Despite the widespread use of anesthetics, we still don't know exactly how they work. The reason we don't fully understand the mechanism behind them is that we don't truly understand how consciousness works. New research from the University of Queensland is shedding new light on what exactly is going on in our brain when we're knocked out by a general anesthetic – and it's much more complex that simply falling asleep.

A recent book by Kate Cole-Adams called Anesthesia: The Gift of Oblivion and the Mystery of Consciousness relates a variety of odd and unsettling stories about people who hear things while under anesthesia or experience odd forms of conscious awareness. The overwhelming thesis of the book suggests that we could be more aware of our surroundings during a general anesthetic than we realize. And more frighteningly is the implication that anesthesia fundamentally rewires our memories.

Research over the last decade is suggesting that anesthetics result in unconsciousness by disrupting the brain's ability to communicate with itself. Blocking transmissions between different areas in the cortex seems to result in our consciousness vanishing. This also seems to result in strange side effects, such as memory loss and post-anesthesia cognitive impairment.

"We know from previous research that general anesthetics including propofol act on sleep systems in the brain, much like a sleeping pill," says Bruno van Swinderen, one of the researchers on the new study. "But our study found that propofol also disrupts presynaptic mechanisms, probably affecting communication between neurons across the entire brain in a systematic way that differs from just being asleep. In this way it is very different than a sleeping pill."

The study examined the anesthetic propofol, which is the most commonly used general anesthetic for humans. Utilizing single-particle tracking photoactivation localization microscopy, the team was able to examine how propofol affects single cells both in vivo and in vitro.

"We found that propofol restricts the movement of a key protein (syntaxin1A) required at the synapses of all neurons," explains van Swinderen. "This restriction leads to decreased communication between neurons in the brain. We think that widespread disruption to synaptic connectivity – the brain's communication pathways – is what makes surgery possible."

This insight into how anesthetics disrupt brain connectivity echoes recent research trying to understand why people often wake up from surgery suffering from cognitive impairments such as memory-loss. Not only can anesthetics induce temporary dementia-like symptoms, but they can potentially cause an acceleration in cognitive deterioration in patients already suffering from conditions such as Alzheimer's disease.

"The discovery has implications for people whose brain connectivity is vulnerable, for example in children whose brains are still developing or for people with Alzheimer's or Parkinson's disease. It has never been understood why general anesthesia is sometimes problematic for the very young and the old. This newly discovered mechanism may be a reason."

It's hoped future studies in animal models focusing on manipulating these specific mechanisms will provide a greater understanding of how general anesthetics knock us out and how our brains fundamentally generate consciousness.

The new study was published in the journal Cell Reports.

Source: Queensland Brain Institute, University of Queensland

View gallery - 2 images