Evidence that ovarian hormones, but not diet and exercise, contribute to the sex disparity in post-traumatic stress disorder.

Females are twice as likely as males to receive a diagnosis of post-traumatic stress disorder (PTSD). One hypothesis for this sex disparity is that ovarian hormones, including estrogen and progesterone, contribute to PTSD risk. Alternatively, sex differences in lifestyle factors, such as diet and exercise, may play a role in PTSD risk. Using data from the Atlantic Partnership for Tomorrow's Health (PATH) cohort (n = 16,899), the relationship between endogenous hormone fluctuations (e.g., menarche, pregnancy, and menopause), exogenous hormone use (e.g., hormonal contraception and hormone replacement therapy (HRT)) and lifestyle variables (diet and exercise habits, as measured by the Mediterranean Diet Adherence Screener, Healthy Eating Index, and International Physical Activity Questionnaire) with PTSD diagnosis and treatment were analyzed. While several hormonal variables, including contraceptive use, higher total number of pregnancies, younger menarche age, and having undergone menopause increased the risk of PTSD, no lifestyle variables contributed to an increased risk of PTSD diagnosis. These findings support the theory that ovarian hormones contribute to the sex-linked disparity in PTSD diagnosis.

Unpredictable mealtimes rather than social jetlag affects acquisition and retention of hippocampal dependent memory.

Some degree of circadian rhythm disruption is hard to avoid in today's society. Along, with many other deleterious effects, circadian rhythm disruption impairs memory. One way to study this is to expose rats to daylengths that are outside the range of entrainment. As a result, circadian processes and behaviors occur during phases of the light dark cycle in which they typically would not. Even brief exposures to these day lengths can impair hippocampal dependent memory. In a recent report, we created an unentrainable light dark cycle that was intended to resemble aspects of social jetlag. As predictable mealtime impacts circadian entrainment, in that report, we also created an unpredictable meal schedule with the idea that failure to entrain to a meal might afford a disadvantage in some instances. Both of these manipulations impaired retention in a spatial water plus-maze task. Using the same manipulations, the present study investigated their effects on acquisition in distributed and massed spatial water plus-maze paradigms. As in other reports with unentrainable daylengths, acquisition was not affected by our lighting manipulation. Conversely, in accordance with our past report, unpredictable mealtimes had a harmful effect on hippocampal dependent memory. Notably, impaired acquisition in the distributed version, and impaired retention in the massed version. In tandem, these data suggest that failure to consolidate or retrieve the information is the likely culprit. The unpredictable mealtime manipulation offers a unique opportunity to study the effects of circadian entrainment on memory.

A local circadian clock for memory?

The master clock, suprachiasmatic nucleus, is believed to control peripheral circadian oscillators throughout the brain and body. However, recent data suggest there is a circadian clock involved in learning and memory, potentially housed in the hippocampus, which is capable of acting independently of the master clock. Curiously, the hippocampal clock appears to be influenced by the master clock and by hippocampal dependent learning, while under certain conditions it may also revert to its endogenous circadian rhythm. Here we propose a mechanism by which the hippocampal clock could locally determine the nature of its entrainment. We introduce a novel theoretical framework, inspired by but extending beyond the hippocampal memory clock, which provides a new perspective on how circadian clocks throughout the brain coordinate their rhythms. Importantly, a local clock for memory would suggest that hippocampal-dependent learning at the same time every day should improve memory, opening up a range of possibilities for non-invasive therapies to alleviate the detrimental effects of circadian rhythm disruption on human health.

Daily Time-Place Learning in Young Children.

Pre-school children find it difficult to correctly report if it is morning or afternoon. The present study tested whether children could learn a non-verbal Time-Place Learning (TPL) task that depended on time of day. Twenty-five 4-year-olds were repeatedly asked to find a toy in one of two boxes. Children in the Cued condition were told the toy was in one box in the morning and in another box in the afternoon. Children in the Not Cued condition were told the toy was sometimes in one box and sometimes in the other box. After 80 trials, children were asked if it was morning or afternoon. About 65% of the children learned the TPL task, and about three-quarters of the children verbally identified if it was morning or afternoon. However, the children who learned the TPL task were not necessarily the children who correctly answered whether it was morning or afternoon, and those in the Cued condition were no more likely to solve the task than those in the Not Cued condition. The implication is that children have a sense of time that can be used to solve spatio-temporal contingencies, but does not depend on the verbal understanding of time of day.

