Conditional Dnmt1 deletion in dorsal forebrain disrupts development of somatosensory barrel cortex and thalamocortical long-term potentiation.

Abstract

The transcriptional mechanisms governing the development and plasticity of somatopic sensory maps in the cerebral cortex have not been extensively studied. In particular, no studies have addressed the role of epigenetic mechanisms in the development of sensory maps. DNA methylation is one the main epigenetic mechanisms available to mammalian cells to regulate gene transcription. As demethylation results in embryonic lethality, it has been very difficult to study the role of DNA methylation in brain development. We have used cre-lox technology to generate forebrain-specific deletion of DNA methyltransferase 1 (Dnmt1), the enzyme required for the maintenance of DNA methylation. We find that demethylation of neurons in the cerebral cortex results in the failure of development of somatosensory barrel cortex. We also find that in spite of functional thalamocortical neurotransmission, thalamocortical long-term potentiation cannot be induced in slices from Dnmt1 conditional mutants. These studies emphasize the importance of DNA methylation for the development of sensory maps and suggest epigenetic mechanisms may play a role in the development of synaptic plasticity.