Updated project metadata. Identification of proteins that are synthesised de novo in response to specific microenvironmental cues is critical for understanding the molecular mechanisms, which underpin vital physiological processes and pathologies. Here, we report that a brief period of pulsed SILAM (Stable Isotope Labeling of Mammals) diet enables determination of biological functions corresponding to actively translating proteins in the mouse brain. Our results demonstrate that the synapse, dendrite and myelin sheath are highly active cellular compart of protein synthesis, rapidly expressing key mediators of nutrient sensing, lipid metabolism, amyloid precursor proteins processing and stability. Together, these findings confirm that protein metabolic activity varies significantly between brain cellular compartments in vivo and indicate that pulsed-SILAM based approaches can identify specific anatomical sites and biological pathways likely to be suitable for drug targeting in neurodegenerative disorders.