Contribution of brainstem GABAergic circuitry to descending antinociceptive controls: II. Electron microscopic immunocytochemical evidence of gabaergic control over the projection from the periaqueductal gray to the nucleus raphe magnus in the rat

Reichling, David B.; Basbaum, Allan I.

doi:10.1002/cne.903020214

Cited by 72 publications

(28 citation statements)

References 68 publications

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“…Approximately 40% of terminals in the PAG are GABAergic and about 50% of PAG cells retrogradely labeled from NRM have GABA-immunoreactive synaptic inputs to their somata and proximal dendrites [33]. And about 50% of NRM cells labeled retrogradely from the spinal cord are postsynaptic to GABA-immunoreactive terminals [34] suggesting that rostroventral medulla cells (including NRM) are under GABAergic inhibitory controls.…”

Section: Discussionmentioning

confidence: 98%

A Comparative Study of Excitatory and Inhibitory Amino Acids in Three Different Brainstem Nuclei

et al. 2007

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This study was designed to shed more light onto the three different brainstem regions which are implicated in the pain pathway for the level of various excitatory and inhibitory neurotransmitters before and following neuronal stimulation. The in vivo microdialysis technique was used in awake, freely moving adult Sprague-Dawley rats. The neurotransmitters studied included aspartate, glutamate, GABA, glycine, and taurine. The three brainstem regions examined included the mid-brain periaqueductal gray (PAG), the medullary nucleus raphe magnus (NRM), and the spinal trigeminal nucleus (STN). Neuronal stimulation was achieved following the administration of the sodium channel activator veratridine. The highest baseline levels of glutamate (P < 0.0001), aspartate (P < 0.0001), GABA (P < 0.01), taurine (P < 0.0001), and glycine (P < 0.001) were seen in the NRM. On the other hand, the lowest baseline levels of glutamate, GABA, glycine, and taurine were found in the PAG, while that of aspartate was found in the STN. Following the administration of veratridine, the highest release of the above neurotransmitters except for the aspartate and glycine was found in the PAG where the level of glutamate increased by 1,310 +/- 293% (P < 0.001), taurine by 1,008 +/- 143% (P < 0.01), and GABA by 10,358 +/- 1,920% (P < 0.0001) when comparison was performed among the three brainstem regions and in relation to the baseline levels. The highest release of aspartate was seen in the STN (2,357 +/- 1,060%, P < 0.001), while no significant difference was associated with glycine. On the other hand, the lowest release of GABA and taurine was found in the STN (696 +/- 91 and 305 +/- 25%, respectively), and glutamate and aspartate in the NRM (558 +/- 200 and 874 +/- 315%, respectively). Our results indicate, and for the first time, that although some differences are seen in the baseline levels of the above neurotransmitters in the three regions studied, there are quite striking variations in the level of release of these neurotransmitters following neuronal stimulation in these regions. In our opinion this is the first study to describe the pain activation/modulation related changes of the excitatory and inhibitory amino acids profile of the three different brainstem areas.

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Section: Discussionmentioning

confidence: 98%

A Comparative Study of Excitatory and Inhibitory Amino Acids in Three Different Brainstem Nuclei

et al. 2007

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“…With some notable exceptions, GABAergic neurons are short-axoned intrinsic interneurons and evidence suggests that the great majority of GABAergic neurons in the POA (Leranth et al, 1985;Herbison et al, 1991), hypothalamus (Brown et al, 1990), and MCG (Reichling and Basbaum, 1990) are intrinsic and exert local control over neuronal excitability. The distribution of GAD mRNA has also been well mapped in the hypothalamus and surrounding regons (Okamura et al, 1990).…”

Section: Distribution Of Gad-synthesizing Neuronsmentioning

confidence: 97%

Estrogen modulation of mRNA levels for the two forms of glutamic acid decarboxylase (GAD) in female rat brain

