IGF-I Governs Cortical Inhibitory Synaptic Plasticity By Astrocyte Activation

Noriega-Prieto, J. A.; Maglio, L. E.; Zegarra-Valdivia, J.; Pignatelli, J.; Fernandez, A. M.; Martinez-Rachadell, L.; Fernandes, J.; Nunez, A.; Araque, A.; Torres-Aleman, I.; Fernandez de Sevilla, D.

doi:10.1101/2020.02.11.942532

bioRxiv · 10.1101/2020.02.11.942532

IGF-I Governs Cortical Inhibitory Synaptic Plasticity By Astrocyte Activation

Noriega-Prieto, J. A.·Maglio, L. E.·Zegarra-Valdivia, J.·Pignatelli, J.·Fernandez, A. M.·Martinez-Rachadell, L.·Fernandes, J.·Nunez, A.·Araque, A.·Torres-Aleman, I.·Fernandez de Sevilla, D.

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Abstract

Insulin-like growth factor-I (IGF-I) signaling plays key regulatory roles in multiple processes of brain physiology and pathology. While the direct effects of IGF-I in neurons have been extensively studied, the astrocyte involvement in IGF-I signaling and the consequences on synaptic plasticity and animal behavior remain unknown. Here we show that IGF-I induces the long-term depression (LTD) of inhibitory synaptic transmission in the mouse barrel cortex. This LTD requires the activation of the IGF-I receptor (IGF-IR) in astrocytes, which stimulates astrocyte Ca2+ signaling and the release of ATP/adenosine that in turn activates A2A adenosine receptors at presynaptic inhibitory terminals. Specific deletion of IGF-IR in cortical astrocytes (IGF-IR-/-) impaired the behavioral performance in a whisker discrimination task. These results show novel mechanisms and functional consequences of IGF-I signaling on cortical inhibitory synaptic plasticity and animal behavior, revealing astrocytes as key elements in these processes.

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Noriega-Prieto, J. A., Maglio, L. E., Zegarra-Valdivia, J., Pignatelli, J., Fernandez, A. M., Martinez-Rachadell, L., Fernandes, J., Nunez, A., Araque, A., Torres-Aleman, I., Fernandez de Sevilla, D.. 2020-02-12. IGF-I Governs Cortical Inhibitory Synaptic Plasticity By Astrocyte Activation. https://doi.org/10.1101/2020.02.11.942532

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