Localization of GABAB (R1) receptors in the rat hippocampus by immunocytochemistry and high resolution autoradiography, with specific reference to its localization in identified hippocampal interneuron subpopulations

Sloviter, Robert S.; Ali-Akbarian, Leila; Elliott, Robert C.; Bowery, B.J.; Bowery, Norman G.

doi:10.1016/s0028-3908(99)00132-x

Cited by 78 publications

(59 citation statements)

References 30 publications

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“…In controls, CGP52432 strongly attenuated the depression of SOM-IPSCs (Figure 4c), but barely affected the depression of PV-IPSCs (Figure 4b), indicating that GABAbR control of SOM-INs is stronger than of PV-INs. This was consistent with the greater sensitivity to baclofen of the SOM-IPSCs than the PV-IPSCs in control mice, suggesting that SOM-INs naturally express more functional GABAbR, which agrees with an earlier finding in the hippocampus that SOM-INs have stronger GABAbR1 immunoreactivity than all other cells (Sloviter et al, 1999). The cell-type specific differences in GABAbR function could be an adaptation to possibly different local concentrations of GABA, high at perisomatic basket-type synapses and low at sparse dendritic synapses.…”

Section: Gababr-dependent Alterations In Pv-in and Som-in Inputs To Lsupporting

confidence: 91%

GABAb Receptor Mediates Opposing Adaptations of GABA Release From Two Types of Prefrontal Interneurons After Observational Fear

Liu

Ito

Morozov

2016

Neuropsychopharmacol

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The observational fear (OF) paradigm in rodents, in which the subject is exposed to a distressed conspecific, elicits contextual fear learning and enhances future passive avoidance learning, which may model certain behavioral traits resulting from traumatic experiences in humans. As these behaviors affected by the OF require dorso-medial prefrontal cortex (dmPFC), we searched for synaptic adaptations in dmPFC resulting from OF in mice by recording synaptic responses in dmPFC layer V pyramidal neurons elicited by repeated 5 Hz electrical stimulation of dmPFC layer I or by optogenetic stimulation of specific interneurons ex vivo 1 day after OF. OF increased depression of inhibitory postsynaptic currents (IPSCs) along IPSC trains evoked by the 5 Hz electrical stimulation, but, surprisingly, decreased depression of dendritic IPSCs isolated after blocking GABAa receptor on the soma. Subsequent optogenetic analyses revealed increased depression of IPSCs originating from perisomatically projecting parvalbumin interneurons (PV-IPSCs), but decreased depression of IPSCs from dendritically projecting somatostatin cells (SOM-IPSCs). These changes were no longer detectable in the presence of a GABAb receptor antagonist CGP52432. Meanwhile, OF decreased the sensitivity of SOM-IPSCs, but not PV-IPSCs to a GABAb receptor agonist baclofen. Thus, OF causes opposing changes in GABAb receptor mediated suppression of GABA release from PV-positive and SOM-positive interneurons. Such adaptations may alter dmPFC connectivity with brain areas that target its deep vs superficial layers and thereby contribute to the behavioral consequences of the aversive experiences.

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Section: Gababr-dependent Alterations In Pv-in and Som-in Inputs To Lsupporting

confidence: 91%

GABAb Receptor Mediates Opposing Adaptations of GABA Release From Two Types of Prefrontal Interneurons After Observational Fear

Liu

Ito

Morozov

2016

Neuropsychopharmacol

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“…Antibodies directed against COOH-and NH 2 -terminal sequences of GABA B(1) and GABA B (2) were produced by several laboratories and are available from a number of commercial sources. Additionally, GABA B(1) subunits can be traced using the photoaffinity cross-linker 125 I-CGP71872 (169) (56,71,213,313) correlates well with physiological and autoradiographic data on the distribution of native GABA B receptors (170). The level of GABA B protein expression in the molecular layer of the cerebellum is not uniform (104,213,267).…”

Section: Cellular and Subcellular Distributionmentioning

confidence: 60%

“…Significantly, electron microscopy confirmed a colocalization of GABA B(1) and GABA B(2) protein at synaptic and extrasynaptic sites (104,170,184). In general, GABA B(1) immunoreactivity appears to be abundant in the cytoplasm of neurons (313). It was therefore speculated that the GABA B (2) protein is the limiting factor that determines the level of expression of the functional heteromer at the cell surface.…”

