Developmental changes in glutamatergic fast synaptic neurotransmission in the dorsal subcoeruleus nucleus

Sleep. 2012 Mar 1;35(3):407-17. doi: 10.5665/sleep.1706.


Study objectives: The dorsal subcoeruleus nucleus (SubCD) is involved in the generation of rapid eye movement sleep (REM), a state distinguished by high-frequency EEG activity, muscle atonia, and ponto-geniculo-occipital (PGO) waves. Activation of the SubCD by injection of the glutamate (GLU) receptor agonist kainic acid (KA) produced a REM sleep-like state with muscle atonia. We tested the hypothesis that developmental changes in the GLU excitability of SubCD neurons could underlie the developmental decrease in REM sleep that occurs in the rat from postnatal days 10-30.

Design: Sagittal sections containing the SubCD were cut using 9-15 day old rat pups. Whole-cell patch clamp recordings were performed on SubCD neurons and responses were measured following electrical stimulation or bath application of the GLU receptor agonists N-methyl-D-aspartic acid (NMDA) or KA.

Measurements and results: Pharmacological or electrical stimulation increased non-cholinergic excitatory postsynaptic currents (EPSCs) in SubCD neurons, which were blocked by GLU receptor antagonists. Although no developmental changes were observed in the relative contribution of AMPA/KA and NMDA receptors to the responses, there was a developmental decrease in the half-width duration of both evoked and miniature EPSCs. Bath application of NMDA or KA revealed a developmental decrease in the direct response of SubCD neurons to these agonists.

Conclusions: The SubCD receives glutamatergic input, which may be involved in activation of SubCD neurons during REM sleep. A developmental decrease in the glutamatergic excitability of these neurons could underlie the developmental decrease in REM sleep observed in humans and rodents.

Keywords: Arousal; NMDA; development; dorsal subcoeruleus nucleus; glutamate; kainic acid; rapid eye movement sleep.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Culture Techniques
  • Electric Stimulation
  • Excitatory Amino Acid Agonists / pharmacology*
  • Kainic Acid / pharmacology
  • Locus Coeruleus / growth & development*
  • Locus Coeruleus / pathology
  • Locus Coeruleus / physiopathology
  • N-Methylaspartate / pharmacology
  • Neurons / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sleep, REM / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Thalamus / growth & development*
  • Thalamus / pathology
  • Thalamus / physiopathology


  • Excitatory Amino Acid Agonists
  • N-Methylaspartate
  • Kainic Acid