IGF-I Governs Cortical Inhibitory Synaptic Plasticity By Astrocyte Activation

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 Ca 2+ signaling and the release of ATP/adenosine that in turn activates A 2A 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.

IGF-1 facilitates extinction of conditioned fear

“…Similarly, its receptor (IGF-1R) is widely expressed among all brain cell types ( Quesada et al, 2007 ; Rodriguez-Perez et al, 2016 ). IGF-1 increases neuronal firing ( Gazit et al, 2016 ; Nuñez et al, 2003 ) and modulates excitatory and inhibitory synaptic transmission in the central nervous system ( Castro-Alamancos and Torres-Aleman, 1993 ; Nilsson et al, 1988 ; Noriega-prieto et al, 2020 ; Seto et al, 2002 ). Furthermore, IGF-1 regulates different ion channels, such as A-type K + channels ( Xing et al, 2006 ) and P/Q-, L-, and N-type voltage-gated Ca 2+ channels ( Blair and Marshall, 1997 ; Shan et al, 2003 ), as well as neurotransmitter receptors activity ( Gonzalez de la Vega et al, 2001 ; Savchenko et al, 2001 ).…”