Interplay of synaptic and backpropagating signals in neurogliaform dendrites

Dendrites in diverse neuronal cell types, including interneurons, are active structures that enhance neuronal computational capabilities. Neurogliaform interneurons exhibit robust synaptic plasticity and supralinear summation of clustered dendritic inputs. However, the principles governing supralinear synaptic integration, its interaction with backpropagating somatic signals, and the interplay of the two in the context of synaptic plasticity, remain incompletely understood. We developed a biophysically realistic, multi-compartmental model of a murine hippocampal neurogliaform interneuron, recapitulating key experimental results on dendritic integration. We simulated diverse synaptic input configurations and action potential backpropagation, generating testable predictions validated through ex vivo patch-clamp electrophysiology and two-photon imaging. We further examined how dendritic supralinear integration interacts with backpropagating action potentials to influence synaptic plasticity. Our results show that while both clustered and dispersed synaptic inputs elicit supralinear responses in neurogliaform interneurons, clustered inputs induce more pronounced local depolarisations and calcium transients. Somatic action potentials backpropagate across the dendritic arbour but are attenuated at branch points. Coincident synaptic input and backpropagating action potentials enhance EPSP amplitude and increase calcium influx along the dendrite, enabling voltage and calcium signal propagation and thereby likely contributing to synaptic plasticity.