title: Mechanisms of retroaxonal barrage firing in hippocampal interneurons.
abstract: We recently described a new form of neural integration and firing in a subset of interneurons, in which evoking hundreds of action potentials over tens of seconds to minutes produces a sudden barrage of action potentials lasting about a minute beyond the inciting stimulation. During this persistent firing, action potentials are generated in the distal axon and propagate retrogradely to the soma. To distinguish this from other forms of persistent firing, we refer to it here as 'retroaxonal barrage firing', or 'barrage firing' for short. Its induction is blocked by chemical inhibitors of gap junctions and curiously, stimulation of one interneuron in some cases triggers barrage firing in a nearby, unstimulated interneuron. Beyond these clues, the mechanisms of barrage firing are unknown. Here we report new results related to these mechanisms. Induction of barrage firing was blocked by lowering extracellular calcium, as long as normal action potential threshold was maintained, and it was inhibited by blocking L-type voltage-gated calcium channels. Despite its calcium dependence, barrage firing was not prevented by inhibiting chemical synaptic transmission. Furthermore, loading the stimulated/recorded interneuron with BAPTA did not block barrage firing, suggesting that the required calcium entry occurs in other cells. Finally, barrage firing was normal in mice with deletion of the primary gene for neuronal gap junctions (connexin36), suggesting that non-neuronal gap junctions may be involved. Together, these findings suggest that barrage firing is probably triggered by a multicellular mechanism involving calcium signalling and gap junctions, but operating independently of chemical synaptic transmission.
authors.affiliation: N. Spruston: Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Dr., Ashburn, VA 20147, USA. sprustonn@janelia.hhmi.org.
authors.forename: Mark E J
authors.initials: ME
authors.lastname: Sheffield
authors.forename: Gabrielle B
authors.initials: GB
authors.lastname: Edgerton
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Heuermann
authors.forename: Tara
authors.initials: T
authors.lastname: Deemyad
authors.forename: Brett D
authors.initials: BD
authors.lastname: Mensh
authors.forename: Nelson
authors.initials: N
authors.lastname: Spruston
mesh_terms: D000200:Action Potentials; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009435:Synaptic Transmission; D000097004:Gap Junction delta-2 Protein
chemical_list: D002118:Calcium; D020746:Calcium Channels, L-Type; D017630:Connexins; D000097004:Gap Junction delta-2 Protein