• Study hints at how early life experience

    From ScienceDaily@1:317/3 to All on Wed Mar 9 21:30:50 2022
    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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