Mechanisms for anesthesia, unawareness, respiratory arrest, memory replay and sleep: MHb→IPN→PAG + DRN + MRN→claustrum→slow-waves.

Opiates are fast pain relievers and anesthetics that can cause respiratory arrest.I show new mechanisms of how mu-opioids and high prenatal nicotine cause respiratory slowdownlinked to slow-wave sleep (SWS): mu-opioids activate medial habenula which activates theinterpeduncular nucleus. This MHb-IPN system decreases respiration and alarm/arousal response tohypercapnia through projections to PAG, DRN, MRN, and LPO→RMTg→vPAG.The natural slowdown of respiration and heart rate is caused by SWS when the body is not moving.The MHb and rostromedial tegmental nucleus are known for dense mu-opioid receptors. Bothregions were claimed to be activated in SWS, together with the MHb→IPN→MRN circuit, thatactivates serotonin release, promotes SWS, rest, immune defense, recovery, sharp-wave ripples,cortical ripples, replay of temporally, spatially, and relationally bound information, synaptogenesisand BDNF linked growth, but inhibits theta states, encoding of new memories, arousal, alertwakefulness, awareness and REM sleep linked circuits (Vadovičová, 2015).My extended neural model proposes new mechanisms for anesthesia and loss of awareness byactivating cortical slow-wave activity (SWA) through MHb→IPN→MRN→ claustrum circuit. Itshows also how the dentate gyrus→triangular septum→MHb→IPN→MRN→ hippocampus +claustrum→SWA circuit induces memory replay/consolidation. This work proposes newmechanisms for anesthetic ketamine and phencyclidine effects: activation of the IPN→ MRN→claustrum→ cortical SWA circuit by the 5-HT2a receptors in IPN and claustrum. It also shows whyare ketamine and psychedelics anxiolytic and antidepressant. How they through activating the 5-HT2a receptors in the vACC/infralimbic cortex, increase safety, well-being, rest, and cognitiveflexibility, and attenuate fear, worries, threat, wanting, and impulsivity.