Histone Deacetylase Can Enhance Inhibitory Transmission

Transcription factors bind to regulatory elements in DNA and activate or suppress gene transcription. DNA is tightly wound around histone proteins, however, and before transcriptional regulators can bind, histones must loosen their grip. This is achieved by acetylation,whichismediatedbyhistoneacetyltransferases (HATs) and reversed by histone deacetylases (HDACs). Both HATs and HDACs have roles in neuronal plasticity; HDAC2, for example, appears to limit memory formation, because exogenous HDAC inhibitors enhance memory formation in mice. Furthermore, overexpression of HDAC2 reduces dendritic spine density, synapse number, and synaptic plasticity, whereas HDAC2 knock-out increases excitatory synapse number and facilitates long-term potentiation (LTP). Hanson et al. now show that HDAC2 regulates inhibitory, as well as excitatory synaptic transmission. Overexpressing HDAC2 in a subset of rat hippocampal neurons reduced the amplitude of miniature (m) EPSCs and increased the amplitude of mIPSCs. HDAC2 knockdown had the opposite effects. The reduction in mIPSC amplitude appeared to result in part from reduced synaptic targeting of GABAA receptors.