Role of activating transcription factor 4 (ATF4) in mGluR-LTD

Metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) is an essential mechanism of synaptic plasticity across various brain regions and is closely linked to numerous learning processes. Previous studies have demonstrated the interplay between mGluR-LTD and the phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α), a key component of the integrated stress response (ISR) pathway. However, the role of activating transcription factor 4 (ATF4)—the primary downstream effector of the integrated stress response (ISR)—in the mechanisms underlying mGluR-LTD has not been thoroughly investigated. In this study, we examine the role of ATF4 in mGluR-LTD and identify several targets that show differential expression when the gene encoding ATF4 is deleted in excitatory neurons.