A subthreshold synaptic mechanism regulating BDNF expression and resting synaptic strength

Recent studies have demonstrated that protein translation can be regulated by spontaneous excitatory neurotransmission. However, the impact of spontaneous neurotransmitter release on gene transcription remains unclear. Here, we study the effects of the balance between inhibitory and excitatory spontaneous neurotransmission on brain-derived neurotrophic factor (BDNF) regulation and synaptic plasticity. Blockade of spontaneous inhibitory events leads to an increase in the transcription of Bdnf and Npas4 through altered synaptic calcium signaling, which can be blocked by antagonism of NMDA receptors (NMDARs) or L-type voltage-gated calcium channels (VGCCs). Transcription is bidirectionally altered by manipulating spontaneous inhibitory, but not excitatory, currents. Moreover, blocking spontaneous inhibitory events leads to multiplicative downscaling of excitatory synaptic strength in a manner that is dependent on both transcription and BDNF signaling. These results reveal a role for spontaneous inhibitory neurotransmission in BDNF signaling that sets excitatory synaptic strength at rest.

Automated summary

Recent studies have shown that protein translation can be regulated by spontaneous excitatory neurotransmission, while the impact of spontaneous neurotransmitter release on gene transcription remains unclear. Blocking spontaneous inhibitory events increases the transcription of BDNF and Npas4 through altered synaptic calcium signaling, which can be prevented by antagonism of NMDA receptors or L-type voltage-gated calcium channels. Transcription can be bidirectionally altered by manipulating spontaneous inhibitory, but not excitatory, currents. Moreover, blocking spontaneous inhibitory events results in multiplicative downscaling of excitatory synaptic strength, dependent on transcription and BDNF signaling. These findings highlight the role of spontaneous inhibitory neurotransmission in setting excitatory synaptic strength at rest.