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Nobelist neuroscientist Tom Südhof still spiraling in on the secrets of the synapse

spiral staircase"History," said Winston Churchill (or was it Arnold Toynbee or Edna St. Vincent Millay?), "is just one damn thing after another." In many respects, so is good science.

And that's just how it should be, Stanford neuroscientist and molecular physiologist Tom Südhof, MD, told me a few years ago when I interviewed him for a story I wrote in connection with the Lasker Award, a prestigious prize he'd won shortly before receiving the 2013 Nobel Prize in physiology or medicine:

Asked to recall any defining "eureka!" moments that had catapulted his hunches forward to the status of certainty, Südhof noted that in his experience, science advances step by step, not in jumps. "I believe strongly that most work is incremental," he said. The systematic solution of highly complex problems requires a long view and plenty of patience.

Climbing a long ladder to the Nobel one small step at a time, Südhof continually raised the power of his conceptual microscope over the decades as he probed the intricate workings of synapses: the all-important junctions in the nervous system where information, in the form of chemical messengers called neurotransmitters, gets passed from one nerve cell to another.

From an explanation of Südhof's synaptic studies:

The firing patterns of our synapses underwrite our consciousness, emotions and behavior. The simple act of taking a step forward, experiencing a fleeting twinge of regret, recalling an incident from the morning commute or tasting a doughnut requires millions of simultaneous and precise synaptic firing events throughout the brain and peripheral nervous system.

A philosopher might say that synapses collectively constitute the physiological substrate for the soul. A futurist might write (as I once did):

With nanobots monitoring every critical neural connection’s involvement in a thought or emotion or experience, you’ll be able to back up your brain - or even try on someone else’s - by plugging into a virtual-reality jack. The brain bots feed your synapses the appropriate electrical signals and you’re off and running, without necessarily moving.

Shades of Ray Kurzweil! Before segueing smoothly into The Singularity, though, let's take a big, deep breath. Each synapse is a complex universe unto itself, containing its own nanoscale assembly of molecular wheels within wheels, pulleys, portals and power supplies. Due to this complexity, most of Südhof's stepwise progress in understanding how synapses work, lauded in the scientific world, went mostly unnoticed in the popular press (as did those of fellow 2013 Nobel laureate and Stanford structural biologist Mike Levitt, PhD).

Neither the Nobel nor the public's attention deficit has deterred Südhof from further exploration.

Most recently, in a couple of just-published studies (the first in Neuron, the second in CELL), he and teammates including Stanford neuroscientist Rob Malenka, MD, PhD, have unveiled new findings about beta-neurexins, proteins that sit on the surface of a transmitting nerve cell, anchoring it to the next nerve cell in the relay and thus helping maintain stability at the synapse. The first study showed that the exact structures of beta-neurexins vary from one cell type to the next, while the second revealed that these proteins, far from being mere drops of dried glue, can control transmitting nerve-cells' firing propensity by altering receiving nerve cells' output of endocannabinoids, the brain's "inner marijuana."

It's okay to exhale now.

Previously: The reefer connection: Brain's "internal marijuana" signaling system implicated in very early stages of Alzheimer's pathology, Step by step, Sudhof stalked the devil in the details, snagged a Nobel, But is it news? How the Nobel Prize transformed "noteworthy" into "newsworthy" and Stanford molecular neuroscientist Thomas Sudhof wins coveted Lasker Award
Photo by Tom Mrazek

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