Limits...
A behavioral paradigm to evaluate hippocampal performance in aged rodents for pharmacological and genetic target validation.

Gerstein H, Hullinger R, Lindstrom MJ, Burger C - PLoS ONE (2013)

Bottom Line: This task, however, is not practical for pre- and post-pharmacological treatment, as the memory of the task is long lasting.In contrast, the object location memory task, also a spatial learning paradigm, results in a less robust memory that decays quickly.This method provides a tool to evaluate the effect of treatments on cognitive impairment associated with aging and neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Wisconsin-Madison, Medical Sciences Center, Madison, Wisconsin, United States of America.

ABSTRACT
Aged-related cognitive ability is highly variable, ranging from unimpaired to severe impairments. The Morris water maze (a reliable tool for assessing memory) has been used to distinguish aged rodents that are superior learners from those that are learning impaired. This task, however, is not practical for pre- and post-pharmacological treatment, as the memory of the task is long lasting. In contrast, the object location memory task, also a spatial learning paradigm, results in a less robust memory that decays quickly. We demonstrate for the first time how these two paradigms can be used together to assess hippocampal cognitive impairments before and after pharmacological or genetic manipulations in rodents. Rats were first segregated into superior learning and learning impaired groups using the object location memory task, and their performance was correlated with future outcome on this task and on the Morris water maze. This method provides a tool to evaluate the effect of treatments on cognitive impairment associated with aging and neurodegenerative disorders.

Show MeSH

Related in: MedlinePlus

Statistical analysis shows a significant correlation between individual performance on OLM1 and OLM2.Data shown as novelty index, or proportion of total investigation time spent attending to the object in the novel location. (A) First round of OLM (OLM1) [young, n = 15; SL, n = 17; AI, n = 8]. (B) Second round of OLM (OLM2) using the same animals [young, n = 15; SL, n = 17; AI, n = 14]. Aged performance groups on OLM2 are delineated without reference to previous performance on OLM1. (C) For animals ranked as SL or AI on OLM1, a dotted line connects that individual’s performance on OLM1 to their performance on OLM2 (see also Table 1). Only animals classified as SL or AI on OLM1 are shown, and their classification on OLM2 are shown as SL = black triangles, AI = white squares, and intermediates = grey diamonds. (D) Correlation analysis between individual performance on OLM1 and OLM2. Young = grey circles, aged = black diamonds (n = 44, all young, SL, AI, and Intermediate animals included). (E): Correlation analysis for the aged rats. Grey diamonds indicate animals that were categorized differently in OLM1 and OLM2, or were classified as Intermediate in both tests. For details on this group of animals please refer to Tables 1 and 2.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3646843&req=5

pone-0062360-g002: Statistical analysis shows a significant correlation between individual performance on OLM1 and OLM2.Data shown as novelty index, or proportion of total investigation time spent attending to the object in the novel location. (A) First round of OLM (OLM1) [young, n = 15; SL, n = 17; AI, n = 8]. (B) Second round of OLM (OLM2) using the same animals [young, n = 15; SL, n = 17; AI, n = 14]. Aged performance groups on OLM2 are delineated without reference to previous performance on OLM1. (C) For animals ranked as SL or AI on OLM1, a dotted line connects that individual’s performance on OLM1 to their performance on OLM2 (see also Table 1). Only animals classified as SL or AI on OLM1 are shown, and their classification on OLM2 are shown as SL = black triangles, AI = white squares, and intermediates = grey diamonds. (D) Correlation analysis between individual performance on OLM1 and OLM2. Young = grey circles, aged = black diamonds (n = 44, all young, SL, AI, and Intermediate animals included). (E): Correlation analysis for the aged rats. Grey diamonds indicate animals that were categorized differently in OLM1 and OLM2, or were classified as Intermediate in both tests. For details on this group of animals please refer to Tables 1 and 2.

Mentions: Fifty aged (20-month old) and fifteen young (3-month old) F344 rats were used in this part of the study. Total amount of time spent exploring the novel and familiar objects was recorded for each animal and novelty indices were examined in both young and aged animals as described in detail in the methods section. Aged animals with a novelty index equal to or greater than the mean of the young animals (59%±4.5 S.E.M.) were labeled superior learners, those with a novelty index of 51% or less were classified as aged impaired learners, and those performing between the level of SL and AI were labeled as intermediate. For the first round of OLM, 53% of all aged animals (n = 32) were classified as superior learners, 25% as intermediate, and 22% as aged impaired (Fig. 2A).


