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Distinct Effects of BDNF and NT-3 on the Dendrites and Presynaptic Boutons of Developing Olfactory Bulb GABAergic Interneurons In Vitro

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Abstract

Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) are known to regulate neuronal morphology and the formation of neural circuits, yet the neuronal targets of each neurotrophin are still to be defined. To address how these neurotrophins regulate the morphological and synaptic differentiation of developing olfactory bulb (OB) GABAergic interneurons, we analyzed the effect of BDNF and NT-3 on GABA+-neurons and on different subtypes of these neurons: tyrosine hydroxylase (TH+); calretinin (Calr+); calbindin (Calb+); and parvalbumin (PVA+). These cells were generated from cultured embryonic mouse olfactory bulb neural stem cells (eOBNSCs) and after 14 days in vitro (DIV), when the neurons expressed TrkB and/or TrkC receptors, BDNF and NT-3 did not significantly change the number of neurons. However, long-term BDNF treatment did produce a longer total dendrite length and/or more dendritic branches in all the interneuron populations studied, except for PVA+-neurons. Similarly, BDNF caused an increase in the cell body perimeter in all the interneuron populations analyzed, except for PVA+-neurons. GABA+- and TH+-neurons were also studied at 21 DIV, when BDNF produced significantly longer neurites with no clear change in their number. Notably, these neurons developed synaptophysin+ boutons at 21 DIV, the size of which augmented significantly following exposure to either BDNF or NT-3. Our results show that in conditions that maintain neuronal survival, BDNF but not NT-3 promotes the morphological differentiation of developing OB interneurons in a cell-type-specific manner. In addition, our findings suggest that BDNF and NT-3 may promote synapse maturation by enhancing the size of synaptic boutons.

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Acknowledgements

We thank M.J. Román (Instituto Cajal-CSIC, Madrid, Spain) for her technical support and Dr. Mark Sefton (BiomedRed, Madrid, Spain) for English editing.

Funding

This study was funded by grants from MINECO (Grant Numbers: SAF2013-47596-R, SAF2016-80419-R and CIBERNED CB06/05/0065), the Comunidad de Madrid (Grant Number S2011/BMD-2336) and Fundación Ramón Areces (Grant Number CIVP18A3941) to C.V.

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  1. Instituto Cajal-Consejo Superior de Investigaciones Científicas (IC-CSIC), Avenida Doctor Arce 37, 28002, Madrid, Spain

    Vanesa Nieto-Estévez, Çağla Defterali & Carlos Vicario

  2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED-ISCIII), Madrid, Spain

    Vanesa Nieto-Estévez, Çağla Defterali & Carlos Vicario

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  1. Vanesa Nieto-Estévez
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All applicable international, national, and institutional guidelines for the care and use of animals were followed: European Union guidelines (directive 2010/63/EU) and Spanish legislation (Law 32/2007 and RD 53/2013), and the protocols were approved by the Ethical Committee of the Consejo Superior de Investigaciones Científicas (CSIC) and of the Comunidad de Madrid, Spain.

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Nieto-Estévez, V., Defterali, Ç. & Vicario, C. Distinct Effects of BDNF and NT-3 on the Dendrites and Presynaptic Boutons of Developing Olfactory Bulb GABAergic Interneurons In Vitro. Cell Mol Neurobiol 42, 1399–1417 (2022). https://doi.org/10.1007/s10571-020-01030-x

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