biostudies-literatureLandau ATNational Institute of Neurological Disorders and StrokeDefense Advanced Research Projects AgencyLife Sciences Research FoundationNIMH NIH HHSHarvard Medical SchoolBrain Research FoundationNINDS NIH HHSNational Institute of Mental Healthe76993https://www.ebi.ac.uk/biostudies/studies/S-EPMC8979587biostudies-literatureUnknown11Back-propagating action potentials (bAPs) regulate synaptic plasticity by evoking voltage-dependent calcium influx throughout dendrites. Attenuation of bAP amplitude in distal dendritic compartments alters plasticity in a location-specific manner by reducing bAP-dependent calcium influx. However, it is not known if neurons exhibit branch-specific variability in bAP-dependent calcium signals, independent of distance-dependent attenuation. Here, we reveal that bAPs fail to evoke calcium influx through voltage-gated calcium channels (VGCCs) in a specific population of dendritic branches in mouse cortical layer 2/3 pyramidal cells, despite evoking substantial VGCC-mediated calcium influx in sister branches. These branches contain VGCCs and successfully propagate bAPs in the absence of synaptic input; nevertheless, they fail to exhibit bAP-evoked calcium influx due to a branch-specific reduction in bAP amplitude. We demonstrate that these branches have more elaborate branch structure compared to sister branches, which causes a local reduction in electrotonic impedance and bAP amplitude. Finally, we show that bAPs still amplify synaptically-mediated calcium influx in these branches because of differences in the voltage-dependence and kinetics of VGCCs and NMDA-type glutamate receptors. Branch-specific compartmentalization of bAP-dependent calcium signals may provide a mechanism for neurons to diversify synaptic tuning across the dendritic tree.eLifeDendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells.PMC8979587Merck AwardeeScientific InnovationRF1 MH1170421RF1MH117042-01R37NS046579F31 NS113353Harvard Brain InitiativeF31NS113353R37 NS046579Vannevar Bush Faculty FellowshipSabatini BLCohen AELandau ATTian HPark PWong-Campos JDfalseDendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells.Back-propagating action potentials (bAPs) regulate synaptic plasticity by evoking voltage-dependent calcium influx throughout dendrites. Attenuation of bAP amplitude in distal dendritic compartments alters plasticity in a location-specific manner by reducing bAP-dependent calcium influx. However, it is not known if neurons exhibit branch-specific variability in bAP-dependent calcium signals, independent of distance-dependent attenuation. Here, we reveal that bAPs fail to evoke calcium influx through voltage-gated calcium channels (VGCCs) in a specific population of dendritic branches in mouse cortical layer 2/3 pyramidal cells, despite evoking substantial VGCC-mediated calcium influx in sister branches. These branches contain VGCCs and successfully propagate bAPs in the absence of synaptic input; nevertheless, they fail to exhibit bAP-evoked calcium influx due to a branch-specific reduction in bAP amplitude. We demonstrate that these branches have more elaborate branch structure compared to sister branches, which causes a local reduction in electrotonic impedance and bAP amplitude. Finally, we show that bAPs still amplify synaptically-mediated calcium influx in these branches because of differences in the voltage-dependence and kinetics of VGCCs and NMDA-type glutamate receptors. Branch-specific compartmentalization of bAP-dependent calcium signals may provide a mechanism for neurons to diversify synaptic tuning across the dendritic tree.2022-01-01T00:00:00Z2022 Mar2025-04-04T19:10:28.038Z2025-04-04T19:10:28.038ZS-EPMC89795873531946410.7554/eLife.76993