Locus coeruleus-hippocampal pathway activation promotes spatial memory updating during reversal learning

Abstract

Spatial navigation requires animals to integrate current environmental information with previously acquired spatial memories. The locus coeruleus provides neuromodulatory input to the hippocampus, but whether this pathway facilitates spatial learning in general or preferentially supports the updating of established representations remains unclear. Here, we selectively activated LC projections to the dorsal hippocampus while mice performed object-location recognition and an appetitive radial-maze task involving initial spatial learning followed by reversal. LC-hippocampal activation enhanced object-location memory and improved reversal learning, reducing total and working-memory errors, but did not affect initial spatial reference acquisition or retention. To characterize navigation beyond classical performance measures, we developed a graph-based analysis comparing each observed trajectory with paths generated from random, regular, small-world and heuristic goal-directed network models. Radial-maze trajectories contained a structured mixture of goal-directed-like and regular or serial-like patterns that evolved across learning. In addition, agreement with the goal-directed model was associated with fewer errors and greater proximity to the rewarded arm. Together, these findings indicate that LC inputs to the hippocampus preferentially facilitate spatial memory updating rather than uniformly enhancing spatial learning, and introduce a complementary framework for quantifying the organization of radial-maze trajectories.