A Neuromodulatory Circuit Amplifies Object-based Head-direction Tuning for Spatial Memory

While the head-direction (HD) system is well-established as the brain’s internal compass, the mechanisms that allow it to be flexibly shaped by landmarks have remained unclear. Here we discovered that histamine release in the anterodorsal thalamus (ADn), a core HD hub, is synchronized with object exploration. During object exploration, objects evoked a localized increase in the peak firing rate of ADn HD cells, an enhancement bidirectionally controlled by histaminergic inputs: chemogenetic activation potentiated it, while inhibition abolished it. Computational modeling (Bicanski–Burgess framework) indicated that this histamine-mediated gain facilitates precise reference-frame transformations. Consistently, optogenetic manipulation confirmed that ADn histamine specifically supports object location memory, but not object recognition memory. Mechanistically, this regulation depends on H3 receptors in the ADn via downstream β-arrestin pathway. Our findings identify a dedicated neuromodulatory circuit for object-based HD tuning and reveal a novel signaling mechanism that shapes cognitive map.