title: Interleukin-1 inhibits putative cholinergic neurons in vitro and REM sleep when microinjected into the rat laterodorsal tegmental nucleus.
abstract: OBJECTIVE
  REM sleep is suppressed during infection, an effect mimicked by the administration of cytokines such as interleukin-1 (IL-1). In spite of this observation, brain sites and neurochemical systems mediating IL-1-induced suppression of REM sleep have not been identified. Cholinergic neurons in the brainstem laterodorsal tegmental nucleus (LDT) are part of the neuronal circuitry responsible for REM sleep generation. Since IL-1 inhibits acetylcholine synthesis and release, the aim of this study was to test the two different, but related hypotheses. We hypothesized that IL-1 inhibits LDT cholinergic neurons, and that, as a result of this inhibition, IL-1 suppresses REM sleep.
  To test these hypotheses, the electrophysiological activity of putative cholinergic LDT neurons was recorded in a rat brainstem slice preparation. Interleukin-1 significantly inhibited the firing rate of 76% of recorded putative cholinergic LDT neurons and reduced the amplitude of glutamatergic evoked potentials in 60% of recorded neurons. When IL-1 (1 ng) was microinjected into the LDT of freely behaving rats, REM sleep was reduced by about 50% (from 12.7% +/- 1.5% of recording time [after vehicle] to 6.1% +/- 1.4% following IL-1 administration) during post-injection hours 3-4.
  
  
  CONCLUSIONS
  Results of this study support the hypothesis that IL-1 can suppress REM sleep by acting at the level of the LDT nucleus. Furthermore this effect may result from the inhibition of evoked glutamatergic responses and of spontaneous firing of putative cholinergic LDT neurons.
authors.affiliation: Department of Human Physiology, University of Milan Medical School, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Brambilla
authors.forename: Isabella
authors.initials: I
authors.lastname: Barajon
authors.forename: Susanna
authors.initials: S
authors.lastname: Bianchi
authors.forename: Mark R
authors.initials: MR
authors.lastname: Opp
authors.forename: Luca
authors.initials: L
authors.lastname: Imeri
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D000109:Acetylcholine