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

• DOI: 10.1523/jneurosci.0005-21.2021
• Publication Date: 2021-04-28T17:50:30Z
• Authors: José Antonio Nori...; Laura Eva Maglio; Jonathan A. Zegar...; Jaime Pignatelli; Ana M. Fernandez; Laura Martinez-Ra...; Jansen Fernandes; Ángel Núñez; Alfonso Araque; Ignacio Torres-Al...; David Fernández d...
• Keywords: Male; Adenosine; Medicina; Down-Regulation; Receptor, IGF Type 1; Mice; 03 medical and health sciences; Memory; Animals; Learning; long-term depression; long-term potentiation; 0303 health sciences; Long-term depression; Neuronal Plasticity; Behavior, Animal; Long-Term Synaptic Depression; Pyramidal Cells; astrocytes; sensory discrimination; Somatosensory Cortex; IGF-I; Mice, Inbred C57BL; Astrocytes; barrel cortex

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, involvement astrocytes consequences synaptic plasticity animal behavior remain unknown. We found that induces long-term potentiation (LTP IGFI ) postsynaptic potentials is caused by depression inhibitory transmission mice. demonstrated this long-lasting decrease evoked astrocytic activation through its receptors (IGF-IRs). show LTP not only increases output pyramidal neurons, but also favors NMDAR-dependent LTP, resulting crucial information processing at barrel cortex since specific deletion IGF-IR cortical impairs whisker discrimination task. Our work reveals novel mechanism functional behavior, revealing are elements these SIGNIFICANCE STATEMENT regulatory roles multiple processes brain physiology, such as memory. Yet, underlying mechanisms largely undefined. Here we demonstrate respond to signaling, elevating their intracellular Ca 2+ stimulating release ATP/adenosine, which triggers LTD synapses, thus regulating behavioral task performance related sensory processing. Therefore, present represents major conceptual advance our knowledge cellular basis function, including for first time mediators actions plasticity, behavior.