Impaired visually guided behavior in a mouse model of Parkinson's disease.

IF 2.1 3区 医学 Q3 NEUROSCIENCES
Journal of neurophysiology Pub Date : 2025-09-01 Epub Date: 2025-08-29 DOI:10.1152/jn.00307.2025
Gamaliel Mendoza-Cuevas, Job Perez-Becerra, Ricardo Velazquez-Contreras, Vladimir Calderon, Luis Carrillo-Reid
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引用次数: 0

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons. PD is usually defined by motor deficits such as rest tremor, bradykinesia, and rigidity. Nevertheless, some sensory impairments that may appear before motor dysfunctions or throughout the disease drastically reduce the quality of life of patients with PD. Patients with PD often present difficulties discriminating against basic properties of objects, indicating alterations in visual processing. However, how visual discrimination is affected in animal models of PD remains unknown. The use of l-DOPA continues as the most effective therapy for motor deficits observed in patients diagnosed with PD, but little is known about the effect of low doses of l-DOPA on visual discrimination. In the present study, we measured behavioral responses of control and parkinsonian adult male mice trained in a visually guided task. Control mice progressively developed stereotyped behaviors reflecting successful discrimination of Go and No-Go signals, whereas parkinsonian mice were unable to discriminate between different orientations of visual stimuli. Using electrophysiological recordings, we observed diminished visual responses in primary visual cortex of unilaterally dopamine-depleted mice, indicating that alterations of visual information processing could contribute to visual discrimination deficits. Remarkably, parkinsonian mice systemically injected with a low concentration of l-DOPA before each session of the visually guided task partially developed stereotyped behaviors and improved task performance, demonstrating a beneficial effect of l-DOPA. Further experiments are necessary to characterize the role of dopamine in visual discrimination in normal and pathological conditions.NEW & NOTEWORTHY Sensory deficits are commonly observed in patients with neurodegenerative diseases. Declined vision is frequently reported in Parkinson's disease (PD). However, visual impairments in animal models of PD are poorly understood. We observed visual discrimination deficits in parkinsonian mice that were improved by low concentrations of chronically injected l-DOPA. Future clinical research could help to elucidate the effect of pharmacological treatments in the amelioration of visual deficits of patients with PD.

帕金森病小鼠模型的视觉引导行为受损。
帕金森病(PD)是一种以多巴胺能神经元逐渐丧失为特征的神经退行性疾病。PD通常被定义为运动缺陷,如静止性震颤、运动迟缓和僵硬。然而,在运动功能障碍之前或整个疾病过程中可能出现的一些感觉障碍会大大降低PD患者的生活质量。PD患者经常表现出辨别物体基本属性的困难,这表明视觉处理发生了变化。然而,PD动物模型的视觉辨别如何受到影响尚不清楚。左旋多巴仍然是治疗帕金森病患者运动障碍最有效的治疗方法,但低剂量左旋多巴对视觉辨别的影响尚不清楚。在本研究中,我们测量了在视觉引导任务中训练的对照和帕金森病成年雄性小鼠的行为反应。对照小鼠逐渐形成了反映成功区分Go和No-Go信号的刻板行为,而帕金森小鼠无法区分视觉刺激的不同方向。通过电生理记录,我们观察到单侧多巴胺缺失小鼠初级视觉皮层的视觉反应减弱,表明视觉信息加工的改变可能导致视觉识别缺陷。值得注意的是,在每次视觉引导任务前全身注射低浓度左旋多巴的帕金森小鼠部分发展了刻板行为并改善了任务表现,证明了左旋多巴的有益作用。在正常和病理条件下,多巴胺在视觉辨别中的作用有待进一步的实验研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of neurophysiology
Journal of neurophysiology 医学-神经科学
CiteScore
4.80
自引率
8.00%
发文量
255
审稿时长
2-3 weeks
期刊介绍: The Journal of Neurophysiology publishes original articles on the function of the nervous system. All levels of function are included, from the membrane and cell to systems and behavior. Experimental approaches include molecular neurobiology, cell culture and slice preparations, membrane physiology, developmental neurobiology, functional neuroanatomy, neurochemistry, neuropharmacology, systems electrophysiology, imaging and mapping techniques, and behavioral analysis. Experimental preparations may be invertebrate or vertebrate species, including humans. Theoretical studies are acceptable if they are tied closely to the interpretation of experimental data and elucidate principles of broad interest.
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