Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system

• DOI: 10.7554/elife.78813
• Publication Date: 2022-09-05T14:00:19Z
• Authors: Ákos Babiczky; Ferenc Matyas
• Keywords: 0301 basic medicine; laminar topography; nucleus accumbens; QH301-705.5; Science; ventral tegmental area; Prefrontal Cortex; Nucleus Accumbens; Mice; 03 medical and health sciences; Neural Pathways; Animals; Biology (General); Neurons; prefrontal cortex; 0303 health sciences; pyramidal cell types; Q; Ventral Tegmental Area; R; cortical organization; R850-854 Experimental medicine / kisérleti orvostudomány; Medicine; Neuroscience

Prefrontal cortical influence over the mesolimbic system - including nucleus accumbens (NAc) and ventral tegmental area (VTA) is implicated in various cognitive processes behavioral malfunctions. The functional versatility of this could be explained by an underlying anatomical complexity; however, detailed characterization medial prefrontal (mPFC) innervation NAc VTA still lacking. Therefore, combining classical retrograde conditional viral tracing techniques with multiple fluorescent immunohistochemistry, we sought to deliver a precise, cell- layer-specific description cortico-mesolimbic pathways mice. We demonstrated that NAc- (mPFCNAc) VTA-projecting mPFC (mPFCVTA) populations show different laminar distribution (layers 2/3-5a 5b-6, respectively) express molecular markers. Specifically, calbindin Ntsr1 are specific mPFCNAc neurons, while mPFCVTA neurons high levels Ctip2 FoxP2, indicating these mostly separated at cellular level. directly tested double Canine adenovirus type 2-mediated labeling found there indeed minimal overlap between two populations. Furthermore, whole-brain analysis revealed projection pattern also throughout brain. Taken together, innervated two, nonoverlapping profile. These results can contribute advancement our understanding mesocorticolimbic functions its disorders future studies.