A cortico-hippocampal network for reference frame coordination and dysfunction in Alzheimer’s disease

Navigation and memory require coordination between map-like allocentric representations and body-centered egocentric actions. Aaron Wilber examines how the parietal–retrosplenial–anterior thalamic–hippocampal network performs these transformations, and how disrupted coordination contributes to spatial deficits in aging and Alzheimer’s disease.

Rat sequence-task experiments reveal bidirectional hippocampal–parietal interactions across route-centered, place and egocentric representations. Because that task does not isolate reference-frame use, the laboratory developed a freely available task separating egocentric, allocentric and transformation conditions. Validation indicates that parietal cortex and anterior thalamus are required for transformation; ongoing work examines population states associated with each condition.

The talk then connects impaired hippocampal–cortical communication during sleep to navigation deficits in 3xTg-AD mice, reporting recovery of circuit function and cognition after early, circuit-targeted 40 Hz entrainment. Related investigations examine this network during waking navigation. In TgF344-AD rats, egocentric impairments appear before transformation deficits, addressing the shortage of rodent studies of reference-frame coordination in Alzheimer’s disease.