Assessing Cognition in Mice

Sabine M. Hölter1, Lillian Garrett1, Jan Einicke1, Bettina Sperling1, Petra Dirscherl2, Annemarie Zimprich1, Helmut Fuchs3, Valerie Gailus‐Durner3, Martin Hrabě de Angelis4, Wolfgang Wurst5

1 German Mouse Clinic, Helmholtz Zentrum München, Munich, 2 Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, 3 Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, 4 German Center for Diabetes Research, Neuherberg, 5 Munich Cluster for Systems Neurology (SyNergy), Munich
Publication Name:  Current Protocols in Mouse Biology
Unit Number:   
DOI:  10.1002/9780470942390.mo150068
Online Posting Date:  December, 2015
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Genetically modified mouse models have proven useful to study learning and memory processes and the neurocircuitry and molecular mechanisms involved, as well as to develop therapies for diseases involving cognitive impairment. A variety of tests have been developed to measure cognition in mice, and here we present those established and regularly used in the German Mouse Clinic. The test paradigms have been carefully chosen according to reliability of results and disease relevance of the cognitive functions assessed. Further criteria were time efficiency and ease of application. All tests assess slightly different but also overlapping or interacting aspects of learning and memory so that they can be used to complement each other in a comprehensive assessment of cognitive function. The five protocols described are for spontaneous alternation in the Y‐maze, social discrimination, object recognition, automated assessment of learning and memory using the IntelliCage, and olfactory discrimination learning. © 2015 by John Wiley & Sons, Inc.

Keywords: Y‐maze; social discrimination; object recognition; IntelliCage; olfactory discrimination learning

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Table of Contents

  • Introduction
  • Basic Protocol 1: Spontaneous Alternation in the Y‐Maze
  • Basic Protocol 2: Social Discrimination to Test Social Recognition Memory
  • Basic Protocol 3: Object Recognition Memory Test
  • Basic Protocol 4: IntelliCage: Automated Assessment of Cognitive Function in Group‐Housed Mice
  • Basic Protocol 5: Olfactory Discrimination Test To Assess Olfactory Learning And Memory
  • Commentary
  • Literature Cited
  • Figures
  • Tables
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Basic Protocol 1: Spontaneous Alternation in the Y‐Maze

  • Mice of interest
  • Disinfectant solution (e.g., Pursept‐A Xpress)
  • Sound‐attenuated testing room with adjustable light source
  • Light meter
  • Y‐maze (internal dimensions: arm length 29.5 cm; arm width 8 cm; height 15 cm) built in‐house
  • Sample data sheet #1 Y‐maze.xls: datasheet containing list of mouse identification, cage number, genotype, sex, file number, date, and weight (see
  • Timer
  • Scale (for weighing mice)
  • Fresh housing cage

Basic Protocol 2: Social Discrimination to Test Social Recognition Memory

  • Mice of interest
  • Ovariectomized (OVX) females
  • Handheld computer (e.g., Psion Workabout) with event logging software (e.g., Pocket Observer, Noldus)
  • sample data sheet #2 SD.xls: datasheet containing list of mouse identification, cage number, genotype, sex, file number, date, and weight (see
  • Sound‐attenuated testing room with adjustable light source
  • Paint markers (at least two different colors)
  • Light meter
  • Fresh cages with minimal litter and no food or water
  • Timer
  • Scale (for weighing mice)

Basic Protocol 3: Object Recognition Memory Test

  • Mice of interest
  • Disinfectant solution (e.g., Pursept‐A Xpress)
  • Sample data sheet #3 OR.xls: datasheet containing list of mouse identification, cage number, genotype, sex, file number, date, weight, and object allocations (see
  • Sound‐attenuated testing room with adjustable light source
  • Light meter
  • Empty mouse cages (for habituation; e.g., Bioscape, Type IIL, 29.5 cm l × 18.5 cm w × 13 cm h)
  • Mouse cages with two identical objects (e.g., two metal weights) firmly affixed to the base (spaced 3 cm apart)
  • Mouse cages with two different objects (e.g., metal weight and Lego piece) firmly affixed to the base (spaced 3 cm apart)
  • Mouse cages with two different objects (e.g., metal weight and colored board game counter) firmly affixed to the base (spaced 3 cm apart)
  • Mouse cages with bedding (for housing mice during delays and inter‐trial intervals)
  • Handheld computer (e.g. Psion Workabout) with event logging software (e.g., Pocket Observer program, Noldus Information Technology)
  • Timer

Basic Protocol 4: IntelliCage: Automated Assessment of Cognitive Function in Group‐Housed Mice

  • Mice of interest
  • Isoflurane
  • Standard rodent food
  • Disinfectant solution (e.g., Pursept‐A Xpress)
  • Sample data sheet #4 IC.xls: datasheet containing list of mouse identification, cage number, genotype, sex, transponder and IntelliCage identifications, date, and weight (see
  • Transponder injector (e.g., Planet ID GmbH)
  • Transponder (e.g., Planet ID GmbH)
  • Barcode scanner
  • Transponder reader (e.g., RFID Breeder Reader, Planet ID)
  • Inhalation anesthetic device (for administering isoflurane)
  • IntelliCage (TSE Systems) and associated equipment
  • Water bottles
  • Bedding
  • Mouse houses
  • Sound‐attenuated testing room with a controlled environment
  • Computer running Designer and Controller software (TSE Systems) and spreadsheet program (e.g., Microsoft Excel)

Basic Protocol 5: Olfactory Discrimination Test To Assess Olfactory Learning And Memory

  • Mice of interest
  • Standard rodent food
  • Phenethyl acetate [S+]
  • Methyl trans‐cinnamate [S−]
  • Diethyl phthalate
  • Chocolate sprinkles
  • Disinfectant solution (e.g., Pursept‐A Xpress)
  • Sample data sheet #5 olfaction.xls: datasheet containing list of mouse identification, cage number, genotype, sex, trial number, date, and weight (see
  • Scale (for weighing mice)
  • Shavings (e.g., Lignocel bedding, J. Rettenmaier & Söhne)
  • Zipper storage bag or 50‐ml conical tube
  • Sound‐attenuated testing room
  • Fresh housing cage equipped with a removable barrier and lid and a small amount of bedding
  • Caps from 50‐ml conical tubes (to be used as dishes)
  • Upside down T‐shaped carrier (see Fig.  )
  • Double‐sided tape
  • Forceps
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