Research reveals new molecular mechanisms that contribute to plasticity of the adult brain

The team's findings describe for the first time the changes that take place in the genetic material of excitatory neurons in the hippocampus of adult mice when they activate.

An international study headed by researchers of the Neurosciences Institute, mixed center of the Universidad Miguel Hernández (UMH) and the Spanish National Research Council (CSIC), has revealed a new analysis of the changes in the organization of the genetic material of neurons that is triggered by neural activation, both in a pathological (epilepsy) and physiological (learning and memory creation) context. The changes initiated by neural activation are more complex and act on more levels than was believed until now. Some of these changes are stable and can be detected even days after the neural activation, as a type of genetic memory of past activation. The work, conducted on rodents and published in the journal Nature Neuroscience, reveals new molecular mechanisms that contribute to the plasticity of the adult brain.

These findings, carried out by an international team headed by the laboratory of ángel Barco at the Institute of Neurosciences UMH CSIC, describe for the first time the changes that take place in the genetic material of excitatory neurons in the hippocampus of adult mice when they activate. The purpose of this study was to learn how the activation of a neuron changes its own future response. According to Barco, this process is a type of cellular memory that is essential for the creation of memories. To do so, they have used several neurogenomic techniques that have been applied for the first time in the untouched brain of a mouse.

Researchers wanted to learn what happens in a neuron that activates when the person is in a new context. According to the researchers, learning this process is important for the creation of memory, but it is very difficult to address experimentally. When the attention focuses on something specific, a very small group of neurons distributed diffusely in the brain activate, making it difficult to select them and see what happens inside.

In the experiment, researchers caused a mass activation of the mouse's neurons, as happens in an epileptic process, and they looked at the changes that take place in the chromatin. Chromatin is the form that DNA adopts in the cell nucleus. With what they learned in the epilepsy simulation, researchers have confirmed the changes that take place in a more mundane situation, such as the activation of groups of neurons that take place in the brain of a mouse when they explore a new location.

These changes - called epigenetic because they do not affect the information included in the genetic material, but their expression - can modify the expression and future response capacity of the genes involved in the cognitive function in the long term or permanently, which would thus represent a type of genomic memory.

This epigenetic footprint that lingers in the chromatin could represent a suitable substrate for long-term behavioral changes, which could take part in establishing memories that influence the future response of neurons to the same stimuli that caused the change or to different ones. Furthermore, some of these long-term changes could be linked to brain disorders like epilepsy and cognitive dysfunction.