Gamma-aminobutyric Acid Ergic Neurons Research Articles

Expression of a ClC chloride channel in Caenorhabditis elegans gamma-aminobutyric acid-ergic neurons

In this study, we report the complete cDNA sequence, genomic organization and expression pattern of the Caenorhabditis elegans ClC chloride channel gene, clh-6. Two different types of reporter gene fusions suggest that clh-6 expression is restricted to two gamma-aminobutyric acid-ergic RME neurons. These results are in striking contrast with the wide tissue distribution of messenger RNA for the related mammalian isoforms, ClC-6 and ClC-7. The restricted expression pattern of clh-6 provides a unique opportunity to study the biological function of a neuronal ClC chloride channel.

Evolution of GABAergic circuitry in the mammalian medial geniculate body.

Many features in the mammalian sensory thalamus, such as the types of neurons, their connections, or their neurotransmitters, are conserved in evolution. We found a wide range in the proportion of gamma-aminobutyric acidergic (GABAergic) neurons in the medial geniculate body, from <1% (bat and rat) to 25% or more (cat and monkey). In the bat, some medial geniculate body subdivisions have no GABAergic cells. Species-specific variation also occurs in the somesthetic ventrobasal complex. In contrast, the lateral geniculate body of the visual system has about the same proportion of GABAergic cells in many species. In the central auditory pathway, only the medial geniculate body shows this arrangement; the relative number of GABAergic cells in the inferior colliculus and auditory cortex is similar in each species. The range in the proportion of GABAergic neurons suggests that there are comparative differences in the neural circuitry for thalamic inhibition. We conclude that the number of GABAergic neurons in thalamic sensory nuclei may have evolved independently or divergently in phylogeny. Perhaps these adaptations reflect neurobehavioral requirements for more complex, less stereotyped processing, as in speech-like communication.

Analysis of gamma-aminobutyric acidergic synaptic contacts in the thalamic reticular nucleus of the monkey.

Gamma-aminobutyric acidergic (GABAergic) neurons in the thalamic reticular nucleus (TRN) spontaneously generate a synchronous bursting rhythm during slow-wave sleep in most mammals. A previous study at the electron microscopic level in cat anterior TRN has suggested that synchronous bursting activity could result from the large number of presumably GABAergic dendrodendritic synaptic contacts. However, little is known about the synaptology of the monkey thalamic reticular nucleus and whether it contains dendrodendritic contacts. To address this issue, we examined tissue obtained from Macaca fascicularis that was prepared for electron microscopy using postembedding techniques to demonstrate GABA immunoreactivity. Examination of the anterior (motor) and posterior (somatosensory) portions of the TRN disclosed the following: The majority of synaptic contacts (87.5% of 958) were formed by axon terminals showing no GABA immunoreactivity and making asymmetric synaptic contacts on dendrites or cell bodies. A further 6.4% of synaptic contacts was composed of GABA-immunoreactive presynaptic terminals making symmetric contacts with the dendrites of TRN neurons. The majority resembled the pleomorphic vesicle containing F-terminals seen in the dorsal thalamus and known to originate from axons of TRN. A subset or possible second class did not resemble any previously described class of GABA-immunoreactive terminals in the TRN. Both classes of these terminals making symmetric contacts may originate wholly or partially within the nucleus. There was one dendrodendritic synaptic contact and only a small number (3.2%) of axodendritic contacts with synaptic vesicles visible both pre- and postsynaptically. We conclude that dendrodendritic contacts are probably not responsible for the synchronized bursting neuronal activity seen in the slow-wave sleep of monkeys, and that, if TRN neurons are coupled synaptically, the most likely mechanism is through the synapses formed by recurrent axon collaterals of TRN neurons onto TRN dendrites.

Parvalbumin immunoreactivity in the thalamus of guinea pig: Light and electron microscopic correlation with gamma‐aminobutyric acid immunoreactivity

The relationship of the calcium binding protein parvalbumin (PV) with gamma-aminobutyric acidergic (GABAergic) neurons differs within different thalamic nuclei and animal species. In this study, the distribution of PV and GABA throughout the thalamus of the guinea pig was investigated at the light microscopic level by using immunoperoxidase methods. Intense PV labelling was found in all the GABAergic neurons of the reticular nucleus and in scattered GABAergic neurons in the anteroventral nucleus, whereas GABAergic interneurons in the ventrobasal and lateral geniculate nuclei were not PV labelled. At the electron microscopic level, preembedding immunoperoxidase for PV was combined with postembedding immunogold for GABA. In the ventrobasal nucleus, four types of profiles were recognized: 1) terminals with flattened vesicles and forming symmetric synapses, which were labelled with both PV and GABA and could therefore be identified as afferents from the reticular nucleus; 2) boutons morphologically similar to presynaptic dendrites of interneurons, labelled only with GABA; 3) large terminals with round vesicles and asymmetric synapses, labelled only with PV, which contacted GABAergic presynaptic dendrites in glomerular arrangements and resembled ascending excitatory afferents; and 4) terminals unlabelled by either antiserum. In the ventrobasal nucleus of the guinea pig a double immunocytochemical labelling permits therefore the differentiation of two populations of GABAergic vesicle-containing profiles, i.e., the terminals originating from reticular nucleus (that are double labelled) and the presynaptic dendrites originating from interneurons (that are GABA-labelled only). The possibility to differentiate GABAergic inputs from the reticular nucleus and from interneurons can shed light to the functional interpretation of synaptic circuits in thalamic sensory nuclei.

