How many short-term memories become long-term? Unveiling the answer through the study of sex differences

The process of memory consolidation involves the transfer of information from short-term memory (STM) to long-term memory (LTM). Memory consolidation requires activation of the dorsal hippocampus (dHP), especially under conditions of high memory load. In this study, we asked whether there is a limit to the memory capacity, that is, the amount of information that can be stored during unique experiences. Using male and female outbred CD1 mice subjected to a modified version of the object recognition test, we found that females, despite having the same 6- object STM capacity as males, appear to transfer only 4 objects into the LTM, whereas males remember all 6. Using c-Fos expression as a marker of neural activation, we found that female mice show greater activation of the ventral median thalamus (VMT), while males hyperactivate the dHP, when exposed to 6 objects to remember. Optogenetic inhibition of the VMT-dHP pathway during off-line memory consolidation allowed the maintenance of the 6-object LTM in females, whereas chemogenetic activation of VMT-dHP impairs it in males. These results identify a subcortical-cortical circuit sensitive to biological sex differences that controls the amount of information spontaneously transferred from the STM to the LTM.