Showing papers on "GABAergic published in 1990"
TL;DR: It is suggested that GABA is the numerically dominant neurotransmitter in the hypothalamus, and the importance of inhibitory circuits in theothalamus is emphasized.
Abstract: To study the organization and distribution of the inhibitory amino acid neurotransmitter GABA in the medial hypothalamus, we used a postembedding immunocytochemical approach with colloidal gold. Quantitative analysis showed that half (49%) of all synapsing boutons studied were immunoreactive for GABA, based on immunogold staining of the suprachiasmatic, arcuate, supraoptic, and paraventricular nuclei. This was corroborated with pre-embedding peroxidase immunostaining with antisera against glutamate decarboxylase, the GABA synthetic enzyme. These data suggest that GABA is the numerically dominant neurotransmitter in the hypothalamus, and emphasize the importance of inhibitory circuits in the hypothalamus. Serial ultrathin sections were used to reconstruct GABA immunoreactive boutons and axons in three dimensions. With this type of analysis we found less morphological heterogeneity between GABA immunoreactive boutons than with single ultrathin sections. Single sections sometimes showed boutons containing only small clear vesicles, and other with both clear vesicles and small dense core vesicles. However, with serial sections through individual boutons, dense core vesicles were consistently found at the periphery of the pre-synaptic GABA immunoreactive boutons, suggesting probable co-localization of GABA with unidentified peptides in most if not all boutons throughout the hypothalamus. A positive correlation was found between the density of small clear vesicles and the intensity of immunostaining with colloidal gold particles. GABA immunoreactive axons generally made symmetrical type synaptic specializations, although a small percentage made strongly asymmetrical synaptic specializations. Vesicles in GABA immunoreactive boutons were slightly smaller than those in non-reactive boutons. Synaptic efficacy is related to the position of the synapse on the post-synaptic neuron. While the majority of GABA immunoreactive axons made synaptic contact with dendrites, the distribution of GABA immunoreactive synapses on somata and dendrites was the same as would be expected from a random distribution of all boutons. No preferential innervation of cell bodies by GABA immunoreactive terminals was found. Serial ultrathin sections showed that a GABA immunoreactive axon would sometimes make repeated synaptic contacts with a single postsynaptic neuron, indicating a high degree of direct control by the presynaptic GABAergic cell. Other immunoreactive axons made synaptic contact with a number of adjacent dendrites and cells, suggesting a role for GABA in synchronizing the activity of hypothalamic neurons. Based on the density of immunogold particles per unit area, varying concentrations of immunoreactive GABA were found in different presynaptic boutons in the hypothalamus.
546 citations
TL;DR: The results show that the mechanism by which the serotonergic pathway may exert a powerful influence on hippocampal function involves the modulation of local inhibitory circuits, as well as among the subcortical input pathways originating in the septum and raphe.
Abstract: Information flow and processing in hippocampal neuronal networks is determined by a wide range of inhibitory mechanisms [e.g., feedforward or feedback, gamma-aminobutyrate (GABA) A or B receptor-mediated, perisomatic shunting, or distal dendritic inhibition], each subserving specialized functions. These forms of local inhibition are mediated by morphologically and neurochemically well-defined, mostly GABA-containing, interneurons, which control large populations of principal cells through their extensive axonal arborizations. These neurons can serve as ideal targets for subcortical pathways, such as those originating in the septum or raphe, which exercise a global control over hippocampal activity. This intriguing possibility prompted us to study whether the profound effect of the serotonergic raphe-hippocampal pathway is mediated by inhibitory interneurons or whether a direct diffuse action on the principal cells is dominant. We demonstrate that axons of this pathway form multiple synaptic contacts with hippocampal GABAergic interneurons. Interestingly, the serotonergic afferents selectively innervate the somata and dendritic trees of GABAergic neurons that contain the 28-kDa calcium-binding protein calbindin D28K, but never those that contain another calcium-binding protein, parvalbumin. These results show that the mechanism by which the serotonergic pathway may exert a powerful influence on hippocampal function involves the modulation of local inhibitory circuits. Furthermore, the selectivity in the choice of target GABAergic interneurons suggests a strong functional specialization among inhibitory circuits, as well as among the subcortical input pathways originating in the septum and raphe.
354 citations
TL;DR: Staining with parvalbumin antibodies can be used to identify a single class of GABAergic aspiny interneurons that is present in both patch and matrix compartments, and whose processes cross the borders between these compartments.
