Cairns, Brian (The University of British Columbia)

Purpose

The sensory ganglia are often considered a passive conduit of action potentials that arise in the periphery and travel to the central nervous system. Until relatively recently, very little attention has been paid to the possibility that the ganglion could potentially modify sensory transmission. However, several groups have reported that intraganglionic injection of small interfering RNA against targets such as the gamma-aminobutyric acid (GABA) A receptor, or viral vectors containing genes for various enzymes have effects on sensory transmission. Trigeminal ganglia are comprised of ganglion neurons and two types of glial cells, satellite glial cells (SGCs) and Schwann cells. The soma of the trigeminal ganglion neuron is surrounded by SGCs, with a gap of about 20 nm between the neuronal and SGC cell membranes. It is thought that SGCs modulate the activity of ganglion neurons by releasing neuromodulatory substances into this gap. Trigeminal ganglion neurons express receptors for many neurotransmitters, but the functional effect of activation of these receptors on sensory transmission is largely unknown. We investigated whether activated SGCs release the excitatory amino acid glutamate and if this would depolarize trigeminal ganglion neurons to cause ectopic action potential generation towards the brain (orthodromic) and the periphery (antidromic). We found that artificially elevated glutamate levels in the trigeminal ganglion did cause trigeminal ganglion neurons to fire action potentials and that this was associated with mechanical sensitization of trigeminal afferent fibers that innervate facial tissues. Action potential discharge evoked by injection of glutamate into the trigeminal ganglion was mediated by N-Methyl-D-Aspartate (NMDA) receptor activation and could be enhanced by blocking excitatory amino acid transporters (EAATs) that were found on both neurons and SGCs. These findings suggest that alteration in glutamate concentration in the ganglion can alter sensory thresholds and offer the possibility that sensory information may be modulated at this level by other neurotransmitters. This application proposes to investigate the effect neurotransmitters on the activity of trigeminal ganglion neurons and satellite glial cells, and to determine how these neuroactive substances alter sensory transmission through the ganglia and whether there are sex-related differences appear to influence peripheral processing of sensory information. An overarching goal of this research is to determine whether significant neural processing of sensory information occurs at the level of the trigeminal sensory ganglion. The goal is to understand how ganglion neuron – satellite glial cell communication modifies the transmission of sensory information through the ganglion. This work may identify peripheral mechanisms that could be targeted to modify altered sensory input.