A brain protein partnership that erases outdated memories to boost flexible thinking

What is it about?

The brain’s ability to adapt to new situations — called cognitive flexibility — depends on updating memories by replacing outdated information with new, more relevant information. This process works by strengthening or weakening connections between neurons, though the detailed mechanisms underlying this process remain uncertain. We discovered that two proteins, Kv4.2 and mGluR5, work together to weaken previously strengthened neuronal connections — a process key to updating memories. In mice with a mutation that disrupts normal Kv4.2 activity, mGluR5 became more active, making it easier to weaken those connections. These mice showed better cognitive flexibility in behavioral tests, and this improvement was directly tied to mGluR5 activity. Our findings suggest that the way these two proteins traffic and interact within brain cells is a key driver of cognitive flexibility. Targeting this process could one day lead to treatments for conditions involving cognitive rigidity, such as autism, PTSD, and anxiety disorders.

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Photo by Jesús Vidal on Unsplash

Photo by Jesús Vidal on Unsplash

Why is it important?

The hippocampus is a brain region critical for learning and memory. Previous longitudinal recordings of neurons in behaving rodents suggest that neurons are constantly being strengthened and weakened as mice continuously learn — suggesting the brain remains far more adaptable during learning than we previously thought. We identified an important protein complex that regulates the ability to make these connections flexible, making it easier for the brain to update memories and adjust behavior as circumstances change.

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