Section: Cellular and Subcellular Distributionmentioning

confidence: 91%

Molecular Structure and Physiological Functions of GABA_BReceptors

Bettler

Kaupmann

Mosbacher

et al. 2004

Physiological Reviews

805

720

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GABAB receptors are broadly expressed in the nervous system and have been implicated in a wide variety of neurological and psychiatric disorders. The cloning of the first GABAB receptor cDNAs in 1997 revived interest in these receptors and their potential as therapeutic targets. With the availability of molecular tools, rapid progress was made in our understanding of the GABAB system. This led to the surprising discovery that GABAB receptors need to assemble from distinct subunits to function and provided exciting new insights into the structure of G protein-coupled receptors (GPCRs) in general. As a consequence of this discovery, it is now widely accepted that GPCRs can exist as heterodimers. The cloning of GABAB receptors allowed some important questions in the field to be answered. It is now clear that molecular studies do not support the existence of pharmacologically distinct GABAB receptors, as predicted by work on native receptors. Advances were also made in clarifying the relationship between GABAB receptors and the receptors for γ-hydroxybutyrate, an emerging drug of abuse. There are now the first indications linking GABAB receptor polymorphisms to epilepsy. Significantly, the cloning of GABAB receptors enabled identification of the first allosteric GABAB receptor compounds, which is expected to broaden the spectrum of therapeutic applications. Here we review current concepts on the molecular composition and function of GABAB receptors and discuss ongoing drug-discovery efforts.

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“…The commercially available guinea pig anti-GABA B R1 antibody was developed against a common sequence in 2 GABA B receptor isomers and produced a 130-kDa protein band corresponding to the GABA B R1A isomer that is also prevalent in the rat neostriatum (Yung et al 1999) and dorsal root ganglia (Towers et al 2000). The other isomer, GABA B R1B, has a molecular weight of 100 kDa (Kaupmann et al 1998;Margeta-Mitrovic et al 1999;Sloviter et al 1999) and was not found in spider tissue. Both of the anti-GABA B R2 antibodies that we tested in the spider brain homogenate produced an expected 105-kDa band in the Western blot analysis and the guinea pig antibody also produced a similar band in the peripheral tissue.…”

Section: Anti-gaba B Receptor Immunoreactivity In the Spider Brain Anmentioning

confidence: 99%

Distribution and Function of GABA_BReceptors in Spider Peripheral Mechanosensilla

Panek

Meisner

Torkkeli

2003

Journal of Neurophysiology

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. The mechanosensilla in spider exoskeleton are innervated by bipolar neurons with their cell bodies close to the cuticle and dendrites attached to it. Numerous efferent fibers synapse with peripheral parts of the mechanosensory neurons, with glial cells surrounding the neurons, and with each other. Most of these efferent fibers are immunoreactive to ␥-aminobutyric acid (GABA), and the sensory neurons respond to agonists of ionotropic GABA receptors with a rapid and complete inhibition. In contrast, little is known about metabotropic GABA B receptors that may mediate longterm effects. We investigated the distribution of GABA B receptors on spider leg mechanosensilla using specific antibodies against 2 proteins needed to form functional receptors and an antibody that labels the synaptic vesicles on presynaptic sites. Both anti-GABA B receptor antibodies labeled the distal parts of the sensory cell bodies and dendrites but anti-GABA B R1 immunoreactivity was also found in the axons and proximal parts of the cell bodies and some glial cells. The fine efferent fibers that branch on top of the sensory neurons did not show GABA B receptor immunoreactivity but were densely labeled with anti-synapsin and indicated synaptic vesicles on presynaptic locations to the GABA B receptors. Intracellular recordings from sensory neurons innervating the slit sensilla of the spider legs revealed that application of GABA B receptor agonists attenuated voltageactivated Ca 2ϩ current and enhanced voltage-activated outward K ϩ current, providing 2 possible mechanisms for controlling the neurons' excitability. These findings support the hypothesis that GABA B receptors are present in the spider mechanosensilla where their activation may modulate information transmission.

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Localization of GABAB (R1) receptors in the rat hippocampus by immunocytochemistry and high resolution autoradiography, with specific reference to its localization in identified hippocampal interneuron subpopulations

Cited by 78 publications

References 30 publications

GABAb Receptor Mediates Opposing Adaptations of GABA Release From Two Types of Prefrontal Interneurons After Observational Fear

GABAb Receptor Mediates Opposing Adaptations of GABA Release From Two Types of Prefrontal Interneurons After Observational Fear

Molecular Structure and Physiological Functions of GABA_BReceptors

Distribution and Function of GABA_BReceptors in Spider Peripheral Mechanosensilla

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Localization of GABAB (R1) receptors in the rat hippocampus by immunocytochemistry and high resolution autoradiography, with specific reference to its localization in identified hippocampal interneuron subpopulations

Cited by 78 publications

References 30 publications

GABAb Receptor Mediates Opposing Adaptations of GABA Release From Two Types of Prefrontal Interneurons After Observational Fear

GABAb Receptor Mediates Opposing Adaptations of GABA Release From Two Types of Prefrontal Interneurons After Observational Fear

Molecular Structure and Physiological Functions of GABABReceptors

Distribution and Function of GABABReceptors in Spider Peripheral Mechanosensilla

Contact Info

Product

Resources

About

Molecular Structure and Physiological Functions of GABA_BReceptors

Distribution and Function of GABA_BReceptors in Spider Peripheral Mechanosensilla