A new understanding of the complex ways in which general anesthetics act on the brain could eventually lead to improved drugs for surgery. It remains unclear how general anesthesia works, even though it is one of the most common medical procedures worldwide.

Associate professor Bruno van Swinderen, conducting research at the University of Queensland, says his team has overturned previous understanding of what general anesthetics do to the brain, finding the drugs do much more than induce sleep.

“We looked at the effects of propofol — one of the most common general anaesthetic drugs used during surgery — on synaptic release,” van Swinderen says.

Synaptic release is the mechanism by which neurons — or nerve cells — communicate with each other.

“We know from previous research that general anesthetics including propofol act on sleep systems in the brain, much like a sleeping pill,” van Swinderen says. “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.”

PhD student Adekunle Bademosi says the discovery sheds new light on how general anesthetics work on the brain.

“We found that propofol restricts the movement of a key protein (syntaxin1A) required at the synapses of all neurons,” Bademosi explains. “This restriction leads to decreased communication between neurons in the brain.”

The finding contributed to understanding how general anaesthetics worked, and could explain why people experienced grogginess and disorientation after coming out of surgery, says van Swinderen.

“We think that widespread disruption to synaptic connectivity — the brain’s communication pathways — is what makes surgery possible, although effective anesthetics such as propofol do put you to sleep first,” he notes. “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.”

More research is needed to determine if general anesthetics had any lasting effects in these vulnerable groups of people.

“Studying these effects in model systems such as rats and flies allows us to address these questions by manipulating the likely mechanisms involved, which we can’t do in humans” says van Swinderen.