Training neural circuits early in development improves response

Date:
August 6, 2020
Source:
University of Illinois at Urbana-Champaign, News Bureau
Summary:
When it comes to training neural circuits for tissue engineering
or biomedical applications, a new study suggests a key parameter:
Train them young.



FULL STORY ==========================================================================
When it comes to training neural circuits for tissue engineering or
biomedical applications, a new study suggests a key parameter: Train
them young.


========================================================================== Techniques for training engineered neural circuits usually involve
training them after the cells have fully matured. Using light-sensitive
neurons derived from mouse stem cells, researchers at the University of Illinois, Urbana- Champaign found that training them throughout early
cell development and network formation led to lasting improvements in
the connections, responsivity and gene expression of the resulting neural network. They published their results in the journal Scientific Reports.

"It's like an old dog learning new tricks versus a young puppy," said
graduate student Gelson Pagan-Diaz, the first author of the study. "When
we're training a network, if we stimulate it when it's still like a
puppy, we can get a better response to the training than if it were
already mature." Improved neural training has many applications in bioengineering and regenerative medicine. For example, the Illinois team
hopes to use trained neural circuits to control the movement and behavior
of miniature bio-hybrid machines. The types of improvements yielded by
early training could give the machines and circuits more functionality
and give the researchers more precise control over those functions.

"As we advance the field of building machines with living cells,
being able to stimulate and program neuronal cells and networks with
light early in their development could be an important tool in our
engineering repository," said study leader Rashid Bashir, a professor
of bioengineering and dean of the Grainger College of Engineering
at Illinois. "Furthermore, this work could have implications for
developmental biology, regenerative medicine and brain research."
To train the neurons, the researchers used timed pulses of light to
stimulate the cells. The researchers began the training regimen when
the cells were early in their development -- clusters of stem cells,
called embryoid bodies, primed to become motor neurons. They continued
the training as the cells differentiated, becoming fully mature neurons,
and further continued it after transferring the cells to plates to
connect and form neural circuits.

They then compared the early trained circuits with those cultured first
and trained later -- the usual method.

The researchers saw a number of differences between the groups,
Pagan-Diaz said. In the neurons trained during development, they saw
more extensions indicating connections between cells, an increase in neurotransmitter packages sent between cells, and more structured nerve
firing, indicating greater network stability. The effects of the early
training were long-lasting, whereas cells trained later tended to have transient responses.

"You can think of the neurons being like athletes in training," Pagan-Diaz said. "The light stimulation was like a regular workout for the neurons
-- they were stronger and more athletic, and did their jobs better."
To determine the underlying basis for these changes, the researchers
analyzed the neurons' genetic activity. They saw an increase in gene
expression for genes related to network maturity and neural function, indicating that the early training could have permanently altered genetic pathways as the cells developed, Bashir said.

The researchers are continuing to explore what kinds of activities
could be enhanced or programmed by early neuron training in the embryoid
body phase.

Embryoid bodies could be useful building-block components for biological machines, Pagan-Diaz said, and also hold promise for regenerative
medicine.

"Previous studies have shown that embryoid bodies with motor
neurons implanted into mice that had been injured could improve the regeneration of tissue," Pagan-Diaz said. "If we can improve or enhance
the functionality of these embryoid bodies prior to putting them into an injured model, then theoretically we could enhance the recovery beyond
what has been seen with injecting them and then stimulating them later."

========================================================================== Story Source: Materials provided by University_of_Illinois_at_Urbana-Champaign,_News_Bureau.

Original written by Liz Ahlberg Touchstone. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Gelson J. Pagan-Diaz, Jenny Drnevich, Karla P. Ramos-Cruz,
Richard Sam,
Parijat Sengupta, Rashid Bashir. Modulating electrophysiology
of motor neural networks via optogenetic stimulation during
neurogenesis and synaptogenesis. Scientific Reports, 2020; 10 (1)
DOI: 10.1038/s41598-020- 68988-y ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200806153641.htm

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