title: GABAB receptor subtypes differentially modulate synaptic inhibition in the dentate gyrus to enhance granule cell output.
abstract: OBJECTIVE
  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, GABA(B(1a,2)) and GABA(B(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.
  
  
  METHODS
  The localization of GABAB subtypes was revealed immunohistochemically using subunit-selective antibodies in GABA(B1a)(-/-) and GABA(B1b)(-/-) mice. Effects of subtype activation by the GABAB receptor agonist, baclofen, were examined on the perforant path-stimulated GC population activities in brain slices.
  
  
  RESULTS
  GABA(B(1a,2)) receptors were concentrated in the inner molecular layer, the neuropil of the hilus and hilar neurons at the border zone; while GABA(B(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 GABA(B1b)(-/-) mice, demonstrating exclusively disinhibitory roles of the GABA(B(1a,2)) receptors. Conversely, in the GABA(B1a)(-/-) mice baclofen not only enhanced but also inhibited the population spike during GABAA blockade, revealing both disinhibitory and inhibitory effects of GABA(B(1b,2)) receptors.
  
  
  CONCLUSIONS
  The GABA(B(1a,2)) and GABA(B(1b,2)) receptor subtypes differentially modulate GC outputs via selective axonal terminal and dendritic locations in the hilar pathways. The GABA(B(1a,2)) receptors exclusively mediate disinhibition, thereby playing a greater role in gating signal transfer for hippocampal spatial and pattern learning.
authors.affiliation: Department of Biochemistry and Physiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Foster
authors.forename: Ian
authors.initials: I
authors.lastname: Kitchen
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bettler
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology* / Q000502:physiology*; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D055786:Gene Knockout Techniques; D007395:Interneurons / Q000502:physiology; D008297:Male; D051379:Mice; D018080:Receptors, GABA-B / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D055366:Synaptic Potentials / Q000502:physiology*
chemical_list: D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D001418:Baclofen