Different pools of postsynaptic GABA_A receptors mediate inhibition evoked by low‐ and high‐frequency presynaptic stimulation at hippocampal synapses

Abstract

Patterns of short-term synaptic plasticity could considerably differ between synapses of the same axon. This may lead to separation of synaptic receptors transmitting either low- or high-frequency signals and, therefore, may have functional consequences for the information transfer in the brain. Here, we estimated a degree of such separation at hippocampal GABAergic synapses using a use-dependent GABAA receptor antagonist, picrotoxin, to selectively suppress a pool of GABAA receptors monosynaptically activated during the low-frequency stimulation. The relative changes in postsynaptic responses evoked by the high-frequency stimulation before and after such block were used to estimate the contribution of this GABAA receptor pool to synaptic transmission at high frequencies. Using this approach, we have shown that IPSCs evoked by low-frequency (0.2 Hz) stimulation and asynchronous currents evoked by high-frequency (20-40 Hz) stimulation are mediated by different pools of postsynaptic GABAA receptors. Thus, our findings suggest that inhibition produced by a single hippocampal interneuron may be selectively routed to different postsynaptic targets depending on the presynaptic discharge frequency.

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

“…Recent studies demonstrate that nonsynchronous forms of neurotransmitter release are important to the regulation of synaptic plasticity, memory processing, and antidepressant action (Autry et al, 2011;Xu et al, 2012;Nosyreva et al, 2013;Cho et al, 2015). The precision of the synaptic message is maintained at the postsynaptic level as variations in presynaptic release differentially affect receptors and downstream targets (Atasoy et al, 2008;Autry et al, 2011;Sara et al, 2011;Stepanyuk et al, 2014). This differential postsynaptic signaling is enabled by presynaptic segregation of vesicle-trafficking pathways that mediate spontaneous and synchronous evoked release (Kavalali, 2015).…”