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

Performance on OLM correlates with performance on the MWM probe trial.(A) Task acquisition on the MWM in young and aged rats, four trials per day. The first eight trials (Days 1 & 2) represent the visual version of the task. Young animals learn the task quickly, although aged superior learners learn the task soon afterward. Aged impaired learners do not show high acquisition of the task. Asterisk indicates a significant difference of AI and SL performance on the MWM over time. (B) Percent of total swim distance spent in target quadrant during probe trial (Day 10) was the criterion by which animals were grouped into SL, AI, or intermediate. Both young and SL animals cover >40% of their total swim distance in the target quadrant. AI animals perform close to the chance level (25%). (C) Percent of total time spent in the target platform during probe trial show significant differences performance between SL, AI and young rats. (D) Platform crossings during probe trial show statistical differences in performance between SL, AI and young rats. (E) Individual novelty index on OLM2 significantly correlates to performance on the probe trial of the MWM when young (grey circles) and aged groups (black diamonds) are included (n = 55, young, SL, AI, and intermediate animals included). [Young, n = 15; SL, n = 22; AI, n = 11, and intermediate, n = 7, as defined by % total target swim distance]. (F): Correlation analysis for the aged rats. Grey diamonds indicate animals that were categorized differently in OLM2 and MWM, or were classified as intermediate on both. For details on these groups of animals, please refer to Tables 2 and 3.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3646843&req=5

pone-0062360-g003: Performance on OLM correlates with performance on the MWM probe trial.(A) Task acquisition on the MWM in young and aged rats, four trials per day. The first eight trials (Days 1 & 2) represent the visual version of the task. Young animals learn the task quickly, although aged superior learners learn the task soon afterward. Aged impaired learners do not show high acquisition of the task. Asterisk indicates a significant difference of AI and SL performance on the MWM over time. (B) Percent of total swim distance spent in target quadrant during probe trial (Day 10) was the criterion by which animals were grouped into SL, AI, or intermediate. Both young and SL animals cover >40% of their total swim distance in the target quadrant. AI animals perform close to the chance level (25%). (C) Percent of total time spent in the target platform during probe trial show significant differences performance between SL, AI and young rats. (D) Platform crossings during probe trial show statistical differences in performance between SL, AI and young rats. (E) Individual novelty index on OLM2 significantly correlates to performance on the probe trial of the MWM when young (grey circles) and aged groups (black diamonds) are included (n = 55, young, SL, AI, and intermediate animals included). [Young, n = 15; SL, n = 22; AI, n = 11, and intermediate, n = 7, as defined by % total target swim distance]. (F): Correlation analysis for the aged rats. Grey diamonds indicate animals that were categorized differently in OLM2 and MWM, or were classified as intermediate on both. For details on these groups of animals, please refer to Tables 2 and 3.

Mentions: The Morris water maze was performed in the same group of young and aged rats used for the two OLM tasks described above. Animals began the 10-day long MWM two days after completing OLM2. Days 1 and 2 consisted of habituation/training with a visible platform. The hidden platform version of the MWM was performed on Days 3–10 of the task, with four trials per day. Total swim path distance to find the escape platform on each trial was measured in centimeters and binned by day to assess task acquisition (learning curve) (Fig. 3A). At the end of the last training trial, the platform was removed and a probe trial was run in which the swim path of the rat was tracked for 90 s. Percent of total distance and time spent in the target quadrant (that previously contained the escape platform) and number of platform crossings (number of times the rat crossed the exact prior location of the platform) were measured in the probe trial (Fig. 3B–D). Aged rats were classified as SL, intermediate, and AI based on the percent of total distance spent in target quadrant during the probe trial. Animals were classified as SL when they spent 40% or more of their total swim distance in the target quadrant [the bottom of young performance range]. Animals were classified as AI when they spent approximately chance levels of total swim distance in the target quadrant [25% of total distance+S.E.M. from young performance] (Fig. 3B).


