Expression of 10 GABAA receptor subunit messenger RNAs in the motor-related thalamic nuclei and basal ganglia of Macaca mulatta studied with in situ hybridization histochemistry

doi:10.1016/S0306-4522(97)00634-9

Neuroscience

Volume 85, Issue 1, 26 March 1998, Pages 179-204

https://doi.org/10.1016/S0306-4522(97)00634-9 Get rights and content

Abstract

In situ hybridization histochemistry technique with [³⁵S]UTP-labelled riboprobes was used to study the expression pattern of 10 GABA_A receptor subunit messenger RNAs in the basal ganglia and motor thalamic nuclei of rhesus monkey. Human transcripts were used for the synthesis of α₂, α₄, β₂, β₃, γ₁ and δ subunit messenger RNA probes. Rat complementary DNAs were used for generating α₁, α₃, β₁ and γ₂ subunit messenger RNA probes. Nigral, pallidal and cerebellar afferent territories in the ventral tier thalamic nuclei all expressed α₁, α₂, α₃, α₄, β₁, β₂, β₃, δ and γ₂ subunit messenger RNAs but at different levels. Each intralaminar nucleus displayed its own unique expression pattern. In the thalamus, γ₁ subunit messenger RNA was detected only in the parafascicular nucleus. Comparison of the expression patterns with the known organization of GABA_A connections in thalamic nuclei suggests that (i) the composition of the receptor associated with reticulothalamic synapses, except for those in the intralaminar nuclei, may be α₁α₄β₂δ, (ii) receptors of various other subunit compositions may operate in the local GABAergic circuits, and (iii) the composition of receptors at nigro- and pallidothalamic synapses may differ, with those at nigrothalamic probably containing β₁ and γ₂ subunits. In the medial and lateral parts of the globus pallidus, the subthalamic nucleus and the substantia nigra pars reticularis, the α₁, β₂ and γ₂ messenger RNAs were co-expressed at a high level suggesting that this subunit composition was associated with all GABAergic synapses in the direct and indirect striatal output pathways. Various other subunit messenger RNAs were also expressed but at a lower level. In the substantia nigra pars compacta the most highly expressed messenger RNAs were α₃, α₄ and β₃; all other subunit messenger RNAs studied, except for γ₁, α₁ and α₂, were expressed at a moderate to high level. In the striatum, the following subunit messenger RNAs were expressed (listed in order of decreasing signal intensity): α₄, β₃, α₂, α₃, β₂, δ, γ₂, α₁.

The expression patterns found in the monkey were similar to those described in comparable nuclei in the rat by Wisden et al. [J. Neurosci. (1992) 12, p. 1040]; however, the monkey nuclei displayed a much greater variety of GABA_A receptor subunit messenger RNAs.

Section snippets

Experimental procedures

Four adult Rhesus monkeys with weights ranging from 3.5 to 5.2 kg purchased from LABS (Yemassee, SC) were used in this study. The experimental protocol was approved by The University of Iowa Animal Care Committee and was in compliance with the National Institute of Health Guide for Humane Treatment and Care of Laboratory Animals. Ethyl ether anaesthesia was administered by placing each monkey into an airtight chamber to which ether vapours were then delivered. Monkeys were decapitated when their

Topography of nuclei of interest in the thalamic levels analysed

Three representative thalamic levels were used for analysis. The cytoarchitecture and nuclear topography of these levels are illustrated in Nissl-stained sections in Fig. 1. The “medial” thalamic level (Fig. 1A) is distinguished by the mammillothalamic tract surrounded by the ventral anterior nucleus pars magnocellularis (VAmc), the major recipient of the nigrothalamic pathway.8, 31The other nuclei at this level that receive input from the basal ganglia are the lateral habenula and the

Discussion

The results of this study demonstrate differential distribution of the mRNAs of the 10 GABA_A receptor subunits in the thalamus of the Rhesus monkey. Most of the previous studies in the thalamus were done in the rat, and only recently has a study on the monkey appeared.[30]Huntsman et al.[30]used monkey-specific cDNAs to study the expression of 10 GABA_A receptor subunit mRNAs, nine of which were the same as those analysed here. In addition, those authors studied expression of α₅ mRNA, whereas

Conclusion

In summary, the distribution pattern of the GABA_A receptor subunit mRNAs in different basal ganglia nuclei suggests that there may be one common subunit combination, α₁β₂γ₂, in all synapses downstream from the striatum that are part of the direct and indirect striatal output pathways that include striatopallidal synapses in both parts of the globus pallidus, striatonigral (striatum–SNr) synapses and pallidosubthalamic (GPl–STN) synapses. At the same time, GABA_A receptors in the internal basal

Acknowledgements

This study was made possible by RO1 NS30983 to KKI. With our sincere gratitude and warm memory the paper is dedicated to the late Dolan Pritchett who was an enthusiastic supporter of this study at its onset.

