Brains cells born together wire and fire together for life



According to a recent study, brain cells with the same "birthdate" are more likely to connect into cooperative signaling circuits that perform a variety of tasks, including memory storage.

The new study on the growing brains of mice led by scientists from NYU Grossman School of Medicine discovered that brain cells (neurons) with the same birthdate displayed distinctive connectivity and activity throughout the animals' adult lives, whether they were asleep or awake.

The results, which were published online on August 22 in Nature Neuroscience, imply that evolution used the organized birth of neurons — by gestational day — to create specialized microcircuits in the hippocampus, the part of the brain responsible for memory formation. The researchers hypothesize that the brain may make use of the neuronal layers' gradual development to generate neural templates, or "Lego parts," that connect each new event to an old template as it is remembered.

According to the scientists, these principles of circuit building would imply that cells that are born next to one another are more likely to encode memories together and fail together, thus linking neuronal birthday to disorders like autism and Alzheimer's. The developing brain may be more susceptible to viral infections, poisons, or alcohol on specific gestational days due to variations in the number of cells born at various days.

According to senior study author György Buzsáki, MD, PhD, the Biggs Professor in the Department of Neuroscience and Physiology at NYU Langone Health, "the results of our study suggest that which day a hippocampal neuron is born strongly influences both how that single cell performs, and how populations of such cells signal together throughout life." According to Buzsáki, who is also a faculty member of the Neuroscience Institute at NYU Langone, "this work may change how we examine neurodevelopmental disorders, which have typically been looked at from a molecular or genetic, rather than a developmental, lens."

The novel aspect of the current study is the ability to follow the neuronal activity of a specific birthday into adulthood. The researchers used a method that allowed them to insert DNA into cells that were dividing into neurons in the womb to achieve this. Similar to a barcode, the DNA expressed markers that identified brain cells that were born on the same day. The researchers were subsequently able to analyze these neurons in the adult animal using this labeling technique.

The latest research discovered that neurons with the same birthday had a propensity to "co-fire" together, which is characterized by coordinated swings in their positive and negative charges and enables them to convey electrical messages jointly. The scientists speculate that the co-firing may be caused by shared synapses connecting neurons with the same birthday.

Studies in the past had demonstrated that patterns of combined neuronal activity during waking and sleeping can be used to define activity in the hippocampus. For example, hippocampal neurons engage in a cyclical burst of activity known as the "sharp wave-ripple" during sleep, when the day's memories are organized for long-term memory storage. This burst of activity is named for the shape it takes when graphically captured by EEG, a technology that records brain activity with electrodes.

According to lead author Roman Huszár, a graduate student in Buzsáki's group, "our results reveal that neurons generated on the same day become part of the same cooperating assemblies, participate in the same sharp wave-ripples, and represent the same memories." The storing of memories about a person, location, or event is a crucial implication of these associations and the pre-set templates they encode for hippocampus function.

The researchers will conduct more research in the future to determine the genes involved in behavior and memory development in neurons with the same birthday located in various brain areas.

The study's other authors, in addition to Buzsáki and Huszár, were Heike Blockus of the Department of Neuroscience and Zuckerman Mind Brain Behavior Institute at Columbia University, and Yunchang Zhang from the NYU Neuroscience Institute and the Center for Neural Science at New York University. National Institutes of Health grants RO1 MH122391 and U19 NS107616 funded the work.

NYU Langone Health / NYU Grossman School of Medicine

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