In the brain, RNA molecules are expressed in a cell-type-specific manner within specific subcellular compartments, including the synapse, where they facilitate many functions underlying synaptic plasticity, learning and memory. Currently, the study of cell-specific synaptic RNA ‘signatures’ that are dynamic in response to activity, requires laborious and error prone manual techniques such as cell sorting and subcellular fractionation, which can negatively influence the yield and quality of RNA data. In order to overcome these challenges, we have adapted Halo-Seq, a photoactivated proximity labelling system capable of analysing RNA populations within a temporally controlled, subcellular compartment- and cell-type-specific manner. In this study, we examine the effect of neural activity on RNA expression in the postsynaptic compartment in excitatory neurons using PSD-95-Halo. This work is an important first step in creating high-resolution RNA profiling system for in vivo use and represents a significant advance in capability to investigate the functional role of RNA in the brain across time and space.