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Continuous pontine cholinergic microinfusion via mini-pump induces sustained alterations in rapid eye movement (REM)
Abstract:
Although there is much evidence that single microinjections of cholinomimetics into the pontine reticular formation (PRF) evokes rapid eye movement sleep (REMS), no study has yet demonstrated whether protracted manipulations of PRF cholinergic levels can produce sustained alteration of this sleep state. In this study, in rats, an indwelling, chronically implanted osmotic mini-pump was used to infuse carbachol, scopolamine, or saline solutions into various brainstem regions or the fourth ventricle for a period of five consecutive days. Throughout the period of pump operation, carbachol infusions chiefly in the PRF produced sustained REMS augmentation primarily during the night cycle, whereas scopolamine produced a sustained decrease in REMS primarily during the day cycle. The findings provide considerable support for a PRF cholinergic hypothesis of REMS generation and regulation and suggest that the alterations in REMS result from a muscarinic receptor mediated change in PRF neuronal activity.
Insights
Protracted infusions of carbachol into the pontine reticular formation (PRF) sustained REM sleep, while scopolamine decreased it. This supports a cholinergic mechanism in the PRF for REM sleep regulation.
Area of Science:
- Neuroscience
- Sleep Science
- Cholinergic Systems
Background:
- Single microinjections of cholinomimetics into the pontine reticular formation (PRF) are known to evoke rapid eye movement sleep (REMS).
- However, the effects of sustained alterations in PRF cholinergic levels on REMS regulation remain largely unexplored.
Purpose of the Study:
- To investigate whether protracted manipulation of cholinergic activity in the PRF can induce sustained changes in REMS.
Main Methods:
- Rats were infused with carbachol, scopolamine, or saline via chronically implanted osmotic mini-pumps for five consecutive days.
- Infusions targeted various brainstem regions, including the PRF, and the fourth ventricle.
Main Results:
- Continuous carbachol infusion, primarily in the PRF, led to a sustained increase in REMS, particularly during the night.
- Conversely, scopolamine infusion resulted in a sustained decrease in REMS, predominantly during the day.
Conclusions:
- These findings strongly support the hypothesis that cholinergic mechanisms within the PRF are crucial for the generation and regulation of REMS.
- The observed alterations in REMS are likely mediated by changes in PRF neuronal activity via muscarinic receptors.