Reference number : GC-2017-Q1-01460, amendment number : , agreement type : G, recipient legal name : Cairns, Brian (The University of British Columbia), recipient country : CA, recipient province : nan, recipient city : British Columbia|Colombie-Britannique, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : 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 &ndash; 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., program purpose french : 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 &ndash; 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., agreement title english : Role of the trigeminal ganglion in sensory processing, agreement title french : Role of the trigeminal ganglion in sensory processing, agreement number : RGPIN, agreement value : 125000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada