Learning and memory impairments in a congenic C57BL/6 strain of mice that lacks the M2 muscarinic acetylcholine receptor subtype

Natalie K. Bainbridge, Lisa R. Koselke, Jongrye Jeon, Kathleen R. Bailey, Jürgen Wess, Jacqueline Crawley, Craige C. Wrenn

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The neurotransmitter acetylcholine is an important modulator of cognitive functions including attention, learning, and memory. The actions of acetylcholine are mediated by five distinct muscarinic acetylcholine receptor subtypes (M1-M5). The lack of drugs with a high degree of selectivity for these subtypes has impeded the determination of which subtypes mediate which components of cholinergic neurotransmission relevant to cognitive abilities. The present study examined the behavioral functions of the M2 muscarinic receptor subtype by utilizing congenic C57BL/6 mice possessing a null-mutation in the M2 muscarinic receptor gene (M2 -/- mice). Comprehensive assessment of general health and the neurological function found no major differences between M2 -/- and wild-type (M2 +/+) mice. In the tests of learning and memory, M2 -/- mice were impaired in the acquisition (trials to criterion), but not the retention (72 h) of a passive avoidance task. In a novel open field, M2 -/- mice were impaired in between-sessions, but not within-session habituation. In a holeboard test of spatial memory, M2 -/- mice committed more errors in working memory than M2 +/+ mice. Reference memory did not differ between the genotypes. M2 -/- mice showed no impairments in either cued or contextual fear conditioning. These findings replicate and extend earlier findings in a hybrid strain and solidify the interpretation that the M2 receptor plays a critical role in specific components of cognitive abilities.

Original languageEnglish (US)
Pages (from-to)50-58
Number of pages9
JournalBehavioural Brain Research
Volume190
Issue number1
DOIs
StatePublished - Jun 26 2008
Externally publishedYes

Fingerprint

Muscarinic Receptors
Learning
Muscarinic M2 Receptors
Aptitude
Acetylcholine
Congenic Mice
Inbred C57BL Mouse
Short-Term Memory
Synaptic Transmission
Cognition
Cholinergic Agents
Fear
Neurotransmitter Agents
Genotype
Mutation
Health
Pharmaceutical Preparations
Genes

Keywords

  • Acetylcholine
  • Habituation
  • Holeboard
  • Knockout
  • M
  • Memory
  • Muscarinic
  • Passive avoidance

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Learning and memory impairments in a congenic C57BL/6 strain of mice that lacks the M2 muscarinic acetylcholine receptor subtype. / Bainbridge, Natalie K.; Koselke, Lisa R.; Jeon, Jongrye; Bailey, Kathleen R.; Wess, Jürgen; Crawley, Jacqueline; Wrenn, Craige C.

In: Behavioural Brain Research, Vol. 190, No. 1, 26.06.2008, p. 50-58.

Research output: Contribution to journalArticle

Bainbridge, Natalie K. ; Koselke, Lisa R. ; Jeon, Jongrye ; Bailey, Kathleen R. ; Wess, Jürgen ; Crawley, Jacqueline ; Wrenn, Craige C. / Learning and memory impairments in a congenic C57BL/6 strain of mice that lacks the M2 muscarinic acetylcholine receptor subtype. In: Behavioural Brain Research. 2008 ; Vol. 190, No. 1. pp. 50-58.
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