Abstract: Antibodies to the intracellular calcium binding protein parvalbumin were shown to label specifically a distinct group of neostriatal GABAergic neurons. These neurons corresponded to the intensely staining subclass of neostriatal GABAergic neurons that have previously been shown to be a class of aspiny interneurons in the neostriatum. The parvalbumin neurons were aspiny neurons with varicose dendrites distributed throughout the neostriatum in a pattern identical to the intensely stained GABA neurons, and both populations of neurons showed increased numbers in the lateral part of the neostriatum. Double labeling of single neurons with both the GABA and parvalbumin antisera showed that all parvalbumin neurons were positive for GABA, but some GABA labelled neurons were not immunoreactive for parvalbumin. These parvalbumin-negative GABAergic neurons were morphologically similar to the spiny projection neurons, which are GABAergic but usually are not so heavily stained. The relationship of the GABA-containing parvalbumin neurons to the striatal mosaic organization was determined by using immunocytochemistry for another calcium binding protein, calbindin D28K, to label the matrix compartment of the striatum. The distribution of parvalbumin-positive neurons relative to the calbindin-positive matrix and calbindin-poor patches was determined by using pairs of adjacent sections stained with the calbindin and parvalbumin antisera. This analysis showed that the somata of the parvalbumin neurons were present in both patch and matrix compartments, and their axons and dendrites crossed the boundaries between compartments. A quantitative analysis of the number of neurons in each compartment revealed that the neurons showed no preferential distribution in either compartment, but instead were present according to the area occupied by that compartment. Approximately 10% of parvalbumin neurons were in the patch compartment, and in these same sections, the patch compartment occupied approximately 10% of the area of those sections. Staining with parvalbumin antibodies can therefore be used to identify a single class of GABAergic aspiny interneurons that is present in both patch and matrix compartments, and whose processes cross the borders between these compartments.
287 citations
TL;DR: Analysis of the size, shape, and orientation of stained cell bodies and proximal dendrites demonstrated that each subpopulation contained several different types of smooth stellate cells, suggesting that Cal‐IR and PV‐IR are found in functionally and morphologically heterogeneous subpopulations of GABA neurons.
Abstract: Recent studies have shown that the presence of immunoreactivity for parvalbumin (PV-IR) and calbindin-D 28k (Cal-IR) can be used as markers for certain types of gamma-aminobutyric acid (GABA) immunoreactive interneurons in monkey cerebral cortex. Little quantitative information is available regarding the features that distinguish these two subpopulations, however. Therefore, in this study we localized PV-IR and Cal-IR neurons in Macaca monkey striate cortex and analyzed quantitatively their laminar distribution, cell morphology, and co-localization with GABA by double-labeling immunocytochemistry. PV-IR was found in nonpyramidal cells in all layers of the cortex, although PV-IR cells in layer 1 were rare. In contrast, Cal-IR was found mainly in nonpyramidal cells in two bands corresponding to layers 2-3 and 5-6. We found very few double-labeled PV-IR/Cal-IR cells but confirmed that almost all PV-IR and Cal-IR cells are GABAergic. Overall, 74% of GABA neurons in striate cortex displayed PV-IR compared to only 12% that displayed Cal-IR and 14% that were GABA-IR only. Quantitative analysis indicated that the relative proportion of GABA cells that displayed PV-IR or Cal-IR showed conspicuous laminar differences, which were often complementary. Cell size measurements indicated that PV-IR/GABA cells in layers 2-3 and 5-6 were significantly larger than Cal-IR/GABA cells. Analysis of the size, shape, and orientation of stained cell bodies and proximal dendrites further demonstrated that each subpopulation contained several different types of smooth stellate cells, suggesting that Cal-IR and PV-IR are found in functionally and morphologically heterogeneous subpopulations of GABA neurons. There was a thick bundle of PV-IR axons in the white matter underlying the striate but not prestriate cortex. PV-IR punctate labeling matched the cytochrome oxidase staining pattern in layers 4A and 4C, suggesting that PV-IR is present in geniculocortical afferents as well as intrinsic neurons. Cal-IR neuropil staining was high in layers 1, 2, 4B, and 5, where cytochrome oxidase staining is relatively low. We did not find a preferential localization of either PV-IR or Cal-IR cell bodies in any cytochrome oxidase compartments in layers 2-3 of the cortex. These findings indicate that PV and Cal are distributed into different neuronal circuits.
280 citations
TL;DR: It is demonstrated that dopaminergic neurones in the substantia nigra receive symmetrical synaptic input from GABAergic and substance P-containing terminals, and show that a proportion of these terminals contain both substance P and GABA and that a part of this innervation is derived from the striatum.
