Burst firing is required for induction of Hebbian LTP at lateral perforant path to hippocampal granule cell synapses

High frequency burst firing is critical in summation of back-propagating action potentials (APs) in dendrites, which may greatly depolarize dendritic membrane potential. The physiological significance of burst firings of hippocampal dentate GCs in synaptic plasticity remains unknown. We found that GCs with low input resistance could be categorized into regular-spiking (RS) and burst-spiking (BS) cells based on their initial firing frequency (F-init) upon somatic rheobase current injection, and investigated how two types of GCs differ in long-term potentiation (LTP) induced by high-frequency lateral perforant pathway (LPP) inputs. Induction of Hebbian LTP at LPP synapses required at least three postsynaptic APs at F-init higher than 100 Hz, which was met in BS but not in RS cells. The synaptically evoked burst firing was critically dependent on persistent Na+ current, which was larger in BS than RS cells. The Ca2+ source for Hebbian LTP at LPP synapses was primarily provided by L-type calcium channels. In contrast, Hebbian LTP at medial PP synapses was mediated by T-type calcium channels, and could be induced regardless of cell types or F-init of postsynaptic APs. These results suggest that intrinsic firing properties affect synaptically driven firing patterns, and that bursting behavior differentially affects Hebbian LTP mechanisms depending on the synaptic input pathway.

Automated summary

High frequency burst firing plays a crucial role in dendritic membrane potential depolarization. The physiological significance of burst firings in hippocampal dentate granule cells (GCs) remains unclear. This study found that GCs can be categorized into regular-spiking (RS) and burst-spiking (BS) cells based on their initial firing frequency (F-init) and investigated their differences in long-term potentiation (LTP) induced by high-frequency inputs. The results showed that Hebbian LTP at lateral perforant pathway (LPP) synapses required burst firing, which was dependent on persistent Na+ current and larger in BS cells. Calcium channels also played a role in LTP, with L-type channels involved in LPP synapses and T-type channels in medial perforant pathway (PP) synapses.