References
Query Results -- Details
MGI Accession ID: MGI:3603698
J Number: J:101275
Other Accession IDs:
Title: Stressor-related impairment of synaptic transmission in hippocampal slices from alpha-synuclein knockout mice.
Authors: Martin ED; Gonzalez-Garcia C; Milan M; Farinas I; Cena V
Journal: Eur J Neurosci
Volume: 20
Issue: 11
Date: 2004 Dec
Year: 2004
Pages: 3085-91
Review Status: Peer Reviewed
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.
Additional Information:
