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Finding the source of our earliest brain activity
University of Maryland (UMD) neuroscientists have identified the source of our earliest brain activity. The brain cells that support our earliest structural development also transmit sensory information. This discovery could enable early diagnosis of autism and other cognitive deficits
Some expectant parents play classical music for their unborn babies, hoping to boost their children's cognitive capacity later in life. Although some research supports a link between prenatal sound exposure and improved brain function, scientists had not identified any structures responsible for this link in the developing brain up to now.
However, a new study led by UMD neuroscientists is the first to identify a mechanism that could explain such an early link between sound input and cognitive function, often called the "Mozart effect."
Working with an animal model, researchers found how a type of cell present in the brain's primary processing area during early development, long thought to form structural scaffolding with no role in transmitting sensory information, may actually conduct such signals after all.
Their results could have implications for the early diagnosis of autism and other cognitive deficits, and are published in the online early edition of the Proceedings of the National Academy of Sciences (PNAS) on November 6, 2017.
"Previous research documented brain activity in response to sound during early developmental phases, but it was hard to determine where in the brain these signals were coming from," explains Patrick Kanold PhD, a professor of biology at UMD and the senior author of the research. "Our study is the first to measure these signals in an important cell type in the brain, providing important new insights into early sensory development in mammals."
Working with young ferrets, Kanold and his team observed sound-induced nerve impulses in subplate neurons for the first time. In development, subplate neurons are among the first neurons to form in the cerebral cortex — the outer part of the mammalian brain that controls perception, memory and, in humans, higher functions such as language and abstract reasoning. Subplate neurons help guide formation of neural circuits, in the same way that a temporary scaffold helps a construction crew build walls and install windows on a new building.
And like construction scaffolding, subplate neurons are thought to be temporary. Once the brain's permanent neural circuits form, most of the subplate neurons die off and disappear. According to Kanold, researchers assumed that subplate neurons had no role further role.
Conventional wisdom suggested mammalian brains transmit their first sensory signals in response to sound following the thalamus connecting to the cerebral cortex. In many mammals, the connection of the thalamus and the cortex also coincides with the opening of the ear canals, allowing sounds to activate the inner ear. This coincident timing provided more support for the traditional model of when sound processing begins in the brain.
However, researchers struggled to reconcile this conventional model with observations that sound-induced brain activity began much earlier in development. Until Kanold's group captured and measured the response of subplate neurons to sound.
Kanold: "Our work is the first to suggest that subplate neurons do more than bridge the gap between the thalamus and the cortex, forming the structure for future circuits. They form a functional scaffolding that actually processes and transmits information before other cortical circuits are activated. It is likely that subplate neurons help determine the early functional organization of the cortex in addition to its structural organization."
By identifying a source of early sensory nerve signals, the current study may lead to new ways to diagnose autism and other cognitive deficits that emerge early in development. Early diagnosis is an important first step toward early intervention and treatment.
"Now that we know subplate neurons are transmitting sensory input, we can begin to study their functional role in development in more detail," adds Kanold. His findings are already drawing interest from researchers who study sensory development in humans. Rhodri Cusack, a professor of cognitive neuroscience at Trinity College Dublin, in Ireland, noted that the results could have implications for the care of premature infants.
"This paper shows that our sensory systems are shaped by the environment from a very early age. In human infants, this includes the third trimester, when many preterm infants spend time in a neonatal intensive care unit. The findings are a call to action to identify enriching environments that can optimize sensory development in this vulnerable population."
Sensory experience, even at prenatal periods, can shape brain connectivity. Thus, the emergence of sensory responses is a key step in cortical development. Sensory cortical responses are thought to emerge in cortical layer 4, which is the adult target of thalamic projections. However, in developing animals, thalamic fibers do not target layer 4 but instead target subplate neurons in the white matter. We show that subplate neurons respond to sounds before layer 4 is activated by thalamic axons. Moreover, early local field potential (LFP) responses demonstrate nascent topographic organization. Together we find that sound-evoked cortical activity and topographic organization emerge in a different layer than thought. Since subplate circuits are disrupted in autism spectrum disorder (ASD) models, disrupted emergence of sensory activity could be utilized for diagnosis and intervention.
In utero experience, such as maternal speech in humans, can shape later perception, although the underlying cortical substrate is unknown. In adult mammals, ascending thalamocortical projections target layer 4, and the onset of sensory responses in the cortex is thought to be dependent on the onset of thalamocortical transmission to layer 4 as well as the ear and eye opening. In developing animals, thalamic fibers do not target layer 4 but instead target subplate neurons deep in the developing white matter. We investigated if subplate neurons respond to sensory stimuli. Using electrophysiological recordings in young ferrets, we show that auditory cortex neurons respond to sound at very young ages, even before the opening of the ears. Single unit recordings showed that auditory responses emerged first in cortical subplate neurons. Subsequently, responses appeared in the future thalamocortical input layer 4, and sound-evoked spike latencies were longer in layer 4 than in subplate, consistent with the known relay of thalamic information to layer 4 by subplate neurons. Electrode array recordings show that early auditory responses demonstrate a nascent topographic organization, suggesting that topographic maps emerge before the onset of spiking responses in layer 4. Together our results show that sound-evoked activity and topographic organization of the cortex emerge earlier and in a different layer than previously thought. Thus, early sound experience can activate and potentially sculpt subplate circuits before permanent thalamocortical circuits to layer 4 are present, and disruption of this early sensory activity could be utilized for early diagnosis of developmental disorders.
Authors: Jessica M. Wessa, Amal Isaiaha, Paul V. Watkinsa, and Patrick O. Kanolda
In addition to Kanold, UMD-affiliated co-authors of the research paper include former graduate student Jessica Wess (Ph.D. '17, neuroscience and cognitive science) and former postdoctoral researchers Amal Isaiah and Paul Watkins.
The research paper, "Subplate neurons are the first cortical neurons to respond to sensory stimuli," Jessica Wess, Amal Isaiah, Paul Watkins and Patrick Kanold, was published November 6, 2017 in the online early edition of the Proceedings of the National Academy of Sciences.
This work was supported by the National Institutes of Health (Award No. R01DC009607) and the Alfred P. Sloan Foundation. The content of this article does not necessarily reflect the views of these organizations.
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Subplate neurons are among the first neurons to form in the cerebral cortex and were thought to serve primarily in a structural role in brain development. Now research suggests these neurons, in fact, transmit sensory information - as reflected in this image responding to higher frequencies, especially at low volume. Increased volume expanded the cell's frequency range of response.
Image credit: Patrick Kanold