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A pressure-reversible cellular mechanism of general anesthetics capable of altering a possible mechanism for consciousness.

Vadakkan KI - Springerplus (2015)

Bottom Line: Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines.The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia.The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurology, Department of Medicine, University of Toronto, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Room A4-08, Toronto, ON M4N 3M5 Canada.

ABSTRACT
Different anesthetics are known to modulate different types of membrane-bound receptors. Their common mechanism of action is expected to alter the mechanism for consciousness. Consciousness is hypothesized as the integral of all the units of internal sensations induced by reactivation of inter-postsynaptic membrane functional LINKs during mechanisms that lead to oscillating potentials. The thermodynamics of the spontaneous lateral curvature of lipid membranes induced by lipophilic anesthetics can lead to the formation of non-specific inter-postsynaptic membrane functional LINKs by different mechanisms. These include direct membrane contact by excluding the inter-membrane hydrophilic region and readily reversible partial membrane hemifusion. The constant reorganization of the lipid membranes at the lateral edges of the postsynaptic terminals (dendritic spines) resulting from AMPA receptor-subunit vesicle exocytosis and endocytosis can favor the effect of anesthetic molecules on lipid membranes at this location. Induction of a large number of non-specific LINKs can alter the conformation of the integral of the units of internal sensations that maintain consciousness. Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines. Externally applied pressure can transduce from the middle ear through the perilymph, cerebrospinal fluid, and the recently discovered glymphatic pathway to the extracellular matrix space, and finally to the paravenular space. The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia. Changes in membrane composition and the conversion of membrane hemifusion to fusion due to defects in the checkpoint mechanisms can lead to cytoplasmic content mixing between neurons and cause neurodegenerative changes. The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics.

No MeSH data available.


Related in: MedlinePlus

Formation of C-semblance for consciousness and the role of oscillating potentials. Spontaneous activity occurring during events such as dendritic spikes occurring at the islets of inter-LINKed postsynapses (IILPS) can lead to semblance at all the postsynapses that are activated thorough the LINKs (in the absence of arrival of activity from their presynaptic terminals). In addition, reactivation of large number of scattered single inter-postsynaptic functional LINKs (B–D) within the cortices also induce semblances. Background sensory stimuli both from within the body (respiration and heart beat) and from the environment reactivate several inter-postsynaptic functional LINKs and also induce semblances. The net result of all the semblances induced at the postsynapses lead to C-semblance for consciousness. C-semblance is a function of (a) the reactivated inter-postsynaptic LINKs that in turn is a function of existing innate inter-postsynaptic LINKs, (b) some of the acquired inter-postsynaptic LINKs induced by associative learning during life that are reactivated during oscillation of potentials and (c) the complexity of the nervous system of a given species. The synaptic transmission between vertically oriented neuronal orders provides vertical component and the lateral spared of potentials among the postsynapses during dendritic spikes provide horizontal component that lead to surface or extracellular recorded oscillating potentials. These oscillating potentials eventually give rise to neuronal firing (somatic spikes) in an oscillating manner (shown by a wave-form). Additional factors that provide components for oscillations include recurrent collaterals, laterally connected layer 1 neurons, cortico-thalamo-cortical connections and activity arriving from the thalamus (in response to background sensory stimuli) and the brain stem (connections with respiratory drive). When frequency of oscillating potentials changes, the nature of consciousness will change (example, in sleep). C C-semblance, Cs subjective changes to C-semblance due to contributions of semblances induced through reactivation of inter-postsynaptic functional LINKs formed by different associative learning events during life. P–Q Represents background sensory inputs. Wave shape Represents oscillating pontentials. A Presynaptic terminal where inputs from oscillatory neuronal activity arrives. B Postsynaptic terminal of the synapse A–B. D Postsynaptic terminal which is functionally LINKed to the postsynaptic terminal B. B–D Inter-postsynaptic functional LINK. Corresponding presynaptic terminal of postsynapse D is not shown. N Neurons that are firing. P–Q Represents background sensory inputs arriving at the nervous system either from the environment or from the body such as respiration and heartbeat. IILPS Islet of inter-LINKed postsynapses (Figure modified from Vadakkan 2010)
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Fig4: Formation of C-semblance for consciousness and the role of oscillating potentials. Spontaneous activity occurring during events such as dendritic spikes occurring at the islets of inter-LINKed postsynapses (IILPS) can lead to semblance at all the postsynapses that are activated thorough the LINKs (in the absence of arrival of activity from their presynaptic terminals). In addition, reactivation of large number of scattered single inter-postsynaptic functional LINKs (B–D) within the cortices also induce semblances. Background sensory stimuli both from within the body (respiration and heart beat) and from the environment reactivate several inter-postsynaptic functional LINKs and also induce semblances. The net result of all the semblances induced at the postsynapses lead to C-semblance for consciousness. C-semblance is a function of (a) the reactivated inter-postsynaptic LINKs that in turn is a function of existing innate inter-postsynaptic LINKs, (b) some of the acquired inter-postsynaptic LINKs induced by associative learning during life that are reactivated during oscillation of potentials and (c) the complexity of the nervous system of a given species. The synaptic transmission between vertically oriented neuronal orders provides vertical component and the lateral spared of potentials among the postsynapses during dendritic spikes provide horizontal component that lead to surface or extracellular recorded oscillating potentials. These oscillating potentials eventually give rise to neuronal firing (somatic spikes) in an oscillating manner (shown by a wave-form). Additional factors that provide components for oscillations include recurrent collaterals, laterally connected layer 1 neurons, cortico-thalamo-cortical connections and activity arriving from the thalamus (in response to background sensory stimuli) and the brain stem (connections with respiratory drive). When frequency of oscillating potentials changes, the nature of consciousness will change (example, in sleep). C C-semblance, Cs subjective changes to C-semblance due to contributions of semblances induced through reactivation of inter-postsynaptic functional LINKs formed by different associative learning events during life. P–Q Represents background sensory inputs. Wave shape Represents oscillating pontentials. A Presynaptic terminal where inputs from oscillatory neuronal activity arrives. B Postsynaptic terminal of the synapse A–B. D Postsynaptic terminal which is functionally LINKed to the postsynaptic terminal B. B–D Inter-postsynaptic functional LINK. Corresponding presynaptic terminal of postsynapse D is not shown. N Neurons that are firing. P–Q Represents background sensory inputs arriving at the nervous system either from the environment or from the body such as respiration and heartbeat. IILPS Islet of inter-LINKed postsynapses (Figure modified from Vadakkan 2010)

