Specific roles of GABA B (1) receptor isoforms in cognition

Laura H. Jacobson; Peter H. Kelly; Klemens Kaupmann; Bernhard Bettler; John F Cryan

doi:10.1016/j.bbr.2007.03.033

Specific roles of GABA B (1) receptor isoforms in cognition

Laura H. Jacobson
, Peter H. Kelly
, Klemens Kaupmann
, Bernhard Bettler
, John F Cryan

Novartis

Research output: Contribution to journal › Article › peer-review

Abstract

The GABA_B receptor is a heterodimer of GABA_B(1) and GABA_B(2) subunits. There are two isoforms of the GABA_B(1) subunit: GABA_B(1a) and GABA_B(1b). Recent studies with mutant mice suggest a differential role for the two GABA_B(1) isoforms in behavioural processes. As pharmacological and genetic studies have implicated GABA_B receptors in cognition we investigated the behaviour of GABA_B(1a)^-/- and GABA_B(1b)^-/- mice in different types of cognitive paradigms. GABA_B(1a)^-/- and GABA_B(1b)^-/- mice were both impaired relative to wildtype controls in a continuous spontaneous alternation behaviour test of working spatial memory. In contrast to the reported phenotype of GABA_B(1)^-/- mice, however, neither GABA_B(1a)^-/- nor GABA_B(1b)^-/- mice were deficient in a passive avoidance task. On the other hand, GABA_B(1a)^-/- mice were impaired in familiar and novel object recognition. We conclude that GABA_B(1) isoforms contribute differentially to GABA_B receptor-mediated cognitive processes.

Original language	English
Pages (from-to)	158-162
Number of pages	5
Journal	Behavioural Brain Research
Volume	181
Issue number	1
DOIs	https://doi.org/10.1016/j.bbr.2007.03.033
Publication status	Published - 19 Jul 2007
Externally published	Yes

Keywords

GABA isoforms
Object recognition
Passive avoidance
Spatial memory

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title = "Specific roles of GABA B (1) receptor isoforms in cognition",

abstract = "The GABAB receptor is a heterodimer of GABAB(1) and GABAB(2) subunits. There are two isoforms of the GABAB(1) subunit: GABAB(1a) and GABAB(1b). Recent studies with mutant mice suggest a differential role for the two GABAB(1) isoforms in behavioural processes. As pharmacological and genetic studies have implicated GABAB receptors in cognition we investigated the behaviour of GABAB(1a)-/- and GABAB(1b)-/- mice in different types of cognitive paradigms. GABAB(1a)-/- and GABAB(1b)-/- mice were both impaired relative to wildtype controls in a continuous spontaneous alternation behaviour test of working spatial memory. In contrast to the reported phenotype of GABAB(1)-/- mice, however, neither GABAB(1a)-/- nor GABAB(1b)-/- mice were deficient in a passive avoidance task. On the other hand, GABAB(1a)-/- mice were impaired in familiar and novel object recognition. We conclude that GABAB(1) isoforms contribute differentially to GABAB receptor-mediated cognitive processes.",

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year = "2007",

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doi = "10.1016/j.bbr.2007.03.033",

language = "English",

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T1 - Specific roles of GABA B (1) receptor isoforms in cognition

AU - Jacobson, Laura H.

AU - Kelly, Peter H.

AU - Kaupmann, Klemens

AU - Bettler, Bernhard

AU - Cryan, John F

PY - 2007/7/19

Y1 - 2007/7/19

N2 - The GABAB receptor is a heterodimer of GABAB(1) and GABAB(2) subunits. There are two isoforms of the GABAB(1) subunit: GABAB(1a) and GABAB(1b). Recent studies with mutant mice suggest a differential role for the two GABAB(1) isoforms in behavioural processes. As pharmacological and genetic studies have implicated GABAB receptors in cognition we investigated the behaviour of GABAB(1a)-/- and GABAB(1b)-/- mice in different types of cognitive paradigms. GABAB(1a)-/- and GABAB(1b)-/- mice were both impaired relative to wildtype controls in a continuous spontaneous alternation behaviour test of working spatial memory. In contrast to the reported phenotype of GABAB(1)-/- mice, however, neither GABAB(1a)-/- nor GABAB(1b)-/- mice were deficient in a passive avoidance task. On the other hand, GABAB(1a)-/- mice were impaired in familiar and novel object recognition. We conclude that GABAB(1) isoforms contribute differentially to GABAB receptor-mediated cognitive processes.

AB - The GABAB receptor is a heterodimer of GABAB(1) and GABAB(2) subunits. There are two isoforms of the GABAB(1) subunit: GABAB(1a) and GABAB(1b). Recent studies with mutant mice suggest a differential role for the two GABAB(1) isoforms in behavioural processes. As pharmacological and genetic studies have implicated GABAB receptors in cognition we investigated the behaviour of GABAB(1a)-/- and GABAB(1b)-/- mice in different types of cognitive paradigms. GABAB(1a)-/- and GABAB(1b)-/- mice were both impaired relative to wildtype controls in a continuous spontaneous alternation behaviour test of working spatial memory. In contrast to the reported phenotype of GABAB(1)-/- mice, however, neither GABAB(1a)-/- nor GABAB(1b)-/- mice were deficient in a passive avoidance task. On the other hand, GABAB(1a)-/- mice were impaired in familiar and novel object recognition. We conclude that GABAB(1) isoforms contribute differentially to GABAB receptor-mediated cognitive processes.

KW - GABA isoforms

KW - Object recognition

KW - Passive avoidance

KW - Spatial memory

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M3 - Article

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JO - Behavioural Brain Research

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IS - 1

ER -

Specific roles of GABA B (1) receptor isoforms in cognition

Abstract

Keywords

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