Communications down in anesthetized brain

Nov 8 2012

By Eleanor McDermid, Senior medwireNews Reporter

Two studies indicate that inhaled anesthetics disrupt communication between distant cortical areas before directly activating sleep-inducing neuronal circuitry.

In one study, Patrick Purdon (Massachusetts General Hospital, Boston, USA) and colleagues looked at neural activity in humans at the point of losing consciousness after propofol administration, defined as the time from which the participants failed to press a button in response to an auditory stimulus.

The three patients in the study were undergoing surgery for epilepsy. The point at which they lost consciousness was marked by a sudden and sustained 35-70% increase in slow oscillations.

Neuronal spiking still occurred after loss of consciousness, and was highly variable, sometimes approaching levels seen while the patients were awake. But bouts of activity were interspersed with silence, and these changes were strictly tied to the slow oscillation cycle.

Purdon et al found that slow oscillation cycles in different parts of the cortex were not in synch with each other. The fact that the phase of the oscillation cycle appears to govern neuronal spiking means that neurons in distant (>2 cm apart) cortical areas will be active at different times, they say.

This will therefore "disrupt communication between distant cortical areas, because one cortical area frequently will be profoundly suppressed when another area is active," the team writes in the Proceedings of the National Academy of Sciences.

In the second study, which appears in Current Biology, Max Kelz (Children's Hospital of Philadelphia, Pennsylvania, USA) and team show that, rather than merely preventing waking, general anesthetics actively induce sleep.

They found that, in mice, anesthesia with isoflurane caused a dose-dependent effect on the number of active neurons in the ventrolateral preoptic (VLPO) nucleus - a predominantly sleep-active nucleus. The team determined activation via expression of the neuronal activity marker c-Fos; for example, 2 hours of exposure to 0.6% isoflurane caused a 215% increase in c-Fos expression. Increased expression only occurred if the anesthetic dose was sufficient to cause sedation.

Activation occurred in a specific subset of VLPO neurons, which do not depolarize in response to norepinephrine and are believed to be the sleep-promoting neurons within the VLPO nucleus. Furthermore, targeted destruction of neurons within the VLPO nucleus altered the sensitivity of the mice to isoflurane. They needed, on average, a 12% higher dose to lose their righting reflex, relative to sham-treated mice, at 6 days after treatment.

Although significant, this relatively small shift suggests that "though it may play an important role, the VLPO is neither the sole nor the master mediator of anesthetic-induced hypnosis," comment Kelz et al.

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