Brain cells born together connect together for life


According to a new study, brain cells with the same “date of birth” are more likely to connect into cooperative signaling circuits that perform many functions, including storing memories.

Led by researchers at NYU Grossman School of Medicine, the new study of the brains of mice developing in the womb found that brain cells (neurons) with the same date of birth exhibited distinct connectivity and activity throughout throughout the adult life of animals, whether they sleep or sleep. awake.

Published online August 22 in Natural neuroscience, the results suggest that evolution has taken advantage of the orderly birth of neurons – by day of gestation – to form localized microcircuits in the hippocampus, the region of the brain that forms memories. Rather than trying to create each new memory from scratch, the researchers suggest that the brain could exploit the gradual formation of neural layers to establish neural patterns, like “Lego pieces”, that associate each new experience with a existing model as it is stored.

These circuitry rules would suggest that cells born together are more likely to encode memories together and fail together, potentially implicating neuronal birthdate in diseases like autism and Alzheimer’s disease, claim the authors. With changes in the number of cells born on different days, the developing brain may be vulnerable on certain days of gestation to viral infections, toxins, or alcohol.

“The results of our study suggest that the day of birth of a hippocampal neuron strongly influences both the performance of this single cell and how populations of these cells signal together throughout life,” says the researcher. lead study author, György Buzsaki, MD, PhD, Biggs Professor of Neuroscience. in the Department of Neuroscience and Physiology at NYU Langone Health. “This work may reshape the way we study neurodevelopmental disorders, which have traditionally been examined through a molecular or genetic lens, rather than a developmental one,” says Dr. Buzsáki, also a member of the Neuroscience Institute at NYU Langone.

The innovation of the current study is based on monitoring the activity of neurons from a given date of birth until adulthood. To do this, the researchers relied on a technique that allowed them to transfer DNA into cells in the process of dividing into neurons in the uterus. The DNA expressed markers that marked brain cells born on the same day, like a barcode. This labeling method then allowed researchers to study these neurons in adult animals.

Using a combination of techniques, the new study found that neurons of the same date of birth tend to “co-fire” together, characterized by synchronized oscillations of their positive and negative charges, allowing them to transmit electrical signals collectively. According to the authors, a likely reason for co-firing is that neurons with the same date of birth are connected via shared neurons.

Previous work had shown that activity in the hippocampus could be described in terms of patterns of collective neural activity during wakefulness and sleep. During sleep, for example, when memories from each day are consolidated for long-term memory storage, neurons in the hippocampus engage in a cyclical burst of activity called a “high-wave ripple.” named after the shape it takes when graphically captured by EEG, a technology that records brain activity with electrodes.

“Our results show that neurons born on the same day are part of the same cooperating assemblies, participate in the same high-wave ripples, and represent the same memories,” says first author Roman Huszár, a graduate student in Dr. Buzsáki’s lab. “These relationships, and the predefined patterns they encode, have a key implication for hippocampal function: the storage of a memory about a place or event.”

In the future, the team plans additional experiments to identify active genes in the same birth neurons in different brain regions and to test their role in memory formation and behavior.

Reference: Huszár R, Zhang Y, Blockus H, Buzsáki G. Preconfigured dynamics in the hippocampus are guided by embryonic birth date and rate of neurogenesis. Nat Neurosci. 2022. do: 10.1038/s41593-022-01138-x

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