Dendritic Shaft Constrictions Shape Dendritic Integration in Granule Cells

Tony Kelly¹, Michela Barboni¹, Philipp Bethge², Micheal Döngi³, Marco Mainardi⁴, Francesco Gobbo⁴, Antonio Cattaneo⁴, Joanna Komorowska⁵, Michel Herde¹, Jens Schweihoff¹, Martin Schwarz¹, U. Valentin Nägerl², Heinz Beck¹

¹ IEECR, University of Bonn Medical Center
² IINS, Université de Bordeaux
³ Dept. Physiology,University of Bonn
⁴ Scuola Normale Superiore
⁵ IZN, University of Bonn Medical Center

The dentate gyrus processes polysensory information from the entorhinal cortex. The main excitatory cell type in this region, the dentate granule cell, is thought to receive spatial and non-spatial/contextual information in an ordered fashion at proximal and distal dendrites, respectively. We show that the nano-scale morphological features and biophysical properties of distal and proximal dendrites contribute to the integration of synaptic inputs at these different input sites.

Using super-resolution techniques (Stimulated Emission Depletion Microscopy and expansion microscopy), we observed localized reductions in the dendritic shaft diameter to values below 250 nm. These dendritic shaft constrictions (DSCs) occurred primarily in the distal dendrites (>150 µm from the soma) creating dendritic sub-compartments. Computational modeling predicts that these sub-compartments have a high impedance that leads to rapid saturation of local synaptic voltage signals and sublinear integration. Two-photon glutamate uncaging combined with Ca²⁺ imaging confirmed strongly sublinear integration of synaptic inputs at distal sites. Pharmacological experiments revealed that sublinear integration was not caused by GABAergic mechanisms or voltage-gated K⁺ conductances. Next, we investigated how inputs in distal and proximal dendritic compartments interact and found that paired stimulation of proximal and distal inputs at gamma frequency potentiated synaptic input at the proximal site in a branch-specific manner.

Taken together, the data suggest that high impedance compartments in the distal dendrite result in local voltage saturation and sublinear integration to synchronous synaptic input. Furthermore the data suggest that distal inputs may act as a gating mechanism instructing the potentiation of proximal inputs in a branch-specific manner.