Brain cells with the same 鈥渂irthdate鈥 are more likely to wire together into cooperative signaling circuits that carry out many functions, including the storage of memories, a new study finds.
Led by researchers from NYU Grossman School of Medicine, the new study on the brains of mice developing in the womb found that brain cells (neurons) with the same birthdate showed distinct connectivity and activity throughout the animals鈥 adult lives, whether they were asleep or awake.
, the findings suggest that evolution took advantage of the orderly birth of neurons鈥攂y gestational day鈥攖o form localized microcircuits in the hippocampus, the brain region that forms memories. Rather than attempting to create each new memory from scratch, the researchers suggest, the brain may exploit the stepwise formation of neuronal layers to establish neural templates, like 鈥淟ego pieces,鈥 that match each new experience to an existing template as it is remembered.
These rules of circuit assembly would suggest that cells born together are more likely to encode memories together, and to fail together, potentially implicating neuronal birthdate in diseases like autism and Alzheimer鈥檚 disease, say the authors. With changes to the number of cells born at different days, the developing brain may be vulnerable on some gestational days to viral infections, toxins, or alcohol.
鈥淥ur study鈥檚 results 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,鈥 says senior study author , the Biggs Professor of Neuroscience in the at 嘿嘿视频 Health. 鈥淭his work may reshape how we study neurodevelopmental disorders, which have traditionally been looked at through a molecular or genetic, rather than a developmental, lens,鈥 says Dr. Buzs谩ki, also a member of the at 嘿嘿视频.
New Understanding of Memory Storage
Fluorescence microscopy shows groups of brain cells that are born together on the same days (pink) and different days (blue) in the hippocampus of a mouse embryo. Many more neurons are born on embryonic day 15.5 (E15.5) than on earlier or later days. The study found that cells with the same birthdates during development form circuits that work together to encode similar memories.
Image: Courtesy of Roman Husz谩r et al., Nature Neuroscience
The current study鈥檚 innovation rests on tracking the activity of neurons of a given birthdate into adulthood. To accomplish this, the researchers relied on a technique that allowed them to transfer DNA into cells that were undergoing division into neurons in the womb. The DNA expressed markers that tagged brain cells that were born on same day, akin to a barcode. This labeling method then enabled the researchers to study these neurons in the adult animal.
Using a combination of techniques, the new study found that neurons of the same birthdate tend to 鈥渃o-fire鈥 together, characterized by synchronized swings in their positive and negative charges, allowing them to transmit electrical signals collectively. A likely reason for the co-firing, say the authors, is that neurons with the same birthdate are connected via shared neurons.
Past work had shown that activity in the hippocampus can be described in terms patterns of collective neuronal activity during waking and sleep. During sleep, for instance, when each day鈥檚 memories are consolidated for long-term memory storage, hippocampal neurons engage in a cyclical burst of activity called the 鈥渟harp wave-ripple,鈥 named for the shape it takes when captured graphically by EEG, a technology that records brain activity with electrodes.
鈥淥ur results show that neurons born on the same day become part of the same cooperating assemblies, and participate in the same sharp wave-ripples and represent the same memories,鈥 says first author Roman Husz谩r, a graduate student in Dr. Buzs谩ki鈥檚 lab. 鈥淭hese relationships, and the pre-set templates they encode, have a key implication for hippocampal function: the storage of a memory about a place or event.鈥
Moving forward, the team plans additional experiments to identify the genes active in the same birthdate neurons in different brain regions, and to test their role in memory formation and behavior.
Along with Dr. Buzs谩ki and Husz谩r, the other study authors were Yunchang Zhang from the Neuroscience Institute at 嘿嘿视频 and the Center for Neural Science at NYU; and Heike Blockus of the Department of Neuroscience and the Zuckerman Mind Brain Behavior Institute at Columbia University. Funding for the study was provide by National Institutes of Health grants RO1 MH122391 and U19 NS107616.
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