How do tonic glutamatergic synapses evade receptor desensitization?

Abstract

Photoreceptor output synapses are the best known tonic chemical synapses in the nervous system, in which glutamate is continuously released in darkness, activating AMPA/kainate receptors in postsynaptic neurons. It has been shown that glutamate receptors in certain types of second-order retinal cells are largely desensitized in darkness, leading to small postsynaptic currents and reduced response dynamic ranges. Here we show that the tonic glutamatergic synapses between photoreceptors and rod-dominated hyperpolarizing bipolar cells (HBC(R)s) in the salamander retina evade postsynaptic receptor desensitization by using (1) multiple invaginating ribbon junctions as releasing sites for low-frequency, synchronized multiquantal release at each site; and (2) the GluR4 AMPA receptors as the postsynaptic receptors. The multiquantal events exhibit faster decay time than the GluR4 receptor desensitization time constant and therefore self-desensitization is minimized, and the average inter-event duration in darkness is much longer than the GluR4 desensitization recovery time and thus mutual desensitization is avoided. Consequently, the HBC(R)s are not desensitized in darkness, allowing light signals to be encoded by the full operating range of the glutamate-gated postsynaptic currents. Our study illustrates for the first time how a tonic glutamatergic synapse avoids postsynaptic receptor desensitization, a strategy that may be shared by many other synapses in the nervous system that need extended operation capacity.