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Transcriptional and Epigenetic Mechanisms of Neuronal Plasticity

Principal investigator: Angel Barco , Ph.D.

Group research focus

We are interested in the molecular mechanisms underlying learning and memory storage, more precisely in the role of transcriptional and epigenetic processes in neuronal plasticity. We also investigate how the malfunction of these mechanisms may lead to pathological situations in the nervous system. To investigate these questions, we use a multidisciplinary approach that combines mouse genetics, molecular biology, physiology and behavioral studies.

Neurons of the dentate gyrus

Neurons of the dentate gyrus

In particular, among other findings, our research has helped to explain how synaptic specificity can be achieved after nuclear activation by synaptic inputs and pioneered the field of neuroepigenetics. We have also demonstrated the dual function of CREB in the regulation of both synaptic and intrinsic plasticity, characterized several mouse models for Rubinstein-Taybi syndrome and investigated the role of histone acetylation in neuronal plasticity and neuropathology. More recently, we have undertaken a global approach for understanding the relationship between specific epigenetic marks in neuronal chromatin, gene expression and neuronal plasticity in physiological and pathological conditions.

Our future research focuses on the following two areas:

Nuclei and dendrites in the hippocampus.

Nuclei and dendrites in the hippocampus.

  1. Role of activity-dependent gene expression in neuronal plasticity: Alterations in patterns of gene expression are thought to underlie the long-lasting changes in the strength of synaptic connections between neurons responsible for the encoding of memories in the nervous system. A number of transcription factors have been involved in this process. We are investigating the details of the participation of the CREB family of transcription factors, as well as other activity-regulated transcription factors, in plasticity and memory. Towards this end, we will apply genome-wide analytical approaches, such as RNAseq and ChIPseq, for identifying candidate genes downstream of these transcription factors.
  2. Chromatin remodeling and neuronal plasticity: Histone modification is a well-known mechanism for the regulation of gene expression. Specifically, the acetylation and methylation of nucleosomes provides a mechanism for epigenetic regulation of the activity of loci that are relevant in neuronal plasticity and behaviour. We are interested in exploring the contribution of histone modifications to learning, memory and other long-lasting modification of the animal’s behavior. We also investigate on different mouse model for neurological conditions, such as Huntington disease and some intellectual disability syndromes, in which these epigenetic mechanisms seem to be affected.

Ongoing collaborative research

Recent publications