Improved cognition and mood by inducing neurogenesis via optogenetic stimulation of the brain


The scientists used optogenetic techniques to stimulate specific brain cells to increase production of neural stem cells and neurons relevant to memory and emotion processing in animal models.

We humans lose mental acuity, an unfortunate side effect of aging. And for individuals with neurodegenerative conditions such as Alzheimer’s and Parkinson’s, the loss of cognitive function often accompanied by mood disorders such as anxiety is a harrowing experience. One way to push back against cognitive decline and anxiety would be to spur the creation of new neurons. For the first time, the scientists have targeted a specific kind of neuron in mice to increase the production of neural stem cells and spur on the creation of new adult neurons to affect behavior.

Targeting these cells, as reported in the journal Nature Neuroscience, modulated memory retrieval and altered anxiety-like behaviors in mice. Essentially, the scientists boosted the electrical activity between cells in the hypothalamus and the hippocampus to create new neurons – an important process called neurogenesis.

“Targeting the hypothalamic neurons to enhance adult hippocampal neurogenesis will not only benefit brain functions,” said senior author, “but also holds the potential to treat cognitive and affective deficits associated with various brain disorders.”

Most neurons we carry for life were created before we were born and get organized during early childhood. But such neurogenesis continues into adulthood and throughout life. In fact, one of the reasons for cognitive decline and anxiety, and even diseases such as Alzheimer’s, is the suspension of neurogenesis. 

The authors knew that adult hippocampal neurogenesis plays a critical role in memory and emotion processing, and that neural circuit activity – think ‘electrical activity’ – regulates this process in a constantly changing manner.

What no one knew is whether this neural circuit activity could be manipulated to spur neurogenesis to such a degree that the effect would be seen as a changed behavior, such as better memory or less anxiety.

To see the effect of modulating neural activity, the lab conducted experiments. They used optogenetics – essentially a method using light to trigger neuronal activity – in a small brain structure called supramammillary nucleus (SuM). The SuM is located inside the hypothalamus region of the brain; it helps manage things from cognition to locomotion and sleep/wakefulness.

When the researchers chronically stimulated the SuM neurons, they discovered a robust promotion of neurogenesis at multiple stages. They observed increased production of neural stem cells and the creation of new adult-born neurons with enhanced properties. Optogenetic stimulation of these new neurons then altered memory and anxiety-like behaviors.

“We also show that the SuM neurons are highly responsive when the mice experienced new things in their environment,” the senior author said. “In fact, in a new environment, mice require these cells for neurogenesis.”

Impaired adult hippocampal neurogenesis correlates with many pathological states, such as aging, neurodegenerative diseases, and mental disorders. “Therefore,” the author added, “targeting the hypothalamic neurons to enhance adult hippocampal neurogenesis will not only benefit brain functions but also holds the potential to treat cognitive and affective deficits associated with various brain disorders.”

https://www.nature.com/articles/s41593-022-01065-x

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