Mechanisms for anesthesia, unawareness, OIRD, sleep and memory replay: MHb→IPN→ PAG + DRN + MRN→claustrum→ slow-waves.
May 26, 2025 DOI: 10.14293/pr2199.000799.v9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper |
|---|---|
| Key points | Argues that the medial habenula-interpeduncular nucleus circuit, projecting to the median and dorsal raphe, periaqueductal gray, and other regions, drives slow wave sleep, memory replay, rest, and recovery while suppressing respiration, arousal, awareness, and new memory encoding. Proposes that activation of this circuit via 5-HT2a receptors in the IPN and claustrum underlies ketamine, nitrous oxide, and phencyclidine anesthesia, and that mu-opioids and other MHb activators promote a serotonin-BDNF-linked restorative state. |
Abstract
My findings show, for the first time, what causes loss of awareness, anesthesia, memory replay, opioids induced respiratory depression (OIRD), and slow wave sleep. Opiates are fast pain relievers and anesthetics that can cause respiratory arrest. I found how mu-opioids and other medial habenula activators slowdown respiration during SWS and anesthesia. Using DTI method I observed that human hippocampus is connected to MHb via posterior septum, while amygdala via anteromedial BNST. MHb projected to pineal gland and contralateral MHb (Vadovičová, 2014). MHb has dense mu-opioids receptors (Gardon and Faget, 2014) and strong projections to IPN. Herkenham (1981) found that MHb and IPN increase their glucose intake during anesthesia. The IPN projects to serotonergic MRN and DRN, and pain/interoception/arousal linked PAG. The question is: What is the MHb-IPN circuit doing? I found how it causes SWS, memory replay, rest and recovery, and decreases respiration and alarm/arousal response through projections to PAG, DRN, MRN, and RMTg. I claimed that MHb-IPN system activates MRN serotonin, promotes sharp-wave ripples, hippocampo-cortical replay of temporally, spatially and relationally bound information, cortical ripples and spindles, repair, synaptogenesis, and serotonin-BDNF-linked growth, but inhibits theta states, encoding of new memories, dopaminergic and noradrenergic nuclei, arousal, alert wakefulness, awareness, REM sleep, and linked circuits (Vadovičová, 2015). Natural slowdown of respiration and heart rate is caused by SWS circuit while it inhibits locomotion and arousal. This extended circuit model explains role of the dentate gyrus→posterior septum→MHb→IPN →MRN→hippocampus + claustrum→cortical slow-wave activity (SWA) in memory replay, loss of awareness, anesthesia and SWS. It proposes new neural mechanisms for anesthetic ketamine, nitrous oxide, and phencyclidine effects: activation of the IPN→MRN→claustrum→cortical SWA circuit by the 5-HT2a receptors in the IPN and claustrum. This brain/circuit model shows why are ketamine and psychedelics anxiolytic and antidepressant. How they by activating the 5-HT2a receptors in vACC/infralimbic cortex increase safety, well-being signal, rest and cognitive flexibility, and attenuate fear, worries, anger, impulsivity, self-defence and wanting. This model suggests that mu-opioids, acetylcholine, nicotine, cannabinoids, adenosine, GLP-1RA, neuropeptide Y, and substance P activate the MHb-IPN-MRN circuit which promotes rest, recovery, repair, serotonin→BDNF→proteins production, spines/synapses growth, anti-inflammatory, and growth-linked state.