Gamaliel Mendoza-Cuevas, Job Perez-Becerra, Ricardo Velazquez-Contreras, Vladimir Calderon, Luis Carrillo-Reid
{"title":"Impaired visually guided behavior in a mouse model of Parkinson's disease.","authors":"Gamaliel Mendoza-Cuevas, Job Perez-Becerra, Ricardo Velazquez-Contreras, Vladimir Calderon, Luis Carrillo-Reid","doi":"10.1152/jn.00307.2025","DOIUrl":null,"url":null,"abstract":"<p><p>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.<b>NEW & NOTEWORTHY</b> 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.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1047-1057"},"PeriodicalIF":2.1000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neurophysiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/jn.00307.2025","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/29 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
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.
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.