A través de células
madre han podido extraer cómo es que las neuronas funcionan de manera rítmica.
Recently, neuroscientists at the Salk Institute
used stem cells to generate diverse networks of self-contained
spinal cord systems in a dish, dubbed circuitoids, to study this rhythmic pattern in
neurons. The work, which appears online in the February 14, 2017, issue
of eLife, reveals that some of the circuitoids–with no external
prompting–exhibited spontaneous,
coordinated rhythmic activity of the kind known to drive repetitive movements.
“It’s still very difficult to contemplate how large
groups of neurons with literally billions if not trillions of connections take
information and process it,” says the work’s senior author, Salk Professor
Samuel Pfaff, who is also a Howard Hughes Medical Institute investigator and
holds the Benjamin H. Lewis Chair. “But we think that developing this kind of
simple circuitry in a dish will allow us to extract some of the principles of
how real brain circuits operate. With that basic information maybe we can begin
to understand how things go awry in disease.”
Nerve cells in your brain and spinal cord connect
to one another much like electronic circuits. And just as electronic circuits
consist of many components, the nervous system contains a dizzying array of
neurons, often resulting in networks with many hundreds of thousands of cells.
To model these complex neural circuits, the Pfaff lab prompted embryonic stem
cells from mice to grow into clusters of spinal cord neurons, which they named
circuitoids. Each circuitoid typically contained 50,000 cells in clumps just large enough to see with the naked eye, and with different
ratios of neuronal subtypes.
With molecular tools, the researchers tagged four
key subtypes of both excitatory (promoting an electrical signal) and inhibitory
(stopping an electrical signal) neurons vital to movement, called V1, V2a, V3
and motor neurons. Observing the cells in the circuitoids in real time using
high-tech microscopy, the team discovered that circuitoids composed only of V2a
or V3 excitatory neurons or excitatory motor neurons (which control muscles)
spontaneously fired rhythmically, but that circuitoids comprising only
inhibitory neurons did not. Interestingly, adding inhibitory neurons to V3
excitatory circuitoids sped up the firing rate, while adding
them to motor circuitoids caused the neurons to form sub-networks, smaller
independent circuits of neural activity within a circuitoid.
“These results suggest that varying the ratios of
excitatory to inhibitory neurons within networks may be a way that real brains
create complex but flexible circuits to govern rhythmic activity,” says Pfaff.
“Circuitoids can reveal the foundation for complex neural controls that lead to
much more elaborate types of behaviors as we move through our world in a
seamless kind of way.”
Because these circuitoids contain neurons that are
actively functioning as an interconnected network to produce patterned firing,
Pfaff believes that they will more closely model a normal aspect of the brain
than other kinds of cell culture systems. Aside from more accurately studying
disease processes that affect circuitry, the new technique also suggests a
mechanism by which dysfunctional brain activity could be treated by altering
the ratios of cell types in circuits.
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