PMID:15579163

Citation	Martín, ED, González-García, C, Milán, M, Fariñas, I and Ceña, V (2004) Stressor-related impairment of synaptic transmission in hippocampal slices from alpha-synuclein knockout mice. Eur. J. Neurosci. 20:3085-91
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.
Links	PubMed Online version:10.1111/j.1460-9568.2004.03801.x
Keywords	4-Aminopyridine/pharmacology; Adenosine/pharmacology; Analgesics/pharmacology; Anesthetics, Local/pharmacology; Animals; Anoxia/genetics; Anoxia/physiopathology; Anoxia/prevention & control; Blotting, Western/methods; Drug Interactions; Excitatory Postsynaptic Potentials/drug effects; Hippocampus/cytology; Hippocampus/drug effects; Mice; Mice, Knockout; Nerve Tissue Proteins/deficiency; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurons/drug effects; Neurons/physiology; Potassium Channel Blockers/pharmacology; Synaptic Transmission/drug effects; Synaptic Transmission/physiology; Synucleins; Tetrodotoxin/pharmacology; Theophylline/administration & dosage; Theophylline/analogs & derivatives; Time Factors; alpha-Synuclein
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