Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nucleus rotundus of the turtles Emys orbicularis and Testudo horsfieldi was analysed by axonal tracing methods and post-embedding GABA immunocytochemistry. After injections of horseradish peroxidase or biotinylated dextran amine into the optic tectum, electron microscopic observations showed that the vast majority of ipsilateral tectorotundal axon terminals were small in size, had smooth contours and contained small, round, densely packed synaptic vesicles. These terminals were GABA-immunonegative, often gathered in clusters, and established asymmetrical synaptic contacts with either small- or medium-sized GABA-negative dendritic profiles and with GABA-immunoreactive (GABA-ir) dendrites, which did not contain synaptic vesicles. Occasional GABA-ir-labelled axon terminals were observed; these may arise from the rare GABAergic neurons in the central tectal layer, or from neurons in the ventral pretectal nucleus, which projects both to the optic tectum and nucleus rotundus. In addition to tracer-labelled axon terminals, we observed both GABA-negative and GABA-ir cell bodies and dendrites also labelled by the tracer. No GABA-ir presynaptic dendritic profiles containing synaptic vesicles were observed. The existence in reptiles of reciprocal connections between the nucleus rotundus and the optic tectum as a phylogenetically ancient feedback system is discussed.
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PMID:Tectorotundal connections in turtles: an electron microscopic tracing and GABA-immunocytochemical study. 1799 57

The ultrastructure of the lateroventral subcomponent of the visual dorsolateral anterior thalamic nucleus of the pigeon (DLLv) was analyzed using hodological techniques and GABA-immunocytochemistry. Two types of GABA-immunonegative hyperpalliopetal neurons and a single type of strongly GABA-immunoreactive (-ir) interneuron were identified, the latter displaying long dendrites with some containing synaptic vesicles (DCSV). Ten types of axon terminal were identified and divided into two categories. The first, GABA-immunonegative and making asymmetrical synaptic contact, contain round (RT1, RT2, RT3) or pleiomorphic synaptic and many dense-core vesicles (DCT). RT1 terminals are retinothalamic and RT2 terminals hyperpalliothalamic; both mainly contact dendrites of projection neurons (72% and 78% respectively), less frequently dendrites of interneurons and sometimes DCSV; RT1 terminals are rarely involved in synaptic triads. The second category are consistently GABA-immunopositive. Four types (PT1-4), distinguished by their pleiomorphic synaptic vesicles, make symmetrical synaptic contact essentially with dendrites of projection neurons, more rarely on dendrites of interneurons (PT2). PT1 terminals are very probably those of interneurons, whereas the rare PT4 terminals are of retinal origin. A fifth type (RgT) contains round synaptic vesicles and makes asymmetrical synaptic contact with dendrites of projection neurons and interneurons. PT2 and RgT terminals occasionally contact DCSV of interneurons, which are sometimes involved in synaptic triads. Two final subcategories (DCgT1-2) contain many dense-core vesicles. Our findings are compared with those of previous studies concerning the fine structure and neurochemical properties of the GLd of reptiles and mammals, with special reference to the origin of the extraretinal and extracortical projections to this structure.
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PMID:Fine structure of the visual dorsolateral anterior thalamic nucleus of the pigeon (Columba livia): a hodological and GABA-immunocytochemical study. 1818 7

The ultrastructure of the retinorecipient layers of the lamprey optic tectum was analysed using tract tracing techniques combined with GABA and glutamate immunocytochemistry. Two types of neurons were identified; a population of large GABA-immunonegative cells, and a population of smaller, highly GABA-immunoreactive interneurons, some of whose dendrites contain synaptic vesicles (DCSV). Five types of axon terminals were identified and divided into two major categories. The first of these are GABA-immunonegative, highly glutamate-immunoreactive, contain round synaptic vesicles, make asymmetrical synaptic contacts, and can in turn be divided into AT1 and AT2 terminals. The AT1 terminals are those of the retinotectal projection. The origin of the nonretinal AT2 terminals could not be determined. AT1 and AT2 terminals establish synaptic contacts with DCSV, with dendrites of the retinopetal neurons (DRN), and with conventional dendritic (D) profiles. The terminals of the second category are GABA-immunoreactive and can similarly be divided into AT3 and AT4 terminals. The AT3 terminals contain pleiomorphic synaptic vesicles and make symmetrical synaptic contacts for the most part with glutamate-immunoreactive D profiles. The AT4 terminals contain rounded synaptic vesicles and make asymmetrical synaptic contacts with DRN, with DCSV, and with D profiles. A fifth, rarely observed category of terminals (AT5) contain both clear synaptic vesicles and a large number of dense-core vesicles. Synaptic triads involving AT1, AT2 or AT4 terminals are rare. Our findings are compared to these of previous studies of the fine structure and immunochemical properties of the retinorecipient layers of the optic tectum or superior colliculus of Gnathostomes.
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PMID:Synaptic circuitry in the retinorecipient layers of the optic tectum of the lamprey (Lampetra fluviatilis). A combined hodological, GABA and glutamate immunocytochemical study. 1925 25

