ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Aging decreases L-type calcium channel currents and pacemaker firing fidelity in substantia nigra dopamine neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 81 citations in OpenAlex.
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- Reduction in the activity of VTA/SNc dopaminergic neurons underlies aging-related decline in novelty seeking.Communications biology · 2023Article
- VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.bioRxiv : the preprint server for biology · 2023Article
- Contributions of the Sodium Leak Channel NALCN to Pacemaking of Medial Ventral Tegmental Area and Substantia Nigra Dopaminergic Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Neuronal Senescence in the Aged Brain.Aging and disease · 2023Review
- Preservation of dendritic D2 receptor transmission in substantia nigra dopamine neurons with age.Scientific reports · 2023Article
- Age-Related Changes in Risky Decision Making and Associated Neural Circuitry in a Rat Model.eNeuro · 2023Article
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- Age-dependent alterations in key components of the nigrostriatal dopaminergic system and distinct motor phenotypes.Acta pharmacologica Sinica · 2022Article
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- Modelling learning in Caenorhabditis elegans chemosensory and locomotive circuitry for T-maze navigation.The European journal of neuroscience · 2022Article
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- Progressive parkinsonism due to mitochondrial impairment: Lessons from the MitoPark mouse model.Experimental neurology · 2021Review
- Dopamine Transporter Is a Master Regulator of Dopaminergic Neural Network Connectivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
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3 authors at 1 institution in 2 countries.
Funding
Abstract
Substantia nigra dopamine neurons are involved in behavioral processes that include cognition, reward learning, and voluntary movement. Selective deterioration of these neurons is responsible for the motor deficits associated with Parkinson's disease (PD). Aging is the leading risk factor for PD, suggesting that adaptations occurring in dopamine neurons during normal aging may predispose individuals to the development of PD. Previous studies suggest that the unique set of ion conductances that drive spontaneous, rhythmic firing of action potentials could predispose substantia nigra dopamine neurons to selective neurodegeneration. Here we show, using patch-clamp electrophysiological recordings in brain slices, that substantia nigra dopamine neurons from mice 25-30 months of age (old) have comparable membrane capacitance and input resistance to neurons from mice 2-7 months of age (young). However, neurons from old mice exhibit slower firing rates, narrower spike widths, and more variable interspike intervals compared with neurons from young mice. Dopamine neurons from old mice also exhibit smaller L-type calcium channel currents, providing a plausible mechanism that likely contributes to the changes in impulse activity. Age-related decrements in the physiological function of dopamine neurons could contribute to the decrease in voluntary movement and other dopamine-mediated behaviors observed in aging populations. Furthermore, as pharmacological antagonism of L-type calcium channels has been proposed as a potential treatment for the early stages of PD, our results could point to a limited temporal window of opportunity for this therapeutic intervention.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.