RT Journal Article
T1 Astrocytic IGF-IRs Induce Adenosine-Mediated Inhibitory Downregulation and Improve Sensory Discrimination
A1 Noriega-Prieto, José A.
A1 Maglio, Laura E.
A1 Zegarra-Valdivia, Jonathan A.
A1 Pignatelli, Jaime
A1 Fernández, Ana M
A1 Martinez-Rachaldell, Laura
A1 Fernandes, Jansen
A1 Nueñez, Ángel
A1 Araque, Alfonso
A1 Torres-Alemán, Ignacio
A1 Fernandez de Sevilla, David
AB AbstractInsulin-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.SIGNIFICANCE STATEMENT Insulin-like growth factor-I (IGF-I) signaling plays key regulatory roles in multiple processes of brain physiology, such as learning and memory. Yet, the underlying mechanisms remain largely undefined. Here we demonstrate that astrocytes respond to IGF-I signaling, elevating their intracellular Ca2+ and stimulating the release of ATP/adenosine, which triggers the LTD of cortical inhibitory synapses, thus regulating the behavioral task performance related to cortical sensory information processing. Therefore, the present work represents a major conceptual advance in our knowledge of the cellular basis of IGF-I signaling in brain function, by including for the first time astrocytes as key mediators of IGF-I actions on synaptic plasticity, cortical sensory information discrimination and animal behavior.
PB Society for Neuroscience
YR 2021
FD 2021-06-02
LK https://hdl.handle.net/20.500.14352/128990
UL https://hdl.handle.net/20.500.14352/128990
LA eng
NO Noriega-Prieto, José Antonio, et al. «Astrocytic IGF-IRs Induce Adenosine-Mediated Inhibitory Downregulation and Improve Sensory Discrimination». The Journal of Neuroscience, vol. 41, n.o 22, junio de 2021, pp. 4768-81. https://doi.org/10.1523/JNEUROSCI.0005-21.2021.
DS Docta Complutense
RD 1 ene 2026