Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia

Figures & data

Table 1 A selection of different types of memory common to both rodents and humans

Name of memory process (reference)	Examples in rodents	Examples in humans
Episodic memory^Citation105	Object recognition, target object recognition, IntelliCage	Mnemonic memory, remembering past experiences and analyzing possible future events, information about the order of events
Recognition memory^Citation51	Object recognition, touch screen	Recognition of faces or well-known objects
Semantic memory^Citation45	Morris water maze, Barnes maze, object recognition	Memory of facts and places
Spatial memory^Citation40	Morris water maze, Barnes maze, Y-maze, radial arm water maze	Navigating through the streets of a hometown, following directions, navigating around rooms of a house, remembering where items are placed
Emotional memory^Citation106	Fear conditioning	Learning to associate cues to negative outcomes, expressing emotional responses (ie, stress)

Table 2 Commonly used tasks to assess rodent memory acquisition

Name of test (reference)	Purpose and type of memory	Methodology	Strengths	Weaknesses
Water maze^Citation40	Spatial memory acquisition, some working memory	4-day spatial memory acquisition followed by probe trial 24 hours later	Well-established test and used in laboratories across the world, easily reproducible, simple procedure	Can be stressful for rodents, expensive, time consuming, can only test one rodent at a time, necessary to have a drainage and fill system for water, necessary for video tracking software
Barnes maze^Citation42	Spatial memory acquisition, some working memory	4-day spatial memory acquisition followed by probe trial 24 hours later	Less stressful for rodents utilizing more natural memory processes, well established, used in laboratories across the world	Time consuming, can only test one rodent at a time, necessary to have a large room for the 1 m wide maze and video tracking equipment
Novel object recognition^Citation50,Citation51	Associative memory, declarative memory, working memory	2-day protocol, replace old object with novel object, calculate “recognition index”	Well-established test, utilizes rodents’ natural exploratory processes, cost-effective, time efficient	Does not assess spatial memory, possible experimenter bias in results analysis
Fear conditioning^Citation107	Associative memory	2-day protocol – teach rodents to associate a “tone” with a foot shock, learning measured by freezing behavior	Short-time commitment from researcher (2 days), well established in the literature, robust results	Stressful for rodents, pain factor involved, expensive equipment, does not exclusively involve hippocampus
Radial arm water maze^Citation108	Spatial and working reference memory	Learned location of one of the eight escape arms, multiple trials over several days	Well established, natural exploring tendencies, short-time commitments, short training protocol, no olfactory cues	Can be expensive, swimming may induce stress, difficult to set up
Y-maze^Citation60	Active working short-term memory	Two trials, “spontaneous alternation” is calculated by the number of entries into the novel arm, quantified as spontaneous alternation	Cost-effective, minimal training, not time consuming, natural exploratory behavior of the animal	Does not measure memory acquisition over long periods of time

Figure 1 The most commonly used memory behavioral tests in rodents.

Notes: (A) Morris water maze: rodent learns to find submerged escape platform over time (black indicates escape platform); (B) Barnes maze: rodent learns to find escape box over time (black indicates escape hole); (C) radial arm water maze: rodent learns the location of the correct arm containing the submerged escape platform (black indicates escape platform); (D) novel object recognition: recognition index calculated as a percentage of time the rodent explores the novel object vs the old object on day 2 (black indicates objects, arrow signifies inter-trial interval); (E) Y maze: number of entries into novel arm quantified after brief training period; and (F) fear conditioning: freezing activity calculated after a brief conditioning phase (lines indicate wires, bolt indicates mild shock).
Abbreviations: CR, calorie restriction; IF, intermittent fasting; LPHC, low-protein, high-carbohydrate.

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