Action potential backpropagation into dentate granule cell dendrites

The dendrites of many principle neurons express a variety of voltage-gated Na+, Ca2+, and K+ channels that may influence passive dendritic membrane properties and potentially support regenerative electrical activity in the form of Na+- or Ca 2+-dependent action potentials (APs). Dendritic APs may be involved in modifying synaptic efficacy and can influence somatic firing characteristics. This thesis investigates the extent to which perisomatically initiated APs invade dentate granule cell (DGC) dendrites, factors that influence this invasion and potential contributions of backpropagating APs (BPAPs) to DGC excitability in the in vitro rat hippocampal slice preparation. Current source density (CSD) analysis was used to determine the amplitude and propagation distance of either antidromically or synaptically evoked BPAPs in the fine calibre dendrites of DGCs. Intrasomatic recordings were used in conjunction with CSD analysis to characterise functional interactions between the somatic and dendritic compartments and the contributions these interactions make to DGC excitability. Voltage-gated ion channel blockers were either focally applied to the dendrites or globally applied via the perfusate to help identify channels involved in regulating AP backpropagation.; The first phase of the project established the extent to which DGC dendrites are invaded by antidromically or synaptically evoked BPAPs. Somatically initiated Na+-dependent APs backpropagated into DGC dendrites, becoming progressively smaller in amplitude with increasing distance from the soma. Antidromically evoked BPAPs failed to invade past the halfway-point of the dendritic projection, while synaptically evoked BPAPs travelled ∼43% further into the dendrites, but failed to propagate past the synaptically activated region.; In the second phase of the study, application of the voltage-gated K + channel blocker, 4-aminopyridine (4-AP), onto DGCs increased the amplitude, duration and backpropagation distance of dendritic APs, and was associated with parallel increases in the amplitude and duration of the somatic depolarising after potential (DAP). Multiple somatic APs fired from the enhanced DAP.; In final phase of the project two series of experiments were performed to establish activity-dependent BPAP invasion characteristics. First, the presence or absence of a conditioning antidromically evoked BPAP did not alter the characteristics of an antidromic test response evoked at a 50 ms delay, suggesting that BPAPs do not contribute to a postsynaptic component previously implicated in the mechanisms responsible for extracellularly recorded paired pulse facilitation in the dentate gyrus. Second, priming DGC dendrites with an antidromically evoked BPAP depressed a subsequent antidromically evoked BPAP initiated within 50 ms. This activity-dependent depression was augmented by 4-AP exposure. In contrast, priming DGC dendrites with a subthreshold field excitatory postsynaptic potential (fEPSP) enhanced subsequent dendritic excitability evoked at a 20 ms delay. This post-fEPSP excitability was reversed following local dendritic 4-AP-sensitive channel blockade.; Taken together the results suggest that DGC dendrites support Na +-dependent BPAPs that are normally regulated by dendritic voltage-gated K+ channels. Blocking or inactivating these K+ channels results in altered BPAP invasion properties, potentially influencing synaptic plasticity and somatic output firing characteristics in DGCs.