Dentate gyrus-selective colchicine lesion and disruption of performance in spatial tasks: Difficulties in ?place strategy? because of a lack of flexibility in the use of environmental cues?

Xavier, Gilberto Fernando; Oliveira‐Filho, Francisco J.B.; Santos, A M G

doi:10.1002/(sici)1098-1063(1999)9:6<668::aid-hipo8>3.0.co;2-9

Cited by 148 publications

(130 citation statements)

References 65 publications

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“…Several studies have indicated that acute CORT replacement is sufficient to at least partially reverse behavioral deficits associated with ADX (Conrad and Roy 1995;McCormick et al 1997). Our current findings, as well as our previous report (Spanswick et al 2007), and those using colchicine as a method to ablate the DG (Sutherland et al 1983;Xavier et al 1999;Jeltsch et al 2001) support the idea that granule cell loss contributes to the deficits.…”

supporting

confidence: 88%

“…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 of the DG produce deficits that are specific to detecting an object/context mismatch. Our results support the idea that the hippocampus (specifically the DG) is critical in situations in which contextual discrimination is important.…”

mentioning

confidence: 70%

“…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).…”

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confidence: 99%

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confidence: 99%

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

Spanswick¹,

Sutherland²

2010

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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...

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confidence: 88%

mentioning

confidence: 70%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Spanswick¹,

Sutherland²

2010

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“…For instance, selective colchicine lesions of the dentate gyrus produce deficits in tasks requiring spatial working and reference memory (Xavier et al 1999). Electrolytic lesions of the dorsal hippocampus induce anterograde deficits in contextual fear conditioning (Maren and Fanselow 1997).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of BDNF mRNA in the Hippocampal Dentate Gyrus after Re-exposure to Cues Previously Associated with Footshock,

Rasmusson

Shi

Duman

2002

Neuropsychopharmacology

235

109

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This study examined the effects of footshock stress and reexposure to cues previously associated with footshock on expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus of male rats. Exposure to twenty 0.5-s 0.4-mA footshocks co-terminating withBrain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors, which also includes nerve growth factor and neurotrophins 3 and 4. BDNF as well as these other neurotrophins, plays an important role in neuronal growth and differentiation during development, and also contributes to the survival, function, and plasticity of neurons in the adult brain (Lewin and Barde 1996). Thus, through a variety of mechanisms in different brain regions, BDNF has been implicated in emergent phenomena such as learning and memory (Patterson et al. 1996;Mu et al. 1999) and even contributes to the modulation of overt behaviors such as aggression (Lyons et al. 1999). The ability of BDNF to influence these processes is related, in part, to the activity dependent regulation of BDNF expression in adult brain (Lewin and Barde 1996).BDNF is also thought to play a role in the cellular and behavioral responses to stress (Duman et al. , 2000. Exposure to physical stress, such as immobilization, downregulates BDNF expression in the hippocampus (Smith et al. 1995, Vaidya et al. 1997 (Duman et al. , 2000. Moreover, downregulation of BDNF could contribute to the hippocampal pathology observed in psychiatric disorders such as post-traumatic stress disorder (PTSD) and depression (Bremner et al. 2000;Mervaala et al. 2000;Vakili et al. 2000). This possibility is supported by the observation that these disorders are sensitive to stressful experiences (Breslau et al. 1995;Kendler et al. 2000). Based on these observations and findings, we became interested in determining whether psychological stress has a measurable impact on hippocampal BDNF expression similar to the effects of physical stressors that have been reported.We therefore tested the effects of psychological stress produced by exposures to cues previously paired with footshock on BDNF mRNA levels in the dentate gyrus of the hippocampus. We hypothesized that re-exposure to cues associated with footshock stress, as well as footshock itself, would decrease BDNF mRNA in the dentate gyrus. The results demonstrate that this type of psychological stress produces a heightened sensitivity to previously neutral cues that results in downregulation of BDNF, and suggest that psychological stress, such as that experienced in association with PTSD and depression, as well as other disorders, could result in decreased neurotrophic support of the hippocampus. MATERIAL AND METHODS AnimalsAdult male Sprague-Dawley rats were kept in a 12:12 h light-dark cycle (lights on at 7:00 A . M .) for 7-10 days before each experiment. The animals were housed two or three per cage and fed ad libitum. Experiments were conducted between 9:00 A . M . and 6:00 P . M . To control for possible effects of diurnal variation on hippoca...

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Use of excitotoxins to lesion the hippocampus: Update

Jarrard

2002

Hippocampus

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Although many of the problems associated with the use of conventional lesion techniques (aspiration, electrolytic, radiofrequency) can be avoided by employing focal injections of excitotoxins, experience gained over the past 12 years has shown that considerable care must be exercised with this newer method, to limit the cell loss to the intended area or structure. Of the toxins that have been used most often to selectively destroy the cells that comprise the hippocampus, ibotenic acid (IBO) and N-methyl-D-aspartate (NMDA) have proved to be nonspecific in their effects on different cell types and these toxins do not cause seizures. In contrast, focal injections of kainate (KA) and quisqualate result in damage that centers primarily in the CA3 pyramidal cell field and hilar cells in the dentate gyrus. In addition, there are obvious seizures and secondary distant damage involving a number of structures and areas associated with mediating seizure activity. Intrahippocampal injections of the toxin colchicine result in a preferential destruction of dentate granule cells but usually also lead to additional cell loss in adjacent areas. Attempts to limit cell loss to specific hippocampal subfields, using different toxins, have met with mixed success. Both the dosage of the agent and the volume injected are important in determining the extent of cell loss, but the volume of the toxin injected has been shown to be especially important in limiting the damage to the intended area. With the development of newer procedures (e.g., immunotoxins, gene knockouts, antisense) that permit more selective cell loss, it should be possible in the future to achieve a level of lesion control that has been lacking in the past. As with the use of excitotoxins, these newer approaches will require special care to limit the damage to the intended area and interpret the results obtained properly.

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Dentate gyrus-selective colchicine lesion and disruption of performance in spatial tasks: Difficulties in ?place strategy? because of a lack of flexibility in the use of environmental cues?

Cited by 148 publications

References 65 publications

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

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

Downregulation of BDNF mRNA in the Hippocampal Dentate Gyrus after Re-exposure to Cues Previously Associated with Footshock,

Use of excitotoxins to lesion the hippocampus: Update

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