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The Distinct Characteristics of Somatostatin Neurons in the Human Brain

Abstract

Somatostatin cells are frequently described as a major population of GABAergic neurons in the cerebral cortex. In this study, we performed a comprehensive analysis of their molecular expression, morphological features, and laminar distribution. We provided a detailed description of somatostatin neurons in the human prefrontal cortex, including their proportion in the total neuron population, laminar distribution, neurotransmitter phenotype, as well as their molecular and morphological characteristics using immunofluorescence and RNAscope in situ hybridization. We found that somatostatin neurons comprise around 7% of neocortical neurons in the human Brodmann areas 9 and 14r, without significant difference between the two regions. Somatostatin cells were NeuN positive and synthesized vesicular GABA transporter and glutamate decarboxylase 1 and 2, confirming their neuronal nature and GABAergic phenotype. Somatostatin cells in the upper cortical layers were small, had a high expression of somatostatin mRNA, a relatively low expression of somatostatin peptide, and co-expressed calbindin. In the lower cortical layers, somatostatin cells were larger with complex somato-dendritic morphology, typically showed a lower expression of somatostatin mRNA and a high expression of somatostatin peptide, and co-expressed neuronal nitric oxide synthase (nNOS) and neuropeptide Y (NPY), but not calbindin. Somatostatin neurons in the white matter co-expressed MAP2. Based on their somato-dendritic morphology, cortical somatostatin neurons could be classified into at least five subtypes. The somatostatin neurons of the human prefrontal cortex show remarkable morphological and molecular complexity, which implies that they have equally complex and distinct functions in the human brain.

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Data Availability

All data presented in this study are available in the article and accompanying supplementary information. Raw data are available on request from the corresponding author.

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Funding

This research was supported by the Croatian Science Foundation Grants No. IP-2019–04-3182 (Brain extracellular matrix in development and in perinatal hypoxia, PI: Nataša Jovanov Milošević) and No. 5943 (Microcircuitry of higher cognitive functions, PI: Zdravko Petanjek), and co-financed by the Scientific Centre of Excellence for Basic, Clinical, and Translational Neuroscience (project “Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain;” GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund).

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Ivan Banovac and Dora Sedmak designed the study. Ivan Banovac acquired the data. All authors analyzed the data, drafted the manuscript, and performed a critical revision of the manuscript.

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Correspondence to Dora Sedmak.

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Banovac, I., Sedmak, D., Esclapez, M. et al. The Distinct Characteristics of Somatostatin Neurons in the Human Brain. Mol Neurobiol 59, 4953–4965 (2022). https://doi.org/10.1007/s12035-022-02892-6

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  • DOI: https://doi.org/10.1007/s12035-022-02892-6

Keywords

  • Somatostatin
  • Prefrontal cortex
  • Human
  • GABA
  • Interneurons
  • Schizophrenia