Temporal Dynamics of Dorsal-Striatal Protein Networks During Radial-Arm Maze Training

Repeated radial-arm maze (RAM) exposure engages spatial, motivational, motor, and reward-related processes, but how the dorsal-striatal proteome is organized across repeated training remains unclear. We profiled bulk dorsal striatum from male mice collected after RAM trials on Days 0, 1, 3, and 5, together with a habituated, food-restricted NoRAM control collected before the first trial, using ion-mobility-enhanced data-independent LC-MS/MS. Complementary exploratory factor analysis and weighted gene co-expression network analysis resolved a dominant RAM-versus-NoRAM difference and superimposed, sampling-dependent changes within the trained series. The broad RAM-associated pattern was enriched in ribosomal and translation-initiation proteins, proteasome components, and synaptic-vesicle trafficking. The Day-1-to-Day-3 contrast shifted emphasis toward actin/cytoskeletal regulation, membrane trafficking, mitochondrial respiration, and ATP-generating processes, whereas later Day-5 contrasts emphasized postsynaptic-density organization, vesicle recycling, protein-quality control, and metabolic support. Integration of the two analytical frameworks identified 65 shared central proteins linking synaptic signaling and receptor organization with proteostasis, energy production, and structural remodeling. Candidate transcription-factor and microRNA target enrichments nominated possible regulatory associations but were not directly measured. Because NoRAM controls were collected before task exposure and no activity-, reward-, or repeated-testing-matched control was included, the observed changes cannot be assigned specifically to spatial learning or a navigational strategy. Moreover, pooled bulk tissue precludes cell-type, subregional, and synapse-specific inference. The study therefore provides a biology-centered, hypothesis-generating map of overlapping dorsal-striatal protein networks associated with repeated RAM exposure and prioritizes molecular systems for direct temporal and functional validation.