Role of superficial grey layer of superior colliculus in reversal learning: importance of nitric oxide synthase.

Reversal learning is the ability to adapt behavior to changing circumstances. It is essential for goal-directed actions and survival, and the superior colliculus (SC) is known to be involved in visual cue-guided reversal learning. The superficial grey layer (SuG) of the SC contributes to the refinement of the retinocollicular pathway and visual processing. Although this layer of the SC is rich in neuronal nitric oxide synthase (nNOS), the role of the enzyme or nitric oxide (NO) in mediating reversal behavior driven by visual cues remains unclear. We aimed to investigate the participation of nitrergic signaling in the SuG in reversal learning. The rats were subjected to training to self-administer food pellets in reversal learning paradigm. The trained rats showed increased expression of nNOS in the SuG and tyrosine hydroxylase, a marker for dopamine, in the ventral tegmental area (VTA), compared with those trained without the reversal task. While intra-SuG 7-nitroindazole (nNOS inhibitor) showed increased active/inactive lever pressings, L-arginine (NO precursor) was not effective. MK801 caused reversal learning deficits, and we found reduced active lever press activity, while increasing inactive lever presses and locomotor behavior, indicating impaired reversal learning in rats. Intra-SuG L-arginine alleviated impaired reversal performance by increasing active lever press activity and reducing GFAP and caspase-3 expression in the SuG. Fluoro-ruby retrograde tracing was performed in the VTA, which revealed a possible nitrergic projection from SuG to VTA. We suggest that nNOS signaling in the SuG might play an important role in visual cue-associated reversal learning in rats.