Topographical Organization of Prefrontal Cortex and Adjacent Areas Projections to the Dorsomedial Caudate–Putamen in Rats: A Retrograde Tracing Study

The dorsomedial caudate-putamen (dmCPu), a key input structure of the basal ganglia, plays a crucial role in goal-directed behaviors and the transition to habits. The functional specialization of the dmCPu along its anteroposterior axis suggests that distinct prefrontal cortex (PFC) subregions may differentially contribute to these processes. However, the precise topographical organization of PFC and adjacent areas projections to the anterior and posterior dmCPu remains poorly understood. We employed retrograde tracing using Fluoro-Gold to map the projections from PFC subregions and adjacent areas to the anterior and posterior dmCPu in male Sprague Dawley rats. Histological verification and immunohistochemical labeling were conducted to confirm injection sites and neuronal labeling. Quantitative analyses were performed to assess the effects of injection site placement (anterior vs. posterior dmCPu), laterality (ipsilateral vs. contralateral), and cortical subregion on projection density. The posterior dmCPu received significantly higher projection densities than the anterior dmCPu, with a pronounced ipsilateral dominance across all cortical subregions. Among the subregions examined, the cingulate cortex exhibited the highest number of labeled neurons projecting to the dmCPu, with distinct patterns of connectivity between anterior and posterior injection sites. Notably, motor and somatosensory cortical projections were more prominent in the posterior dmCPu, whereas cingulate projections demonstrated robust anteroposterior and lateralized differences. These findings provide a comprehensive map of the topographical organization of cortical inputs to the dmCPu, highlighting differential connectivity patterns that may underlie distinct functional roles in goal-directed and habitual behaviors. This work advances our understanding of corticostriatal circuits and their relevance to adaptive behaviors and neuropsychiatric disorders.