Abstract
The mammalian brain differentiates itself from its evolutionary predecessors by the trait of a large and complex cortical network. Cortical circuitry is composed of excitatory and inhibitory neurons having many subsets of integrative firing properties. These firing properties are regulated at the epigenetic level during development and post-replication in neurons by a class of DNA methyltransferase (DNMT) proteins that target a dinucleotide sequence CpG. Methylation can confer a heterochromatic state in DNA by recruitment of methyl-binding proteins such as MBD-1-MBD-4 (Hendrich et al 1998; Boyes et al 1991) and HDACs. We have used a transgenic mouse model in which combinations of the two early-development DNMTs are ablated by use of a conditional knockout allele driven in a specific class of inhibitory neurons. By use of a manual cell-sorting technique (Hempel et al 2007) we collected RNA profiles from a distinct class of parvalbumin positive inhibitory neurons. Results of RNA-Sequencing brought to attention the differential expression of a previously classified family of genes, α-takusan, which regulate synaptic activity. The broad down regulation of α-takusan can be related to a previously found reduction in excitatory post-synaptic amplitude and frequency data obtained from prior electrophysiological experiments. From these findings we believe the down regulation of certain α-takusan genes by DNMT activity is causal in the reduction of postsynaptic excitation in parvalbumin-positive inhibitory interneurons in L5 motor cortex.