Abstract
Astrocytes are well known to scale synaptic structural and functional plasticity, while the role in learning and memory, such as conditioned fear memory, is poorly elucidated. Here, using pharmacological approach, we find that fluorocitrate (FC) significantly inhibits the acquisition of fear memory, suggesting that astrocyte activity is required for fear memory formation. We further demonstrate that fear conditioning downregulates astrocytic Rac1 activity in basolateral amygdala (BLA) in mice and promotes astrocyte structural plasticity. Ablation of astrocytic Rac1 in BLA promotes fear memory acquisition, while overexpression or constitutive activation of astrocytic Rac1 attenuates fear memory acquisition. Furthermore, temporal activation of Rac1 by photoactivatable Rac1 (Rac1-PA) induces structural alterations in astrocytes and in vivo activation of Rac1 in BLA astrocytes during fear conditioning attenuates the formation of fear memory. Taken together, our study demonstrates that fear conditioning-induced suppression of BLA astrocytic Rac1 activity, associated with astrocyte structural plasticity, is required for the formation of conditioned fear memory.
Highlights
Astrocytes, the most abundant glial cells in the central nervous system, have been generally believed to maintain the homeostasis of metabolism and ionic environment (Allen and Barres, 2009; Weber and Barros, 2015)
To determine whether astrocytes are involved in the conditioned fear memory, we investigated the effects of FC, an astroglial metabolism inhibitor to block the function of astrocytes (Fonnum et al, 1997), on the formation of fear memory
Our results provide a fundamentally new insight to the basis by which astrocytes regulate the formation of conditioned fear memory
Summary
Astrocytes, the most abundant glial cells in the central nervous system, have been generally believed to maintain the homeostasis of metabolism and ionic environment (Allen and Barres, 2009; Weber and Barros, 2015). Astrocytes secrete various molecules shaping synaptic formation, maturation and even deletion (Christopherson et al, 2005; Allen et al, 2012; Chung et al, 2013), during the development of nervous system. Emerging evidence demonstrates the contribution of astrocytes to physiological behaviors, such as breathing, feeding and sleeping (Halassa et al, 2009; Gourine et al, 2010; Kim et al, 2014). Though some studies have begun paying attention to the role of astrocytes in learning
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