(A) Driving 3 Hz bursting of CA1 neurons stimulates MEF2A/D -dependent transcriptional activation through a Ca2 +influx through L-type voltage-gated Ca2+ channels (VGCCs). Bursting-activated MEF2A/D induces Arc mRNA, as well as other target genes, that function together to silence excitatory synapses through selective depression of AMPAR-mediated synaptic transmission. Based on results from Elmer et al., (Elmer et al., 2013) this may be through synaptic removal of GluA1-containing AMPARs. (B) Chronic (24 hr) bursting depresses both AMPA and NMDAR-mediated synaptic transmission and eliminates spines through activation of L-type VGCCs, transcription (Goold and Nicoll, 2010), translation, and Arc, but independent of MEF2A/D. Other activity-dependent transcription factors may contribute Arc expression and synapse elimination in response to chronic bursting activity.