Epigenetic Regulation of Alternative Splicing of Plasticity-Related Genes in Neuron Cultures

Synaptic plasticity is the activity-dependent change in synaptic strength, which is widely assumed to be the crucial component of learning and memory. Alternative splicing is one of the mechanisms of synaptic plasticity: changes in the composition of protein isoforms influence the whole system of synaptic protein interactions, transform it and, along with the other factors, alter the efficiency of synaptic transmission. A complex system of alternative splicing regulation has been discovered, and epigenetic modifications are an important part of this system. In particular, histone acetylation affects splice site choice, by increasing the RNA-polymerase elongation rate. Here, we used the histone deacetylase inhibitor trichostatin A (TSA) on rat cortical neuron cultures to investigate how exactly histone acetylation influences alternative splicing of some plasticity-related genes, such as: Nrxn1, Nrxn2, Shank2, Ank3 and Syngap1 and a gene that is directly involved in the regulation of alternative splicing - Psip1. We also showed with calcium imaging that molecular rearrangements induced by histone acetylation increase the synchronization of neural network activity in rat cortical neuron cultures.