Lesions to the lateral mammillary nuclei disrupt spatial learning in rats.

The head direction (HD) signal is thought to originate in the reciprocal connections between the dorsal tegmental nuclei (DTN) and the lateral mammillary nuclei (LMN) and lesions to these structures disrupt the HD signal in downstream structures. Lesions to the DTN also disrupt performance on spatial tasks where directional heading is thought to be important. In Experiment 1, rats with bilateral electrolytic lesions of the LMN and sham controls were trained on 2 tasks previously shown to be sensitive to DTN damage. Rats were first trained on either a direction or rotation problem in a water T maze. LMN-lesioned rats were impaired relative to sham controls, on both the first block of 8 trials and on the total number of trials taken to reach criterion. In the food-foraging task, rats were trained to leave a home cage at the periphery of a circular table, find food in a food cup at the center of the table, and return to the home cage. Again, LMN-lesioned rats were impaired relative to sham rats, making more errors on the return component of the foraging trip. In Experiment 2, rats with electrolytic LMN lesions were also impaired on a dry land version of the direction and rotation problems and had difficulty discriminating between reinforced and nonreinforced locations on a 12-arm maze. These results build on previous behavioral and cell-recording studies and demonstrate the importance of the direction system to spatial learning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Consistent meal times improve performance on a daily time-place learning task.

The ability of an animal to learn the spatiotemporal variability of stimuli is known as time-place learning (TPL). The present study investigated the role of the food-entrainable oscillator (FEO) in TPL. Rats were trained in an operant conditioning chamber which contained two levers that distributed a food reward, such that one lever provided food rewards in morning sessions, while the other lever provided food rewards in afternoon sessions. We expected that having access to the FEO would provide rats with more accurate depictions of time of day, leading to better performance. Rats received either one meal per day (1M group), which permitted FEO access, or many meals per day (MM group), which prevented FEO access. As predicted, 1M rats had a significantly higher percentage of correct first presses than MM rats. Once rats successfully learned the task, probe tests were conducted to determine the timing strategy used. Of the 10 rats that successfully learned the time-place discrimination, six used a circadian timing strategy. Future research should determine whether the advantage in learning seen in the rats having access to the FEO is specific to the daily TPL task used in this study, or to learning and memory tasks more generally.

Rats in a levered T-maze task show evidence of time-place discriminations in two different measures.

It is difficult for rats to learn to go to an arm of a T-maze to receive food that is dependent on the time of day, unless the amount of food in each daily session is different. In the same task, rats show evidence of time-place discriminations if they are required to press levers in the arms of the T-maze, but learning is only evident when the first lever press is considered, and not the first arm visited. These data suggest that rats struggle to use time as a discriminative stimulus unless the rewards/events differ in some dimension, or unless the goal locations can be visited prior to making a response. If both of these conditions are met in the same task, it might be possible to compare time-place learning in two different measures that essentially indicate performance before and after entering the arms of the T-maze. In the present study, we investigated time-place learning in rats with a levered T-maze task in which the amounts of food varied depending on the time of day. The first arm choices and first lever presses both indicated that the rats had acquired time-place discriminations, and both of these measures became significantly different from chance during the same block. However, there were subtle differences between the two measures, which suggest that time-place discrimination is aided by visiting the goal locations.

Mice use start point orientation to solve spatial problems in a water T-maze.

Behavioral work has demonstrated that rats solve many spatial problems using a conditional strategy based on orientation at the start point. The present study assessed whether mice use a similar strategy and whether the strategy would be affected by the poorer directional sensitivity of mice. In Experiment 1, mice were trained on a response, a direction or one of two place problems to locate a hidden platform in a water T-maze located in two positions. In the response task, mice made a right (or left) turn from two different start points located 180° apart. In the direction task, the maze was shifted (to the left or right) and the start points rotated by 180° across trials, but the platform was in a constant direction relative to room cues. In the translation place task, the mice were trained to locate the platform in a fixed location relative to extra-maze cues when the maze was shifted across trials, but the orientation of the start arm did not change. In the rotation place task, the mice were trained to locate the platform in a fixed location when the maze was shifted and the start points rotated by 90° across trials. As previously reported with rats, mice had difficulty solving the translation place problem compared with the other three problems. Unlike rats, mice learned the direction problem in significantly fewer trials than the rotation problem. This difference between acquisition of the direction and rotation problems was replicated in Experiment 2. The difficulty mice have in discriminating start point orientations that are 90° apart as opposed to 180° apart can be attributed to the broader firing ranges of HD cells in mice compared with rats.

