Abstract
NMDA receptor (NMDAR) activation is critical for maintenance and modification of synapse strength. Specifically, NMDAR activation by spontaneous glutamate release has been shown to mediate some forms of synaptic plasticity as well as synaptic development. Interestingly, there is evidence that within individual synapses each release mode may be segregated such that postsynaptically there are distinct pools of responsive receptors. To examine potential regulators of NMDAR activation because of spontaneous glutamate release in cultured hippocampal neurons, we used GCaMP6f imaging at single synapses in concert with confocal and super-resolution imaging. Using these single-spine approaches, we found that Ca2+ entry activated by spontaneous release tends to be carried by GluN2B-NMDARs. Additionally, the amount of NMDAR activation varies greatly both between synapses and within synapses, and is unrelated to spine and synapse size, but does correlate loosely with synapse distance from the soma. Despite the critical role of spontaneous activation of NMDARs in maintaining synaptic function, their activation seems to be controlled factors other than synapse size or synapse distance from the soma. It is most likely that NMDAR activation by spontaneous release influenced variability in subsynaptic receptor position, release site position, vesicle content, and channel properties. Therefore, spontaneous activation of NMDARs appears to be regulated distinctly from other receptor types, notably AMPARs, within individual synapses.
Footnotes
The authors declare no competing financial interests.
This work was supported by F31-MH105105 and T32-GM008181 to S.R.M., R01-MH080046 and NS090644 to T.A.B. We thank Sai Sachin Divakaruni, Aaron Levy, and other members of the Blanpied Laboratory for helpful discussion, and Minerva Contreras for invaluable technical assistance.
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