title: Bicuculline-sensitive primary afferent depolarization remains after greatly restricting synaptic transmission in the mammalian spinal cord.
abstract: Primary afferent neurotransmission is the fundamental first step in the central processing of sensory stimuli. A major mechanism producing afferent presynaptic inhibition is via a channel-mediated depolarization of their intraspinal terminals which can be recorded extracellularly as a dorsal root potential (DRP). Based on measures of DRP latency it has been inferred that this primary afferent depolarization (PAD) of low-threshold afferents is mediated by minimally trisynaptic pathways with GABAergic interneurons forming last-order axoaxonic synapses onto afferent terminals. We used an in vitro rat spinal cord preparation under conditions that restrict synaptic transmission to test whether more direct low-threshold pathways can produce PAD. Mephenesin or high divalent cation solutions were used to limit oligosynaptic transmission. Recordings of synaptic currents in dorsal horn neurons and population synaptic potentials in ventral roots provided evidence that conventional transmission was chiefly restricted to monosynaptic actions. Under these conditions, DRP amplitude was largely unchanged but with faster time to peak and reduced duration. Similar results were obtained following stimulation of peripheral nerves. Even following near complete block of transmission with high Mg(2+)/low Ca(2+)-containing solution, the evoked DRP was reduced but not blocked. In comparison, in nominally Ca(2+)-free or EGTA-containing solution, the DRP was completely blocked confirming that Ca(2+) entry mediated synaptic transmission is required for DRP genesis. Overall these results demonstrate that PAD of low-threshold primary afferents can occur by more direct synaptic mechanisms, including the possibility of direct negative-feedback or nonspiking dendroaxonic pathways.
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Shreckengost
authors.forename: Jorge
authors.initials: J
authors.lastname: Calvo
authors.forename: Jorge
authors.initials: J
authors.lastname: Quevedo
authors.forename: Shawn
authors.initials: S
authors.lastname: Hochman
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D008159:Lumbar Vertebrae; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D010525:Peripheral Nerves / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D002118:Calcium; D001640:Bicuculline
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