Hyperactivity and intact hippocampus-dependent learning in mice lacking the M1 muscarinic acetylcholine receptor

Tsuyoshi Miyakawa, Masahisa Yamada, Alokesh Duttaroy, Jürgen Wess

Research output: Contribution to journalArticle

278 Citations (Scopus)

Abstract

Members of the muscarinic acetylcholine receptor family are thought to play key roles in the regulation of a large number of important functions of the CNS. However, the precise roles of the individual muscarinic receptor subtypes in modulating these processes are not well understood at present, primarily because of the lack of ligands with sufficient receptor subtype selectivity. To investigate the behavioral significance of the M1 muscarinic receptor (M1R), which is abundantly expressed in the forebrain, we subjected M1 receptor-deficient mice (M1R-/- mice) to a battery of behavioral tests. M1R-/- mice showed no significant impairments in neurological reflexes, motor coordination, pain sensitivity, and prepulse inhibition. Strikingly, however, M1R-/- mice consistently exhibited a pronounced increase in locomotor activity in various tests, including open field, elevated plus maze, and light/dark transition tests. Moreover, M1R-/- mice showed reduced immobilization in the Porsolt forced swim test and reduced levels of freezing after inescapable footshocks, suggesting that M1R-/- mice are hyperactive under stressful conditions as well. An increased number of social contacts was observed in a social interaction test. Surprisingly, M1R-/- mice displayed no significant cognitive impairments in the Morris water maze and in contextual fear conditioning. M1R-/- mice showed slight performance deficits in auditory-cued fear conditioning and in an eight-arm radial maze, most likely because of the hyperactivity phenotype displayed by the M1R-/- mice. Our results indicate that M1 muscarinic receptors play an important role in the regulation of locomotor activity but appear to be less critical for cognitive processes, as generally assumed.

Original languageEnglish
Pages (from-to)5239-5250
Number of pages12
JournalJournal of Neuroscience
Volume21
Issue number14
Publication statusPublished - 15-07-2001
Externally publishedYes

Fingerprint

Muscarinic M1 Receptors
Muscarinic Receptors
Hippocampus
Learning
Locomotion
Fear
Interpersonal Relations
Prosencephalon
Immobilization
Freezing
Reflex
Ligands
Phenotype
Light
Pain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Miyakawa, Tsuyoshi ; Yamada, Masahisa ; Duttaroy, Alokesh ; Wess, Jürgen. / Hyperactivity and intact hippocampus-dependent learning in mice lacking the M1 muscarinic acetylcholine receptor. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 14. pp. 5239-5250.
@article{2ae6ad19dc6d4a03bd015aeebe19a0f4,
title = "Hyperactivity and intact hippocampus-dependent learning in mice lacking the M1 muscarinic acetylcholine receptor",
abstract = "Members of the muscarinic acetylcholine receptor family are thought to play key roles in the regulation of a large number of important functions of the CNS. However, the precise roles of the individual muscarinic receptor subtypes in modulating these processes are not well understood at present, primarily because of the lack of ligands with sufficient receptor subtype selectivity. To investigate the behavioral significance of the M1 muscarinic receptor (M1R), which is abundantly expressed in the forebrain, we subjected M1 receptor-deficient mice (M1R-/- mice) to a battery of behavioral tests. M1R-/- mice showed no significant impairments in neurological reflexes, motor coordination, pain sensitivity, and prepulse inhibition. Strikingly, however, M1R-/- mice consistently exhibited a pronounced increase in locomotor activity in various tests, including open field, elevated plus maze, and light/dark transition tests. Moreover, M1R-/- mice showed reduced immobilization in the Porsolt forced swim test and reduced levels of freezing after inescapable footshocks, suggesting that M1R-/- mice are hyperactive under stressful conditions as well. An increased number of social contacts was observed in a social interaction test. Surprisingly, M1R-/- mice displayed no significant cognitive impairments in the Morris water maze and in contextual fear conditioning. M1R-/- mice showed slight performance deficits in auditory-cued fear conditioning and in an eight-arm radial maze, most likely because of the hyperactivity phenotype displayed by the M1R-/- mice. Our results indicate that M1 muscarinic receptors play an important role in the regulation of locomotor activity but appear to be less critical for cognitive processes, as generally assumed.",
author = "Tsuyoshi Miyakawa and Masahisa Yamada and Alokesh Duttaroy and J{\"u}rgen Wess",
year = "2001",
month = "7",
day = "15",
language = "English",
volume = "21",
pages = "5239--5250",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "14",

}

Hyperactivity and intact hippocampus-dependent learning in mice lacking the M1 muscarinic acetylcholine receptor. / Miyakawa, Tsuyoshi; Yamada, Masahisa; Duttaroy, Alokesh; Wess, Jürgen.

