**6. m6A and Brain Function**

Specific deletion of *Mettl3* in CaMKIIα-expressing neurons impairs long-term potentiation, which enhances long-term memory consolidation via the modulation of the translation of immediate-early genes, such as Arc, Egr1, and c-Fos [41]. Genetic ablation of *Mettl14* in dopamine D1 receptor (D1R)-expressing striatonigral neurons or dopamine D2 receptor (D2R)-expressing striatopallidal neurons also decreased the expression of neuron- and synapse-specific proteins, decreased the number of striatal cells double-labeled for mature neuronal marker NeuN and Mettl14, and increased neuronal excitability [42]. Behavioral tests show that *Mettl14* deficiency in these two types of neurons impairs sensorimotor learning and reversal learning [42].

The constitutive or NSC-specific deletion of *Fto* not only causes aberrant neurogenesis, it also impairs the learning and memory abilities of mice [13,15]. In addition, fear condition training induced dynamic m6A modification, and the majority peaks were present in mRNAs. *Fto*-specific knockdown in the mouse medial prefrontal cortex (mPFC) enhanced the cued fear memory [43]. *Ythdf1*-KO mice exhibit deficits in spatial learning and memory and contextual learning [31]. *Ythdf1* deficiency also impaired basal synaptic transmission and long-term potentiation of mice, which can be rescued by ectopic Ythdf1 [31]. Ythdf1 modulates learning and memory formation mainly by promoting the translation of neuronal-stimulation-related transcripts. Heat shock stress can specifically increase m6A modification in 50UTR and can alter the cellular localization and expression of Ythdf2, but not Fto, Mettl3, Mettl14, and Wtap [44]. The level of m6A modification in 50UTR was correlated with the expression of a set of transcripts, especially the Hsp70 gene *Hspa1a* [44].
