title: Stressor-related impairment of synaptic transmission in hippocampal slices from alpha-synuclein knockout mice.
abstract: The role of alpha-synuclein (alpha-Syn) has recently received considerable attention because it seems to play a role in Parkinson's disease (PD). Missense mutations in the alpha-Syn gene were found in autosomal dominant PD and alpha-Syn was shown to be a major constituent of protein aggregates in sporadic PD and other synucleinopathies. Under normal conditions, alpha-Syn protein is found exclusively in synaptic terminals. However, the potential participation of alpha-synuclein in maintaining and regulating synaptic efficacy is unknown. We have investigated the excitatory synaptic modulation of alpha-synuclein in CA1 pyramidal neurons, using the in vitro hippocampal slice technique. The 4-aminopyridine-induced increase of both spontaneous excitatory postsynaptic current (EPSC) frequency and amplitude was significantly higher in alpha-Syn wild-type than knockout mice, whereas basal spontaneous EPSC frequency and amplitude was similar in both animals. As the spontaneous synaptic activity was abolished by tetrodotoxin, which indicates that it was a result of action potential-mediated transmitter release from presynaptic terminals, spontaneous EPSC changes observed in alpha-Syn knockout mice suggest that these animals present a modification of synaptic transmission with a presynaptic origin. Presynaptic depression of evoked EPSCs by hypoxia or adenosine was significantly larger in alpha-Syn knockout than in wild-type mice, further supporting the hypothesis of regulation of synaptic transmission by alpha-Syn. Together, these observations indicate that the loss of alpha-Syn reduces synaptic efficacy when the probability of transmitter release is modified. We conclude that alpha-Syn might have important actions on the maintenance of the functional integrity of synaptic transmission and its regulation in hippocampus.
authors.affiliation: Unidad Asociada Neurodeath, UCLM-CSIC, Departamento de Ciencias Médicas, Universidad de Castilla-La Mancha, Avda. de Almansa s/n, 02071, Albacete, Spain.
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Martín
authors.forename: Carmen
authors.initials: C
authors.lastname: González-García
authors.forename: Miguel
authors.initials: M
authors.lastname: Milán
authors.forename: Isabel
authors.initials: I
authors.lastname: Fariñas
authors.forename: Valentín
authors.initials: V
authors.lastname: Ceña
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D004347:Drug Interactions; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D000860:Hypoxia / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D051843:Synucleins; D013779:Tetrodotoxin / Q000494:pharmacology; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D051844:alpha-Synuclein
chemical_list: D000700:Analgesics; D000779:Anesthetics, Local; D009419:Nerve Tissue Proteins; D026902:Potassium Channel Blockers; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein; C053907:8-cyclopentyl-1,3-dimethylxanthine; D013779:Tetrodotoxin; D015761:4-Aminopyridine; D013806:Theophylline; D000241:Adenosine