Abstract
Brain networks rely on complex circuitry and neurotransmitter communication between neurons to relay information. Because of their criticality, even when disruptions arise, these networks have to readjust themselves in order to maintain proper function. Networks can be disrupted by changes in gene expression due to alterations in methylation patterns after excisions in DNA methyltransferase genes DNMT1 and DNMT3a or prolonged activity deprivation. Interneurons with decreased methylation have a decrease in excitatory synaptic input while neuronal cultures subjected to prolonged activity deprivation show both altered synaptic changes and are more excitable. I investigated what genes might be responsible for the observed synaptic and intrinsic excitability changes in both conditions. RT-qPCR and immunohistochemistry show that in the DNMT1/3 double mutant there is a difference in the gene expression and a decrease in the protein levels of ErbB4, a receptor involved in regulating synapse size and number. Western blot analysis of activity deprived organotypic cultures shows non-significant decreases in ErbB4 and Twik1, a potassium channel, levels and a large but non-significant increase in cortisol releasing factor binding protein (CRFBP). These results provide a set of molecular pathways that are changed in response to alterations in activity and DNA methylation and can provide a mechanism to explain the observed physiological changes.