Global spatial errors and local feature errors drive oculomotor learning.

Major depressive disorder (MDD) is a highly prevalent and recurrent psychiatric disorder characterized by persistent mood disturbances, cognitive deficits, and functional disability [, ]. In addition to its clinical burden, MDD is closely associated with an increased risk of recurrence, reduced quality of life, and an elevated risk of suicidal behavior [, ]. Although multiple brain regions and molecular pathways have been implicated in the pathophysiology of MDD, the cellular and molecular mechanisms linking chronic stress to neural circuit dysfunction remain incompletely understood []. Chronic stress is considered one of the major environmental risk factors for depression and can induce persistent changes in gene expression through epigenetic and post-transcriptional mechanisms, including DNA methylation, histone modification, and noncoding RNA-mediated regulation [–]. Among these stress-responsive alterations, neuronal injury and apoptosis in stress-sensitive brain regions, particularly the hippocampus, may represent an important pathological substrate contributing to depressive-like phenotypes. MicroRNAs (miRNAs) are small noncoding RNAs that regulate post-transcriptional gene expression and have emerged as key modulators of stress-related neuronal dysfunction []. Accumulating evidence indicates that dysregulated miRNAs contribute to MDD pathogenesis by affecting synaptic plasticity, neurogenesis, inflammatory responses, and neuronal survival [–]. miR-140-3p is a highly conserved miRNA that has been implicated in inflammation, apoptosis, and neuronal injury [, ]. However, previous studies have reported apparently divergent biological effects of miR-140-3p in different neuronal injury models. These discrepancies suggest that the net function of miR-140-3p may depend on the disease model, injury type, temporal stage, cellular context, and dominant downstream targets involved. Aberrant expression of miR-140-3p has been observed in several central nervous system disorders, suggesting its potential involvement in neuronal homeostasis and disease-related neural remodeling [–]. Nevertheless, whether miR-140-3p contributes directly to chronic stress-induced hippocampal neuronal apoptosis and depressive-like behaviors remains unclear. Recent bioinformatic analyses have predicted that orthodenticle homeobox 2 (OTX2), a transcription factor involved in neural development and circuit stability, could serve as a downstream target of miR-140-3p; however, this regulatory relationship has not been functionally validated in the context of depression. The upstream mechanism underlying stress-induced dysregulation of miR-140-3p also remains poorly defined. Recent studies have revealed that -methyladenosine (mA), the most abundant internal RNA modification in eukaryotic transcripts, is a critical epitranscriptomic regulator of RNA metabolism and noncoding RNA processing. Our proteomic analysis of hippocampal tissues from control and chronic unpredictable mild stress (CUMS) rats showed that methyltransferase-like 3 (METTL3), a core mA methyltransferase, was significantly upregulated. METTL3 regulates miRNA biogenesis by methylating primary miRNA transcripts and facilitating their recognition and processing by the microprocessor complex [–]. Moreover, several studies have demonstrated links between METTL3-mediated mA modification and stress responses, neuronal homeostasis, and molecular remodeling in neuropsychiatric diseases [, ]. Nevertheless, it remains to be elucidated whether METTL3 promotes miR-140-3p maturation through an mA-dependent mechanism under chronic stress conditions.