Intracellular recording of potentials was used in isolated spinal cord segments from the frog Rana ridibunda to compare the inhibitory effects of GABA and glycine on the motoneuron membrane. At equal concentrations, the response (a change in membrane potential) to application of glycine was 1.5-2 times greater than the response to GABA in terms of amplitude, and EC(50) values were 0.75 and 1.57 mM, respectively. The response to simultaneous application of GABA and glycine averaged 79.1 +/- 2.4% (n = 19) of the sum of the individual responses and 130.1 +/- 1.5% (n = 19) of the glycine response (partial occlusion). Preliminary application of glycine decreased the GABA response by 85.3 +/- 0.2% (n = 10), while preapplication of GABA decreased the glycine response by only 52.9 +/- 0.3% (n = 11). The glycine and GABA responses were specifically suppressed by strychnine and bicuculline. These results provide evidence that as in mammals, amphibian motoneurons have both glycine (predominantly) and GABA(A) receptors; they also show that asymmetrical cross inhibition can occur.
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PMID:Differences in the activation of inhibitory motoneuron receptors in the frog Rana ridibunda by GABA and glycine and their interaction. 1977 30

The structure of neurons changes during development and in response to injury or alteration in sensory experience. Changes occur in the number, shape, and dimensions of dendritic spines together with their synapses. However, precise data on these changes in response to learning are sparse. Here, we show using quantitative transmission electron microscopy that a simple form of learning involving mystacial vibrissae results in approximately 70% increase in the density of inhibitory synapses on spines of neurons located in layer IV barrels that represent the stimulated vibrissae. The spines contain one asymmetrical (excitatory) and one symmetrical (inhibitory) synapse (double-synapse spines), and their density increases threefold as a result of learning with no apparent change in the density of asymmetrical synapses. This effect seems to be specific for learning because pseudoconditioning (in which the conditioned and unconditioned stimuli are delivered at random) does not lead to the enhancement of symmetrical synapses but instead results in an upregulation of asymmetrical synapses on spines. Symmetrical synapses of cells located in barrels receiving the conditioned stimulus also show a greater concentration of GABA in their presynaptic terminals. These results indicate that the immediate effect of classical conditioning in the "conditioned" barrels is rapid, pronounced, and inhibitory.
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PMID:Rapid, learning-induced inhibitory synaptogenesis in murine barrel field. 2008 26

The gamma-aminobutyric acid type B receptor (GABA(B)R), one of the family C G-protein-coupled receptor members, exists as a heterodimer comprised of subunits GB1 and GB2. To clarify the ligand-induced activation mechanism of the GABA(B)R, each subunit was fused with either Cerulean or enhanced yellow fluorescent protein at its intracellular loop, and fluorescence resonance energy transfer (FRET) changes upon agonist application were monitored. As a result, FRET decreases were observed between GB1a loop 2 and GB2 loop 2 and between GB1a loop 2 and GB2 loop 1, suggesting the dissociation of intracellular domains during the receptor activation. Both intersubunit FRET pairs were expected to faithfully capture the activation of the original receptor as their pharmacological properties were highly similar to that of the wild-type receptor. However, the intrasubunit data suggest that the receptor activation does not involve major structural changes within the transmembrane domain of each subunit. By combining the results obtained from two different levels, it was concluded that the GABA(B)R activation by agonist is associated with an asymmetrical intersubunit rearrangement of GB1a and GB2 on the membrane. This type of activation mode, an intersubunit rearrangement without apparent intrahelical structural changes, appears commonly shared by the GABA(B)R and the metabotropic glutamate receptor 1alpha, another family C G-protein-coupled receptor previously studied by our group. Nevertheless, the directions of intracellular domain movements and its asymmetry observed here highlight the qualitative difference between the two receptors.
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PMID:Ligand-induced rearrangements of the GABA(B) receptor revealed by fluorescence resonance energy transfer. 2012 19

Although the major mode of transmission for serotonin in the brain is volume transmission, previous anatomical studies have demonstrated that serotonergic axons do form synaptic contacts. The olfactory glomeruli of the olfactory bulb of mammals receive a strong serotonergic innervation from the dorsal and medial raphe nuclei. In the present report, we investigate the synaptic connectivity of these serotonergic axons in the glomerular neuropil of the rat olfactory bulb. Our study shows that serotonergic axons form asymmetrical synaptic contacts on dendrites within the glomerular neuropil. Analyzing the neurochemical nature of the synaptic targets, we have found that 55% of the synapses were on GABA-immunopositive profiles and 45% on GABA-immunonegative profiles. These data indicate that barely half of the contacts were found in GABA-immunonegative profiles and half of the synapses in GABA-positive dendrites belonging to type 1 periglomerular cells. Synaptic contacts from serotonergic axons on dendrites of principal cells cannot be excluded, since some of the GABA-immunonegative postsynaptic profiles contacted by serotonergic axons had the typical ultrastructural features of bulbar principal cell dendrites. Altogether, our results suggest a complex action of the serotonergic system in the modulation of the bulbar circuitry.
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PMID:Synaptic connectivity of serotonergic axons in the olfactory glomeruli of the rat olfactory bulb. 2049 30

