PT - JOURNAL ARTICLE AU - Zohre Azimi AU - Katharina Spoida AU - Ruxandra Barzan AU - Patric Wollenweber AU - Melanie D. Mark AU - Stefan Herlitze AU - Dirk Jancke TI - Subtraction and division of visual cortical population responses by the serotonergic system AID - 10.1101/444943 DP - 2018 Jan 01 TA - bioRxiv PG - 444943 4099 - http://biorxiv.org/content/early/2018/10/16/444943.short 4100 - http://biorxiv.org/content/early/2018/10/16/444943.full AB - Normalization is a fundamental operation throughout neuronal systems to adjust dynamic range. In the visual cortex various cell circuits have been identified that provide the substrate for such a canonical function, but how these circuits are orchestrated remains unclear. Here we suggest the serotonergic (5-HT) system as another player involved in normalization. 5-HT receptors of different classes are co-distributed across different cortical cell types, but their individual contribution to cortical population responses is unknown. We combined wide-field calcium imaging of primary visual cortex (V1) with optogenetic stimulation of 5-HT neurons in mice dorsal raphe nucleus (DRN) — the major hub for widespread release of serotonin across cortex — in combination with selective 5-HT receptor blockers. While inhibitory (5-HT1A) receptors accounted for subtractive suppression of spontaneous activity, depolarizing (5-HT2A) receptors promoted divisive suppression of response gain. Added linearly, these components led to normalization of population responses over a range of visual contrasts.