The effects of lesions to the postsubiculum or the anterior dorsal nucleus of the thalamus on spatial learning in rats.

To investigate the role of the head direction (HD) cell circuit in spatial navigation, rats with bilateral, neurotoxic lesions to the postsubiculum (PoS; Experiment 1) or the anterior dorsal nucleus of the thalamus (ADN; Experiment 2) were compared to sham controls on 2 tasks that could be solved using directional heading. Rats were first trained on a direction problem in a water T maze where they learned to travel either east or west from 2 locations in the experimental room. ADN lesioned rats were impaired relative to sham controls on the first block of 8 trials, but not on the total trials taken to reach criterion. This transient deficit was not observed in rats with lesions to the PoS. In the food-foraging task, rats were trained to leave a home cage at the periphery of a circular table, find food in the center of the table, and return to the home cage. Both PoS and ADN lesioned rats showed impairments on this task relative to sham rats, making more errors on the return component of the foraging trip. The spatial deficits produced by lesions to the PoS and the ADN, downstream structures in the HD cell circuit, are not as severe as those observed in earlier studies in rats with lesions to the dorsal tegmental nucleus.

In a daily time-place learning task, time is only used as a discriminative stimulus if each daily session is associated with a distinct spatial location.

It is difficult for rats to acquire daily time-place (TP) learning tasks. One theory suggests that rats do not use time of day as a stimulus signaling a specific response. In the present study, we tested rats' ability to use time of day as a discriminative stimulus. A fixed-interval procedure was used in which one lever provided reinforcement on a FI-5-s schedule in morning sessions, and the same lever provided reinforcement on a FI-30-s schedule in afternoon sessions. Because only one place was used in this paradigm, the rats could only use time of day to acquire the task. Mean responses during the first 5 s of the first trial in each session indicated that the rats did not discriminate between the two sessions. In Phase II, a different lever location was used for each of the two daily sessions, which meant that both spatial and temporal information could be used to acquire the task. The rats readily acquired the task in this phase, and probe trials indicated that the rats were using a combination of spatial and temporal information to discriminate between the two different trial types. When the spatial cue was removed in Phase III, rats no longer discriminated the two sessions, suggesting that time can only be used as a discriminative stimulus when each daily session is associated with a distinct spatial location.

Hippocampal spatial mapping and the acquisition of competing responses.

Response reversal learning is facilitated in many species, including humans, when competing responses occur in separate contexts. This suggests hippocampal maps may facilitate the acquisition of competing responses and is consistent with the hypothesis that contextual encoding permits rapid acquisition of new behaviors in similar environments. To test this hypothesis, the pattern of Arc expression was examined after rats completed a series of left/right response reversals in a T-maze. This reversal training occurred in the same room, two different rooms, or within a single room but with the maze enclosed in wall-length curtains of different configurations (i.e., black/white square or circle). Across CA1 and CA3, successive T-maze exposures in the same room recruited the same cells to repeatedly transcribe Arc, while a unique population of cells transcribed Arc in response to each of two different rooms as well as to the two unique curtain configurations in the same room. The interference from original learning that was evident on the first reversal in animals without a context switch was absent in groups that experienced changes in room or curtain configuration. However, only the use of unique rooms, and not changes in the curtained enclosure, facilitated learning across response reversals relative to the groups exposed to only one room. Thus, separate hippocampal maps appear to provide protection from the original learning interference but do not support improved reversals over trials. The present data suggest changes in heading direction input, rather than remapping, are the source of facilitation of reversal learning.

The effects of bilateral lesions to the dorsal tegmental nucleus on spatial learning in rats.

