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GABAergic regulation of noradrenergic spinal projection neurons of the A5 cell group in the rat: an electron microscopic analysis. 1993

G C Kwiat, and H Liu, and A M Williamson, and A I Basbaum
Keck Center for Integrative Neuroscience, University of California San Francisco 94143.

Recent studies have demonstrated an important contribution of the A5 noradrenergic cell group of the rostral medulla in the regulation of nociceptive messages at the level of the spinal cord. These noradrenergic controls parallel those arising from the serotonin-containing neurons of the nucleus raphe magnus. In the present study, we used postembedding immunogold staining to identify GABA-immunoreactive terminals that synapse upon identified spinally projecting noradrenergic neurons of the A5 cell group in the rat. A5 projection neurons were identified by Fluoro-Gold transport from the spinal cord; sections containing retrogradely labelled cells were then immunoreacted for tyrosine hydroxylase (TH) to identify the catecholamine-containing, presumed noradrenergic, neurons. Double-labelled A5 cells were intracellularly filled with Lucifer Yellow (LY) and then the LY was photo-oxidized to an electron-dense product. Seven intracellularly filled TH-immunoreactive projection neurons were studied with postembedding immunocytochemistry. Each A5 neuron received a significant GABA-immunoreactive terminal input. Out of a pooled total of 151 terminal profiles found in apposition to intracellularly labelled somatic and dendritic profiles, 31 (20.5%) were GABA-immunoreactive. The proportion of GABA-immunoreactive terminals that contacted somatic profiles (12/72; 17%) was similar to the proportion that contacted TH-labelled dendritic profiles (19/79; 24%). There was a discernible synaptic specialization in about 50% of the labelled terminals that contacted the TH projection neuron. Both symmetric and asymmetric synaptic specializations were found. Labelled terminals contained round or pleiomorphic vesicles, but not flat vesicles; many also contained dense-core vesicles. Our results indicate that noradrenergic neurons of the A5 cell group, which contribute to both antinociceptive and cardiovascular controls through their projection to the spinal cord, are regulated by local GABAergic, presumably inhibitory, mechanisms. Whether the initiation of A5 neuron activity results from a lifting of tonic GABAergic inhibitory control, as has been proposed for the neurons of the nucleus raphe magnus, remains to be determined.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D008297 Male Males
D008526 Medulla Oblongata The lower portion of the BRAIN STEM. It is inferior to the PONS and anterior to the CEREBELLUM. Medulla oblongata serves as a relay station between the brain and the spinal cord, and contains centers for regulating respiratory, vasomotor, cardiac, and reflex activities. Accessory Cuneate Nucleus,Ambiguous Nucleus,Arcuate Nucleus of the Medulla,Arcuate Nucleus-1,External Cuneate Nucleus,Lateral Cuneate Nucleus,Nucleus Ambiguus,Ambiguus, Nucleus,Arcuate Nucleus 1,Arcuate Nucleus-1s,Cuneate Nucleus, Accessory,Cuneate Nucleus, External,Cuneate Nucleus, Lateral,Medulla Oblongatas,Nucleus, Accessory Cuneate,Nucleus, Ambiguous,Nucleus, External Cuneate,Nucleus, Lateral Cuneate
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D009434 Neural Pathways Neural tracts connecting one part of the nervous system with another. Neural Interconnections,Interconnection, Neural,Interconnections, Neural,Neural Interconnection,Neural Pathway,Pathway, Neural,Pathways, Neural
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009619 Nociceptors Peripheral AFFERENT NEURONS which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the DORSAL ROOT GANGLIA. Their peripheral terminals (NERVE ENDINGS) innervate target tissues and transduce noxious stimuli via axons to the CENTRAL NERVOUS SYSTEM. Pain Receptors,Receptors, Pain,Nociceptive Neurons,Neuron, Nociceptive,Neurons, Nociceptive,Nociceptive Neuron,Nociceptor,Pain Receptor
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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