論文 - 詳細
| RRC ID | 34776 |
|---|---|
| 著者 | Masi A, Narducci R, Resta F, Carbone C, Kobayashi K, Mannaioni G. |
| タイトル | Differential contribution of Ih to the integration of excitatory synaptic inputs in substantia nigra pars compacta and ventral tegmental area dopaminergic neurons. |
| ジャーナル | Eur J Neurosci |
| Abstract |
The selective vulnerability of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons is an enigmatic trait of Parkinson's disease (PD), especially if compared to the remarkable resistance of closely related DA neurons in the neighboring ventral tegmental area (VTA). Overall evidence indicates that specific electrophysiological, metabolic and molecular factors underlie SNc vulnerability, although many pieces of the puzzle are still missing. In this respect, we recently demonstrated that 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of the parkinsonizing toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), alters the electrophysiological properties of SNc DA neurons in vitro by inhibiting the hyperpolarization-activated current (Ih). Here, we present an electrophysiological investigation of the functional role of Ih in the integration of synaptic inputs in identified SNc and VTA DA neurons, comparatively, in acute midbrain slices from TH-GFP mice. We show that pharmacological suppression of Ih increases the amplitude and decay time of excitatory postsynaptic potentials, leading to temporal summation of multiple excitatory potentials at somatic level. Importantly, these effects are quantitatively more evident in SNc DA neurons. We conclude that Ih regulates the responsiveness to excitatory synaptic transmission in SNc and VTA DA neurons differentially. Finally, we present the hypothesis that Ih loss of function may be linked to PD trigger mechanisms, such as mitochondrial failure and ATP depletion, and act in concert with SNc-specific synaptic connectivity to promote selective vulnerability. |
| 巻・号 | 42(9) |
| ページ | 2699-706 |
| 公開日 | 2015-11-1 |
| DOI | 10.1111/ejn.13066 |
| PMID | 26354486 |
| MeSH | Animals Dopamine / metabolism Dopaminergic Neurons / metabolism Dopaminergic Neurons / physiology* Excitatory Postsynaptic Potentials* Female Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / physiology* Male Mice Mice, Transgenic Pars Compacta / metabolism Pars Compacta / physiology* Postsynaptic Potential Summation* Tyrosine 3-Monooxygenase / metabolism Ventral Tegmental Area / metabolism Ventral Tegmental Area / physiology* |
| IF | 3.115 |
| 引用数 | 16 |
| WOS 分野 | NEUROSCIENCES |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02095 |