Loffredo V., Torromino G., Esposito F., Carboncino A., Cecere A., Mele A., De Leonibus E. "Sex regulates memory capacity"

Memory Capacity (MC) is the number of information maintained in memory. MC is regulated by fronto-striatal dopamine circuit and hippocampus (HP). Using a modified version of the object recognition task, the DOT/IOT, we have recently showed that adult naïve male mice could discriminate 3,4,6 but not 9 different objects after a 1 min or 24 hrs delay. Moreover, it has been reported that male mice use the HP, as well as humans, to solve the task (Sannino et al 2012, Olivito et al 2014; Sugita et al 2015). To report sex differences influencing MC, we have challenged 3 months old mice (males and females) with the 6-DOT (highest memory load), testing them at different time points. We have found that 3 months old female mice properly perform the 6-DOT when tested at 1 min delay (Short Term Memory, STM), but they are impaired when tested 24 hr later (Long Term Memory, LTM). Female mice properly perform the 6-IOT (lowest memory load) independently on the delay. We hypothesized that the impairment in LTM could reflect sex regulated differences in the use of different neuronal circuits to solve the task. Therefore, we are performing c-fos immunohistochemical analysis as an index of stimuli-induced neuronal activation on the HP and the prefrontal cortex, at different time points after exposing the animals to the 6-DOT. Preliminary data show that female mice, differently from males, do not activate the HP. Sex-regulated neuronal activation might be relevant to understand the higher impact of dementia in women as compared to men.