Sex differences in the timing behavior performance of 3xTg-AD and wild-type mice in the peak interval procedure

Interval timing is disrupted in female 5xFAD mice: An indication of altered memory processes

“…In the current study, mice were housed under an inverted light:dark cycle and the testing took place only during the dark phase. Our primary motivation behind this procedural choice was to test the mice during their natural awake period as we did in our previous study with 3xTg‐AD mice (Gür et al, ). Most relevant to this procedural aspect of the current study, the effects of testing interval timing performance at different times of day were reported in both rodents and humans (see Agostino, Golombek, & Meck, for a review).…”

“…The apparatus and procedure follow those described by Gür et al (). Testing was conducted in a mouse nine‐hole box (Cambridge Cognition Ltd., England) with a lick tube attached to a peristaltic pump, house lights, and speakers (mounted on both sides of the inner walls).…”

“…Despite these empirical observations in clinical patients and animal lesion studies, behavioral phenotyping of transgenic mouse models of AD has focused primarily on learning and memory processes. In the one study that investigated interval timing performance in a mouse model of AD, Gür et al () tested 10‐month‐old male and female 3xTg‐AD mice in the peak interval (PI) procedure with a target duration of 15 s. This study found no genotype differences in the timing ability of 3xTg‐AD mice and their B6129F2/J wild‐type (WT) controls in the PI procedure but found a sex difference in the motivational aspects of timing behavior (start time of anticipatory responding and amplitude of the response curve/gradient), with female mice of both genotypes initiating their timed anticipatory responses later in the trial than the male mice. Although 3xTg‐AD mice mimic the neuropathological symptoms of AD, having both plaque and tangle formations, the findings of this study did not indicate a timing deficit in the 3xTg‐AD mice as observed in patients with AD.…”

“…The current study tested the interval timing behavior of 9‐month‐old female 5xFAD and WT mice in the PI procedure. The age at testing was chosen so that the mice were older than when they have been shown to exhibit temporal implicit memory deficit (Ohno et al, ) but also close to the age of the 3xTg‐AD mice previously tested in the same PI procedure and task parameters (Gür et al, ). Female mice were chosen because the prevalence of AD is known to be higher in women than in men (Laws, Irvine, & Gale, ; Viña & Lloret, ) and female 5xFAD mice exhibit higher levels of APP, Aβ‐42 (Oakley et al, ), and Aβ plaque density (in the hippocampus and entorhinal cortex) than age‐matched male 5xFAD mice (Bhattacharya, Haertel, Maelicke, & Montag, ).…”

“…Female mice were chosen because the prevalence of AD is known to be higher in women than in men (Laws, Irvine, & Gale, ; Viña & Lloret, ) and female 5xFAD mice exhibit higher levels of APP, Aβ‐42 (Oakley et al, ), and Aβ plaque density (in the hippocampus and entorhinal cortex) than age‐matched male 5xFAD mice (Bhattacharya, Haertel, Maelicke, & Montag, ). Furthermore, Gür et al () found a lower proportion of well‐timed trials in female 3xTg‐AD mice compared to male 3xTg‐AD mice suggesting a stronger phenotype in females. Based on previous findings regarding the effect of hippocampal lesions (Meck et al, ; Olton et al, ) and trace conditioning deficits in 5xFAD mice (Ohno et al, ), we hypothesized that 5xFAD mice would display a memory‐dependent interval timing deficit that would result in the overestimation (underreproduction) of time intervals both in comparison to the WT controls and the fixed interval used in the task.…”