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. Author manuscript; available in PMC: 2013 Mar 17.
Published in final edited form as: Behav Brain Res. 2011 Dec 22;228(2):447–451. doi: 10.1016/j.bbr.2011.12.024

Age-Related Changes in Detection of Spatial Novelty

David W Maasberg a, Laura E Shelley a, Paul E Gilbert a,b
PMCID: PMC3268849  NIHMSID: NIHMS348698  PMID: 22203158

Abstract

Age-related changes in novelty detection for object-place associations was assessed in 6-mo and 25-mo-old Fisher 344/Brown Norway (F344/BN) rats. Old rats showed significant deficits compared to young rats in detecting spatial displacement of objects. The data suggest that object-place novelty detection is impaired in aged F344/BN rats using a rapidly acquired, exploratory-based task. The results may have important implications for the selection of efficient memory paradigms for future aging studies.

Keywords: Aging, Spatial, Object, Novelty Detection, Exploration

The detection of changes in a previously explored environment may require a comparison between sensory information from the current environment and an internal representation of the environment stored in memory. The hippocampus has been suggested to be an important substrate to support a match-mismatch process to compare current environmental sensory information with an internal memory representation [1–5]. Recent studies have shown that tasks measuring natural exploratory behavior may be useful and time efficient paradigms for studying memory, and particularly this match-mismatch process [3,6]. As discussed by Lee et al. [3], normal animals tend to recognize changes in a familiar environment by increasing exploration of stimuli moved to a novel location, relative to unchanged stimuli. However, animals with damage to the hippocampus [6] or its subregions [3] do not demonstrate increased exploration of spatial changes in the environment, indicating that the hippocampus may play a critical role in processing novel spatial information.

There is an extensive literature from human and animal research implicating the medial temporal lobes, and particularly the hippocampus, in age-related deficits in learning and memory [7]. Some studies have reported preserved numbers of neurons in the hippocampus of aged rats [8–10] and nonhuman primates [11]; however, others have reported decreased neuronal density in rats [12]. In addition, some studies have reported a lack of a relationship between hippocampal cell numbers and spatial learning deficits [8,12]; however, hippocampal volume (measure by MRI) has been reported to correlate with water maze performance in aged rats [12]. Since neuronal loss in the hippocampus is unlikely to fully account for the memory deficits in aged animals and humans, it has been postulated that age-related memory decline may stem from functional changes in the hippocampus [12–14], localized synaptic loss [15], and subregion-specific epigenetic and transcriptional changes in the hippocampus [16]. For example, neurogenesis is reduced in aged animals [17] and is related to performance on hippocampal dependent tasks and hippocampal volume [12]. Recent evidence has suggested that these newborn neurons may be involved in mnemonic processes particularly dependent on the dentate gyrus subregion of the hippocampus [18].

Since subtle but significant age-related changes occur in various regions of the hippocampal formation, normal aging often is associated with impairments on tasks that rely on intact functioning of the hippocampus and surrounding regions. For example, aged nonhuman primates and rodents demonstrate parallel impairments to animals with hippocampal damage on a variety of memory tasks, including tasks measuring spatial memory [19–24], temporal order memory [25], contextual memory [26], delayed recognition memory [27–29], odor memory [30], and transitive inference [31].

The present study was designed to assess age-related changes in novelty detection for object-place associations in Fischer 344/Brown Norway (F344/BN) rats using a rapidly acquired, exploratory-based task utilized in previous studies [3,6]. Thirty-Six F344/BN male rats (Harlan Laboratories) approximately 6-mo (n = 18) and 25-mo (n = 18) of age were used as subjects. The F344BN is a hybrid between female Fisher 344 rats and male Brown Norway rats. Subjects were housed in pairs in standard plastic containers located in a colony room and supplied continuous access to food and water. To maximize exploratory behavior, rats were handled 5–10 minutes everyday for 14 days prior to testing to minimize neophobia. The colony room was kept on a 12hr:12hr light:dark cycle and all testing was conducted during the light phase. All experimental procedures were reviewed and approved by the Institutional Animal Use and Care Committee at San Diego State University.

The testing apparatus consisted of a 90 cm square platform that was 1.5cm in thickness and elevated 65cm above the floor. The apparatus was constructed of wood, painted white, and was located in a small, well-lit room with a video camera mounted to the ceiling to record exploration. Various visually dissimilar objects 10–15 cm in height were used for the task, for example a toy truck, rubber duck, water bottle, and dog toy. The objects were similar to those used in previously published experiments [3,25]. Objects were mounted on metal washers and held in place on the apparatus using magnets to prevent a rat from displacing the objects. Multiple copies of each object were used during testing to minimize specific olfactory cues associated with a particular object.

The behavioral procedure was adapted from a paradigm used in previously published studies [3,6]. Testing on each task involved seven 6-min exploratory sessions, each with a 3-min inter-session interval where the rat was removed from the testing room and placed in plastic housing containers. During Session 1, each rat was introduced to the testing environment with no stimuli present to allow for habituation to the environment. During Sessions 2–4, four objects (AD) were arranged in a rectangular configuration (45 cm × 40 cm), with the fifth object (E) located at the approximate center of the configuration (see Figure 1). For Sessions 5–6, the rectangular configuration was changed to a polygon configuration where Object D was moved to a novel peripheral location and object E, which had previously been located in the center position, was moved to the location previously occupied by Object D. For Session 7, the polygon configuration was maintained; however, Object C was replaced with a novel object (F). The assignment of objects to specific locations varied randomly for each rat.

Figure 1.

Figure 1

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A schematic representation of the task paradigm showing the locations of the various objects (A–F) used during the seven 6-min exploratory sessions. Each session was followed by a 3-min intersession interval.

A camera mounted on the ceiling above the apparatus recorded exploratory behavior during all test sessions. The software program WINTV2000 was used to store all video files electronically for later analysis. Object exploration was defined as the animal’s nose entering a 1 cm halo around the perimeter of the stimulus as measured by the Object Scan software package (Clever Sys. Inc.). The Object Scan software enables the researcher to specifically track the nose of the animal to accurately measure object exploration.

Index scores were calculated as described by Lee et al. [3]. An object habituation index was calculated by subtracting the total interaction time of all five objects from Session 4 from the total interaction time of all five objects from Session 2 (a positive score indicating that there was more interaction during Session 2 than Session 4). A spatial mismatch index (SMI) was used to examine the exploration of the displaced objects during Sessions 5–6. The SMI was calculated by taking the sum of the exploration time for the displaced objects for Sessions 5–6 (i.e. Object D and Object E) and subtracting the sum of the exploration time for these displaced objects for Sessions 3–4 (a positive score indicating that there was more interaction with the displaced objects than the same objects in the familiar locations). Additionally, a within session SMI was calculated to examine exploration of displaced versus non-displaced objects by taking the exploration time of displaced objects and subtracting the exploration time of non-displaced objects within session 5. Session 7 was used to create an object mismatch index. This index was calculated to quantify the identification of object change by subtracting the total interactions of the unchanged objects during Session 7 (Objects A–E) from the sum of the interactions with the novel object (Object F).

Figure 2A shows the habituation index scores for 6-mo and 25-mo-old rats. A one-way analysis of variance (ANOVA) showed that the habituation index scores of 6-mo-old rats were not significantly different from those of 25-mo-old rats F(1, 34) = .53, p = .47. An analysis also was conducted to examine age-related differences in total object exploration and habituation across Sessions 2, 3, and 4. A 2 × 3 ANOVA with group (6-mo, 25-mo) as a between group variable and session (2, 3, 4) as within group variable revealed a significant main effect of session F(2, 68) = 30.58, p < .001. However, the analysis did not detect a significant main effect of group F(1, 34) = .20, p = .66, or a group x session interaction F(2, 68) = .24, p = .79. As shown in Figure 3, both groups showed habituation to the objects across sessions 2–4. However, there were no significant age-related differences in total object exploration or habituation.

Figure 2.

Figure 2

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Mean habituation index scores (A), spatial mismatch index scores (B), and object mismatch index scores (C) for 6 mo and 25 mo old rats. * Indicates statistically significant group difference.

Figure 3.

Figure 3

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Mean total exploration of all objects during Sessions 2–7 for 6 mo and 25 mo old rats.

Figure 2B shows the spatial mismatch index scores for 6-mo and 25-mo-old rats. A one-way ANOVA showed that the SMI scores of 6-mo-old rats were significantly higher than those of 25-mo-old rats, F(1, 34) = 4.23, p < .05. To examine exploration differences between Object E (in location previously occupied by Object D) and Object D (moved to novel location), a 2 × 2 × 2 ANOVA was conducted to examine with group (6-mo, 25-mo) as a between group variable, and session (5, 6) and object (D, E) as within group variables. The analysis revealed that overall exploration of Object E [6-mo = 11.53 (SE 3.45), 25-mo = 5.68 (SE 3.55)] was significantly greater than exploration of Object D [6-mo = 1.29 (SE .34), 25-mo = .65 (SE .34)] across both group and session F(1, 35) = 9.23, p < .01. However, the analysis did not reveal significant main effects of session F(1, 35) = .11, p = .75 or group F(1, 35) = 1.73, p = .20.

Since differences between 6-mo and 25-mo-old rats on SMI scores could be due to age-related differences in total object exploration or motivation, an analysis was conducted to examine total object exploration time during Sessions 5 and 6. A 2 × 2 ANOVA with group (6-mo, 25-mo) as a between group variable and session (5, 6) as within group variable did not reveal significant main effects for group F(1, 34) = 1.31, p = .26 or session F(1, 34) = .70, p = .80. In addition, the analysis did not reveal a significant group x session interaction F(1, 34) = .06, p = .79. As shown in Figure 3, there were no significant age-related differences in total object exploration during Sessions 5 and 6. A one-way ANOVA on the within session SMI scores revealed no significant group differences during Session 5 F(1, 35) = .65, p = .43. This analysis also suggests that age-related differences on the SMI scores shown in Figure 2B were not likely due to group differences in overall exploration time.

To examine whether there were group differences in the total number of objects explored during Sessions 5 and 6, a 2 × 2 × 5 ANOVA with group (6-mo, 25-mo) as a between group variable and session (5, 6) and object (A, B, C, D, E) as within group variables was used. The analysis revealed a significant main effect of object F(4, 140) = 13.72, p < .001. However, the analysis did not reveal significant main effects of group F(1, 35) = .40, p = .53 or session F(1, 35) = .12, p = .73, or any significant interactions. In addition, a one-way ANOVA with group (6-mo, 25-mo) as a between group variable and time spent exploring the periphery of the test environment as the dependent measure revealed no significant group differences in exploration F(1, 35) = .17, p = .682 during Sessions 5 and 6.

Figure 2C shows the object mismatch index scores for 6-mo and 25-mo-old rats. A one-way ANOVA revealed no significant age-related differences on object mismatch index scores, F(1, 34) = .349, p = .56. Although higher object mismatch scores were found in 6-mo-old rats compared to 25-mo-old rats, single sample t-tests revealed that neither group differed significantly from zero. As shown in Figure 3, a one-way ANOVA revealed no significant differences in total object exploration during Session 7 between 6-mo and 25-mo-old rats F(1, 34) = .41, p = .53.

The results of the present study demonstrate that aged rats do not detect changes in object-place associations when exploring an environment. These findings are in accordance with prior studies [32–34]. However, exploration of the novel object during Session 7 was not particularly strong in either group. Although the primary aim of this study was to examine age-related changes in the detection of spatial novelty, it is not possible to make conclusions regarding changes in novel object exploration. An analysis of total object exploration during Sessions 5 and 6 (involving spatial manipulations) revealed no significant age-related differences, suggesting that differences on spatial index mismatch scores were not due to decreased motivation in the 25-mo-old rats. In addition, there were no significant differences between 6-mo and 25-mo-old rats in habituation or exploration during Sessions 2–4, suggesting that the results also are not explained by age-related differences in habituation. It is difficult to rule out the possibility that age-related sensorimotor deficits may have contributed to group differences on Sessions 5 and 6. However, the lack of a difference between young and aged rats on measures of object habituation, overall exploration, and frequency contacts with objects suggest that sensorimotor deficits alone did not account for the group differences in detection of spatial novelty during Sessions 5 and 6. The present study is one of the few to use an exploratory-based task to examine age-related memory changes in a rodent model of aging [32–35] and only the second, to the authors’ knowledge, to do so using the F344/BN hybrid strain [see also 25]. The present age-related differences may stem from difficulties comparing sensory information from the current environment and an internal representation of the environment stored in memory. In addition, Wilson and colleagues [15] suggest that age-related changes in the hippocampus may result in the strengthening of stored information at the cost of processing new information resulting in poorer encoding. Therefore, it also is possible that the age-related differences may be the result of poorer encoding of object-place associations in aged rats. This hypothesis is supported by the finding that during Sessions 5 and 6, overall exploration of Object E (object in location previously occupied by object D) was significantly greater than exploration of object D (object moved to novel location). However, using the present task, it is not possible to establish whether the age-related differences in exploration are due to impaired encoding, storage, or retrieval.

