Role of dorsal and ventral hippocampus in working memory load capacity

In this study we found functional differences between the dorsal and ventral subregions of the HP in regulating object WMC but any difference was found in regulating allocentric spatial WMC. A major involvement of the ventral HP in regulating egocentric spatial memory was found. A recent study in CD1 mice reported a role for the dorsal HP in WM in high memory load (Sannino, Russo et al. 2012) confirming the results found in monkeys and in humans (Levy, Manns et al., 2003, Beason-Held, Rosene et al., 1999). Anatomic, genetic and behavioral studies suggested that the HP is subdivided into a dorsal and a ventral portion (Swanson and Cowan, 1977, Moser and Moser, 1993; Thompson and Pathak, 2008). Whether these two HP subregions differently regulate WMC has never been explorated. In this study we investigated if there is a functional differentiation between the dorsal and the ventral HP in regulating the limited capacity of WM using a neurotoxic selective dorsal and ventral HP lesion approach. First, we explorated the role of these two subregions in object WMC testing the dorsal HP and the ventral HP lesion groups in the 6 DOT described in Sannino et al., 2012. Here, we confirmed the role of the dorsal HP in object WMC and we did not find any involvement of the ventral part of the HP. Then, we investigated the role of these two regions in spatial WMC testing both lesion groups in a WMC version of the classical radial arm maze task using a modified protocol of the version described in Olivito et al., 2016. In our study we modulated the memory load by changing the number of open arms between 3, 6 and 8 open arms and exposing the mice to an allocentric version of the task (the confinement procedure) in the first 4 days and to a version where both allocentric and egocentric spatial memory can be used (the no-confinement procedure) in the last 4 days. In the confinement procedure the animals were confined in the 90 central zone of the apparatus to prevent the use of the egocentric strategies that are otherwise developed when the animals are free to explore the maze (noconfinement procedure). In this procedure we found an impairment in both dorsal HP and ventral HP lesion groups in high memory load suggesting a complementary role of the dorsal and ventral HP in mediating allocentric spatial WMC. A dissociation between the two regions was found in the no-confinement procedure where the involvement of the ventral HP was major than the dorsal HP. This major involvement of the ventral HP is parallel to a major impairment in the use of the sequential strategy found in the ventral HP lesion group suggesting a crucial role for the ventral HP in mediating the acquisition of egocentric strategies to solve the task. A no- confinement procedure, not preceded by a confinement procedure confirmed the crucial role of the ventral HP in regulating the use of egocentric strategies. In a final analysis of the effects of our dorsal HP and ventral HP lesions on a classical task used in literature to dissociate their function, we found the specific involvement of the ventral HP in mediating anxiety-like behavior confirming the results present in literature.