Mechanisms of retroaxonal barrage firing in hippocampal interneurons
Autor: | Mark E. J. Sheffield, Gabrielle B. Edgerton, Robert J. Heuermann, Brett D. Mensh, Tara Deemyad, Nelson Spruston |
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Rok vydání: | 2013 |
Předmět: |
education.field_of_study
Action potential Interneuron Physiology musculoskeletal neural and ocular physiology Population Chemical synaptic transmission Neurotransmission Biology Inhibitory postsynaptic potential Antidromic chemistry.chemical_compound medicine.anatomical_structure nervous system BAPTA chemistry medicine education Neuroscience |
Zdroj: | The Journal of Physiology. 591:4793-4805 |
ISSN: | 0022-3751 |
DOI: | 10.1113/jphysiol.2013.258418 |
Popis: | Key points • Persistent firing can be triggered in a population of inhibitory interneurons found in the hippocampus and neocortex. Repeated stimulation eventually triggers an autonomous barrage of spikes that is generated and maintained in the axon, followed by antidromic propagation to the soma. • This barrage of spikes is generated and maintained in the axon, followed by antidromic propagation to the soma. The mechanisms underlying this ‘retroaxonal barrage firing’ are unknown. • We find that retroaxonal barrage firing is Ca2+ dependent, is inhibited by the L-type Ca2+ channel blockers cadmium, nifedipine and verapamil, and does not require synaptic transmission. Loading the stimulated interneuron with BAPTA did not block barrage firing, suggesting that the required Ca2+ entry may occur in other cells. • Retroaxonal barrage firing was observed in mice lacking the Cx36 isoform (most common neuronal isoform), indicating that this particular isoform is not required. 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. |
Databáze: | OpenAIRE |
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