Functional specialization of the hippocampus along its dorso-ventral axis: from span to supraspan in working memory capacity

Abstract

Working memory (WM) is characterized by a limited capacity or span, beyond which performance deteriorates, the supraspan condition. Human neuropsychology and neuroimaging studies have implicated the medial temporal lobe (MTL), including the hippocampus (HPC), in WM particularly when memory load exceeds span, yet no animal model has been established to investigate supraspan mechanisms. Here, we present a novel rodent model of supraspan memory and examine the distinct roles of dorsal and ventral HPC. Using selective NMDA lesions in mice combined with object recognition tasks and a modified radial arm maze (RAM), we manipulated memory load and strategy constraints to assess span and supraspan performance. Dorsal HPC lesions impaired object memory span, while ventral lesions spared this ability. In the RAM, span performance (number of correct arm visits before the first error) was unaffected by either lesion under allocentric conditions. However, once animals exceeded span, following the first error, here defined as the supraspan condition, both dorsal and ventral lesions caused catastrophic disorientation and error escalation. Under free-choice conditions, ventral HPC lesions selectively reduced the occurrence of trials with no errors in the first 5 choices, increased errors overall, and disrupted sequential egocentric strategies. Together, these results demonstrate that supraspan performance can be modeled in rodents, revealing a dorsal contribution to object memory under high load, a ventral contribution to egocentric spatial strategies, and a shared hippocampal role in supraspan memory performance. This paradigm provides a translational framework for investigating supraspan deficits observed in MTL patients and Alzheimers disease.