262 citations
TL;DR: The present results demonstrate that the GABAergic septohippocampal pathway can control a wide range of putative inhibitory circuits, and thereby influence the pattern of electrical activity in the hippocampal formation.
247 citations
TL;DR: Findings strongly suggest that the accumbens-ventral pallidal GABAergic circuitry is a substrate for the decrease in sensorimotor gating induced by mesolimbic DA overactivity.
210 citations
TL;DR: The present immunocytochemical data demonstrate directly what has previously been inferred from biochemical and autoradiographic evidence: that the mechanisms for high-affinity GABA uptake is selectively and differentially localized in GABAergic neurons and in glial cells.
Abstract: Polyclonal antibodies were raised against the GABA transporter (GABA- Tp) purified from rat brain tissue (Radian et al., 1986) and used for immunocytochemical localization of the antigen in several rat brain areas, including the cerebellum, hippocampus, substantia nigra, and cerebral cortex. Light microscopic studies with the peroxidase- antiperoxidase and biotin-avidin-peroxidase techniques suggested that GABA-Tp is localized in the same types of axons and terminals that contain endogenous GABA, as judged by comparison with parallel sections incubated with antibodies against glutaraldehyde-conjugated GABA. However, as expected from biochemical results, different neurons differed in their relative contents of GABA-Tp and GABA; thus, GABA-Tp was relatively low in striatonigral and Purkinje axon terminals and relatively high in nerve plexus around the bases of cerebellar Purkinje cells and hippocampal pyramidal and granule cells. The GABA-Tp antiserum did not produce detectable labeling of nerve cell bodies. Electron microscopic studies supported the light microscopic observations and provided direct evidence of cellular co-localization of GABA-Tp and GABA (as visualized by the peroxidase-antiperoxidase technique and postembedding immunogold labeling, respectively). The ultrastructural studies indicated the presence of GABA-Tp also in glial processes but not in glial cell bodies. The relative intensity of the neuronal and glial staining varied among regions: glial staining predominated over neuronal staining in the substantia nigra, whereas the converse was true in the cerebellum and hippocampus. The present immunocytochemical data demonstrate directly what has previously been inferred from biochemical and autoradiographic evidence: that the mechanisms for high-affinity GABA uptake is selectively and differentially localized in GABAergic neurons and in glial cells.
209 citations
TL;DR: The binding of this ligand to brain tissue taken at autopsy has demonstrated a decreased density of GABA uptake sites in the hippocampus in schizophrenia, providing a link between neuropathology, evidence of laterality, and the dopamine hypothesis of the disease.
197 citations
TL;DR: It has been demonstrated that stress, like anxiogenic drugs, decreases the function of GABAA receptor complex, an effect mimicked by the in vivo administration of different inhibitors of GABAergic transmission and antagonized by anxiolytic benzodiazepines.
188 citations
TL;DR: Intracellular recordings from rat hippocampal neurons in vitro during the first postnatal week revealed the presence of spontaneous giant depolarizing potentials (GDPs), which were generated by the synchronous discharge of a population of neurons.
TL;DR: It is proposed that an activation of residual basal forebrain cholinergic neurons can be achieved most physiologically via inhibitory modulation of afferent GABAergic transmission, which may have a therapeutic value in treating behavioral syndromes associated with cortical cholinesterase denervation.
Abstract: The hypothesis that the cognitive decline in senile dementia is related to the loss of cortical cholinergic afferent projections predicts that pharmacological manipulations of the remaining cholinergic neurons will have therapeutic effects. However, treatment with cholinesterase inhibitors or muscarinic agonists has been, for the most part, largely unproductive. These drugs seem to disrupt the normal patterning of cholinergic transmission and thus may block proper signal processing. An alternative pharmacological strategy which focuses on the amplification of presynaptic activity without disrupting the normal patterning of cholinergic transmission appears to be more promising. Such a strategy may make use of the normal GABAergic innervation of basal forebrain cholinergic neurons in general, and in particular of the inhibitory hyperinnervation of remaining cholinergic neurons which may develop under pathological conditions. Disinhibition of the GABAergic control of cholinergic activity is assumed to intensify presynaptic cortical cholinergic activity and to enhance cognitive processing. Although the extent to which compounds such as the benzodiazepine receptor antagonistβ-carboline ZK 93 426 act via the basal forebrain GABA-cholinergic link is not yet clear, the available data suggest that the beneficial behavioral effects of this compound established in animals and humans are based on indirect cholinomimetic mechanisms. It is proposed that an activation of residual basal forebrain cholinergic neurons can be achieved most physiologically via inhibitory modulation of afferent GABAergic transmission. This modulation may have a therapeutic value in treating behavioral syndromes associated with cortical cholinergic denervation.
TL;DR: Results indicate that GABAergic projections constitute a very minor component of the PAG‐NRM‐spinal cord pathway; however, there is a significant contribution of GABAergic neurons to the spinal projections that originate lateral to the NRM.
Abstract: The fact that GABA receptor agonists and antagonists influence nociceptive thresholds when microinjected into the rostroventral medulla or in the spinal cord may reflect the involvement of GABAergic neuronal elements in endogenous antinociceptive pathways. In the present study we used immunocytochemistry and retrograde tract tracing to investigate the contribution of GABAergic projection neurons to the antinociceptive network linking the midbrain periaqueductal gray matter (PAG), the nucleus raphe magnus (NRM), and the spinal cord dorsal horn. The tracer, WGAapoHRP-Au was injected into either the NRM or the spinal cord and the distribution of labeled neurons in sections of the PAG and medulla, respectively, was studied. The same sections were immunostained to demonstrate GABA-immunoreactive neurons. Although GABA-immunoreactive neurons were abundant in the PAG, only 1.5% were retrogradely labeled from the NRM. Similarly, very few GABA-immunoreactive neurons within the cytoarchitectural boundaries of the NRM were retrogradely labeled from the spinal cord. A much higher proportion of GABA-immunoreactive neurons in the region lateral to the NRM, however, were retrogradely labeled from the spinal cord. Eighteen percent of GABA-immunoreactive neurons were retrogradely labeled in the nucleus reticularis paragigantocellularis; conversely, 15% of the retrogradely labeled neurons in this region were GABA-immunoreactive. These results indicate that GABAergic projections constitute a very minor component of the PAG-NRM-spinal cord pathway; however, there is a significant contribution of GABAergic neurons to the spinal projections that originate lateral to the NRM. The majority of GABAergic neurons in the PAG and NRM are presumed to be inhibitory interneurons that directly or indirectly regulate activity in efferent pathways from these regions.
TL;DR: The results confirm and extend previous results designating the pyramidal cell dendritic tree as the main synaptic target of DA cortical afferents in rat and primate cerebral cortex.
Abstract: The aim of this study was to identify, at the ultrastructural level, the neuronal targets of dopamine afferents to the medial prefrontal and the anterior cingulate cortex of the adult rat. Since, in addition to pyramidal neurons, the cortical neuronal population mainly consists of GABAergic nonpyramidal intrinsic neurons, the simultaneous visualization of both dopamine- and GABA-containing neurons should leave the pyramidal neurons as the only unlabelled dopamine postsynaptic target. In this context, we used a double labelling immunocytochemical procedure: a pre-embedding PAP immunostaining to visualize monoclonal conjugated-dopamine (DA) antibody, followed by postembedding immunogold staining with a polyclonal conjugated-GABA antibody. In a single section sampling of 369 DA-immunoreactive (DA-IR) varicosities observed and the GABA-containing elements, 75% of the DA-IR terminals showed no indication of any contact with a GABA neuron. Twenty-five per cent were found in nonsynaptic contiguity with a GABA-immunoreactive neuronal element: axon, dendrite or cell body. When a DA varicosity was in nonsynaptic contiguity with a neuronal perikaryon (5% of cases), this cell was GABA positive. Ten per cent of the DA varicosities were contiguous to a GABA axon, but axoaxonic synapses in either direction were never observed. A symmetrical synapse between a DA varicosity and a GABA-containing dendrite was observed only once. The other 13 DA-IR terminals exhibiting a clear synaptic junction were apposed to nonGABA-containing dendrites, spines and shafts. Triads were observed in which a DA varicosity, forming or not a symmetrical synapse, was apposed to an unlabelled dendrite already receiving a symmetrical junction from another unlabelled axon. These data confirm and extend previous results designating the pyramidal cell dendritic tree as the main synaptic target of DA cortical afferents in rat and primate cerebral cortex. However, a direct effect of dopamine on a subpopulation of intrinsic GABA neurons cannot be excluded.
TL;DR: This chapter focuses on receptors for the neurotransmitter molecule GABA (γ-aminobutyric acid) with particular emphasis on insect GABA receptors, and discusses GABA receptors of the insect nervous system and insect muscle.
