Brain Neurons Born Together Wire and Fire Together for Life

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

The findings of our study indicate that a hippocampus neuron's birthdate has a significant impact on both its individual performance and how groups of such cells communicate with one another over the course of a lifetime. — Dr. György Buzsáki, Ph.D.

According to the study, which looked at how mice's brains developed while they were still in the womb, neurons with the same birthdate displayed distinctive connections and activity throughout the animals' adult life, whether they were awake or asleep. Researchers from NYU Grossman School of Medicine were in charge of the study.

The research, which was published online today (August 22, 2022) in the journal Nature Neuroscience, suggests that the hippocampus, the part of the brain responsible for memory formation, evolved localized microcircuits as a result of the orderly birth of neurons, by gestational day. The researchers propose that rather than starting from zero with every new memory, the brain may use the sequential development of neuronal layers to generate neural templates. These perform the function of "LEGO components," matching each new experience to a previously established template as it is recalled.

These principles of circuit formation, according to the authors, could implicate the neuronal birthday in disorders like autism and Alzheimer's since it would imply that cells that are born together are more likely to encode memories together and to fail together. The growing brain may be more susceptible to viral infections, alcoholism, or poisons on specific gestational days due to variations in the number of cells born on different days.

In the hippocampus of a mouse embryo, the image displays clusters of brain cells that are born on the same day (pink) and on a different day (blue). On embryonic day 15.5, many more neurons are born than on earlier or later days. According to the study, during development, cells with the same birthday create circuits that cooperate to encode memories with a similar structure. By permission of Nature Neuroscience

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 scientists used a method that allowed them to insert DNA into cells that were dividing into neurons in the womb to achieve this. Brain cells that were born on the same day were marked with markers that the DNA expressed, acting as a kind of barcode. The researchers were subsequently able to analyze these neurons in the adult animal using this labeling technique.

The new research found 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 together. According to the authors, the co-firing is most likely caused by shared synapses connecting neurons with the same birthday.

Previous studies have demonstrated that patterns of collective 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 research team will conduct additional studies in the future to determine the genes involved in behavior and memory development in neurons with the same birthday located in other brain areas.

Preconfigured dynamics in the hippocampus are influenced by the neurogenesis rate and embryonic birthdate, according to the cited study. Nature Neuroscience, August 22, 2022.

The study's other authors, in addition to Buzsáki and Huszár, were Heike Blockus from 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. The National Institutes of Health awarded the study funding through grants RO1 MH122391 and U19 NS107616.

By NYU GROSSMAN SCHOOL OF MEDICINE