Chemically Mediated Cross-Excitation in Rat Dorsal Root Ganglia

Abstract

Primary afferent neurons in mammalian dorsal root ganglia (DRGs) are anatomically isolated from one another and are not synaptically interconnected. As such, they are classically thought to function as independent sensory communication elements. However, it has recently been shown that most DRG neurons are transiently depolarized when axons of neighboring neurons of the same ganglion are stimulated repetitively. Here we further characterize this functional coupling. In electrophysiological recordings made from excised rat DRGs, we found that DRG "cross-depolarization" is excitatory in that it is accompanied by an increase in the probability of spiking in response to otherwise subthreshold test pulses delivered intracellularly. Cross-depolarization contributes to this mutual cross-excitation. However, at least as important a contribution comes from a net increase in the neurons' input resistance (Rin) triggered by the stimulation of neighboring neurons. This change in Rin occurs even when cross-depolarization is absent or is balanced out. The amplitude of cross-depolaration was found to be voltage-dependent, with a reversal potential at approximately -23mV. Reversibility and the change in Rin both indicated that activity of neighboring neurons causes a membrane conductance change that is chemically mediated. Thus, far from being isolated, most DRG neurons participate in ongoing mutual interactions in which neuronal excitability is continuously modulated by afferent spike activity. This intraganglionic dialog appears to be mediated, at least in part, by an activity-dependent diffusable substance(s) released from neuronal somata and/or adjacent axons, and detected by neighboring cell somata and/or axons.

Burst Discharge in Primary Sensory Neurons: Triggered by Subthreshold Oscillations, Maintained by Depolarizing Afterpotentials

“…Signals were bandpass filtered at DC -10 kHz and recorded digitally on magnetic videotape (Neurodata DR-484) for off-line analysis. We categorized DRG neurons as A-or C -neurons by axon conduction velocity (C V) and the waveform of the intracellularly recorded spike as described elsewhere (Koerber and Mendell, 1992;Amir and Devor, 1996). A-neurons were f urther categorized: A inf neurons, which have an inflection on the falling phase of the action potential as assessed by analog differentiation, and relatively low C V (Amir and Devor, 1996), include many A␦ afferents and probably most of the myelinated nociceptors.…”

“…We categorized DRG neurons as A-or C -neurons by axon conduction velocity (C V) and the waveform of the intracellularly recorded spike as described elsewhere (Koerber and Mendell, 1992;Amir and Devor, 1996). A-neurons were f urther categorized: A inf neurons, which have an inflection on the falling phase of the action potential as assessed by analog differentiation, and relatively low C V (Amir and Devor, 1996), include many A␦ afferents and probably most of the myelinated nociceptors. A 0 neurons, neurons without an inflection and with faster C V, are predominantly A␤ afferents, most of which are low-threshold mechanoreceptors (Koerber and Mendell, 1992;Amir and Devor, 1996).…”

“…A-neurons were f urther categorized: A inf neurons, which have an inflection on the falling phase of the action potential as assessed by analog differentiation, and relatively low C V (Amir and Devor, 1996), include many A␦ afferents and probably most of the myelinated nociceptors. A 0 neurons, neurons without an inflection and with faster C V, are predominantly A␤ afferents, most of which are low-threshold mechanoreceptors (Koerber and Mendell, 1992;Amir and Devor, 1996). Some neurons showed a post-spike DAP.…”

“…Most DRG neurons show transient depolarization during tetanic stimulation of neurons that share the same DRG (Utzschneider et al, 1992;Amir and Devor, 1996). Here, two alternative stimulation protocols were used to induce this "DRG cross-excitation."…”

GABAB receptors inhibit low-voltage activated and high-voltage activated Ca2+ channels in sensory neurons via distinct mechanisms

“…chronic pain or 'phantom' itch) [1]. Although main somatosensory integration and processing is performed by CNS, growing evidence suggest that peripheral neurons themselves can communicate with each other, both electrically and chemically [2,3,4]. Accordingly, cell bodies of sensory neurons express various receptors for classical neurotransmitters such as acetylcholine, glutamate and GABA [5].…”