Unique properties of dually innervated dendritic spines in pyramidal neurons of the somatosensory cortex uncovered by 3D correlative light and electron microscopy

PLoS Biol. 2021 Aug 24;19(8):e3001375. doi: 10.1371/journal.pbio.3001375. eCollection 2021 Aug.


Pyramidal neurons (PNs) are covered by thousands of dendritic spines receiving excitatory synaptic inputs. The ultrastructure of dendritic spines shapes signal compartmentalization, but ultrastructural diversity is rarely taken into account in computational models of synaptic integration. Here, we developed a 3D correlative light-electron microscopy (3D-CLEM) approach allowing the analysis of specific populations of synapses in genetically defined neuronal types in intact brain circuits. We used it to reconstruct segments of basal dendrites of layer 2/3 PNs of adult mouse somatosensory cortex and quantify spine ultrastructural diversity. We found that 10% of spines were dually innervated and 38% of inhibitory synapses localized to spines. Using our morphometric data to constrain a model of synaptic signal compartmentalization, we assessed the impact of spinous versus dendritic shaft inhibition. Our results indicate that spinous inhibition is locally more efficient than shaft inhibition and that it can decouple voltage and calcium signaling, potentially impacting synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling
  • Dendritic Spines / physiology
  • Dendritic Spines / ultrastructure*
  • Excitatory Postsynaptic Potentials*
  • Female
  • Inhibitory Postsynaptic Potentials*
  • Mice
  • Microscopy, Electron, Scanning / methods
  • Models, Neurological*
  • Neuronal Plasticity
  • Pregnancy
  • Pyramidal Cells / ultrastructure*
  • Somatosensory Cortex / physiology
  • Somatosensory Cortex / ultrastructure

Grant support

This work was supported by INSERM, the Agence Nationale de la Recherche (https://anr.fr/)(ANR-13-PDOC-0003 and ANR-17-ERC3-0009 to C.C.), the European Research Council (https://erc.europa.eu/) (ERC starting grant 803704 to C.C.), the Labex Memolife (https://www.memolife.biologie.ens.fr/?lang=fr) (901/IBENS/LD09 to O.G.), the company NIKON France via the CIFRE program (convention n° 2015/1049 to O.G.) and the European Union's Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2 to P.S.). We are grateful to the IBENS Imaging Facility (France BioImaging, supported by ANR-10-INBS-04, ANR-10-LABX-54 MEMO LIFE, and ANR-11- IDEX-000-02 PSL* Research University, ‘‘Investments for the future’’; NERF 2011-45; FRM DGE 20111123023; and FRC Rotary International France). he funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.