This lecture discusses the application of proteomics in neuroscience, focusing on the analysis of cortical neurons and their interactions with striatal neurons. The instructor begins by outlining the classes of proteomic experiments, including expression proteomics, which profiles total protein composition across different conditions. The challenges of classical proteomics, which often leads to a loss of tissue structure resolution, are highlighted. The lecture introduces innovative genetic-based methods for targeting specific cell types, such as cortical neurons, using techniques like APEX and TurboID. A detailed example is presented, showcasing a study that engineered cortical neurons to express APEX peroxidase, allowing for selective biotinylation of proteins in these neurons. This method enables the analysis of cortical neuron proteomes and phosphoproteomes at various developmental stages, revealing key proteins and kinases involved in axon growth and branching. The findings emphasize the importance of targeted proteomics in understanding the complex interactions within the nervous system.