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Immediate and deferred epigenomic signatures of in vivo neuronal activation in mouse hippocampus.

Fernandez-Albert J, Lipinski M, Lopez-Cascales MT, Rowley MJ, Martin-Gonzalez AM, del Blanco B, Corces VG, Barco A

Nat Neurosci. In press
Published: 09 September 2019

Press Release CSIC (spanish)

The study, conducted in rodents, describes for the first time the changes in the organization of genetic material in hippocampal excitatory neurons from adult animals upon activation. To achieve this goal the team introduced several techniques in neurogenomic that are applied for the first time in an intact mouse brain. The result is a extensive and novel multi-omic analysis of the changes in the organization of the genetic material of neurons triggered by neuronal activation both in a pathological (epilepsy) and in a physiological context (learning and memory). The research revealed that in both cases the neuronal activation led to a transcriptional "burst" (i.e., a very strong activation of specific genes) that produces proteins important for neuronal plasticity and memory consolidation. The changes initiated by neuronal activation are more complex and act at more levels than previously thought. This activation is associated with an increase in the accessibility to the chromatin and the appearance of new interactions between separate chromatin regions that are necessary for gene activation. The longitudinal analysis of the changes also shows that some of these changes are long-lasting and can be detected even days after neuronal activation, as a form of genomic memory of the past neuronal activation. The dynamic and large-scale adjustments of the genome topology observed in our study probably contribute to the rapid and coordinated transcriptional response associated with neuronal activation in both normal and pathological conditions. These epigenetic fingerprints in the chromatin could represent an appropriate substrate for lasting changes in behavior. They could participate in the establishment of memories by influencing the future response of neurons to the same stimuli that caused the change or to different ones. In addition, some of these lasting changes could be related to brain disorders such as epilepsy and cognitive dysfunction.

The study has been conducted by an international team led by researchers from the Instituto de Neurosciencias, UMH-CSIC in Alicante, with the participation of Prof. Victor G Corces’ laboratory at Emory University in Atlanta (AT, USA).

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