Regulation of action potential waveforms by axonal GABAA receptors in cortical pyramidal neurons.

Yang Xia,Mingpo Yang,Yousheng Shu,Shaoqun Zeng,Yuan Zhao,Fabien Tell

doi:10.1371/journal.pone.0100968

Abstract

GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb) of the main axon trunk of layer –5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs) and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors.

Highlights

The dendrites and cell body receive and summate synaptic inputs, whereas the axon is responsible for action potential (AP) initiation and propagation
To examine whether these receptors are expressed at the main axon trunk of layer –5 pyramidal neurons in prefrontal cortex, we performed whole-cell recordings from axon blebs, the resealed cut ends of axons formed during slicing, and applied GABA locally to the axon via iontophoresis using sharp electrodes (Figure 1A)
Application of GABA at a lateral site b that was 25 mm away from the bleb could not induce any response; in contrast, at the site c we could observe GABA responses similar to those at the recorded bleb. These results indicate the presence of GABA receptors at both the bleb and the main axon trunk

Summary

Introduction

The dendrites and cell body receive and summate synaptic inputs, whereas the axon is responsible for action potential (AP) initiation and propagation. The axon usually functions as a reliable cable conducting APs in all-or-none (digital) mode; this long-held view of the axon has recently been challenged Emerging evidences has shown that subthreshold changes in presynaptic membrane potential (Vm) can regulate the amplitude of AP-triggered postsynaptic responses, indicating that neurons communicate in an analog mode [1,2,3] This mode of neuronal communication may result from activities of axonal ion channels [4,5] and receptors [6,7] that regulate AP waveforms, presynaptic Ca2+ signals and, neurotransmitter release [8,9]. There were several lines of evidence implicating a role for axonal GABAA receptors in regulating neuronal activities [14,15]

Methods

Results

Conclusion