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GABAB receptor subtypes differentially modulate synaptic inhibition in the dentate gyrus to enhance granule cell output

Foster, Joshua D. and Kitchen, Ian and Bettler, Bernhard and Chen, Ying. (2013) GABAB receptor subtypes differentially modulate synaptic inhibition in the dentate gyrus to enhance granule cell output. British journal of pharmacology, Vol. 168, no. 8. pp. 1808-1819.

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Official URL: http://edoc.unibas.ch/dok/A6124474

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Abstract

Activation of GABAB receptors in the dentate gyrus (DG) enhances granule cell (GC) activity by reducing synaptic inhibition imposed by hilar interneurons. This disinhibitory action facilitates signal transfer from the perforant path to the hippocampus. However, as the two main molecular subtypes, GABAB (1a,2) and GABAB (1b,2) receptors, prefer axonal terminal and dendritic compartments, respectively, they may modulate the hilar pathways at different synaptic localizations. We examined their relative expression and functions in the DG.; The localization of GABAB subtypes was revealed immunohistochemically using subunit-selective antibodies in GABAB 1a (-/-) and GABAB 1b (-/-) mice. Effects of subtype activation by the GABAB receptor agonist, baclofen, were examined on the perforant path-stimulated GC population activities in brain slices.; GABAB (1a,2) receptors were concentrated in the inner molecular layer, the neuropil of the hilus and hilar neurons at the border zone; while GABAB (1b,2) receptors dominated the outer molecular layer and hilar neurons in the deep layer, showing their differential localization on GC dendrite and in the hilus. Baclofen enhanced the GC population spike to a larger extent in the GABAB1b (-/-) mice, demonstrating exclusively disinhibitory roles of the GABAB (1a,2) receptors. Conversely, in the GABAB1a (-/-) mice baclofen not only enhanced but also inhibited the population spike during GABAA blockade, revealing both disinhibitory and inhibitory effects of GABAB (1b,2) receptors.; The GABAB (1a,2) and GABAB (1b,2) receptor subtypes differentially modulate GC outputs via selective axonal terminal and dendritic locations in the hilar pathways. The GABAB (1a,2) receptors exclusively mediate disinhibition, thereby playing a greater role in gating signal transfer for hippocampal spatial and pattern learning.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
UniBasel Contributors:Bettler, Bernhard
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publishing Group
ISSN:0007-1188
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:13
Deposited On:16 Aug 2013 07:32

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