While stressors are known to increase medial prefrontal cortex (PFC) glutamate (GLU) levels, the mechanism(s) subserving this response remain to be elucidated. We used microdialysis and local drug applications to investigate, in male Long-Evans rats, whether the PFC GLU stress response might reflect increased interhemispheric communication by callosal projection neurons. We report here that tail-pinch stress (20 min) elicited comparable increases in GLU in the left and right PFC that were sodium and calcium dependent and insensitive to local glial cystine-GLU exchanger blockade. Unilateral ibotenate-induced PFC lesions abolished the GLU stress response in the opposite hemisphere, as did contralateral mGlu(2/3) receptor activation. Local dopamine (DA) D(1) receptor blockade in the left PFC potently enhanced the right PFC GLU stress response, whereas the same treatment applied to the right PFC had a much weaker effect on the left PFC GLU response. Finally, the PFC GLU stress response was attenuated and potentiated, respectively, following alpha(1)-adrenoreceptor blockade and GABA(B) receptor activation in the opposite hemisphere. These findings indicate that the PFC GLU stress response reflects, at least in part, activation of callosal neurons located in the opposite hemisphere and that stress-induced activation of these neurons is regulated by GLU-, DA-, norepinephrine-, and GABA-sensitive mechanisms. In the case of DA, this control is asymmetrical, with a marked regulatory bias of the left PFC DA input over the right PFC GLU stress response. Together, these findings suggest that callosal neurons and their afferentation play an important role in the hemispheric specialization of PFC-mediated responses to stressors.
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PMID:Interhemispheric regulation of the medial prefrontal cortical glutamate stress response in rats. 2051 37

Spike timing dependent plasticity (STDP) has been demonstrated in various neural systems of many animals. It has been shown that STDP depends on the target and the location of the synapse and is dynamically regulated by the activity of adjacent synapses, the presence of postsynaptic calcium, presynaptic GABA inhibition or the action of neuromodulators. Recent experimental evidence has reported that the profile of STDP in the CA1 pyramidal neuron can be classified into two types depending on its dendritic location: (1) A symmetric STDP profile in the proximal to the soma dendrites, and (2) an asymmetric one in the distal dendrites. Bicuculline application revealed that GABA(A) is responsible for the symmetry of the STDP curve. We investigate via computer simulations how GABA(A) shapes the STDP profile in the CA1 pyramidal neuron dendrites when it is driven by excitatory spike pairs (doublets). The model constructed uses calcium as the postsynaptic signaling agent for STDP and is shown to be consistent with classical long-term potentiation (LTP) and long-term depression (LTD) induced by several doublet stimulation paradigms in the absence of inhibition. Overall, simulation results provide computational evidence for the first time that the switch between the symmetrical and the asymmetrical STDP operational modes is indeed due to GABA inhibition. Furthermore, gamma frequency inhibition and not theta one is responsible for the transition from asymmetry-to-symmetry. The resulted symmetrical STDP profile is centered at +10 ms with two distinct LTD tails at -10 and +40 ms. Finally, the asymmetry-to-symmetry transition is strongly dependent on the strength (conductance) of inhibition and its relative onset with respect to pre- and postsynaptic spike stimulation.
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PMID:GABA inhibition modulates NMDA-R mediated spike timing dependent plasticity (STDP) in a biophysical model. 2083 91

In the vertebrate CNS, fast synaptic inhibition is mediated by GABA and glycine receptors. We recently reported that the time course of these synaptic currents is slower when intracellular chloride is high. Here we extend these findings to measure the effects of both extracellular and intracellular chloride on the deactivation of glycine and GABA currents at both negative and positive holding potentials. Currents were elicited by fast agonist application to outside-out patches from HEK-293 cells expressing rat glycine or GABA receptors. The slowing effect of high extracellular chloride on current decay was detectable only in low intracellular chloride (4 mm). Our main finding is that glycine and GABA receptors "sense" chloride concentrations because of interactions between the M2 pore-lining domain and the permeating ions. This hypothesis is supported by the observation that the sensitivity of channel gating to intracellular chloride is abolished if the channel is engineered to become cation selective or if positive charges in the external pore vestibule are eliminated by mutagenesis. The appropriate interaction between permeating ions and channel pore is also necessary to maintain the channel voltage sensitivity of gating, which prolongs current decay at depolarized potentials. Voltage dependence is abolished by the same mutations that suppress the effect of intracellular chloride and also by replacing chloride with another permeant ion, thiocyanate. These observations suggest that permeant chloride affects gating by a foot-in-the-door effect, binding to a channel site with asymmetrical access from the intracellular and extracellular sides of the membrane.
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PMID:Chloride ions in the pore of glycine and GABA channels shape the time course and voltage dependence of agonist currents. 2197 94


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