Synaptic and dendritic architecture of different types of hippocampal somatostatin interneurons

PLoS Biol. 2024 Mar 12;22(3):e3002539. doi: 10.1371/journal.pbio.3002539. eCollection 2024 Mar.

Abstract

GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning, and memory in many brain areas including the hippocampus, and are implicated in several neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) cells and hippocampo-septal (HS) cells. These cell types show many similarities in their soma-dendritic architecture, but they have different axonal targets, display different activity patterns in vivo, and are thought to have distinct network functions. However, a complete understanding of the functional roles of these interneurons requires a precise description of their intrinsic computational properties and their synaptic interactions. In the current study we generated, analyzed, and make available several key data sets that enable a quantitative comparison of various anatomical and physiological properties of OLM and HS cells in mouse. The data set includes detailed scanning electron microscopy (SEM)-based 3D reconstructions of OLM and HS cells along with their excitatory and inhibitory synaptic inputs. Combining this core data set with other anatomical data, patch-clamp electrophysiology, and compartmental modeling, we examined the precise morphological structure, inputs, outputs, and basic physiological properties of these cells. Our results highlight key differences between OLM and HS cells, particularly regarding the density and distribution of their synaptic inputs and mitochondria. For example, we estimated that an OLM cell receives about 8,400, whereas an HS cell about 15,600 synaptic inputs, about 16% of which are GABAergic. Our data and models provide insight into the possible basis of the different functionality of OLM and HS cell types and supply essential information for more detailed functional models of these neurons and the hippocampal network.

MeSH terms

  • Animals
  • Hippocampus* / physiology
  • Interneurons* / physiology
  • Mice
  • Neurons
  • Somatostatin

Substances

  • Somatostatin

Grants and funding

This work was supported by the Frontline Research Excellence Program of the Hungarian National Research, Development and Innovation Office (nkfih.gov.hu, NRDI Fund 133837), the Hungarian Brain Research Program NAP3.0 (agykutatas.hu, NAP2022-I-1/2022) and the European Union project RRF-2.3.1-21-2022-00011 within the framework of the Translational Neuroscience National Laboratory to G.N.; the European Union Human Brain Project (www.humanbrainproject.eu, SGA3, 945539) and the Hungarian Brain Research Program NAP2.0 (agykutatas.hu, 2017-1.2.1-NKP-2017-00002) to T.F.F. and G.N.; the European Union project RRF-2.3.1-21-2022-00004 within the framework of the Artificial Intelligence National Laboratory to S.K. and G.N.; the New National Excellence Program of the Ministry for Innovation and Technology and the Ministry of Human Capacities, (nkfih.gov.hu, ÚNKP-19-2-I-SE-36 and ÚNKP-18-2-I-SE-20 to A.M, ÚNKP-19-3-I-SE-9 to M.M, ÚNKP-23-2-II-DE-146 to H.S. and ÚNKP-23-3-I-SE-48 to Á.O.); and the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation to G. N. and H.S (www.edu-sci.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.