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

Memory span, a key constraint on memory capacity (MC), defines the number of items that can be maintained over a short time interval before performance deteriorates. When this limit is exceeded, performance enters a supraspan condition. While humans’ studies implicate the medial temporal lobe (MTL), and particularly the hippocampus (HPC), in supraspan performance, no animal model has explicitly captured this transition. Here, we investigated the contribution of the dorsal and intermediate-ventral hippocampus (HPC) to span and supraspan-like performance in mice. Using selective N-methyl-D-aspartate (NMDA) lesions combined with modified versions of the object recognition task and of the radial arm maze (RAM), we manipulated memory load and strategy constraints to dissociate subregion-specific contributions. Dorsal HPC lesions impaired object memory under high memory load, whereas intermediate-ventral HPC lesions did not. In the RAM under allocentric conditions, neither lesion significantly affected Span, operationally defined as the number of correct choices before the first error within a trial. However, both lesions increased supraspan errors, operationally defined as the mean number of errors committed after span had been exceeded. When egocentric strategies were permitted, intermediate-ventral HPC lesions selectively reduced the Span, increased errors, and disrupted sequential choice strategies. These findings reveal functional dissociation along the hippocampal axis, with dorsal regions supporting high-load object memory and intermediate-ventral regions supporting egocentric spatial strategies, alongside a shared role in sustaining performance beyond span limits. Although not directly homologous to human supraspan memory, this paradigm provides a translational framework to investigate memory deficits associated with MTL dysfunction, including Alzheimer’s disease.