each trial. A block of stimuli consisted of each stimulus and a catch trial in pseudorandom order (each was presented once per block). A single session of behavior contained repeated blocks until the animal disengaged from the task, missing an entire block of stimuli (A = [0, 2, 4, 8, 16]°). Animals had to complete a minimum of n = 50 trials per session. Data was collected prior to (Pre-Lesion) and following (Post-Lesion) 6-hydroxydopamine (6-OHDA) injection. 

NWB File Generation:

Data has been provided both in NWB format and as MATLAB files to allow for the running of our code for figure generation. NWB files include information about stimulus presentation, trial information, and processed behavioral data. 

NWB data is stored in a hierarchical structure based on the Hierarchical Data Format version 5 (HDF5). Within the General file folder you can access data related to the experimenter, institution data was collected at, session ID, and animal information (e.g. animal ID, sex, species, pre- or post-lesion, etc.). The intervals folder contains a trials folder that holds information pertinent to stimulus presentation such as stimulus type, trial start time, trial stop time, and time of stimulus presentation. The processing folder contains behavior data, specifically lick data. Within the lick sub-folder information about the number of licks during the trial (licks_trial_index) and their timing (licks_trial), as well as the number of licks between trials (licks_ITI_index) and their timing (licks_ITI) is presented. The trial_classification table describes whether the animal aborted the trial, made a correct hit, missed the stimulus, made a correct rejection, or incorrectly licked in the absence of stimuli. Finally, within the stimulus folder data representing the stimulus waveform is presented in the stimulus_waveform sub-folder.

 

All other analyses were performed with custom MATLAB programs (R2022a).  All provided data and code can be accessed with MATLAB. The dataset is structured as follows:

Behav_data: These files contain processed psychometric data from each animal (e.g. “mouse21_RT.mat). All files can be loaded and accessed via MATLAB (see code under “Manuscript_Figs”

Code_for_figures: This folder contains all necessary MATLAB code to re-produce the main figures of the manuscript. Within each code, loading files, data analysis/statistics and plotting procedures are described step-by-step.Psychometric data analysis and curve fits were performed using open-source software psignifit toolbox version 2.5.6 for MATLAB version 5 and up (Wichmann & Hill, 2001 a,b).https://uni-tuebingen.de/en/fakultaeten/mathematisch-naturwissenschaftliche-fakultaet/fachbereiche/informatik/lehrstuehle/neuronale-informationsverarbeitung/research/software/psignifit/MATLAB Download: https://github.com/wichmann-lab/psignifit/archive/master.zippython Download: https://github.com/wichmann-lab/python-psignifit/archive/master.zip

Histology: This folder contains histology images in the form of TIF files that were used for the manuscript (Fig. 1). All other histology images are available from the corresponding author upon reasonable request.For detailed questions about the data and computer code, please contact the corresponding author christian.waiblinger@gatech.edu

nwb: This folder contains all behavioral data in nwb format as well as the code used on raw files to convert data to NWB format. 

Rotation_data: This folder contains an excel spreadsheet with data collected from rotameter testing. The numbers found within this file can also be found within "Code_for_figures".  Ipsilateral (L) and contralateral (R) turns relative to the site of the lesion were recorded. Turns were counted at 45 degrees and findings were presented as percent left turns, where one turn is equivalent to 360 degrees (8 x 45 degrees). The number in parentheses (XX full) indicates the number of times 360 degrees was completed according to the 45 degree count (i.e. 337 45 degree turns divided by 8 yields 42 full turns). 

 

Funding provided by:

McCamish Parkinson’s Disease Innovation Program Blue Sky grant.

NIH R01NS124764

NIH Brain Grants RF1NS128896 and R01NS104928.