The Presynaptic Differences In Glutamatergic And GABAergic Synapses

The balance between excitatory and inhibitory synapses is crucial to the regulation of neural circuits, so glutamatergic and GABAergic synapses have always been a focus of interest. While early studies are more concerned with the differences between the postsynaptic compartments of excitatory and inhibitory synapses, discrimination of the presynaptic compartment is generally not taken into consideration despite a number of studies that investigate only glutamatergic synapses.In our study, we employed high pressure freezing to compare the vesicle morphology for excitatory and inhibitory synapses of mice cortex using3D reconstruction. We found that while the majority of presynaptic vesicles in GABAergic synapses are over60nm in diameter, those in excitatory synapses are approximately50nm in diameter; We marked vesicles in GABAergic and glutamatergic synapses destined for functional presynaptic uptake using horseradish peroxidase, and observed changes in their morphology at different time points after uptake. Results showed that in GABAergic synapses, vesicles uptake by the presynaptic membrane were mostly comparable to endosomes in diameter. After uptake, the large vesicles undergo fission over a15min period. This phenomenon was not significant in Glutamatergic synapses. Next, we marked vesicles with a dye FM4-46, and observed presynaptic vesicle release in neurons in response to stimulation under a fluorescence microscope. We found that after presynaptic uptake, vesicles in GABAergic neurons could be completely released in response to stimulation, while those in glutamatergic neurons could only be partially released leaving a reserved pool of vesicles that continue to release after prolong depolarization by high concentration of KC1. Finally, we used double whole cell patch-clamp recording to compare the current recovery rate of glutamatergic and GABAergic synapses after tetanized stimulation. The results showed that after stimulation, glutamatergic synapse recovered to a initial strength faster. In conclusion, we hypothesize the presence of distinct mechanisms for presynaptic vesicle recycling in glutamatergic and GABAergic synapses, which offers a new concept in the field.