Thalamo-hippocampal pathway regulates incidental memory capacity in mice

AbstractMemory can be challenged by increasing both its required duration and the amount of information to be encoded, namely the memory load. The dorsal hippocampus (dHP) has been involved in memory consolidation, which is the stabilization of a trace from short-term (STM) to long-term memory (LTM), as well as in the ability to process high information load. However, how memory load influences memory consolidation, and the underlying neural mechanisms, are yet unknown.To address this question, we used male and female mice that, despite having in our Different Object recognition Task (DOT) the same STM capacity of 6 objects, spontaneously show differences in the number of objects directly transferred to LTM, when tested over longer delays. Males memorize all 6 objects encoded, while females remember only up to 4, both at 1 and 24 h delays. Interestingly, males activate more the dHP (as measured by c-Fos expression), while females the thalamic nucleus reuniens (RE). Optogenetic inhibition of the RE-dHP pathway during off-line memory consolidation favors 6-object LTM retention in females by removing inhibitory control over dHP activation, while chemogenetic RE-activation impairs it in males.Our data represent a first demonstration of a sub-cortical control of dHP recruitment, that might underlie its sex-dependent activation during incidental memory, with potential also for clinical application.

Incidental memory can be challenged by increasing either the retention delay or the memory load. The dorsal hippocampus (dHP) appears to help with both consolidation from short-term (STM) to long-term memory (LTM), and higher memory loads, but the mechanism is not fully understood. Here we find that female mice, despite having the same STM capacity of 6 objects and higher resistance to distraction in our different object recognition task (DOT), when tested over 1 h or 24 h delays appear to transfer to LTM only 4 objects, whereas male mice have an STM capacity of 6 objects in this task. In male mice the dHP shows greater activation (as measured by c-Fos expression), whereas female mice show greater activation of the ventral midline thalamus (VMT). Optogenetic inhibition of the VMT-dHP pathway during off-line memory consolidation enables 6-object LTM retention in females, while chemogenetic VMT-activation impairs it in males. Thus, removing or enhancing sub-cortical inhibitory control over the hippocampus leads to differences in incidental memory.