The distribution of observed frequencies for spontaneous responses shows clustering around a mean rate of 0.78 events / ROI / minute (Figure 2B).
(A) Example results from an experiment where each mark is a single response from one of the 50 ROI’s.Marks are scattered randomly in the y axis to facilitate visualization of responses that overlap in time.Each image is a maximum intensity projection – average intensity projection for an 8 min recording both with (right) and without (left) the ROI selections.(B) Example images showing a section of dendrite (gray outline) during baseline fluorescence, peak fluorescence of a spontaneous event, and peak fluorescence of stimulus evoked events. (C) Example traces from a GCamp6f-PSD95 puncta before and after AP5 treatment.However, it is still unclear how this separation of NMDA receptors is distributed across individual synapses.
In a previous paper (Reese and Kavalali, 2015) we showed that NMDA receptor mediated spontaneous transmission signals to the postsynaptic protein translation machinery through Ca release.
More recent experiments in the Drosophila neuromuscular junction have come to mixed conclusions about the propensity of a single active zone to participate in both evoked and spontaneous transmission; finding either considerable overlap, but with a population of spontaneous only active zones or limited overlap with a negative correlation between the two modes of transmission (Melom et al., 2013; Peled et al., 2014).
To date, no such measurement has been made in mammalian synapses.
Previous studies by our group and others have shown that spontaneous neurotransmission is critical in the homeostatic regulation of synaptic strength and this regulation may have implications for the efficacy of rapidly acting antidepressants (Nosyreva et al., 2013; Gideons et al., 2014; Sutton et al., 2006).
In particular, our recent work has shown that the Ca transients — and in turn activates postsynaptic signaling — but it remains unclear if these transients are generated at the same synapses that participate in evoked release.
Under these conditions we detected spontaneous and evoked response rates consistent with earlier estimates of evoked and spontaneous release probabilities at single synapses (Murthy et al., 1997; Leitz and Kavalali, 2011, 2014).