The ability to remember sequences of events is fundamental to episodic memory. While rodent studies have examined sex and estrous cycle in episodic-like spatial memory tasks, little is known about these biological variables in memory for sequences of events that depend on representations of temporal context. We investigated the role of sex and estrous cycle in rats during training and testing stages of a cross-species validated sequence memory task (Jayachandran et al., 2019). Rats were trained on a two four-odor sequence memory task delivered on opposite ends of a linear track. Training occurred in six successive stages starting with learning to poke in a nose-port for ≥1.2 s; eventually demonstrating sequence memory by holding their nose in the port ≥1 s for in-sequence odors and <1 s for out-of-sequence odors. Performance was analyzed across sex and estrous cycle (proestrus, estrus, metestrus, and diestrus), the latter being determined by cellular composition of a daily vaginal lavage. We found no evidence of sex differences in asymptotic sequence memory performance, similar to humans performing an analogous task (Reeders et al., 2021). Likewise, no differences in sequence memory performance were found across the estrous cycle. Some caveats are that males acquired out-of-sequence trials faster during training with a 3-odor sequence, but this apparent advantage did not carry over to the 4-odor sequence. Additionally, males had shorter poke times overall which seem consistent with a decreased overall response inhibition because they occurred regardless of sequence demands. Together, these results suggest sex and estrous cycle are not major factors in sequence memory capacities.

The ability to remember sequences of events is fundamental to episodic memory. While rodent studies have examined sex and estrous cycle in episodic-like spatial memory tasks, little is known about these biological variables in memory for sequences of events that depend on representations of temporal context. We investigated the role of sex and estrous cycle in rats during all training and testing stages of a cross-species validated sequence memory task (Jayachandran et al., 2019). Rats were trained on a task composed of two sequences, each with four unique odors delivered on opposite ends of a linear track. Training occurred in six successive stages starting with learning to poke in a nose port for ≥1.2s; eventually demonstrating sequence memory by holding their nose in the port for ≥1s for in-sequence odors and <1s for out-of-sequence odors in order to receive a water reward. Performance was analyzed across sex and estrous cycle (proestrus, estrus, metestrus, and diestrus), the latter being determined by the cellular composition of a daily vaginal lavage. We found no evidence of sex differences in asymptotic sequence memory performance, similar to published data in humans performing the analogous task (Reeders et al., 2021). Likewise, we found no differences in performance across the estrous cycle. One minor difference was that female rats tended to have slightly longer poke times, while males had slightly more short poke times but this did not affect their decisions. These results suggest sex and estrous cycle are not major factors in sequence memory capacities.