Abstract: Publisher Summary This chapter focuses on receptors for the neurotransmitter molecule GABA (γ-aminobutyric acid) with particular emphasis on insect GABA receptors. It discusses GABA receptors of the insect nervous system and insect muscle. GABAergic neurons are found in the brain, spinal cord, and ganglia of the mammalian nervous system. Ionophoretic application of GABA on to mammalian neurons normally results in an increased membrane conductance and an inhibitory (hyperpolarizing) response of the cell under test. GABA-sensitive cells have been detected in sympathetic ganglia cerebral cortex and Deiter's nucleus. Most responses are attributable to a GABA-operated chloride channel; they are blocked by bicuculline, the active form of which is the 1S,9R-(-)isomer and picrotoxin. The chapter also discusses GABA receptors of invertebrates other than insects, insect GABA receptors as targets for insecticides, and GABA receptors as members of a ligand-operated receptor super-family.
TL;DR: A previously unknown but sizable direct gamma-aminobutyric acid (GABA)-containing neuronal pathway from the zona incerta to the neocortex in rats was found to project bilaterally to the entire neocortex and exhibited a rough corticotopic organization.
Abstract: Retrograde fluorescent tracers were used to demonstrate a previously unknown but sizable direct gamma-aminobutyric acid (GABA)-containing neuronal pathway from the zona incerta to the neocortex in rats. This incertocortical pathway was found to project bilaterally to the entire neocortex and exhibited a rough corticotopic organization. Many of the zona incerta neurons projecting to the parietal and occipital cortices could also be immunohistochemically stained with antibodies to glutamic acid decarboxylase and GABA. Few of these neurons were immunoreactive to tyrosine hydroxylase antibodies, which identify dopamine-containing neurons. Injections in the frontal and entorhinal cortices labeled many neurons near or within the dopaminergic A13 subdivision of the zona incerta. In addition, the incertocortical system was found to be significantly larger during early postnatal (2 to 3 weeks) development. The projection pattern of this newly discovered pathway resembles that of the monoaminergic and cholinergic systems, arising from the brainstem and forebrain, suggesting possible similarities of function.
TL;DR: Immunostaining of the cat superior olivary complex with antisera against glycine, calbindin, GABA, and its synthetic enzyme, glutamate decarboxylase reveals considerable new information about neural connections that underlie processing of binaural signals.
TL;DR: The results of this study demonstrate that the pallidosubthalamic projection is organized according to a mediolateral and rostrocaudal topography and that the proximal dendrites of the subthalamic cells are the major targets of the GABA‐immunoreactive pallido‐subthalamic terminals.
Abstract: The anterograde transport of Phaseolus vulgaris-leucoagglutinin (PHA-L) was combined with postembedding immunocytochemistry for gamma-aminobutyric acid (GABA) to study the topography, the synaptic organization and the neurotransmitter content of the pallidosubthalamic projection in the rat. After injections of PHA-L in different parts of the globus pallidus a rich plexus of anterogradely labelled fibres and terminals was found in the ipsilateral subthalamic nucleus. The immunoreactive elements were distributed according to a mediolateral and rostrocaudal topography. Injections of PHA-L restricted to the lateral two-thirds of the globus pallidus gave rise to a massive anterograde labelling confined to the lateral half of the subthalamic nucleus. On the other hand, injections of PHA-L strictly confined to the medial part of the globus pallidus resulted in anterograde labelling that occupied the ventromedial pole of the subthalamic nucleus. In some cases a few retrogradely labelled cells were found in the subthalamic nucleus after PHA-L injections in the globus pallidus. The perikarya and the primary dendrites of these labelled cells were sometimes surrounded by anterogradely labelled terminals suggesting a close reciprocal connection between the globus pallidus and the subthalamic nucleus. Electron microscopic analysis of the PHA-L-labelled terminals revealed that they contain many mitochondria, numerous small round or slightly pleomorphic vesicles and occasionally one or two large dense core vesicles. They form symmetrical synaptic contacts predominantly with the proximal dendrites (39%) and less frequently with the perikarya (31%) and the distal dendrites (30%) of the subthalamic cells. Quantitative measurements showed that the pallidosubthalamic varicosities have a diameter ranging from 0.7 to 4.5 microm and a mean cross-sectional area of 0.79 +/- 0.26 microm2 (Mean +/- SD). Postembedding immunocytochemistry for GABA revealed that the PHA-L-immunoreactive pallidosubthalamic axon terminals display GABA immunoreactivity. The results of our study demonstrate that the pallidosubthalamic projection is organized according to a mediolateral and rostrocaudal topography and that the proximal dendrites of the subthalamic cells are the major targets of the GABA-immunoreactive pallidosubthalamic terminals. This suggests that the globus pallidus exerts a powerful control over the subthalamic cells through an inhibitory GABAergic pathway.