The hippocampus has been suggested to be an important substrate to support a match-mismatch process [1–5] and rats with hippocampal lesions demonstrate deficits in the detection of changes to object-place associations on the present task [3,6]. Therefore, age-related changes in the hippocampus may contribute to the present findings in 25 mo old rats. Furthermore, prior studies have reported age-related impairment on other hippocampal dependent spatial tasks in rodent models of aging [19–23,25,26]. The encoding of contextual information may be critical to the formation of episodic memories due to the need to form associations among stimuli, actions, and places that compose an event [36]. The hippocampus may be particularly important for the formation of associations between a place and a stimulus [37] and may be important for forming configurable associations [38]. Eichenbaum and Robitsek [30] suggest that hippocampal neurons in the aging brain may be unable differentiate contextual information and this impairment may underlie age-related decline in spatial memory. In addition, Oler and Markus [39] report that age-related deficits in episodic memory may result from an inability of the hippocampal network to respond to meaningful environmental changes, which is consistent with the present findings. The results from the current study add to the literature suggesting that normal aging results in impairments in associative memory for contextual stimuli, which may contribute to age-related changes in episodic memory.

Many previous behavioral studies in aged rats, including one examining spatial exploratory behavior [33], have used 22–24-mo-old Fisher 344 (F344) rats. The present study was conducted using a F344/BN hybrid strain, which is recommended and bred (via Harlan Laboratories) by the National Institute on Aging (NIA). However, a relatively small number of behavioral studies have been published examining cognitive deficits in this hybrid strain. The F344/BN strain has been shown to live longer than F344 rats. The 50% survival age for F344/BN male rats is 34-mo, whereas the 50% survival age for F344 male rats is 24-mo (National Institute on Aging). Therefore, the rats in the present study showed significant memory impairments at 25-mo of age despite having longer average longevity than other strains of aged rats used in prior spatial exploratory studies [33]. The present finding is consistent with other studies that have reported age-related behavioral deficits in F344/BN rats 24–25-mo of age on various cognitive tasks [12,25,26,40–42]. However, 24-mo-old F344/BN rats have been shown to match young rats on some behavioral measures such as trace and delayed eyeblink conditioning paradigms [43]. Approximately 50% of animals 28–29-mo of age showed deficits in trace eyeblink coditioning, whereas rats 34–35-mo of age showed severe deficits in trace conditioning and mild deficits in delayed conditioning [43].

The present findings add to the relatively small but growing literature demonstrating behavioral age-related learning and memory impairments in the F344/BN hybrid strain. The present findings suggest that aged rodents may be a suitable animal model for studying the effects of aging on a hypothesized match-mismatch process to compare current environmental sensory information with an internal representation in memory. In addition, the present task may be very attractive to researchers examining spatial memory changes in aged rats because the task is rapidly administered. Thus, the results may have important implications for the selection of memory paradigms for future research studies on aging. Driscoll et al. [12] report that the observed pattern of age-related change in aged F344/BN rats closely resembles the changes found in non-demented older adults. Therefore, the present study provides further evidence that this strain of rats, recommended by NIA, may serve as a useful animal model to study the effects of aging on cognitive function.

Research Highlights.

  • We examined age-related changes in novelty detection for object-place associations.

  • No age-related differences were found in habituation to the objects.

  • Old rats showed significant deficits in detecting spatially displaced objects.

  • Age-impaired object-place memory was found with a rapidly acquired, exploratory task.

  • The results have implications for selecting efficient memory tasks for future studies.

Acknowledgments

This work was supported by the National Institutes of Health (5R01 AG026505). The authors thank Karen Guzman, Erin Weston, and Andrew Galleta for their assistance with data collection and Drs. Raymond Kesner, Naomi Goodrich-Hunsaker, M. Ryan Hunsaker, and Jeffrey Long for their technical advice.

Footnotes

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