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 studied the effects of the balance between inhibitory and excitatory spontaneous neurotransmission on BDNF regulation and synaptic plasticity. Blockade of spontaneous inhibitory events led to an increase in the transcription of Bdnf and Npas4 through altered synaptic calcium signaling, which could be blocked by antagonism of NMDARs or L-type VGCCs. Transcription was bidirectionally altered by manipulating spontaneous inhibitory, but not excitatory, currents. Moreover, blocking spontaneous inhibitory events led to multiplicative downscaling of excitatory synaptic strength in a manner that was 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.