Mecp2 is required for activity-dependent maturation of olfactory circuits.

DEGANO AL; RONNETT, G.

Huerta Grande, Córdoba

Congreso; IIRCN-Segunda Reunión Conjunta (SAN: XXV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias y TAN: XII Taller Argentino de Neurociencias).; 2010

Methyl Cytosine Binding Protein 2 (MeCP2) is a transcriptional repressor that binds to methylated DNA. Alterations in the expression levels of Mecp2 have been related to autism spectrum disorders. Studies in mouse models of Mecp2 deficiency have shown that this protein is important for neuronal maturation, neurite complexity, synaptogenesis and synaptic plasticity, although the underlying mechanisms are not completely understood. Our working hypothesis proposes that Mecp2 plays a role in the formation of neural circuits during development. To test this hypothesis we use the olfactory system as a neurodevelopmental model. This system undergoes postnatal neurogenesis and axons from olfactory neurons form highly stereotyped projections to higher-order neurons, facilitating the detection of possible defects in the course of the establishment of connectivity. Using this system, we previously described that Mecp2 plays a role in neuronal terminal differentiation and synaptic formation during postnatal development. Our present results show defective postnatal refinement in olfactory circuits from Mecp2-null mice after odorant stimulation. This defect was associated with deficient activity-induced responses in Mecp2-null mice (i.e. increase in BDNF expression). These results suggest that Mecp2 plays a role in activity-dependent maturation of neural circuits and may have broad implications for understanding the molecular pathophysiology of autism spectrum disorders.