Mentions: Continuous formation of semblances occurs during dendritic spikes and other spontaneous activations of the postsynaptic terminals (in the absence of the arrival of activity at the presynaptic terminals). The composition of all the background semblances induced in a modular fashion at different cortices in the resting state leads to the formation of C-semblance (the net semblance for consciousness) responsible for consciousness (Fig. 4) (Vadakkan 2010). Since lower forms of animals show intentionality to carry out basic motor behaviors for feeding and reproduction, which are essential for maintaining the species, a robust circuit property is expected to be present in all the nervous systems that induce internal sensations for maintaining states equivalent to awareness. Consciousness is strongly associated with the specific frequency of the surface or extracellular recorded oscillating potentials. The dendritic spikes that involve a large number of synapses at one location are likely to activate postsynapses within islets of inter-LINKed postsynapses providing the required horizontal component for oscillating potentials for C-semblance. Synaptic transmission between the vertically oriented neuronal orders in the cortex provides the vertical component for the oscillations. C-semblance act as a background or buffer during active computations—for example, during the matching process of the formed internal sensation of retrieved memory with that of the learned item.Fig. 4


A pressure-reversible cellular mechanism of general anesthetics capable of altering a possible mechanism for consciousness.

Vadakkan KI - Springerplus (2015)

Formation of C-semblance for consciousness and the role of oscillating potentials. Spontaneous activity occurring during events such as dendritic spikes occurring at the islets of inter-LINKed postsynapses (IILPS) can lead to semblance at all the postsynapses that are activated thorough the LINKs (in the absence of arrival of activity from their presynaptic terminals). In addition, reactivation of large number of scattered single inter-postsynaptic functional LINKs (B–D) within the cortices also induce semblances. Background sensory stimuli both from within the body (respiration and heart beat) and from the environment reactivate several inter-postsynaptic functional LINKs and also induce semblances. The net result of all the semblances induced at the postsynapses lead to C-semblance for consciousness. C-semblance is a function of (a) the reactivated inter-postsynaptic LINKs that in turn is a function of existing innate inter-postsynaptic LINKs, (b) some of the acquired inter-postsynaptic LINKs induced by associative learning during life that are reactivated during oscillation of potentials and (c) the complexity of the nervous system of a given species. The synaptic transmission between vertically oriented neuronal orders provides vertical component and the lateral spared of potentials among the postsynapses during dendritic spikes provide horizontal component that lead to surface or extracellular recorded oscillating potentials. These oscillating potentials eventually give rise to neuronal firing (somatic spikes) in an oscillating manner (shown by a wave-form). Additional factors that provide components for oscillations include recurrent collaterals, laterally connected layer 1 neurons, cortico-thalamo-cortical connections and activity arriving from the thalamus (in response to background sensory stimuli) and the brain stem (connections with respiratory drive). When frequency of oscillating potentials changes, the nature of consciousness will change (example, in sleep). C C-semblance, Cs subjective changes to C-semblance due to contributions of semblances induced through reactivation of inter-postsynaptic functional LINKs formed by different associative learning events during life. P–Q Represents background sensory inputs. Wave shape Represents oscillating pontentials. A Presynaptic terminal where inputs from oscillatory neuronal activity arrives. B Postsynaptic terminal of the synapse A–B. D Postsynaptic terminal which is functionally LINKed to the postsynaptic terminal B. B–D Inter-postsynaptic functional LINK. Corresponding presynaptic terminal of postsynapse D is not shown. N Neurons that are firing. P–Q Represents background sensory inputs arriving at the nervous system either from the environment or from the body such as respiration and heartbeat. IILPS Islet of inter-LINKed postsynapses (Figure modified from Vadakkan 2010)
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Related In: Results  -  Collection