TL;DR: The results suggest that dopamine via D1 receptors modulates the release of GABA from striatal GABAergic terminals.
TL;DR: The relationship between GABA‐IR profiles and central terminals in glomerular complexes in lumbar cord of the monkey and other neural elements are analyzed in order to better understand the processing of sensory input in the spinal cord.
Abstract: It is hypothesized that terminals containing γ-aminobutyric acid (GABA) participate in presynaptic inhibition of primary afferents. To date, few convincing GAB A-immunoreactive (GABA-IR) axo-axonic synapses have been demonstrated in support of this theory. The goal of this study is to document the relationship between GABA-IR profiles and central terminals in glomerular complexes in lumbar cord of the monkey (Macaca fascicularis). In addition, the relationship between GABA-IR profiles and other neural elements are analyzed in order to better understand the processing of sensory input in the spinal cord.
GABA-IR cell bodies were present in Lissauer's tract (LT) and in all laminae in the spinal gray matter except lamina IX, GABA-IR fibers and terminals were heavily concentrated in LT: laminae I, II, and III; and present in moderate concentration in the deeper laminae of the dorsal horn, ventral horn (especially in association with presumed motor neurons), and lamina X. Electron microscopic analysis confined to LT and laminae I, II, and III demonstrated GABA-IR cell bodies, dendrites, and myelinated and unmyelinated fibers. GABA-IR cell bodies received sparse synaptic input, some of which was immunoreactive for GABA. The majority of the synaptic input to GABA-IH neurons occurred at the dendritic level. Furthermore, the presence of numerous vesicle-containing GABA-IR dendrites making synaptic interactions indicated that GABA-IR dendrites also provided a major site of output. Two consistent arrangements were observed in laminae I–III concerning vesicle-containing GABA-IR dendrites: (1) they were often postsynaptic to central terminals and (2) they participated in reciprocal synapses. The majority of GABA-IR axon terminals observed contained round clear vesicles and varying numbers of dense core vesicles. Only on rare occasions were GABA-IR terminals with flattened vesicles observed. GABA-IR terminals were not observed as presynaptic elements in axo-axonic synapses; however, on some occasions, GABA-IR profiles presumed to be axon terminals were observed postsynaptic to large glomerular type terminals.
Our findings suggest that a frequent synaptic arrangement exists in which primary afferent terminals relay sensory information into a GABAergic system for further processing. Furthermore, GABA-IR dendrites appear to be the major source of input and output for this inhibitory system. The implications of this GABAergic neurocircuitry are discussed in relation to the processing of sensory input in the superficial dorsal horn and in terms of mechanisms of primary afferent depolarization (PAD).
TL;DR: Abundance of GABAergic cells in many hypothalamic nuclei indicates that GABA represents quantitatively the most important transmitter of hypothalamic neurons, and may be involved in neuroendocrine and autonomic regulatory functions.
TL;DR: Gamma-aminobutyric acid containing neurons were characterized in human association cortex by a combination of Golgi impregnation and immunohistochemistry and show that GABAergic neurons are heterogeneous with respect to their dendritic and axonal patterns.
Abstract: Gamma-aminobutyric acid (GABA) containing neurons were characterized in human association cortex by a combination of Golgi impregnation and immunohistochemistry. Neurons were Golgi impregnated, gold toned, drawn and then classified on the basis of their dendritic and axonal arborization in layers I-VI. An antiserum to GABA was used to determine which of the impregnated neurons were immunopositive. Twenty-four GABA-positive cells were Golgi impregnated: 7 were bitufted with their dendrites predominantly radially oriented, and 17 were multipolar stellate cells. Three of the multipolar cells with large somata in the deep layers showed dendritic patterns similar to previously described basket cells. Nine of the multipolar stellate cells in layers III-VI showed characteristics of 'neurogliaform' neurons (Ramon y Cajal, 1899). The somata and the dendritic field of these cells were spherical, with diameters of about 10-15 microns and 200 microns, respectively. Their dendrites were smooth and slightly beaded. The axon collaterals were densely distributed in and around the dendritic field, in a spherical area with a diameter of at least 300 microns. The thin axon collaterals had only occasional 'en passant' swellings. Contacts between the axons of neurogliaform cells and the distal dendrites of Golgi-impregnated pyramidal cells were observed. Electron microscopic immunocytochemistry revealed that GABA immunopositive nerve terminals formed symmetric synaptic contacts with somata, with GABA immunonegative and immunopositive dendritic shafts and with dendritic spines. The results show that GABAergic neurons are heterogeneous with respect to their dendritic and axonal patterns. In addition to the chandelier and basket cells, which have been shown in animal studies to contain GABA, other cell types, most prominently the neurogliaform cells, terminating on the distal parts of neurons, also contain GABA and may have a inhibitory function. Many of the GABAergic terminals make synapses on dendritic spines and shafts in the human cerebral cortex.
