Topoisomerases are enzymes that resolve DNA supercoiling during cell division and gene transcription. Inhibitors of these enzymes are used to treat multiple forms of cancer. Recently we found that topoisomerase inhibitors have profound effects on synaptic genes expressed in the brain. Here we examine the contribution of a clinically used topoisomerase inhibitor on the expression of synaptic proteins and synaptic transmission. We find that inhibition of topoisomerase 1 (TOP1) dampens excitatory and inhibitory synaptic transmission in cortical neurons. Additionally, these effects are fully reversible, because synaptic protein levels and synaptic transmission recover upon washout of the TOP1 inhibitor. These findings provide insights into how inhibition of TOP1 impacts synaptic function in neurons
