Scientists Discover Source Of New Neurons Throughout Life In Brain’s Hippocampus

This looks like abstract art but it’s actually the memory center of a little mouse brain with neural stem cells. Berg et al./Cell

Scientists believe they have found the source of our lifetime stock of new neurons in the hippocampus, the vital region of the brain devoted to learning and memory.

"We've shown for the first time, in mammals, that neurons in the dentate gyrus of the hippocampus grow and develop from a single population of stem cells, over an entire lifespan," said senior author Hongjun Song in a statement.

This new growth is paramount because young, immature neurons are more flexible in making connections than mature ones. The study by University of Pennsylvania researchers is published in the journal Cell.

So how did they track extraordinarily tiny cells in mouse brains? First, they labeled the neural stem cells when they were still embryos in development. They next tracked the lineage of these cells from birth into adulthood, revealing a rather enigmatic process. 

New neural stem cells with the precursor label were making neurons throughout the course of the mouse’s life. They confirmed their findings by identifying a common molecular signature in the lineage cells via multiple analyses. 

"This process is unique in the brain," said co-senior author Guo-li Ming. "In the hippocampus, these cells never stop replicating and contribute to the flexibility of the brain in mammals.”

This mental flexibility is known as plasticity, the ability of the brain to form new connections and modify existing ones. This is not only needed for everyday use, but also in the event of injury or disease. Without plasticity, the infant brain could not form into the adulthood one in later years. 

"Earlier studies have suggested that specific parts of the brain, such as the olfactory bulb and the hippocampus, can generate neurons," Song said. "Until this study, it wasn't clear how this happens.”

The dentate gyrus of mouse hippocampus at postnatal day 7, blue is nuclei marker, green is progeny of HOPX-expressing progenitor cells, and red is marker of cell proliferation. Daniel A. Berg and Allison M. Bond

The news comes on the heels of a study published this week in Nature Medicine that found we make new neurons in the hippocampus well into our 90s. That study was on donated human brain tissue, whereas this research is an exploration of cells in the hippocampus of live mice.

Neurogenesis, the process of forming new neurons, is a controversial topic in neuroscience circles. The main reason is due to limited technology and the need to rely on donated brain tissue, which often is made messier by different preservation methods. 

In 2013, a study found that around 700 neurons in the hippocampus are made each day in adult brains. However, a 2018 study refuted that idea, finding that the hippocampus does not form new brain cells. 

To add to the fodder, Song notes: “We've shown for the first time in a mammalian brain that development is ongoing from the beginning, and that this one process happens over a continuum that lasts a lifetime.”

Of course, more research is needed to determine whether this stem cell generation in mice also happens in humans. 

"This paper has implications for understanding how the brain maintains a 'young' state for learning and memory," said co-senior author Guo-li Ming of the Perelman School of Medicine. Additionally, "if we could harness this capacity and this mechanism, we may be able to repair and regenerate parts of the brain.”

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