The head-direction (HD) signal is believed to originate in the dorsal tegmental nucleus (DTN) and lesions to this structure have been shown to disrupt HD cell firing in other areas along the HD cell circuit. To investigate the role of the DTN in spatial navigation, rats with bilateral, electrolytic (Experiment 1), or neurotoxic (Experiment 2) lesions to the DTN were compared with sham controls on two tasks that differed in difficulty and could be solved using directional heading. Rats were first trained on a direction problem in a water T maze where they learned to travel either east or west from two locations in the experimental room. DTN-lesioned rats were impaired relative to sham controls, both early in training, on the first block of eight trials, and on the total trials taken to reach criterion. In the food-foraging task, rats were trained to leave a home cage at the periphery of a circular table, find food in the center of the table and return to the home cage. Again, DTN-lesioned rats were impaired relative to sham rats, making more errors on the return component of the foraging trip. These data extend previous cell-recording studies and behavioral tests in which rats with electrolytic DTN lesions were used, and they demonstrate the importance of the direction system to spatial learning.

The effects of response cost and species-typical behaviors on a daily time-place learning task.

Two theories that have been hypothesized to mediate acquisition in daily time-place learning (TPL) tasks were investigated in a free operant daily TPL task: the response cost hypothesis and the species-typical behavior hypothesis. One lever at the end of one of the choice arms of a T-maze provided food in the morning, and 6 h later, a lever in the other choice arm provided food. Four groups were used to assess the effect of two possible sources of response cost: physical effort of the task and costs associated with foraging ecology. One group was used to assess the effect of explicitly allowing for species-typical behaviors. If only first arm choice data were considered, there was little evidence of learning. However, both first press and percentage of presses on the correct lever prior to the first reinforcement revealed evidence of TPL in most rats tested. Unexpectedly, the high response cost groups for both of the proposed sources did not perform better than the low response cost groups. The groups that allowed animals to display species-typical behaviors performed the worst. Skip session probe trials confirmed that the majority of the rats that acquired the task were using a circadian timing strategy. The results from the present study suggest that learning in free operant daily TPL tasks might not be dependent on response cost.

Individual differences in conceptual and procedural fraction understanding: the role of abilities and school experience.

Recent research on children's conceptual and procedural knowledge has suggested that there are individual differences in the ways that children combine these two types of knowledge across a number of mathematical topics. Cluster analyses have demonstrated that some children have more conceptual knowledge, some children have more procedural knowledge, and some children have an equal level of both. The current study investigated whether similar individual differences exist in children's understanding of fractions and searches for explanations for these differences. Grade 6 students (n=119) and Grade 8 students (n=114) were given measures of conceptual and procedural knowledge of fractions as well as measures of general fraction knowledge, general conceptual ability, and general procedural ability. Grade 6 children demonstrated a four-cluster solution reflecting those who do poorly on procedural and conceptual fraction knowledge, those who do well on both, those whose strength is procedural knowledge, and those whose strength is conceptual knowledge. Grade 8 children demonstrated a two-cluster solution reflecting those whose strength is procedural knowledge and those whose strength is conceptual knowledge. Cluster in either grade, however, did not vary in distribution across schools and was not related to general conceptual ability or general procedural ability. Overall, these results provide a more detailed picture of individual differences in conceptual and procedural knowledge in mathematical cognition.

Interval time-place learning in young children.

While previous research has investigated the ability of animals to learn the spatial and temporal contingencies of biologically significant events (known as time-place learning), this ability has not been studied in humans. Children ranging from 5 to 10 years old were tested on a modified interval time-place learning task using a touchscreen computer. Results demonstrate the children were able to quickly learn both the timing and the sequence of this task. Despite a lack of anticipation on baseline trials, the children continued to follow the spatio-temporal contingencies in probe sessions where these contingencies were removed. Performance on the probe sessions provide strong evidence that the children had learned the spatio-temporal contingencies. Future research is needed to determine what age-related changes in iTPL occur. Furthermore, it is argued that this procedure can be used to extend interval timing in research in children, including, but not limited to, investigation of scalar timing with longer durations than have previously been investigated.

Strain differences in a high response-cost daily time-place learning task.

