arXiv subjects

Karin Vadovičová

Publications and source records attributed to Karin Vadovičová.

4 recordsLinked to original sources

arXiv2025

Mechanisms for anesthesia, unawareness, respiratory depression, memory replay and sleep: MHb > IPN > PAG + DRN + MRN > claustrum > cortical slow waves

My findings show what causes loss of awareness, anesthesia, memory replay, opioid induced respiratory depression (OIRD), and slow-wave sleep (SWS). Opiates are fast pain relievers and anesthetics that can cause respiratory arrest. I found how mu-opioids and anesthetics by activating medial habenula (MHb) and/or interpeduncular nucleus (IPN) induce unawareness and slowdown respiration. MHb projects to IPN and both increase their glucose intake during anesthesia (Herkenham, 1981). The question is: What is the MHb-IPN circuit doing? I found that it promotes SWS, memory replay, sharp-wave ripples, spindles, hippocampo-cortical replay, synaptogenesis, rest and recovery, by activating median raphe (MRN) serotonin, and by inhibiting the theta state circuit, new memories encoding, awareness, arousal, alert wakefulness, and REM sleep. It causes also natural slowdown of respiration and heart rate, while it inhibits locomotion and arousal. This extended model adds role of the dentate gyrus>posterior septum>MHb>IPN>MRN>hippocampus + BF + claustrum>cortical slow-waves in memory replay, ripples, loss of awareness, SWS, and anesthesia. It proposes new neural mechanism 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. My 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, socializing, and cognitive flexibility, and attenuate fear, worries, anger, impulsivity, self-defence, and wanting. This model claims that mu-opioids, acetylcholine, nicotine, endocannabinoids, adenosine, GLP-1RA, and substance P activate the MHb-IPN-MRN circuit which promotes rest, recovery, repair, serotonin-BDNF-protein production, spines growth, and anti-inflammatory state.

q-bio.NC↗

arXiv2016

SWS promoting MHb-IPN-MRN circuit opposes the theta promoting circuit, active wake and REM sleep

Hippocampus was by multisynaptic axonal tracts linked to medial habenula in my DTI study. These tracts linked hippocampus to septum, and amygdala to BNST. Septal and BNST axons passed by anteromedial thalamic nucleus to MHb, which projected to pineal gland. Question is what is the MHb doing and why it receives information from hippocampus via septum? This study explores the MHb connectivity, predicts its functional role and how it is linked to memory. Combination of known findings about the septum and MHb connectivity and function led to this circuit-based idea that posterior septum activates MHb, MHb activates IPN,and IPN stimulates MRN and its serotonin release. Proposed idea is that this MHb-IPN-MRN circuit promotes slow wave sleep (SWS), high serotonin and low acetylcholine state. My prediction is that this SWS-promoting circuit reciprocally suppresses the theta oscillations promoting circuit, linked to high acetylcholine levels in brain, and formed by supramamillary area projections to the medial septum (MS) that induces theta rhythm in hippocampus and other theta-coupled regions. The MHb-IPN-MRN pathway likely inhibits, possibly reciprocally,some regions that have stimulating input to the theta-generating SUM and MS, such as the wake promoting nucleus incertus, posterior and lateral hypothalamus and LDT, but also the REM sleep inducing neurons in LDT and PnO. Thus, proposed SWS- promoting circuit attenuates the output of theta-promoting regions, both the active wake-on and REM-on regions. The theta rhythm in wake state is linked to recording and binding information with their spatio-temporal and relational context by hippocampus, while the SWS supports rest and replay of hippocampaly stored information and their cortical reactivations, e. g. in retrosplenial cortex linked to autobiographic memory or in prefrontal cortex that can combine information from any source.

q-bio.NC↗

arXiv2014

Reward and adversity processing circuits, their competition and interactions with dopamine and serotonin signaling

We propose that dACC, AI and caudolateral OFC(clOFC) project to lateral habenula (LHb) and D2 loop of ventral striatum (VS), forming a functional adversity processing circuit, directed towards inhibitory avoidance and self-control. This circuit learns what is bad or harmful to us and predicts risks, to stop us from going/moving for bad or suboptimal choices that decrease our well-being and survival chances. Proposed dACC role is to generate a WARNING signal when things are going (or might end) bad or wrong to prevent negative consequences: pain, harm, loss or failure. The AI signals about bad low aversive qualities, which make us sick or cause discomfort. These cortical inputs activate directly and indirectly (via D2 loop of VS) the LHb, which inhibits dopamine and serotonin release (and is reciprocally inhibited by VTA, DRN) to avoid choosing and doing things leading to harm or loss, but also to make us feel worse, down when overstimulated. We propose that dopamine attenuates the output of the adversity processing circuit, thus decreasing inhibitory avoidance and self-control, while serotonin attenuates dACC, AI, clOFC, D1 loop of VS, LHb, amygdala and pain pathway. Thus, by reciprocal inhibition, by causing dopamine and serotonin suppression - and by being suppressed by them, the adversity processing circuit competes with reward processing circuit for control of choice behaviour and affective states. We propose stimulating effect of dopamine and calming inhibitory effect of serotonin on the active avoidance circuit involving amygdala, linked to threat processing, anger, fear, self-defense and violences. We describe causes and roles of dopamine and serotonin signaling, and mental dysfunctions. We add new idea on vACC role in signaling that we are doing well and in inducing serotonin, when we gain/reach safety, comfort, valuable resources, social/biological rewards, affection or goals.

q-bio.NC↗

arXiv2014

Affective and cognitive prefrontal cortex projections to the lateral habenula in humans

Anterior insula (AI) and dACC are known to process information about pain, loss, adversities, bad, harmful or suboptimal choices and consequences that threaten survival or well-being. Pain and loss activate also pregenual ACC (pgACC), linked to sad thoughts, hurt and regrets. The lateral habenula (LHb) is stimulated by predicted and received pain, discomfort, aversive outcome, loss. Its chronic stimulation makes us feel worse/low and gradually stops us choosing and moving for suboptimal, hurtful or punished choices, by direct and indirect (via RMTg) inhibition of DRN and VTA/SNc. Response selectivity of LHb neurons suggests their cortical input from affective and cognitive evaluative regions that make expectations about bad or suboptimal outcomes. Based on these facts I predicted direct corticohabenular projections from the dACC, pgACC and AI, as part of the adversity processing circuit that learns to avoid bad outcomes by suppressing dopamine and serotonin signal. Using DTI I found dACC, pgACC, AI, adjacent caudolateral and lateral OFC projections to LHb. I predicted no corticohabenular projections from the reward processing regions: medial OFC and vACC because both respond most strongly to good, high value stimuli and outcomes, inducing serotonin and dopamine release respectively. This lack of LHb projections was confirmed for vACC and likely for mOFC. The surprising findings were the corticohabenular projections from the cognitive prefrontal cortex regions, known for flexible reasoning, planning and combining whatever information are relevant for reaching current goals. I propose that prefrontohabenular projections provide a teaching signal for value-based choice behaviour, to learn to deselect, avoid or inhibit the potentially harmful, low valued or wrong choices, goals, strategies, predictions, models and ways of doing things, to prevent bad or suboptimal consequences.

q-bio.NC↗