Journal of Neuroscience, Vol 15, 3500-3508, Copyright © 1995 by Society for Neuroscience
Time course of Fos-like immunoreactivity associated with cholinergically induced REM sleep
PJ Shiromani, M Malik, S Winston and RW McCarley
VA Medical Center, Brockton, Massachusetts 02401, USA.
Now that the pharmacology and neuronal connectivity underlying REM sleep is
beginning to be understood, it is important to begin investigations that
elucidate the transcriptional response related to the REM sleep process.
The present study focuses on determining the temporal development of
Fos-like immunoreactivity (Fos-LI) in the dorsolateral pons following
cholinergically induced, sustained rapid eye movement (REMc) sleep in cats.
Microinjections (0.25 microliter) of vehicle (n = 3) or carbachol (0.2-4.0
micrograms/0.25 microliters) were made into the medial pontine reticular
formation. Carbachol produced a state with all the signs of natural REM
sleep, and with durations from 0 min to 120 min. Animals were killed either
immediately or at various intervals after the end of REMc. Compared to
vehicle- and carbachol- treated animals without REMc, the animals with REMc
showed a significantly higher number of Fos-LI cells in pontine regions
that have been implicated in REM sleep generation. Regions with REMc-
associated Fos-LI increases included the lateral dorsal tegmental (LDT) and
pedunculopontine tegmental (PPT) nuclei; the locus coeruleus; the dorsal
raphe; and the medial pontine reticular formation. More Fos-LI cells were
found with longer REMc bouts than with shorter-duration REMc bouts.
However, with 2 hr long REMc bouts the number of Fos-LI cells returned to
control levels, suggesting that the c-fos transcriptional cascade is turned
off once a threshold of REMc has been reached. These findings indicate that
pontine neuronal populations implicated in REM sleep express more c-fos in
the course of REMc, and that the extent of expression is related to the
duration of the state.
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