Silencing of Cholinergic Basal Forebrain Neurons Using Archaerhodopsin Prolongs Slow-Wave Sleep in Mice

PLoS One. 2015 Jul 7;10(7):e0130130. doi: 10.1371/journal.pone.0130130. eCollection 2015.

Abstract

The basal forebrain (BF) plays a crucial role in cortical activation. Our previous study showed that activation of cholinergic BF neurons alone is sufficient to suppress slow-wave sleep (SWS) and promote wakefulness and rapid-eye-movement (REM) sleep. However, the exact role of silencing cholinergic BF neurons in the sleep-wake cycle remains unclear. We inhibitied the cholinergic BF neurons genetically targeted with archaerhodopsin (Arch) with yellow light to clarify the role of cholinergic BF neurons in the sleep-wake cycle. Bilateral inactivation of cholinergic BF neurons genetically targeted with archaerhodopsin prolonged SWS and decreased the probability of awakening from SWS in mice. However, silencing these neurons changed neither the duration of wakefulness or REM sleep, nor the probability of transitions to other sleep-wake episodes from wakefulness or REM sleep. Furthermore, silencing these neurons for 6 h within the inactive or active period increased the duration of SWS at the expense of the duration of wakefulness, as well as increasing the number of prolonged SWS episodes (120-240 s). The lost wakefulness was compensated by a delayed increase of wakefulness, so the total duration of SWS and wakefulness during 24 h was kept stable. Our results indicate that the main effect of these neurons is to terminate SWS, whereas wakefulness or REM sleep may be determined by co-operation of the cholinergic BF neurons with other arousal-sleep control systems.

MeSH terms

  • Animals
  • Archaeal Proteins / pharmacology*
  • Basal Forebrain / physiopathology*
  • Cholinergic Neurons / drug effects*
  • Cholinergic Neurons / physiology
  • Cholinergic Neurons / radiation effects
  • Electromyography
  • Electrophysiological Phenomena
  • Immunohistochemistry
  • Light
  • Mice
  • Mice, Transgenic
  • Sleep Stages / physiology*
  • Sleep, REM / physiology
  • Wakefulness / physiology

Substances

  • Archaeal Proteins
  • archaerhodopsin protein, Archaea

Grant support

The authors have no funding or support to report.