Expression and Functional Significance of MAGuKs on Cortical Interneurons

Abstract

GABAergic inhibitory interneurons, which constitute twenty percent of the entire neuron population, are crucial to the function of brain. They have several subgroups with distinct morphological, biochemical and most importantly physiological properties. Parvalbumin (PV) and Somatostatin (SOM) expressing inhibitory interneurons represent two major subgroups of interneurons in the cortex as well as most other brain regions. Their activity is driven by the excitatory input they receive from pyramidal neurons. SAP97 is a scaffolding protein at the postsynaptic density of the excitatory synapses. It has important functional roles in trafficking and clustering of various types of ion channels and therefore is involved in regulation of the electrical activity of neurons. Neither the expression nor the functional role of SAP97 in cortical interneurons have been addressed before. With in situ hybridization and single cell RT-PCR, we showed that the expression of SAP97 is restricted to a fraction of PV and SOM interneurons of both juvenile and adult mouse visual cortex and developmentally regulated. With electrophysiology, we also found that there is a strong correlation with SAP97 expression and various membrane properties of PV interneurons. SAP97 expressing interneurons have less excitable membranes and fire faster action potentials. Moreover, they receive more frequent excitatory input. In agreement with that, when we overexpress SAP97 in PV interneurons that do not have endogenous SAP97, these interneurons showed electrophysiological properties that are similar to endogenous SAP97 expressing PV interneurons. Our results make important contributions to understanding the functional development of neurons, the regulation of their activity.