Abstract
Insulin-like growth factor-I (IGF-I) signaling plays a key role in learning and memory processes. While the effects of IGF-I on neurons have been studied extensively, the involvement of astrocytes in IGF-I signaling and the consequences on synaptic plasticity and animal behavior remain unknown. We have found that IGF-I induces long-term potentiation (LTPIGFI) of the postsynaptic potentials that is caused by a long-term depression of inhibitory synaptic transmission in mice. We have demonstrated that this long-lasting decrease in the inhibitory synaptic transmission is evoked by astrocytic activation through its IGF-I receptors (IGF-IRs). We show that LTPIGFI not only increases the output of pyramidal neurons, but also favors the NMDAR-dependent LTP, resulting in the crucial information processing at the barrel cortex since specific deletion of IGF-IR in cortical astrocytes impairs the whisker discrimination task. Our work reveals a novel mechanism and functional consequences of IGF-I signaling on cortical inhibitory synaptic plasticity and animal behavior, revealing that astrocytes are key elements in these processes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4768-4781 |
| Number of pages | 14 |
| Journal | Journal of Neuroscience |
| Volume | 41 |
| Issue number | 22 |
| DOIs | |
| State | Published - Jun 2 2021 |
Bibliographical note
Funding Information:through the National Fund for Scientific and Technological Development (FONDECYT, Perú). J.F. received a postdoctoral fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; Grants #2017/ 14742-0 and #2019/03368-5). We thank the University of Minnesota Viral Vector and Cloning Core for production of some of the viral vectors used in this study; and Dr. G. Perea and Dr. Washington Buño for helpful comments. *J.A.N.-P. and L.E.M. contributed equally to this research. The authors declare no competing financial interests. Correspondence should be a addressed to David Fernández de Sevilla at david.fernandezdesevilla@uam.es. https://doi.org/10.1523/JNEUROSCI.0005-21.2021 Copyright © 2021 the authors
Funding Information:
This work was supported by Grants BFU2016-80802-P from Agencia Estatal de Investigaci?n Spain/Fondo Europeo de Desarrollo Regional, and from the European Union [Ministerio de Econom?a y Competitividad (MINECO)] to D.F.d.S.; Grants R01-NS-097312 and R01-DA-048822 from National Institutes of Health/National Institute of Neurological Disorders and Stroke to A.A.; and grants from Centro de Investigaci?n Biom?dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) and Grant SAF2016-76462-C2-1-P from MINECO to I.T.-A. J.A.Z.-V. was supported by the National Council of Science, Technology and Technological Innovation (CONCYTEC, Per?) through the National Fund for Scientific and Technological Development (FONDECYT, Per?). J.F. received a postdoctoral fellowship from Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo (FAPESP; Grants #2017/ 14742-0 and #2019/03368-5). We thank the University of Minnesota Viral Vector and Cloning Core for production of some of the viral vectors used in this study; and Dr. G. Perea and Dr. Washington Bu?o for helpful comments.
Funding Information:
This work was supported by Grants BFU2016-80802-P from Agencia Estatal de Investigación Spain/Fondo Europeo de Desarrollo Regional, and from the European Union [Ministerio de Economía y Competitividad (MINECO)] to D.F.d.S.; Grants R01-NS-097312 and R01-DA-048822 from National Institutes of Health/National Institute of Neurological Disorders and Stroke to A.A.; and grants from Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) and Grant SAF2016-76462-C2-1-P from MINECO to I.T.-A. J.A.Z.-V. was supported by the National Council of Science, Technology and Technological Innovation (CONCYTEC, Perú)
Publisher Copyright:
Copyright © 2021 the authors
Keywords
- Astrocytes
- Barrel cortex
- IGF-I
- Long-term depression
- Long-term potentiation
- Sensory discrimination