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)

Performance on OLM correlates with performance on the MWM probe trial.(A) Task acquisition on the MWM in young and aged rats, four trials per day. The first eight trials (Days 1 & 2) represent the visual version of the task. Young animals learn the task quickly, although aged superior learners learn the task soon afterward. Aged impaired learners do not show high acquisition of the task. Asterisk indicates a significant difference of AI and SL performance on the MWM over time. (B) Percent of total swim distance spent in target quadrant during probe trial (Day 10) was the criterion by which animals were grouped into SL, AI, or intermediate. Both young and SL animals cover >40% of their total swim distance in the target quadrant. AI animals perform close to the chance level (25%). (C) Percent of total time spent in the target platform during probe trial show significant differences performance between SL, AI and young rats. (D) Platform crossings during probe trial show statistical differences in performance between SL, AI and young rats. (E) Individual novelty index on OLM2 significantly correlates to performance on the probe trial of the MWM when young (grey circles) and aged groups (black diamonds) are included (n = 55, young, SL, AI, and intermediate animals included). [Young, n = 15; SL, n = 22; AI, n = 11, and intermediate, n = 7, as defined by % total target swim distance]. (F): Correlation analysis for the aged rats. Grey diamonds indicate animals that were categorized differently in OLM2 and MWM, or were classified as intermediate on both. For details on these groups of animals, please refer to Tables 2 and 3.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0062360-g003: Performance on OLM correlates with performance on the MWM probe trial.(A) Task acquisition on the MWM in young and aged rats, four trials per day. The first eight trials (Days 1 & 2) represent the visual version of the task. Young animals learn the task quickly, although aged superior learners learn the task soon afterward. Aged impaired learners do not show high acquisition of the task. Asterisk indicates a significant difference of AI and SL performance on the MWM over time. (B) Percent of total swim distance spent in target quadrant during probe trial (Day 10) was the criterion by which animals were grouped into SL, AI, or intermediate. Both young and SL animals cover >40% of their total swim distance in the target quadrant. AI animals perform close to the chance level (25%). (C) Percent of total time spent in the target platform during probe trial show significant differences performance between SL, AI and young rats. (D) Platform crossings during probe trial show statistical differences in performance between SL, AI and young rats. (E) Individual novelty index on OLM2 significantly correlates to performance on the probe trial of the MWM when young (grey circles) and aged groups (black diamonds) are included (n = 55, young, SL, AI, and intermediate animals included). [Young, n = 15; SL, n = 22; AI, n = 11, and intermediate, n = 7, as defined by % total target swim distance]. (F): Correlation analysis for the aged rats. Grey diamonds indicate animals that were categorized differently in OLM2 and MWM, or were classified as intermediate on both. For details on these groups of animals, please refer to Tables 2 and 3.
Mentions: The Morris water maze was performed in the same group of young and aged rats used for the two OLM tasks described above. Animals began the 10-day long MWM two days after completing OLM2. Days 1 and 2 consisted of habituation/training with a visible platform. The hidden platform version of the MWM was performed on Days 3–10 of the task, with four trials per day. Total swim path distance to find the escape platform on each trial was measured in centimeters and binned by day to assess task acquisition (learning curve) (Fig. 3A). At the end of the last training trial, the platform was removed and a probe trial was run in which the swim path of the rat was tracked for 90 s. Percent of total distance and time spent in the target quadrant (that previously contained the escape platform) and number of platform crossings (number of times the rat crossed the exact prior location of the platform) were measured in the probe trial (Fig. 3B–D). Aged rats were classified as SL, intermediate, and AI based on the percent of total distance spent in target quadrant during the probe trial. Animals were classified as SL when they spent 40% or more of their total swim distance in the target quadrant [the bottom of young performance range]. Animals were classified as AI when they spent approximately chance levels of total swim distance in the target quadrant [25% of total distance+S.E.M. from young performance] (Fig. 3B).

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