Previous research has shown that rats, unlike birds, do not readily demonstrate daily time-place learning (TPL). It has been suggested, however, that rats are more successful at these tasks if the response cost (RC) is increased. Widman et al. (2000) found that female Sprague Dawley (SD) rats learned a daily TPL task in which they were required to climb different towers depending on the time of day to find a food reward. Using a similar apparatus, we found that male SD rats learned the task, while male Long Evans rats did not. While all rats quickly learned to restrict the majority of their searching to the two towers that provided food, only the SD rats learned to go to the correct location at the correct time of day. Thus, there appears to be a strain difference in the effectiveness of a high RC task to promote learning. Tests of the timing strategies used revealed individual differences with one rat using a circadian strategy and another using an ordinal strategy. Post criterion decrements in performance did not allow sufficient testing to determine the timing strategies of the remaining rats. Possible interactions between strain, response cost, species typical behaviors and dependent measures are discussed.

Rats acquire a low-response-cost daily time-place task with differential amounts of food.

Gallistel (1990) theorized that when animals encounter a biologically significant event, they automatically form a tripartite code consisting of the time, place, and nature of the event. Recent research examining such time-place learning (TPL) has shown that rats are reluctant to perform TPL tasks and appear to do so only under high-response-cost situations (Thorpe, Bates, & Wilkie, 2003; Widman, Gordon, & Timberlake, 2000). In the present study, we trained rats on a low-response-cost daily TPL task, in which the amount of food varied with the spatiotemporal contingencies. It was found that rats readily learned this task. We hypothesize that, rather than automatically encoding a tripartite code when faced with a biologically important event, rats instead automatically encode bipartite codes consisting of time-event and event-place information.

The role of spatial and temporal information in learning interval time-place tasks.

In time-place learning (TPL) paradigms animals are thought to form tripartite memory codes consisting of the spatiotemporal characteristics of biologically significant events. In Phase I, rats were trained on a modified TPL task in which either the spatial or temporal component was constant, while the other component varied randomly. If the memory codes are tripartite then when one aspect of the code is random the rats should have difficulty learning the constant aspect of the code. However, rats that were trained with a fixed spatial sequence of food availability and a random duration did in fact learn the task. Rats that were trained with a fixed duration and a random sequence did not learn the task. In Phase II all rats were placed on a TPL task in which food availability was contingent upon both spatial and temporal information. According to the tripartite theory, prior knowledge of either aspect of the code should have little effect on the acquisition of the task. The rats that received fixed spatial training learned the task relatively more quickly. The use of bipartite, rather than tripartite codes, is better able to explain the results of the current study.

Rats' performance on an interval time-place task: increasing sequence complexity.

Rats were trained on an interval time-place learning (TPL) task in which the location of food availability depended on the time since the start of the session. Each of four levers (numbered 1, 2, 3, 4) provided food on an intermittent schedule for two nonconsecutive 3-min periods. The order in which the levers provided food was 1, 2, 4, 3, 2, 3, 1, 4. This order was consistent across sessions. Previous research conducted in our lab has shown that when only four "places" are used, rather than the eight in the present study, rats use a timing strategy to track the location of food. Pizzo and Crystal (2004) recently trained rats on an interval TPL in which each of eight arms of a radial arm maze provided food. They found evidence suggesting that rats used both spatial and temporal information. In the present study, in which a revisiting strategy was used (i.e., each lever provided food on more than one occasion), the rats tracked both the spatial and the temporal availability of food for the first half of the session. Interestingly, in the second half of the sessions, the rats appeared to be timing the availability of food even though they did not know where it would occur. That is, the rats knew the temporal, but not the spatial, contingencies for the second half of the session. It appears that the requirement of revisiting a previously reinforced lever resulted in rats' no longer being able to solve the spatial aspect of the task.

Interval time-place learning by rats: varying reinforcement contingencies.

Two experiments with rats were conducted to study interval time-place learning when the spatiotemporal contingencies of food availability were more similar to those likely to be encountered in natural environments, than those employed in prior research. In Experiment 1, food was always available on three levers on a variable ratio (VR) 35 schedule. A VR8 schedule was in effect on Lever 1 for 5 min, then on Lever 2 for 5 min, and so forth. While rats learned to restrict the majority of their responding to the lever that provided the highest density of reinforcement, they seemed to rely on a win-stay/lose-shift strategy rather than a timing strategy. In Experiment 2, the four levers provided food on variable ratios of 15, 8, 15, and 30, each for 3 min. As expected the rats learned these contingencies. A novel finding was that the rats had a spike in response rate immediately following a change from a higher to lower reinforcement density. It is concluded that rats exposed to spatiotemporal contingencies behave so as to maximize the rate of obtained reinforcement.