TL;DR: The results indicate that PAG may contain a tonically active GABAergic network that operates, at least in part, through GABAA receptors and may modulate activity in descending pain inhibitory pathways emanating from PAG.
Abstract: Injection of GABA into the midbrain periaqueductal gray (PAG) activates medullary neurons that are involved in pain inhibition and potentiates morphine-induced analgesia. These observations suggest that GABAergic mechanisms in the PAG may modulate the descending pain inhibitory system that arises from this structure. In the present study, the effects of GABA and GABA antagonists on membrane properties and baseline activity of PAG neurons were examined using both in vitro and in vivo preparations. Application of bicuculline methiodide (BICM), at a dose that blocked the response to GABA, potently increased the baseline firing rate in 53% of cells recorded in vitro and 74% of cells recorded in the intact preparation. Application of BICM often yielded multiple or burst spiking episodes in both preparations. In 69% of cells the effect of BICM was diminished or totally abolished when the slice was perfused with high-magnesium, calcium-free, physiological saline solution. Intracellular recordings revealed that bicuculline caused depolarization of the membrane (70% of cells), increased the firing frequency (94% of cells) and increased the frequency of excitatory postsynaptic potentials (18% of cells). The effect of bicuculline on membrane resistance was not pronounced and in 64% of neurons it did not cause any measurable change in the resting membrane resistance. PAG neurons responsive to GABA and its antagonists were observed in all regions of the PAG. However, the highest number of neurons that responded to GABA and its antgonists was found in the medial and medioventral parts of the PAG. These results indicate that PAG may contain a tonically active GABAergic network that operates, at least in part, through GABAA receptors. This GABAergic system may modulate activity in descending pain inhibitory pathways emanating from PAG.
TL;DR: A specific change in α1 subunit of the GABAA receptor is demonstrated that is associated with a state of altered GABA sensitivity and provide further support for the regional heterogeneity of chronic diazepam effects.
Abstract: Rats treated chronically with diazepam develop tolerance to diazepam effects and show changes in sensitivity of GABAergic systems. In order to investigate possible molecular mechanisms associated with these changes, we have evaluated the effects of acute and chronic diazepam treatment on levels of mRNA for the α1 and β1 subunits of the GABAA receptor. Northern blots were hybridized with32P-labeled GABA α1 and β1 cDNA probes, and resulting bands were quantified by autoradiography and densitometry. Levels of α1 mRNA were significantly decreased in cerebral cortex but not in cerebellum or hippocampus of chronic diazepam-treated rats. Acute diazepam treatment did not change levels of α1 mRNA in any of the brain regions. Levels of β1 mRNA were examined by Northern blot analysis and also by solution hybridization analysis using a32P-labeled riboprobe. Both methods showed that β1 mRNA was not significantly changed by chronic diazepam treatment. These results demonstrate a specific change in α1 subunit that is associated with a state of altered GABA sensitivity and provide further support for the regional heterogeneity of chronic diazepam effects.
TL;DR: It is indicated that a small decrease in the efficacy of the inhibitory system, whether caused by developmental events or by processes that modulate inhibitory electrogenesis, can lead to NMDA receptor-mediated synchronized afterdischarges, which might play an important role in the functional maturation of the neocortex and in susceptibility to epileptogenesis.
TL;DR: It is established that a GABA-like substance is present in axon terminals presynaptic to Ia afferent boutons in lamina VI of the spinal cord and this evidence provides a morphological basis for Presynaptic inhibition of IA afferent input into laminaVI.
TL;DR: The results demonstrate that the majority of GABAergic synapses exert their action on the membrane of dendrites and spines rather than on the somata and axons of neurons, which is about 48 million/mm3 in the striate cortex.
