FUNCTIONAL PROPERTIES OF NATIVE 5-HT<SUB>3</SUB>A RECEPTOR IN CORTICAL INTERNEURONS

The 5-hydroxytryptamine type-3 receptor (5-HT3R) is a pentameric, cation-selective ion channel, which is expressed on neurons of the peripheral and central nervous system. These receptors are composed of five A and/or B subunits that affect directly the biophysical properties of the channel. To this day, the biophysical properties of native 5-HT3Rs of cortical neurons and the effect of their activation on synaptic transmission in the cortex have not been studied in detail. Here, we analyzed native 5-HT3Rs on layer II/III neocortical interneurons. Gating kinetics as well as apparent affinity and Hill coefficients indicate that cortical interneurons predominantly express heteropentameric 5-HT3A/BRs. Moreover, activation of native 5-HT3Rs leads to desensitization, which is enhanced by intracellular Ca2+ ions. In addition to desensitization, repeated activation of the receptor leads to receptor internalization causing a reduction in current amplitude. After 5-HT-induced internalization, the 5-HT3Rs recycle back to the cell surface within hours. While puff-application of serotonin onto the soma elicits 5-HT3AR-mediated currents, no fast postsynaptic 5-HT3AR-mediated currents could be recorded when activating serotonergic axons. In contrast, paired recordings of 5-HT3R+ interneurons (5-HT3R+ IN) and pyramidal cells (Pyr) or inhibitory interneurons (IN) in LII/III of the somatosensory cortex showed that 5-HT3AR activation affects release probability. This suggests that 5HT3 receptors on layer neurons exert their effect primarily on the presynaptic side and not on the postsynaptic side. Overall, our study provides important information on the nature and function of native 5-HT3Rs in the somatosensory cortex.