• 4-aminopyridine;
  • adenosine;
  • hypoxia;
  • Parkinson's disease;
  • synaptic plasticity


The role of alpha-synuclein (α-Syn) has recently received considerable attention because it seems to play a role in Parkinson's disease (PD). Missense mutations in the α-Syn gene were found in autosomal dominant PD and α-Syn was shown to be a major constituent of protein aggregates in sporadic PD and other synucleinopathies. Under normal conditions, α-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 α-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 α-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 α-Syn knockout than in wild-type mice, further supporting the hypothesis of regulation of synaptic transmission by α-Syn. Together, these observations indicate that the loss of α-Syn reduces synaptic efficacy when the probability of transmitter release is modified. We conclude that α-Syn might have important actions on the maintenance of the functional integrity of synaptic transmission and its regulation in hippocampus.