McCarthy

Kaufman

Brooks

et al. 1995

J of Comparative Neurology

111

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Two separate forms of glutamic acid decarboxylase, now termed GAD65 and GAD67, are the rate limiting enzymes for synthesis of gamma-aminobutyric acid (GABA). Because of the significance of GABA to neuroendocrine processes, numerous attempts have been made to determine the impact of gonadal steroids on enzyme functioning with inconclusive results. Therefore, we attempted to determine the impact of estradiol on mRNA levels for each form of GAD by quantitative in situ hybridization histochemistry in various brain regions. Ovariectomized rats were treated with estradiol benzoate or oil vehicle on 2 consecutive days and the brains collected on the third day. DNA probes specific for GAD65 and GAD67 were radiolabeled with CTP32 using asymmetric polymerase chain reaction. Results of in situ hybridizations for each probe on alternate sections from the same animals were analyzed for magnocellular preoptic area (McPOA), dorsal medial nucleus of the hypothalamus (DMN), zona incerta (ZI), and midbrain central gray (MCG). In the McPOA, estradiol exerted opposite effects on the frequency distribution of pixels per cell for two GAD mRNA probes, significantly increasing GAD65 (P < .05) and decreasing GAD67 (P < .01; Kolmogorov-Smirnov). In the DMN, estradiol treatment significantly increased GAD67 by 60% (P < .05; two-way ANOVA) but decreased GAD65 mRNA by 73% (P < .01). Note the direction of effects are opposite between McPOA and DMN. In MCG, analysis showed no estradiol effect on GAD mRNA levels/cells, but the proportion of cells expressing detectable levels of GAD65 or GAD67 increased by 33-40% in estradiol-treated rats (chi 2, P < .001).

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“…Its specificity of labeling has been confirmed by control studies in which sections that were incubated with primary antiserum that had been preabsorbed for 24 hours with 100 mg/ml GABA-bovine serum albumin conjugate showed no synaptic labeling (Reichling and Basbaum, 1990b;Cho and Basbaum, 1991;Liu et al, 1992).…”

Section: Postembedding Immunocytochemistrymentioning

confidence: 81%

GABA-immunoreactive boutons contact identified OFF and ON cells in the nucleus raphe magnus

et al. 1997

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The pontomedullary raphe magnus (RM) contains two physiologically defined types of neurons that participate in the opioid-induced modulation of dorsal horn nociceptive messages: OFF cells, which decrease, and ON cells, which increase their discharge rates when reflex behavior is evoked by noxious pinch or heat. Because both types of neuron have inhibitory inputs and because there is evidence that gamma-aminobutyric acid (GABA) inhibitory mechanisms within RM contribute to the antinociceptive action of opioids, we have sought anatomical evidence for a direct GABAergic input to OFF and ON cells. In this study, cells of each type located in the RM were electrophysiologically defined and intracellularly filled with horseradish peroxidase or Neurobiotin. One cell of each type was labeled in the cat, and 2-3 cells of each type were labeled in the rat. Thin sections were labeled by a postembedding immunogold procedure by using an antibody directed against glutaraldehyde-conjugated GABA. GABA-immunoreactive (GABA-ir) boutons contained small, round, clear vesicles and made symmetrical synapses with identified dendrites. GABA-ir boutons were apposed to soma and to proximal and distal dendrites of both cell types in both species. These findings demonstrate direct GABAergic input to identified OFF and ON cells in the RM. J. Comp. Neurol. 378:196-204, 1997.

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Contribution of brainstem GABAergic circuitry to descending antinociceptive controls: II. Electron microscopic immunocytochemical evidence of gabaergic control over the projection from the periaqueductal gray to the nucleus raphe magnus in the rat

Cited by 72 publications

References 68 publications

A Comparative Study of Excitatory and Inhibitory Amino Acids in Three Different Brainstem Nuclei

A Comparative Study of Excitatory and Inhibitory Amino Acids in Three Different Brainstem Nuclei

Estrogen modulation of mRNA levels for the two forms of glutamic acid decarboxylase (GAD) in female rat brain

GABA-immunoreactive boutons contact identified OFF and ON cells in the nucleus raphe magnus

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