A behavioral paradigm to evaluate hippocampal performance in aged rodents for pharmacological and genetic target validation.

Gerstein H, Hullinger R, Lindstrom MJ, Burger C - PLoS ONE (2013)

Statistical analysis shows a significant correlation between individual performance on OLM1 and OLM2.Data shown as novelty index, or proportion of total investigation time spent attending to the object in the novel location. (A) First round of OLM (OLM1) [young, n = 15; SL, n = 17; AI, n = 8]. (B) Second round of OLM (OLM2) using the same animals [young, n = 15; SL, n = 17; AI, n = 14]. Aged performance groups on OLM2 are delineated without reference to previous performance on OLM1. (C) For animals ranked as SL or AI on OLM1, a dotted line connects that individual’s performance on OLM1 to their performance on OLM2 (see also Table 1). Only animals classified as SL or AI on OLM1 are shown, and their classification on OLM2 are shown as SL = black triangles, AI = white squares, and intermediates = grey diamonds. (D) Correlation analysis between individual performance on OLM1 and OLM2. Young = grey circles, aged = black diamonds (n = 44, all young, SL, AI, and Intermediate animals included). (E): Correlation analysis for the aged rats. Grey diamonds indicate animals that were categorized differently in OLM1 and OLM2, or were classified as Intermediate in both tests. For details on this group of animals please refer to Tables 1 and 2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646843&req=5

pone-0062360-g002: Statistical analysis shows a significant correlation between individual performance on OLM1 and OLM2.Data shown as novelty index, or proportion of total investigation time spent attending to the object in the novel location. (A) First round of OLM (OLM1) [young, n = 15; SL, n = 17; AI, n = 8]. (B) Second round of OLM (OLM2) using the same animals [young, n = 15; SL, n = 17; AI, n = 14]. Aged performance groups on OLM2 are delineated without reference to previous performance on OLM1. (C) For animals ranked as SL or AI on OLM1, a dotted line connects that individual’s performance on OLM1 to their performance on OLM2 (see also Table 1). Only animals classified as SL or AI on OLM1 are shown, and their classification on OLM2 are shown as SL = black triangles, AI = white squares, and intermediates = grey diamonds. (D) Correlation analysis between individual performance on OLM1 and OLM2. Young = grey circles, aged = black diamonds (n = 44, all young, SL, AI, and Intermediate animals included). (E): Correlation analysis for the aged rats. Grey diamonds indicate animals that were categorized differently in OLM1 and OLM2, or were classified as Intermediate in both tests. For details on this group of animals please refer to Tables 1 and 2.
Mentions: Fifty aged (20-month old) and fifteen young (3-month old) F344 rats were used in this part of the study. Total amount of time spent exploring the novel and familiar objects was recorded for each animal and novelty indices were examined in both young and aged animals as described in detail in the methods section. Aged animals with a novelty index equal to or greater than the mean of the young animals (59%±4.5 S.E.M.) were labeled superior learners, those with a novelty index of 51% or less were classified as aged impaired learners, and those performing between the level of SL and AI were labeled as intermediate. For the first round of OLM, 53% of all aged animals (n = 32) were classified as superior learners, 25% as intermediate, and 22% as aged impaired (Fig. 2A).

Bottom Line: This task, however, is not practical for pre- and post-pharmacological treatment, as the memory of the task is long lasting.In contrast, the object location memory task, also a spatial learning paradigm, results in a less robust memory that decays quickly.This method provides a tool to evaluate the effect of treatments on cognitive impairment associated with aging and neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Wisconsin-Madison, Medical Sciences Center, Madison, Wisconsin, United States of America.

ABSTRACT
Aged-related cognitive ability is highly variable, ranging from unimpaired to severe impairments. The Morris water maze (a reliable tool for assessing memory) has been used to distinguish aged rodents that are superior learners from those that are learning impaired. This task, however, is not practical for pre- and post-pharmacological treatment, as the memory of the task is long lasting. In contrast, the object location memory task, also a spatial learning paradigm, results in a less robust memory that decays quickly. We demonstrate for the first time how these two paradigms can be used together to assess hippocampal cognitive impairments before and after pharmacological or genetic manipulations in rodents. Rats were first segregated into superior learning and learning impaired groups using the object location memory task, and their performance was correlated with future outcome on this task and on the Morris water maze. This method provides a tool to evaluate the effect of treatments on cognitive impairment associated with aging and neurodegenerative disorders.

Show MeSH
Related in: MedlinePlus