In: Journal of Neuroscience, Vol. 21, No. 14, 15.07.2001, p. 5239-5250.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hyperactivity and intact hippocampus-dependent learning in mice lacking the M1 muscarinic acetylcholine receptor

AU - Miyakawa, Tsuyoshi

AU - Yamada, Masahisa

AU - Duttaroy, Alokesh

AU - Wess, Jürgen

PY - 2001/7/15

Y1 - 2001/7/15

N2 - Members of the muscarinic acetylcholine receptor family are thought to play key roles in the regulation of a large number of important functions of the CNS. However, the precise roles of the individual muscarinic receptor subtypes in modulating these processes are not well understood at present, primarily because of the lack of ligands with sufficient receptor subtype selectivity. To investigate the behavioral significance of the M1 muscarinic receptor (M1R), which is abundantly expressed in the forebrain, we subjected M1 receptor-deficient mice (M1R-/- mice) to a battery of behavioral tests. M1R-/- mice showed no significant impairments in neurological reflexes, motor coordination, pain sensitivity, and prepulse inhibition. Strikingly, however, M1R-/- mice consistently exhibited a pronounced increase in locomotor activity in various tests, including open field, elevated plus maze, and light/dark transition tests. Moreover, M1R-/- mice showed reduced immobilization in the Porsolt forced swim test and reduced levels of freezing after inescapable footshocks, suggesting that M1R-/- mice are hyperactive under stressful conditions as well. An increased number of social contacts was observed in a social interaction test. Surprisingly, M1R-/- mice displayed no significant cognitive impairments in the Morris water maze and in contextual fear conditioning. M1R-/- mice showed slight performance deficits in auditory-cued fear conditioning and in an eight-arm radial maze, most likely because of the hyperactivity phenotype displayed by the M1R-/- mice. Our results indicate that M1 muscarinic receptors play an important role in the regulation of locomotor activity but appear to be less critical for cognitive processes, as generally assumed.

AB - Members of the muscarinic acetylcholine receptor family are thought to play key roles in the regulation of a large number of important functions of the CNS. However, the precise roles of the individual muscarinic receptor subtypes in modulating these processes are not well understood at present, primarily because of the lack of ligands with sufficient receptor subtype selectivity. To investigate the behavioral significance of the M1 muscarinic receptor (M1R), which is abundantly expressed in the forebrain, we subjected M1 receptor-deficient mice (M1R-/- mice) to a battery of behavioral tests. M1R-/- mice showed no significant impairments in neurological reflexes, motor coordination, pain sensitivity, and prepulse inhibition. Strikingly, however, M1R-/- mice consistently exhibited a pronounced increase in locomotor activity in various tests, including open field, elevated plus maze, and light/dark transition tests. Moreover, M1R-/- mice showed reduced immobilization in the Porsolt forced swim test and reduced levels of freezing after inescapable footshocks, suggesting that M1R-/- mice are hyperactive under stressful conditions as well. An increased number of social contacts was observed in a social interaction test. Surprisingly, M1R-/- mice displayed no significant cognitive impairments in the Morris water maze and in contextual fear conditioning. M1R-/- mice showed slight performance deficits in auditory-cued fear conditioning and in an eight-arm radial maze, most likely because of the hyperactivity phenotype displayed by the M1R-/- mice. Our results indicate that M1 muscarinic receptors play an important role in the regulation of locomotor activity but appear to be less critical for cognitive processes, as generally assumed.

UR - http://www.scopus.com/inward/record.url?scp=0035879062&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035879062&partnerID=8YFLogxK

M3 - Article

C2 - 11438599

AN - SCOPUS:0035879062

VL - 21

SP - 5239

EP - 5250

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 14

ER -