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Fig4: Formation of C-semblance for consciousness and the role of oscillating potentials. Spontaneous activity occurring during events such as dendritic spikes occurring at the islets of inter-LINKed postsynapses (IILPS) can lead to semblance at all the postsynapses that are activated thorough the LINKs (in the absence of arrival of activity from their presynaptic terminals). In addition, reactivation of large number of scattered single inter-postsynaptic functional LINKs (B–D) within the cortices also induce semblances. Background sensory stimuli both from within the body (respiration and heart beat) and from the environment reactivate several inter-postsynaptic functional LINKs and also induce semblances. The net result of all the semblances induced at the postsynapses lead to C-semblance for consciousness. C-semblance is a function of (a) the reactivated inter-postsynaptic LINKs that in turn is a function of existing innate inter-postsynaptic LINKs, (b) some of the acquired inter-postsynaptic LINKs induced by associative learning during life that are reactivated during oscillation of potentials and (c) the complexity of the nervous system of a given species. The synaptic transmission between vertically oriented neuronal orders provides vertical component and the lateral spared of potentials among the postsynapses during dendritic spikes provide horizontal component that lead to surface or extracellular recorded oscillating potentials. These oscillating potentials eventually give rise to neuronal firing (somatic spikes) in an oscillating manner (shown by a wave-form). Additional factors that provide components for oscillations include recurrent collaterals, laterally connected layer 1 neurons, cortico-thalamo-cortical connections and activity arriving from the thalamus (in response to background sensory stimuli) and the brain stem (connections with respiratory drive). When frequency of oscillating potentials changes, the nature of consciousness will change (example, in sleep). C C-semblance, Cs subjective changes to C-semblance due to contributions of semblances induced through reactivation of inter-postsynaptic functional LINKs formed by different associative learning events during life. P–Q Represents background sensory inputs. Wave shape Represents oscillating pontentials. A Presynaptic terminal where inputs from oscillatory neuronal activity arrives. B Postsynaptic terminal of the synapse A–B. D Postsynaptic terminal which is functionally LINKed to the postsynaptic terminal B. B–D Inter-postsynaptic functional LINK. Corresponding presynaptic terminal of postsynapse D is not shown. N Neurons that are firing. P–Q Represents background sensory inputs arriving at the nervous system either from the environment or from the body such as respiration and heartbeat. IILPS Islet of inter-LINKed postsynapses (Figure modified from Vadakkan 2010)
Mentions: Continuous formation of semblances occurs during dendritic spikes and other spontaneous activations of the postsynaptic terminals (in the absence of the arrival of activity at the presynaptic terminals). The composition of all the background semblances induced in a modular fashion at different cortices in the resting state leads to the formation of C-semblance (the net semblance for consciousness) responsible for consciousness (Fig. 4) (Vadakkan 2010). Since lower forms of animals show intentionality to carry out basic motor behaviors for feeding and reproduction, which are essential for maintaining the species, a robust circuit property is expected to be present in all the nervous systems that induce internal sensations for maintaining states equivalent to awareness. Consciousness is strongly associated with the specific frequency of the surface or extracellular recorded oscillating potentials. The dendritic spikes that involve a large number of synapses at one location are likely to activate postsynapses within islets of inter-LINKed postsynapses providing the required horizontal component for oscillating potentials for C-semblance. Synaptic transmission between the vertically oriented neuronal orders in the cortex provides the vertical component for the oscillations. C-semblance act as a background or buffer during active computations—for example, during the matching process of the formed internal sensation of retrieved memory with that of the learned item.Fig. 4

Bottom Line: Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines.The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia.The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurology, Department of Medicine, University of Toronto, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Room A4-08, Toronto, ON M4N 3M5 Canada.

ABSTRACT
Different anesthetics are known to modulate different types of membrane-bound receptors. Their common mechanism of action is expected to alter the mechanism for consciousness. Consciousness is hypothesized as the integral of all the units of internal sensations induced by reactivation of inter-postsynaptic membrane functional LINKs during mechanisms that lead to oscillating potentials. The thermodynamics of the spontaneous lateral curvature of lipid membranes induced by lipophilic anesthetics can lead to the formation of non-specific inter-postsynaptic membrane functional LINKs by different mechanisms. These include direct membrane contact by excluding the inter-membrane hydrophilic region and readily reversible partial membrane hemifusion. The constant reorganization of the lipid membranes at the lateral edges of the postsynaptic terminals (dendritic spines) resulting from AMPA receptor-subunit vesicle exocytosis and endocytosis can favor the effect of anesthetic molecules on lipid membranes at this location. Induction of a large number of non-specific LINKs can alter the conformation of the integral of the units of internal sensations that maintain consciousness. Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines. Externally applied pressure can transduce from the middle ear through the perilymph, cerebrospinal fluid, and the recently discovered glymphatic pathway to the extracellular matrix space, and finally to the paravenular space. The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia. Changes in membrane composition and the conversion of membrane hemifusion to fusion due to defects in the checkpoint mechanisms can lead to cytoplasmic content mixing between neurons and cause neurodegenerative changes. The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics.

No MeSH data available.


Related in: MedlinePlus