The N6-methyladenosine (m6A) methylation, identified in the 1970s, has become increasingly understood with the development of recent high-throughput sequencing techniques. The discovery of its distinct distribution and associated effectors has enabled many functional studies on this reversible modification. m6A methylation plays an essential role in the post-transcriptional regulation of mRNA, dynamically influencing mRNA metabolism and various cellular functions.In neurons, precise control of protein synthesis is crucial during the activity-dependent transportation of mRNAs. Thus, post-transcriptional regulation offers a potentially ideal mechanism to dynamically drive local translation in neurons, allowing synaptic plasticity regulation and dendritic remodeling. m6A level dramatically increases by adulthood, suggesting its unique role in the adult brain, which is a topic just beginning to be systematically studied. For my thesis, I take advantage of the fact that there are only two prominent neuronal cell types throughout the striatum: the dopamine (DA) D1 and D2 receptor-expressing medium spiny projection neurons (SPNs). Moreover, D1 and D2 SPNs have well-documented opposing functions in motor control, simplifying the molecular studies and allowing comparison of behavioral phenotypes. In the first part of my thesis, by using transgenic mouse models with selective deletion of Mettl14 in D1 and D2 SPNs, I found that Mettl14 deficiency blunted responses to environmental challenges at cellular and behavioral levels in the adult brain. One of m6A modification’s downstream reader proteins, YTHDF1, has been shown to promote protein synthesis in neurons and regulate synaptic plasticity and learning. However, it is unclear if YTHDF1 is the primary downstream mediator of m6A function in the brain. In the second part, I found that Ythdf1 deletion in D1 and D2 SPNs resembled the behavioral impairments caused by Mettl14 deletion in a cell type-specific manner, suggesting YTHDF1 as the primary mediator of the functional consequences of m6A modification in the striatum. Moreover, striatal neurons from Ythdf1 constitutive knockout mice were incapable of adapting to environmental challenges. DA affects striatal neuronal activity and regulates corticostriatal plasticity. In the third part, I examined the role of m6A mRNA methylation in dopaminergic neurons. I found that in all three cell types: D1-SPNs, D2-SPNs, and dopaminergic neurons, Ythdf1 deletion resembled the behavioral impairments caused by Mettl14 deletion. Down-regulation of m6A is found to induce cell apoptosis in the dopaminergic cells in vitro. However, I found no significant difference in tyrosine hydroxylase (TH)-positive cell number in the midbrain of Mettl14 conditional knockout mice. This suggests that m6A depletion did not cause dopaminergic neuron degeneration in any age group. The fourth part is our ongoing experiments to examine the role of m6A modification in maintaining cell identity and normal functions in the adult brain. I found that Mettl14 deletion in D1-SPNs caused behavioral impairments in an age-dependent manner, suggesting the significance of m6A increases as the mice age. In the future, we plan to explore the expression profile of the transcription factors (TFs) and track the temporal features of m6A distribution on these genes in D1 and D2 SPNs.