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Publication : Ablation of STAT3 in Purkinje cells reorganizes cerebellar synaptic plasticity in long-term fear memory network.

First Author  Han JK Year  2021
Journal  Elife Volume  10
PubMed ID  33459594 Mgi Jnum  J:317346
Mgi Id  MGI:6727664 Doi  10.7554/eLife.63291
Citation  Han JK, et al. (2021) Ablation of STAT3 in Purkinje cells reorganizes cerebellar synaptic plasticity in long-term fear memory network. Elife 10:e63291
abstractText  Emotional memory processing engages a large neuronal network of brain regions including the cerebellum. However, the molecular and cellular mechanisms of the cerebellar cortex modulating the fear memory network are unclear. Here, we illustrate that synaptic signaling in cerebellar Purkinje cells (PCs) via STAT3 regulates long-term fear memory. Transcriptome analyses revealed that PC-specific STAT3 knockout (STAT3(PKO)) results in transcriptional changes that lead to an increase in the expression of glutamate receptors. The amplitude of AMPA receptor-mediated excitatory postsynaptic currents at parallel fiber (PF) to PC synapses was larger in STAT3(PKO) mice than in wild-type (WT) littermates. Fear conditioning induced long-term depression of PF-PC synapses in STAT3(PKO) mice while the same manipulation induced long-term potentiation in WT littermates. STAT3(PKO) mice showed an aberrantly enhanced long-term fear memory. Neuronal activity in fear-related regions increased in fear-conditioned STAT3(PKO) mice. Our data suggest that STAT3-dependent molecular regulation in PCs is indispensable for proper expression of fear memory.
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