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¹: Present address: Department of Biosciences, University of Calgary, Calgary, Canada, T2N 1N4.

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Expression of 10 GABAA receptor subunit messenger RNAs in the motor-related thalamic nuclei and basal ganglia of Macaca mulatta studied with in situ hybridization histochemistry

Abstract

Section snippets

Experimental procedures

Topography of nuclei of interest in the thalamic levels analysed

Discussion

Conclusion

Acknowledgements

Trends Neurosci.

J. biol. Chem.

Brain Res. Rev.

Brain Res. Bull.

J. biol. Chem.

Brain Res.

J. biol. Chem.

Neuroscience

Eur. J. Pharmac.

Brain Res.

Trends Neurosci.

Brain Res.

Eur. J. Pharmac.

Neuroscience

Neuron

Brain Res.

Brain Res.

Neuropharmacology

Neuron

Trends Neurosci.

Brain Res.

Brain Res.

J. biol. Chem.

Eur. J. Pharmac.

Neuroscience

Brain Res.

Neuropharmacology

Brain Res. Bull.

Fedn Eur. biochem. Socs Lett.

Neuroscience

Neuronal and synaptic organization of the centromedian nucleus in the Rhesus monkey

J. Neurocytol.

Nigrothalamic projections in the monkey demonstrated by autoradiographic technics

J. comp. Neurol.

Comparative distribution of mRNAs for glutamic acid decarboxylase and tachykinins in the basal ganglia: an in situ hybridization study in the rodent brain

J. comp. Neurol.

Insensitivity to anaesthetic agents conferred by a class of GABAA receptor subunit

Nature

Distribution of central ω1 (benzodiazepine 1) and ω2 (benzodiazepine 2) receptor subtypes in the monkey and human brain. An autoradiographic study with [3H] flunitrazepam and ω1 selective ligand [3H] zolpidem

J. Pharmac. exp. Ther.

A Golgi and ultrastructural study of the monkey globus pallidus

J. comp. Neurol.

Molecular pharmacology of γ-aminobutyric acid type A receptor agonists and partial agonists in oocytes injected with different α, β, and γ receptor subunit combinations

Molec. Pharmac.

The neostriatal mosaic. I. Compartmental organization of projections from the striatum to the substantia nigra in the rat

J. comp. Neurol.

The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia

A. Rev. Neurosci.

Modular organization of projection neurons in the matrix compartment of the primate striatum

J. Neurosci.

An experimental electron microscopic study on the striatonigral projection in the cat

Expl Brain Res.

Topographic organization of the ventral striatal efferent projections in the rhesus monkey: an anterograde tracing study

J. comp. Neurol.

Cloning of cDNAs encoding human α2 and α3 GABA-A receptor subunits and characterisation of the benzodiazepine pharmacology of recombinant α1, α2, α3 and α5 containing human GABA-A receptors

Molec. Pharmac.

The role of the beta subunit in determining the pharmacology of human GABA-A receptors

Molec. Pharmac.

Expression of 10 GABA_A receptor subunit messenger RNAs in the motor-related thalamic nuclei and basal ganglia of Macaca mulatta studied with in situ hybridization histochemistry

Insensitivity to anaesthetic agents conferred by a class of GABA_A receptor subunit

Distribution of central ω₁ (benzodiazepine 1) and ω₂ (benzodiazepine 2) receptor subtypes in the monkey and human brain. An autoradiographic study with [³H] flunitrazepam and ω₁ selective ligand [³H] zolpidem

Cloning of cDNAs encoding human α₂ and α₃ GABA-A receptor subunits and characterisation of the benzodiazepine pharmacology of recombinant α1, α2, α3 and α5 containing human GABA-A receptors