Correlation of miniature synaptic activity and evoked release probability in cultures of cortical neurons

Spontaneous miniature synaptic activity is caused by action potential (AP)- independent release of transmitter vesicles and is regulated at the level o f single synapses. In cultured cortical neurons we have used this spontaneo us vesicle turnover to load the styryl dye FM1-43 into synapses with high r ates of miniature synaptic activity. Automated selection procedures restric ted analysis to synapses with sufficient levels of miniature activity-media ted FM1-43 uptake. After FM1-43 loading, vesicular FM1-43 release in respon se to AP stimulation was recorded at single synapses as a measure of releas e probability. We find that synapses with high rates of miniature activity possess significantly enhanced evoked release rates compared with a control population. Because the difference in release rates between the two popula tions is [Ca2+](o)-dependent, it is most likely caused by a difference in r elease probability. Within the subpopulation of synapses with high miniatur e activity, we find that the probabilities for miniature and AP-evoked rele ase are correlated at single synaptic sites. Furthermore, the degree of min iature synaptic activity is correlated with the vesicle pool size. These fi ndings suggest that both evoked and miniature vesicular release are regulat ed in parallel and that the frequency of miniature synaptic activity can be used as an indicator for evoked release efficacy.