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Information

  1. Immobility. Evidence indicates that the spinal cord is the main site at which anesthetics act to inhibit movement in response to noxious stimulation. This is the end point used in most measurements of anesthetic potency. MAC values for fluorinated volatile anesthetics are unaffected in rats by either decerebration or cervical spinal cord transection.
  2. Autonomic Control. Anesthetics exert profound effects on homeostatic mechanisms through effects on autonomic centers in the brainstem. Cardiovascular perturbations are also mediated in part at autonomic centers. Hypothalamic thermoregulation is also ablated by anesthetics.
  3. Amnesia. Although the neurobiological mechanisms underlying learning, memory consolidation, and memory storage remain unclear, the hippocampus and the amygdala are plausible anesthetic targets for suppressing memory formation.
  4. Unconsciousness. Consciousness is a complex state that can be operationally divided into the components of arousal and awareness that can be individually blocked by anesthetics.
  5. Reticular Activating System and Arousal Centers (RAS). The reticular activating system (RAS) is a diffuse collection of brainstem neurons that mediate arousal. Electrical stimulation of the RAS induces arousal in anesthetized animals.
    1. Multiple lines of evidence suggest that anesthetic inhibition of the tuberomammillary nucleus (TMN) of the dorsal hypothalamus impairs arousal (Fig. 5-2: Diagram of subcortical arousal circuitry implicated in anesthetic-induced unconsciousness).
    2. The perifornical area in the lateral hypothalamus appears to be critical in emergence from rather than induction of anesthetic-induced unconsciousness. It is the sole source of orexin, a neurotransmitter that stabilizes the flip-flopping of the sleep switch.
    3. The precise roles of dopaminergic and noradrenergic arousal centers in anesthetic-induced unconsciousness remain unclear.
  6. Thalamus. The thalamus has been postulated as a likely target for anesthetic ablation of consciousness, but the precise mechanisms remains unclear.
  7. Cerebral Cortex. The cerebral cortex is the major site for integration, storage, and retrieval of information for generating awareness of the external environment.
    1. The disruption of feedback connections by anesthetics may contribute to impaired consciousness by attenuating the integration of information distributed among cortical regions.
    2. The effects of anesthetics on both cortical firing rates and timing of action potentials likely contribute to the ablation of awareness by limiting both the diversity of information that can be represented and the integration of neural information.
    3. Anesthetics alter the topology of distinct networks of frontal, parietal, and temporal cortical areas subserving attention and higher cognitive processes based on patterns of correlated activity.
    4. Anesthetics weaken high-frequency synchronized oscillatory cortical activity that may normally be critical for integrating information across cortical areas into coherent representations.

Outline

Mechanisms of Anesthesia and Consciousness

  1. What is Anesthesia?
  2. How is Anesthesia Measured?
  3. What is the Chemical Nature of Anesthetic Target Sites?
  4. How Do Anesthetics Interfere with the Electrophysiologic Function of the Nervous System?
  5. Anesthetic Actions on Ion Channels
  6. How are the Molecular Effects of Anesthetics Linked to Anesthesia in the Intact Organism?
  7. Where in the Central Nervous System do Anesthetics Work?
  8. Conclusions