Brain uploading for worms...

Caenorhabditis elegans, as the roundworm is properly known, is a tiny,
transparent animal just a millimeter long. In nature, it feeds on the
bacteria that thrive in rotting plants and animals. It is a favorite
laboratory organism for several reasons, including the comparative
simplicity of its brain, which has just 302 neurons and 8,000
synapses, or neuron-to-neuron connections. These connections are
pretty much the same from one individual to another, meaning that in
all worms the brain is wired up in essentially the same way. Such a
system should be considerably easier to understand than the human
brain, a structure with billions of neurons, 100,000 miles of
biological wiring and 100 trillion synapses.

The biologist Sydney Brenner chose the roundworm as an experimental
animal in 1974 with this goal in mind. He figured that once someone
provided him with the wiring diagram of how 302 neurons were
connected, he could then compute the worm’s behavior.

The task of reconstructing the worm’s wiring system fell onJohn G.
White, now at the University of Wisconsin. After more than a decade’s
labor, which required examining 20,000 electron microscope cross
sections of the worm’s anatomy, Dr. White worked out exactly how the
302 neurons were interconnected.

But the wiring diagram of even the worm’s brain proved too complex for
Dr. Brenner’s computational approach to work. Dr. Bargmann was one of
the first biologists to take Dr. White’s wiring diagram and see if it
could be understood in other ways.


After studying the little animal for 24 years, she believes she is
closer to understanding how its nervous system works.

Why is the wiring diagram produced by Dr. White so hard to interpret?
She pulls down from her shelves a dog-eared copy of the journal in
which the wiring was first described. The diagram shows the electrical
connections that each of the 302 neurons makes to others in the
system. These are the same kind of connections as those made by human
neurons. But worms have another kind of connection.

Besides the synapses that mediate electrical signals, there are also
so-called gap junctions that allow direct chemical communication
between neurons. The wiring diagram for the gap junctions is quite
different from that of the synapses.

Not only does the worm’s connectome, as Dr. Bargmann calls it, have
two separate wiring diagrams superimposed on each other, but there is
a third system that keeps rewiring the wiring diagrams. This is based
on neuropeptides, hormonelike chemicals that are released by neurons
to affect other neurons.

The neuropeptides probably help control the brain’s general status, or
mood. A strong hint of how they work comes from the npr-1 gene, which
makes a protein that responds to neuropeptides. When the npr-1 gene is
active, its neuron becomes unavailable to its local circuit.

That may be a reason why the worm’s behavior cannot be computed from
the wiring diagram: the pattern of connections is changing all the
time under the influence of the worm’s 250 neuropeptides.

The connectome shows the electrical connections, and hence the
quickest paths for information to move through the worm’s brain. “But
if only a subset of neurons are available at any time, the connectome
is ambiguous,” she says.

The human brain, too, has neuropeptides that set mood and modify
behavior. Neuropeptides are probably at work when the pain pathways
are cut off in acute crises, allowing people to function despite
serious wounds.

The human brain, though vastly more complex than the worm’s, uses many
of the same components, from neuropeptides to transmitters. So
everything that can be learned about the worm’s nervous system is
likely to help with the human system.

Though the worm’s nervous system is routinely described as simple,
that is true only in comparison with the human brain. The worm has
22,000 genes, almost as many as a person, and its brain is a highly
complex piece of biological machinery. The work of Dr. Bargmann’s and
other labs has deconstructed many of its operational mechanisms.

What would be required to say that the worm’s nervous system was fully
understood? “You would want to understand a behavior all the way
through, and then how the behavior can change,” Dr. Bargmann says.

“That goal is not unattainable,” she adds.

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