LAYER SPECIFIC PREFRONTAL INNERVATION OF THE REWARD SYSTEM
Reward learning is fundamental in animal and human behaviour. The mesolimbic system - including the nucleus accumbens (NAc), the ventral tegmental area (VTA) and the prefrontal cortex (PFc) - has been identified as a central element of the reward circuit. PFc provides a major glutamatergic innervation in both VTA and NAc. However, layer- and cell-specific descriptions of this circuit are still lacking. Therefore, we mapped the prefrontal cortical source of these connections using classical tracing as well as cell-type-specific viral approaches. Our results indicated that VTA-projecting cells formed two clusters in the PFc –in the deep layer VI. (overlapping with FoxP2-expressing cells) and in the layer V. In contrast, NAc-projecting cells were localised mostly in the layer V. and to some extent in the layer II-III. of the PFc. Then, with double retrograde approach, we found that the prefrontal innervation of the VTA and the NAc originated from two distinct, mostly non-overlapping cell groups. Furthermore, we injected AAV viruses into the PFc of different layer-specific mouse strains to selectively reveal their expression and projection pattern. Interestingly, the localization of these layer-specific cells was somewhat different in the PFc compared to the neighboring primary motor cortex. We also found that two of these cortical cell-types (Rbp4 [V.], Thy1 [V.]) showed similar projection pattern in the VTA and the NAc. Conversely, NTSR1-positive cells [VI.] innervated only the NAc. Our data collectively demonstrate that the prefrontal innervation of the VTA and the NAc originates from two distinct cells-clusters of several cortical cell-types.