Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.15.098400v1?rss=1 Authors: Louth, E. L., Jorgensen, R. L., Korshoj, A. R., Sorensen, J. C. H., Capogna, M. Abstract: Synapses in the cerebral cortex constantly change and this dynamic property, together with the action of neuromodulators such as dopamine (DA), is essential for reward learning and memory. DA modulates spike-timing-dependent plasticity (STDP), a cellular model of learning and memory, in juvenile rodent cortical neurons. However, it is unknown whether this neuromodulation also occurs at excitatory synapses of cortical neurons in mature adult mice or in humans. Cortical layer V pyramidal neurons were recorded with whole cell patch clamp electrophysiology and an extracellular stimulating electrode was used to induce STDP. DA was either pharmacologically applied or optogenetically released in slices from mice. Classical STDP induction protocols triggered non-Hebbian excitatory synaptic depression or no plasticity at mouse or human cortical synapses, respectively. DA reverted long term synaptic depression to baseline or elicited long term synaptic potentiation at mouse or human cortical synapses, respectively. Furthermore, when DA was applied during a STDP protocol it depressed presynaptic inhibition in the mouse but not in the human cortex. The data demonstrate that DA gates excitatory synaptic plasticity at mature adult human cortical excitatory synapses showing unique features that differ from the DA modulation observed in cortical synapses from mature adult mice. Our finding that DA can trigger long term synaptic potentiation of cortical excitatory synapses of humans strengthens the importance of this neuromodulator in gating cognitive processes. This result may inform on therapeutic interventions to recover brain function in learning and memory diseases. Copy rights belong to original authors. Visit the link for more info