Cellular mechanisms of brain state-dependent gain modulation in visual cortex

Nat Neurosci. 2013 Sep;16(9):1331-9. doi: 10.1038/nn.3464. Epub 2013 Jul 21.


Visual cortical neurons fire at higher rates to visual stimuli during locomotion than during immobility, while maintaining orientation selectivity. The mechanisms underlying this change in gain are not understood. We performed whole-cell recordings from layer 2/3 and layer 4 visual cortical excitatory neurons and from parvalbumin-positive and somatostatin-positive inhibitory neurons in mice that were free to rest or run on a spherical treadmill. We found that the membrane potential of all cell types became more depolarized and (with the exception of somatostatin-positive interneurons) less variable during locomotion. Cholinergic input was essential for maintaining the unimodal membrane potential distribution during immobility, whereas noradrenergic input was necessary for the tonic depolarization associated with locomotion. Our results provide a mechanism for how neuromodulation controls the gain and signal-to-noise ratio of visual cortical neurons during changes in the state of vigilance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • DNA-Binding Proteins / genetics
  • Female
  • Immobilization
  • Locomotion / drug effects
  • Locomotion / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Neurological*
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurotransmitter Agents / pharmacology
  • Orientation / drug effects
  • Orientation / physiology*
  • Orientation / radiation effects
  • Parvalbumins / genetics
  • Patch-Clamp Techniques
  • Photic Stimulation
  • Signal-To-Noise Ratio
  • Transcription Factors / genetics
  • Visual Cortex / cytology*
  • Visual Cortex / physiology
  • Visual Pathways / physiology*


  • DNA-Binding Proteins
  • Grhl3 protein, mouse
  • Neurotransmitter Agents
  • Parvalbumins
  • Transcription Factors