Tetrodotoxin inactivation of pontine regions: influence on sleep-wake states

Brain Res. 2005 May 17;1044(1):42-50. doi: 10.1016/j.brainres.2005.02.079. Epub 2005 Apr 8.


Studies using various methodologies have implicated n. reticularis pontis oralis (RPO) and n. subcoeruleus (SubC) in the generation of rapid eye movement sleep (REM). In rats, electrolytic lesions in these regions may give rise to the phenomenon of REM without atonia (REM-A), in which the electrophysiological features of REM are normal except that atonia is absent and elaborate behaviors may be exhibited. However, electrolytic lesions damage both cell bodies and fibers of passage, and the neural reorganization and adaptation that can occur post-lesion can complicate interpretation. Tetrodotoxin (TTX) is a sodium channel blocker that temporarily inactivates both neurons and fibers of passage and thus may be functionally equivalent to an electrolytic lesion, but without allowing time for neural adaptation. In this study, we examined the influence of microinjections of TTX into RPO and SubC on sleep in freely behaving rats. Rats (90 day old male Sprague-Dawley) were implanted with electrodes for recording EEG and EMG. Guide cannulae were implanted aimed into RPO or SubC. Each animal received one unilateral microinjection (TTXUH: 5.0 ng/0.2 microl) and two bilateral microinjections (TTXBL: 2.5 ng/0.1 microl; TTXBH: 5.0 ng/0.2 microl) of TTX, and control microinjections of saline alone (SAL). The injections were made 2 h following lights on, and sleep was recorded for the subsequent 22 h. Sleep was scored from computerized records in 10 s epochs. Recordings from the 10-h light period and the 12-h dark period were examined separately. TTX inactivation of RPO could decrease REM and non-REM (NREM), whereas inactivation of SubC produced relatively more specific decreases in REM with smaller effects on NREM. The results complement studies that have implicated RPO and SubC in REM generation. REM-A was not observed, suggesting that REM-A is a complex phenomenon that requires time for reorganization of the nervous system after insult.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Dose-Response Relationship, Drug
  • Functional Laterality
  • Male
  • Microinjections / methods
  • Pons / anatomy & histology
  • Pons / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Sleep / drug effects*
  • Sleep / physiology
  • Sleep, REM / drug effects
  • Sodium Channel Blockers / pharmacology*
  • Tetrodotoxin / pharmacology*
  • Wakefulness / drug effects*
  • Wakefulness / physiology


  • Sodium Channel Blockers
  • Tetrodotoxin