Abstract: The morphology and postsynaptic targets of GABA-containing boutons were determined in the striate cortex of cat, using a postembedding immunocytochemical technique at the electron microscopic level. Two types of terminals, both making symmetrical synaptic contacts, were GABA-positive. The first type (95% of all GABA-positive boutons) contained small pleomorphic vesicles, the second type (5%) contained larger ovoid vesicles. Furthermore, 99% of all cortical boutons containing pleomorphic vesicles were GABA positive, and all boutons with pleomorphic vesicles made symmetrical synaptic contacts. These results together with previously published stereological data (Beaulieu and Colonnier, 1985, 1987) were used to estimate the density of GABA-containing synapses, which is about 48 million/mm3 in the striate cortex. The postsynaptic targets of GABA positive boutons were also identified and the distribution was calculated to be as follows: 58% dendritic shafts, 26.4% dendritic spines, 13.1% somata and 2.5% axon initial segments. A total of 11% of the postsynaptic targets were GABA immunoreactive and therefore originated from GABAergic neurons. The results demonstrate that the majority of GABAergic synapses exert their action on the membrane of dendrites and spines rather than on the somata and axons of neurons.
TL;DR: The results suggest that GABAergic neurones synthesize GABA during neurite outgrowth and that GABA is present in, and can be released from, the growth cones of these neurones.
Abstract: Growth cone fractions isolated from neonatal [postnatal day 3 (P3)] rat forebrain contain GABAergic growth cones as demonstrated by immunofluorescence staining with monospecific antibodies to γ-aminobutyric acid (GABA). HPLC analysis shows that GABAergic growth cones release this endogenous GABA when stimulated with high K+. Endogenous GABA release is Ca2+-independent and, in this respect, similar to that seen previously with [3H]GABA. Isolated growth cone fractions also exhibit a K+-stimulated, Ca2+-independent release of endogenous taurine. None of the other amino acids shown to be present in isolated growth cone fractions were released, including glutamate, aspartate, and glycine. A population of dissociated cerebral cortical neurones prepared from P1 rat forebrain were GABA-immunoreactive after 1 day in culture. The cell body, neurites, and growth cones of these neurones were all stained with GABA antibodies. At this time in culture, neurones did not stain with either of two antibodies to synaptic vesicle antigens, i.e., p65 and synaptophysin. Growth cones isolated from P3 rat forebrain were also not immunoreactive with these antibodies. After about 8 days in culture, when neurones had established extensive networks of long, varicose axons and elaborately branched dendrites, many neurones and their neurites were immunoreactive for GABA antibodies. At this time in culture, p65 and synaptophysin antibodies did stain neuronal cell bodies and particularly their varicose axons. Dendrites were not stained with synaptic vesicle antibodies. These results suggest that GABAergic neurones synthesize GABA during neurite outgrowth and that GABA is present in, and can be released from, the growth cones of these neurones. The presence of GABA in GABAergic growth cones is not associated with synaptic vesicles, which explains the Ca2+ independency of both endogenous and [3H]GABA release from these growth cones.
TL;DR: In this paper, the effects of haloperidol and clozapine on dopamine and GABA release in a rat dorsolateral striatum, fundus striati (a ventral region of striatum) and globus pallidus were measured by microdialysis in halothane-anesthetized rats.
TL;DR: The ultrastructural organization of the pretecto‐olivary projection neurons within the nucleus of the optic tract and dorsal terminal accessory optic nucleus of rabbits was studied by using anti‐GABA immunolabelling and retrograde transport of WGA‐HRP.
Abstract: The ultrastructural organization of the pretecto-olivary projection neurons within the nucleus of the optic tract and dorsal terminal accessory optic nucleus of rabbits was studied by using anti-GABA immunolabelling and retrograde transport of WGA-HRP. GABA-like immunoreactivity was determined with a postembedding colloidal gold technique. WGA-HRP was injected in the dorsal cap of the inferior olive. The WGA-HRP-labelled neurons were incubated with gold-substituted silver peroxidase. Neurons projecting to the inferior olive had large to medium-sized cell bodies and were GABA negative. In the nucleus of the optic tract, projection neurons are found in the rostral parts, while the majority of the local GABAergic interneurons are mainly found in the caudal parts. In the dorsal terminal nucleus both types of neurons are intermingled. The projection neurons were frequently in synaptic contact by GABAergic terminals. These neurons also receive retinal afferents indicating the existence of a two-step synaptic connection from the retina to the inferior olive. It is suggested that this class of projection neurons forms the "direction-selective" neurons that can be antidromically stimulated from the inferior olive. The GABAergic terminals on the identified projection neurons are of axonal origin (F-terminals), whereas presynaptic dendrites of interneurons (P-terminals) were seldom observed to be in synaptic contact with retrogradely labelled profiles. The strong input of GABA on direction-selective neurons indicates that GABA is directly involved in modulating retinal signals to the inferior olive.