Object/context-specific memory deficits associated with loss of hippocampal granule cells after adrenalectomy in rats

Abstract

Chronic adrenalectomy (ADX) causes a gradual and selective loss of granule cells in the dentate gyrus (DG) of the rat. Here, we administered replacement corticosterone to rats beginning 10 wk after ADX. We then tested them in three discrimination tasks based on object novelty, location, or object/context association. Only during testing of the object/context association did ADX rats demonstrate deficits. These findings add to a body of evidence that the hippocampus is necessary when contextual information is important. We also confirm that memory deficits after chronic adrenalectomy are not a result of loss of corticosterone per se.Research with rats (Sutherland and McDonald 1990;Kim and Faneslow 1992;Anagnostaras et al. 2001;Lehmann et al. 2009), nonhuman primates (Machado and Bachevalier 2006;Pascalis et al. 2009), and humans (Alvarez et al. 2008;Marschner et al. 2008) shows that hippocampal damage can disrupt the ability to recall or express information about context. Furthermore, several reports suggest that the hippocampus is important for creating flexible representations of context and object associations. Studies in rats (Mumby et al. 2002;O'Brien et al. 2006) and humans (Pascalis et al. 2009) show that lesions specific to the hippocampus produce deficits in object recognition only when contextual information is altered.Within the hippocampus, the dentate gyrus (DG) is important for certain aspects of memory (Xavier et al. 1999;Garthe et al. 2009). Chronic adrenalectomy (ADX) causes a gradual and selective loss of granule cells in the DG of the rat (Sloviter et al. 1989). This loss of cells is attributed to a lack of circulating corticosterone (CORT) (Sloviter et al. 1989;Woolley et al. 1991). Behavioral deficits as a result of chronic ADX have been reported in the Morris water task (Armstrong et al. 1993;Roozendaal et al. 1998;Spanswick et al. 2007) and open-field task (Islam et al. 1995). There has been debate as to whether the deficits experienced by ADX rats are a result of lost CORT or due to the depletion of the granule cell layer itself. Conrad and Roy (1995) and McCormick et al. (1997) report that acute CORT replacement is sufficient to alleviate some of the deficits in spatial tasks associated with chronic ADX. These findings have led some to conclude that the removal of CORT is responsible for the behavioral deficits experienced by ADX rats and not the loss of granule cells per se. In direct contrast to these findings, Spanswick et al. (2007) report that administration of CORT after 6 wk of ADX does not alleviate spatial deficits in a moving-platform version of the Morris water task. Also in opposition to Conrad and Roy (1995) and McCormick et al. (1997), studies utilizing colchicine as a method to remove granule cells report spatial deficits as a result of cell loss (Sutherland et al. 1983;Xavier et al. 1999;Jeltsch et al. 2001).Here, we show using three versions of a novelty-preference task (novel object, novel place, and object/context mismatch) that lesions limited to the granule cell layer...

Systemic lipopolysaccharide administration impairs retrieval of context–object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation

“…The DG, as well as CA3 and CA1, are all capable of performing pattern separation, and there is evidence that this process facilitates context discrimination (Vazdarjanova and Guzowski, 2004; Leutgeb et al, 2007; McHugh et al, 2007; Nakashiba et al, 2012). In a recent study (Spanswick and Sutherland, 2010), rats with a reduction in granule cells in dentate gyrus due to adrenalectomy could discriminate between a novel and familiar object but not an out-of-context and in-context object. As DG-CA3 circuits in particular are important for pattern separation and context discrimination (McHugh et al, 2007; Nakashiba et al, 2012), the deficit in COD in the present study may stem from disruption in pattern separation processes within the hippocampus which are unnecessary for retrieval in the water maze or NOR.…”

Ontogeny of object-in-context recognition in the rat

“…Likewise, the current literature suggests that the OiC task relies on function of the hippocampal system in adult rats [12, 30, 34, 36, 38, 39], with a few exceptions [18, 37]. The disparate findings regarding the role of the hippocampus in OiC memory may reflect variable delays employed by different studies which differentially recruit short-term vs. long-term memory processes, or variation in the degree of spatial processing required for discrimination of the contexts during the task.…”

Maternal stress during pregnancy causes sex-specific alterations in offspring memory performance, social interactions, indices of anxiety, and body mass

“…An interesting possibility is that different subcomponents of the hippocampus are important for different hippocampal-associated memory types. For example, studies have found that adult adrenalectomy results in a selective loss of cells in the dentate gyrus [36,37]. When spatial, recognition, and contextual memory were assessed following adrenalectomy and corticosterone replacement, only contextual memory impairments were found [37].…”

“…For example, studies have found that adult adrenalectomy results in a selective loss of cells in the dentate gyrus [36,37]. When spatial, recognition, and contextual memory were assessed following adrenalectomy and corticosterone replacement, only contextual memory impairments were found [37]. Thus, it is possible that in the current study elevated corticosterone levels during gestational stress impacted dentate gyrus development differently than other hippocampal subregions, leading to dissociations in hippocampal-associated memory functions in adulthood.…”