Bicuculline-sensitive primary afferent depolarization remains after greatly restricting synaptic transmission in the mammalian spinal cord

Jacob Shreckengost, Jorge Calvo, Jorge Quevedo, Shawn Hochman

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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 Mg2+/low Ca 2+-containing solution, the evoked DRP was reduced but not blocked. In comparison, in nominally Ca2+-free or EGTA-containing solution, the DRP was completely blocked confirming that Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)5283-5288
Number of pages6
JournalJournal of Neuroscience
Issue number15
StatePublished - Apr 14 2010

ASJC Scopus subject areas

  • General Neuroscience


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