Dendritic arborization patterns of cortical interneurons labeled with the lectin, Vicia villosa, and injected intracellularly with lucifer yellow in aldehyde-fixed rat slices

Neurons whose cell bodies had been stained by a lectin, Vicia villosa, which recognizes terminal N-acetylgalactosamine residue, were intracellularly injected with Lucifer yellow (LY), in aldehyde-fixed slices of the parietal cortex of rats. LY was subsequently visualized immunocytochemically. All injected neurons had smooth or only sparsely spiny dendrites and resembled the various forms of gamma-aminobutyric acid-ergic neurons previously described in rat neocortex. In layers II/III, IV and V, most injected neurons were multipolar. In layer VI, most had vertically elongated dendritic fields. Some injected neurons in layer IV had an oval or vertically elongated soma and a bitufted dendritic arborization pattern. There was a gradual increase in the overall dendritic extent in deeper layers of the cortex.

Alterations of benzodiazepine receptor binding in tremor rats with absence-like seizures.

Tremor rats begin to exhibit clinical or electrical absence-like seizures after 6 weeks of age, and by 14 weeks of age, all have seizures. Central-type benzodiazepine receptor binding was investigated in tremor rats and control rats, aged 4 weeks and 16 weeks. Significantly lower benzodiazepine receptor density and no differences in affinity were found in the hippocampus of the tremor rats in comparison with that of control rats at both ages. This abnormality is considered to be due to a tremor gene and may be the cause of absence-like seizures in tremor rats. A significantly lower receptor density was found in the cerebellum at 4 weeks of age in the tremor rats than in the control rats. These changes may be related to tremorous movements in the tremor rats. Receptor density was significantly lower in the brainstems of tremor rats and control rats at 16 weeks of age than at 4 weeks of age, and the decrease was more marked in control rats. These facts may reflect a reduced decrease in the response to the dysfunction of gamma-aminobutyric acidergic neurons, or the function of the gamma-aminobutyric acid/benzodiazepine receptor system may be secondarily increased to suppress seizures in 16-week-old tremor rats.

Ultrastructural localization of gamma amino butyric acid immunoreactivity in B cells of the rat pancreas.

The purpose of this study was to determine the ultrastructural localization of gamma amino butyric acid (GABA) within the B cell of isolated rat islets, particularly with respect to the B cell secretion granules. GABA immunoreactivity was localized ultrastructurally, with colloidal gold, in the B cells and absent in the A cells and D cells. Quantitative analysis of the colloidal gold particle distribution in the B cell revealed 29.5 +/- 5.2 gold particles/micron 2 in the nuclei, 29.3 +/- -6.9 gold particles/micron 2 in the mitochondria and 4.9 +/- 1.0 gold particles/micron 2 in the secretion granules. Particle density in the remainder of the cytoplasm was 41.9 +/- 4.1 particles/micron 2. The paucity of gamma amino butyric acid in the B cell secretion granules differs from observations on gamma amino butyric acidergic neurons, where there is an accumulation of gamma amino butyric acid within the neurosecretory vesicles. These findings indicate that if gamma amino butyric acid is released from the islet, then it is by a nongranular mechanism. In addition, the results are compatible with the hypotheses that gamma amino butyric acid within the B cell functions in the regulation of insulin biosynthesis, and/or functions as an alternative energy source for the B cell through the gamma amino butyric acid shunt.

Cerebral cation shifts and amino acids in Huntington's disease.

The cations, calcium, magnesium, sodium, and potassium, putative amino acid transmitters, and total protein contents were assessed in the frontal cortex, putamen, and substantia nigra of Huntington's disease (HD) patients and age-matched nonneurologic control subjects. In the HD frontal cortex and HD substantia nigra, only small increases in sodium levels and decreases in potassium levels were observed, but in the HD putamen there were major cation shifts, suggesting a twofold increase of the extracellular space. In all three brain areas that were investigated, potassium was positively correlated with gamma-aminobutyric acid and in the putamen sodium was negatively correlated with the amino acid. These correlations suggest loss of gamma-aminobutyric acidergic neurons or nerve terminals in these areas. The elevation of sodium in the HD basal ganglia may be visualized in vivo by nuclear magnetic resonance of sodium.

A postmortem study of amino acid neurotransmitters in Alzheimer's disease.

Concentrations of putative neurotransmitter amino acids were measured in postmortem brains from 10 patients with Alzheimer's disease and 10 controls. Glutamate, aspartate, taurine, gamma-aminobutyric acid (GABA), and alanine levels were examined in 9 cortical regions, hippocampus, thalamus, and basal ganglia using high-performance liquid chromatography with electrochemical detection. There were no significant alterations in aspartate, taurine, or alanine levels in any of the regions examined. Widespread significant reductions in cortical GABA concentrations were observed in the Alzheimer's brains, with the largest decreases in the temporal lobe. Overall values for glutamate concentrations in temporal and frontal cortices showed a significant 12% reduction in Alzheimer's brains, but the only individual cortical region showing a significant reduction in glutamate was the inferior temporal gyrus. These results suggest that gamma-aminobutyric acidergic neurons in Alzheimer's cerebral cortex may be selectively vulnerable to the disease process.