Stereological estimations and neurochemical characterization of neurons expressing GABAA and GABAB receptors in the rat pedunculopontine and laterodorsal tegmental nuclei

AbstractTo better understand GABAergic transmission at two targets of basal ganglia downstream projections, the pedunculopontine (PPN) and laterodorsal (LDT) tegmental nuclei, the anatomical localization of GABAA and GABAB receptors was investigated in both nuclei. Specifically, the total number of neurons expressing the GABAA receptor γ2 subunit (GABAAR γ2) and the GABAB receptor R2 subunit (GABAB R2) in PPN and LDT was estimated using stereological methods, and the neurochemical phenotype of cells expressing each subunit was also determined. The mean number of non-cholinergic cells expressing GABAAR γ2 was 9850 ± 1856 in the PPN and 8285 ± 962 in the LDT, whereas those expressing GABAB R2 were 7310 ± 1970 and 9170 ± 1900 in the PPN and LDT, respectively. In addition, all cholinergic neurons in both nuclei co-expressed GABAAR γ2 and 95–98% of them co-expressed GABAB R2. Triple labeling using in situ hybridization revealed that 77% of GAD67 mRNA-positive cells in the PPT and 49% in the LDT expressed GABAAR γ2, while 90% (PPN) and 65% (LDT) of Vglut2 mRNA-positive cells also expressed GABAAR γ2. In contrast, a similar proportion (~2/3) of glutamatergic and GABAergic cells co-expressed GABAB R2 in both nuclei. The heterogeneous distribution of GABAAR and GABABR among non-cholinergic cells in PPN and LDT may give rise to physiological differences within each neurochemical subpopulation. In addition, the dissimilar proportion of GABAAR γ2-expressing glutamatergic and GABAergic neurons in the PPN and LDT may contribute to some of the functional differences found between the two nuclei.

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An in situ hybridization and immunofluorescence study of GABAA and GABAB receptors in the vestibular nuclei of the intact and unilaterally labyrinthectomized rat

Experimental Brain Research ◽

10.1007/s00221-004-1997-8 ◽

2004 ◽

Vol 160 (2) ◽

pp. 166-179 ◽

Cited By ~ 18

Author(s):

Lyndell Eleore ◽

Isabelle Vassias ◽

Isabelle Bernat ◽

Pierre-Paul Vidal ◽

Catherine de Waele

Keyword(s):

In Situ Hybridization ◽

Vestibular Nuclei ◽

Gabab Receptors ◽

Immunofluorescence Study ◽

Gabaa And Gabab Receptors

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Role of GABA receptor subtypes in inhibition of primate spinothalamic tract neurons: difference between spinal and periaqueductal gray inhibition

Journal of Neurophysiology ◽

10.1152/jn.1996.75.1.109 ◽

1996 ◽

Vol 75 (1) ◽

pp. 109-123 ◽

Cited By ~ 71

Author(s):

Q. Lin ◽

Y. B. Peng ◽

W. D. Willis

Keyword(s):

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Gabab Receptor ◽

Gabab Receptors ◽

Receptor Subtypes ◽

Spinothalamic Tract ◽

Spinal Dorsal ◽

Gabaa And Gabab Receptors ◽

Gabab Antagonists ◽

Excitatory Responses

1. gamma-Aminobutyric acid (GABA) is thought to inhibit both pre- and postsynaptically the transfer of nociceptive signals from primary afferent fibers to spinal dorsal horn sensory cells, including spinothalamic tract (STT) neurons. The inhibition can be mediated by both GABAA and GABAB receptors. We now attempt to characterize the synaptic inhibition of STT cells by spinal GABAA and GABAB receptors in anesthetized monkeys and to analyze the roles of these two receptor subtypes in the inhibition of STT cellular activity produced by stimulation in the periaqueductal gray (PAG). 2. Iontophoretic release of GABA or muscimol (a selective GABAA receptor agonist) onto STT cells elicited a profound and dose-related inhibition of the responses of all cells tested to noxious cutaneous stimuli. Only four cells (16.7%) were found to be inhibited when baclofen (a selective GABAB receptor agonist) was applied iontophoretically. However, a strong and dose-dependent inhibition of the responses to cutaneous mechanical and thermal stimuli was obtained in all cells examined when baclofen was administered into the dorsal horn through a microdialysis fiber. The inhibitory effects were mainly on nociceptive inputs. 3. The inhibition of cellular activity by GABAA and GABAB agonists could be selectively antagonized by specific antagonists applied through a microdialysis fiber. 4. The excitatory responses evoked by pulsed release of glutamic acid (GLUT) were also inhibited in a dose-related manner by iontophoretic application of GABA and muscimol, but not by baclofen. A high dose of baclofen administered by microdialysis resulted in only a small decrease in GLUT-evoked excitatory responses. 5. Infusion of GABAA and GABAB antagonists into the dorsal horn by microdialysis caused an increase in both background activity and responses to cutaneous stimuli, suggesting that there is a tonic GABAergic inhibition of STT cells. 6. The inhibition of responses to mechanical and thermal stimulation of the cutaneous excitatory receptive field resulting from stimulation in PAG was significantly antagonized in most of the STT cells tested when the GABAA antagonist bicuculline was infused into the spinal dorsal horn through a microdialysis fiber. In contrast, the inhibition produced by PAG stimulation in most of the cells examined was not significantly antagonized by the GABAB antagonists phaclofen or 3-amino-propyl(diethoxymethyl)phophinic acid (CGP35348) administered into the spinal dorsal horn by microdialysis. 7. Our results support the contention that GABAergic mechanisms in the spinal dorsal horn normally exert a tonic modulation of nociceptive inputs through both GABAA and GABAB receptors. The evidence provided here indicates that GABAA receptors located on primate STT neurons contribute to a postsynaptic inhibitory effect on the transmission of peripheral nociceptive inputs. A possible presynaptic GABAA action was not investigated. Our finding of a GABAB-receptor-mediated inhibition is consistent with the view that both pre- and postsynaptic GABAB receptors are involved in inhibitory modulation of spinal nociceptive transmission. Finally, it is suggested from this study that primate spinal GABAA, but not GABAB receptors, are involved in mediating the descending inhibition induced by PAG stimulation.

