Separable gain control of ongoing and evoked activity in the visual cortex by serotonergic input

Elife. 2020 Apr 7;9:e53552. doi: 10.7554/eLife.53552.


Controlling gain of cortical activity is essential to modulate weights between internal ongoing communication and external sensory drive. Here, we show that serotonergic input has separable suppressive effects on the gain of ongoing and evoked visual activity. We combined optogenetic stimulation of the dorsal raphe nucleus (DRN) with wide-field calcium imaging, extracellular recordings, and iontophoresis of serotonin (5-HT) receptor antagonists in the mouse visual cortex. 5-HT1A receptors promote divisive suppression of spontaneous activity, while 5-HT2A receptors act divisively on visual response gain and largely account for normalization of population responses over a range of visual contrasts in awake and anesthetized states. Thus, 5-HT input provides balanced but distinct suppressive effects on ongoing and evoked activity components across neuronal populations. Imbalanced 5-HT1A/2A activation, either through receptor-specific drug intake, genetically predisposed irregular 5-HT receptor density, or change in sensory bombardment may enhance internal broadcasts and reduce sensory drive and vice versa.

Keywords: calcium imaging; contrast normalization; integration of cortical activity; mouse; neuroscience; ongoing activity; optogenetics; serotonergic receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Dorsal Raphe Nucleus / drug effects
  • Dorsal Raphe Nucleus / physiology*
  • Light
  • Longitudinal Studies
  • Mice
  • Mice, Transgenic
  • Optogenetics / methods*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology
  • Serotonergic Neurons / physiology*
  • Serotonin / physiology
  • Serotonin Antagonists / administration & dosage
  • Visual Cortex / drug effects
  • Visual Cortex / physiology*


  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin

Associated data

  • Dryad/10.5061/dryad.931zcrjgk