Pathological α-synuclein impairs adult-born granule cell development and functional integration in the olfactory bulb
| Autor: | Jochen Herms, Stylianos Michalakis, Saak V. Ovsepian, Mario M. Dorostkar, Martin Biel, Severin Filser, Aayush Gupta, Johanna Neuner |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Aging metabolism [GABAergic Neurons] Dendritic spine Dendritic Spines General Physics and Astronomy Mice Transgenic Biology Bioinformatics General Biochemistry Genetics and Molecular Biology Article cytology [Olfactory Bulb] Midbrain chemistry.chemical_compound Mice cytology [GABAergic Neurons] medicine Animals metabolism [Mutant Proteins] metabolism [alpha-Synuclein] GABAergic Neurons Alpha-synuclein metabolism [Olfactory Bulb] Multidisciplinary Dopaminergic Excitatory Postsynaptic Potentials Depolarization metabolism [Synapses] Snca protein mouse General Chemistry Granule cell Olfactory Bulb Survival Analysis Olfactory bulb medicine.anatomical_structure metabolism [Dendritic Spines] chemistry nervous system Synapses Excitatory postsynaptic potential alpha-Synuclein Mutant Proteins ddc:500 Neuroscience |
| Zdroj: | Nature Communications Nature Communications 5(1), 3915 (2014). doi:10.1038/ncomms4915 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms4915 |
| Popis: | Although the role of noxious α-synuclein (α-SYN) in the degeneration of midbrain dopaminergic neurons and associated motor deficits of Parkinson’s disease is recognized, its impact on non-motor brain circuits and related symptoms remains elusive. Through combining in vivo two-photon imaging with time-coded labelling of neurons in the olfactory bulb of A30P α-SYN transgenic mice, we show impaired growth and branching of dendrites of adult-born granule cells (GCs), with reduced gain and plasticity of dendritic spines. The spine impairments are especially pronounced during the critical phase of integration of new neurons into existing circuits. Functionally, retarded dendritic expansion translates into reduced electrical capacitance with enhanced intrinsic excitability and responsiveness of GCs to depolarizing inputs, while the spine loss correlates with decreased frequency of AMPA-mediated miniature EPSCs. Changes described here are expected to interfere with the functional integration and survival of new GCs into bulbar networks, contributing towards olfactory deficits and related behavioural impairments. Aggregation-prone forms of α-synuclein lead to degeneration of midbrain dopaminergic neurons, as seen in Parkinson’s disease, but less is known about the effects that the noxious protein has in other brain regions. Here, the authors investigate the effect of a pathological form of α-synuclein on the functional integration of new neurons into the olfactory bulb of adult mice. |
| Databáze: | OpenAIRE |
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