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Faculty Opinions recommendation of GABAB receptor internalisation is regulated by the R2 subunit.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.11047957.12001055 ◽

2011 ◽

Author(s):

Pat Griffin ◽

Graham West

Keyword(s):

Gabab Receptor ◽

R2 Subunit

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Axonal Modulation of Striatal Dopamine Release by Local γ-Aminobutyric Acid (GABA) Signalling

Cells ◽

10.3390/cells10030709 ◽

2021 ◽

Vol 10 (3) ◽

pp. 709

Author(s):

Bradley M. Roberts ◽

Emanuel F. Lopes ◽

Stephanie J. Cragg

Keyword(s):

Gabab Receptors ◽

Striatal Dopamine ◽

Aminobutyric Acid ◽

Gaba Uptake ◽

Short Term Plasticity ◽

Psychomotor Disorders ◽

Gabaa And Gabab Receptors ◽

Uptake Transporters ◽

Gabaergic Modulation ◽

Da Release

Striatal dopamine (DA) release is critical for motivated actions and reinforcement learning, and is locally influenced at the level of DA axons by other striatal neurotransmitters. Here, we review a wealth of historical and more recently refined evidence indicating that DA output is inhibited by striatal γ-aminobutyric acid (GABA) acting via GABAA and GABAB receptors. We review evidence supporting the localisation of GABAA and GABAB receptors to DA axons, as well as the identity of the striatal sources of GABA that likely contribute to GABAergic modulation of DA release. We discuss emerging data outlining the mechanisms through which GABAA and GABAB receptors inhibit the amplitude as well as modulate the short-term plasticity of DA release. Furthermore, we highlight recent data showing that DA release is governed by plasma membrane GABA uptake transporters on striatal astrocytes, which determine ambient striatal GABA tone and, by extension, the tonic inhibition of DA release. Finally, we discuss how the regulation of striatal GABA-DA interactions represents an axis for dysfunction in psychomotor disorders associated with dysregulated DA signalling, including Parkinson’s disease, and could be a novel therapeutic target for drugs to modify striatal DA output.

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Inhibition of Nigrostriatal Dopamine Release by Striatal GABAA and GABAB Receptors

Journal of Neuroscience ◽

10.1523/jneurosci.2028-18.2018 ◽

2018 ◽

Vol 39 (6) ◽

pp. 1058-1065 ◽

Cited By ~ 13

Author(s):

Emanuel F. Lopes ◽

Bradley M. Roberts ◽

Ruth E. Siddorn ◽

Michael A. Clements ◽

Stephanie J. Cragg

Keyword(s):

Dopamine Release ◽

Gabab Receptors ◽

Nigrostriatal Dopamine ◽

Gabaa And Gabab Receptors

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Digital autoradiography on C-14-labelled PMMA impregnated rock samples using the BeaverTM

MRS Advances ◽

10.1557/adv.2018.226 ◽

2018 ◽

Vol 3 (21) ◽

pp. 1161-1166 ◽

Cited By ~ 3

Author(s):

Mikko Voutilainen ◽

Juuso Sammaljärvi ◽

Eveliina Muuri ◽

Jérôme Donnard ◽

Samuel Duval ◽

...

Keyword(s):

Spatial Distribution ◽

Spent Nuclear Fuel ◽

Rock Sample ◽

Crystalline Rock ◽

Imaging Plate ◽

Heterogeneous Distribution ◽

Heterogeneous Structures ◽

In Situ Diffusion

In Finland and Sweden the KBS-3 concept has been chosen for the disposal of spent nuclear fuel in crystalline rock. Recent experiments have shown that heterogeneity of rock may play a major role in the transport of radionuclides. Autoradiographic methods have been proven to be able to assist the characterization of heterogeneous structures. In this study we tested a novel filmless autoradiographic device called BeaverTM which applies a micro patterned gaseous detector in order to quantitatively map beta emissions from C-14 atoms. The studied samples were impregnated with C-14-labelled methylmethacrylate (C-14-MMA) and polymerized to C-14-PMMA with thermal initiator. The BeaverTM was then used to determine the spatial distribution of the C-14-PMMA by measuring the C-14 emissions. The porosity is determined from the amount of C-14-PMMA in the rock sample and results were compared to ones from phosphor imaging plate autoradiography. The resulting images show a heterogeneous distribution of porosity which arises from the different minerals. The samples were chosen from three sites that have been used recently for in situ diffusion experiments: Olkiluoto (Finland), Äspö (Sweden) and Grimsel (Switzerland).

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