Study hints at how early life experiences may affect brain wiring
Observing brain development in mice offers insights into neurological
diseases
Date:
March 9, 2022
Source:
Ohio State University
Summary:
A new study of brain development in mice shortly after birth may
provide insights into how early life events can affect wiring
patterns in the brain that manifest as disease later in life.
FULL STORY ==========================================================================
A new study of brain development in mice shortly after birth may
provide insights into how early life events can affect wiring patterns
in the brain that manifest as disease later in life -- specifically such disorders as schizophrenia, epilepsy and autism.
========================================================================== Researchers focused on two types of brain cells that have been linked
to adult neurological disorders: neurons in a modulating system nestled
deep in the brain and other neurons in the cortex, the brain's outermost
layer, that counteract excitation in other cells using inhibitory
effects. The modulating cells send long-range cables to the cortex to
remotely influence cortical cell activity.
The study is the first to show that these two types of cells communicate
very early in brain development. A chemical released from the modulating
cells initiates the branching, or arborization, of axons, the long,
slender extensions of nerve cell bodies that transmit messages, on the
cortical cells - - and that arborization dictates how effective the
cells in the cortex are at doing their job.
Though there is still a lot to learn about the impact of this cellular interaction in the postnatal brain, the researchers said the study opens
the door to a better understanding of how neurological diseases in adults
may relate to early-life events.
"It's known that abnormal early-life experiences can impact kids'
future sensation and behavior. This finding may help explain that kind of mechanism," said Hiroki Taniguchi, associate professor of pathology in The
Ohio State University College of Medicine and senior author of the study.
"This study provides new insight into brain development and brain
pathology.
It's possible that during development, depending on animals' experiences,
this modulating system activity can be changed and, accordingly, the
cortical circuit wiring can be changed." Taniguchi completed the work
with co-authors Andre' Steinecke and McLean Bolton while he was an
investigator at the Max Planck Florida Institute for Neuroscience.
==========================================================================
The research is published today (March 9, 2022) in the journal Science Advances.
The study involved chandelier cells, a type of inhibitory neurons in the cortical section of the brain, and neurons of the cholinergic system
-- one of the systems that monitor the environment and the internal
state, and send signals to the rest of the brain to trigger memory and appropriate behaviors.
"Both of these types of cells have been separately studied in the context
of adult functions or modulations so far. The developmental role of
cholinergic neurons in the brain wiring remains poorly understood,"
Taniguchi said.
Chandelier cells are named for the spray of signal-transmitting synapses (called synaptic cartridges) at the branch terminals that resemble candles
of a traditional chandelier, a pattern that gives them inhibitory control
over hundreds of cells at a time.
"These cells have output control," said Steinecke, first author of the
study who is now working at Neuway Pharma in Germany. "Chandelier cells
can put a brake on excitatory cells and tell them they're not ready to
fire. As inhibitory cells, chandelier cells are thought to regulate
waves of firing - - which is important, because the waves contain
information that is transmitted over large distances of the brain."
Previous post-mortem studies have shown that the synaptic terminals
located at the end of chandelier cell axons appear to be reduced in the
brains of patients with schizophrenia.
========================================================================== "This axonal 'arbor' being reduced suggests they don't make as many
connections to downstream targets, and the connections themselves are
also altered and don't work that well," Steinecke said.
The team used two techniques to observe chandelier cells during early-life brain development in mice: genetically targeting and using a dye to
label and detect cells that differentiate into chandelier cells, and transplanting genetically manipulated cells back into animals shortly
after birth.
"This enabled us to watch brain development as it happens and manipulate conditions to test what the mechanisms are," Taniguchi said.
The researchers first observed how chandelier cell axons develop their branching structures, noting that small protrusions emerging from axons
were the first signs that branches would sprout. And they identified the chemical needed to start that sprouting process -- the neurotransmitter acetylcholine, which is released by cholinergic system cells.
The interaction between the distant cell types was confirmed
through a series of experiments: Knocking out receptors that bind to acetylcholine and decreasing activity of cholinergic neurons lessened
branch development, and making cholinergic neurons more likely to fire
led to more widespread branching.
"The key is that we didn't previously know how neuromodulatory systems
regulate the cortical circuits -- and both of them have been implicated in brain diseases," Taniguchi said. "Now that we've found that cholinergic
neurons could remotely impact cortical circuit development, especially
cortical inhibitory signals, the question is what kind of environment or emotional state of change can impact cortical inhibitors' development? We
may want to see if we can find a link as a next step." This work was
supported by funding from the Max Planck Society and the Brain Behavior
and Research Foundation.
========================================================================== Story Source: Materials provided by Ohio_State_University. Original
written by Emily Caldwell. Note: Content may be edited for style and
length.
========================================================================== Journal Reference:
1. Andre' Steinecke, McLean M. Bolton, Hiroki
Taniguchi. Neuromodulatory
control of inhibitory network arborization in the developing
postnatal neocortex. Science Advances, 2022; 8 (10) DOI:
10.1126/sciadv.abe7192 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220309140836.htm
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