Astrocytic IGF-IRs Induce Adenosine-Mediated Inhibitory Downregulation and Improve Sensory Discrimination

Author(s):Show less -

Noriega-Prieto, Jose Antonio ^{[1, 2]} ; Maglio, Laura Eva ^{[2, 3, 4]} ; Zegarra-Valdivia, Jonathan A. ^{[5, 6, 7]} ; Pignatelli, Jaime ^{[5, 6]} ; Fernandez, Ana M. ^{[5, 6]} ; Martinez-Rachadell, Laura ^{[5, 6]} ; Fernandes, Jansen ^{[5, 8]} ; Nunez, Angel ^[2] ; Araque, Alfonso ^[1] ; Torres-Aleman, Ignacio ^{[5, 6]} ; de Sevilla, David Fernandez ^[2]

Affiliation

^[1] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 - USA

^[2] Univ Autonoma Madrid, Fac Med, Dept Anat Histol & Neurociencia, Madrid 28029 - Spain

^[3] Univ La Laguna, Dept Ciencias Med Basicas Fisiol, Tenerife 38071 - Spain

^[4] Univ La Laguna, Inst Tecnol Biomed, Tenerife 38071 - Spain

^[5] CSIC, Inst Cajal, Madrid 28002 - Spain

^[6] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031 - Spain

^[7] Univ Nacl San Agustin Arequipa, Arequipa 04001 - Peru

^[8] Univ Fed Sao Paulo, BR-04021001 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF NEUROSCIENCE; v. 41, n. 22, p. 4768-4781, JUN 2 2021.
• Web of Science Citations: 0

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 demon-strated 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 conse-quences of IGF-I signaling on cortical inhibitory synaptic plasticity and animal behavior, revealing that astrocytes are key ele-ments in these processes. (AU)

• FAPESP's process: 17/14742-0 - Effects of prenatal exercise on behavioral, morphological and epigenetic changes in the offspring of immune-challenged mothers
• Grantee: Jansen Fernandes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral