UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here we summarises the results of experimental investigation of changes in intracellular calcium homeostasis in sensory neurones of rats with streptozotocin-induced diabetes mellitus. Decrease in the calcium-accumulating function of both inositol-trisphosphate- as well as caffeine-sensitive endoplasmic reticulum has been detected both in primary sensory neurones of dorsal root ganglia and in secondary neurones of the spinal cord dorsal horn. Predominant depression in the functioning of metabotropic receptors of ligand-gated channels compared with those of ionotropic ones has been demonstrated. Changes in the pharmacological sensitivity of potential-operated calcium channels (predominantly of L-type), linked, probably, with alterations of functional connections between membrane channels and endoplasmic reticulum, are described. A predominant role of changes in the functioning of intracellular Ca(2+)-accumulating structures, leading to prolongation of depolarisation-induced Ca2+ transients in primary and secondary sensory neurones and corresponding changes in the transmission of nociceptive signals during diabetic neuropathy are discussed.
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PMID:[Changes in intracellular mechanisms in sensory neurons in experimental diabetes mellitus]. 1175 62

A model of plasticity is proposed for the olivocerebellar neural network in which the efficiency of the synaptic inputs to different neurons changes simultaneously and interdependently. This effect is based on the following functional characteristics of the network: simultaneous arrival of an afferent signal via mossy fibers to input granule cells and output neurons in the deep cerebellar nuclei; synchronous arrival of the signal from the inferior olive, via climbing fibers and their collaterals, at cells in the input and output layers, and to Purkinje cells, and the existence of local excitatory, inhibitory, and disinhibitory feedback circuits. Increases (decreases) in post-tetanic Ca2+ concentrations relative to the level evoked by the preceding stimulation in these cells are accompanied by decreases (increases) in the activity of cGMP-dependent protein kinase G, with increases (decreases) in the activity of protein phosphatase I. As a result, dephosphorylation (phosphorylation) of ionotropic receptors is accompanied by simultaneous depression (potentiation) of the excitatory input to a given neuron and potentiation (depression) of the inhibitory input to the same neuron. The depolarizing signal from the inferior olive affects synapse modification in different layers of the network in such a way that its presence (absence) depresses (potentiates) the signal sent from the output cells of the cerebellum to other structures.
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PMID:Interrelated modification of excitatory and inhibitory connections in the olivocerebellar neural network. 1176 93

In order to clarify the functional role of glutamate receptors of the gracile nucleus neurons in rats with nerve injury-induced hyperalgesia, pharmacological, electrophysiological and in situ hybridization techniques were used in rats with chronic constriction nerve injury (CCI) of the sciatic nerve. A total of 54 wide dynamic range neurons were recorded from the gracile nucleus in the rats with CCI. Mechanical evoked responses were significantly depressed following application of AMPA receptor antagonist, CNQX, with noxious and non-noxious responses being similarly affected. AP-5, an NMDA receptor antagonist, induced depression of the pressure-evoked response only after application of the 1-microM concentration of this drug. The size of the receptive fields was significantly decreased after CNQX, but not MK-801 or AP-5, application. Afterdischarge was significantly depressed following the application of CNQX (1000 microM). The expression of ionotropic glutamate receptor subunit mRNAs in the gracile nucleus was studied using the in situ hybridization technique. The signals for NMDA subunits, NR2A, -2B and -2C, in the gracile nucleus neurons were not prominent, suggesting a low level expression of functional NMDA receptor complex. AMPA receptor subunits GluR1, -R2, -R3 and -R4 mRNAs were expressed in a large number of gracile nucleus neurons. These data are consistent with the pharmacological results that AMPA receptor antagonists depressed nociceptive neuronal activity, but NMDA receptor antagonists showed limited effects. These results suggest that the ionotropic glutamate receptors, i.e. the AMPA and NMDA receptors, are differentially involved in modulation of the wide dynamic range neuronal activity in the gracile nucleus following peripheral nerve injury.
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PMID:Involvement of glutamate receptors on hyperexcitability of wide dynamic range neurons in the gracile nucleus of the rats with experimental mononeuropathy. 1179 Apr 78

The whole-cell patch-clamp technique was used to examine the effects of retigabine, a novel anticonvulsant drug, on the electroresponsive properties of individual neurons as well as on neurotransmission between monosynaptically connected pairs of cultured mouse cortical neurons. Consistent with its known action on potassium channels, retigabine significantly hyperpolarized the resting membrane potentials of the neurons, decreased input resistance, and decreased the number of action potentials generated by direct current injection. In addition, retigabine potentiated inhibitory postsynaptic currents (IPSCs) mediated by activation of gamma-aminobutyric acid(A) (GABA(A)) receptors. IPSC peak amplitude, 90-to-10% decay time, weighted decay time constant, slow decay time constant, and, consequently, the total charge transfer were all significantly enhanced by retigabine in a dose-dependent manner. This effect was limited to IPSCs; retigabine had no significant effect on excitatory postsynaptic currents (EPSCs) mediated by activation of non-N-methyl-D-aspartate ionotropic glutamate receptors. A form of short-term presynaptic plasticity, paired-pulse depression, was not altered by retigabine, suggesting that its effect on IPSCs is primarily postsynaptic. Consistent with the hypothesis that retigabine increases inhibitory neurotransmission via a direct action on the GABA(A) receptor, the peak amplitudes, 90-to-10% decay times, and total charge transfer of spontaneous miniature IPSCs were also significantly increased. Therefore, retigabine potently reduces excitability in neural circuits via a synergistic combination of mechanisms.
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PMID:Effects of the anticonvulsant retigabine on cultured cortical neurons: changes in electroresponsive properties and synaptic transmission. 1190 Dec 32

At the cerebellar parallel fiber-Purkinje cell synapse, isolated presynaptic activity induces fast excitatory postsynaptic currents via ionotropic glutamate receptors while repetitive, high-frequency, presynaptic activity can also induce a slow excitatory postsynaptic current that is mediated by metabotropic glutamate receptors (mGluR1-EPSC). Here we investigated the involvement of glutamate uptake in the expression of the mGluR1-EPSC. Inhibitors of glutamate uptake led to a large increase of the mGluR1-EPSC. D-aspartate (0.4 mM) and L(-)-threo-3-hydroxyaspartate (0.4 mM) increased the mGluR1-EPSC approximately 4.5 and approximately 9-fold, respectively, while dihydrokainic acid (1 mM), had no significant effect on the mGluR1-EPSC. D-aspartate (0.4 mM) shifted the concentration-response curve of the depression of the mGluR1-EPSC by the low-affinity mGluR1 antagonist (S)-a-Methyl-4-carboxyphenylglycine [(S)-MCPG] to higher concentrations and decreased the stimulus intensity and the number of necessary stimuli to evoke an mGluR1-EPSC. Depression of the mGluR1-EPSC by rapid pressure application of (S)-MCPG at varying time intervals after tetanic stimulation of the parallel fibers indicated that the glutamate concentration in the peri- and extrasynaptic space decayed with time constants of 36 and 316 ms under control conditions and with inhibition of glutamate uptake, respectively. These results show that expression of the slow mGluR-mediated excitatory postsynaptic current is controlled by glutamate transporter activity. Thus in contrast to fast glutamatergic synaptic transmission, metabotropic glutamate receptor-mediated transmission is critically dependent on the activity and capacity of glutamate uptake.
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PMID:Glutamate uptake controls expression of a slow postsynaptic current mediated by mGluRs in cerebellar Purkinje cells. 1192 16

Anoxia-tolerant neurons from several species of animals may offer unparalleled opportunities to identify strategies that might be employed to enhance the hypoxia or ischemia tolerance of vulnerable neurons. In this review, the authors describe how the response of hypoxia-tolerant neurons to limited oxygen supply involves a suite of mechanisms that reduce energy expenditure in concert with decreased energy availability. This response avoids energy depletion, excitotoxic neuronal death, and apoptosis. Suppression of ion channel functions, particularly those of the ionotropic glutamate receptors, is a response common in hypoxia-tolerant neurons. The depression of excitability thereby achieved is essential given that the fundamental response to oxygen lack in anoxia-tolerant cells is a throttling down of metabolism to "pilot-light" levels. Many different types of processes have been found to down-regulate ion channel function. These include phosphorylation control, interactions with intracellular and extracellular ions, removal of active receptors from the neurolemma, and the direct sensing of oxygen by Na+ and K+ channels. Changes in [Ca2+]i may initiate a protective down-regulation of many different pumps or channels. Transcriptional events leading to differential and/or decreased expression of receptors, proteins, and their subunits are probably very important but little studied.
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PMID:Molecular adaptations for survival during anoxia: lessons from lower vertebrates. 1206 3

Paired-pulse depression was studied at the glutamatergic synapse between retinal afferents and thalamocortical cells in the rat dorsal lateral geniculate nucleus. The main objective of this study was to examine the contributions of the pre- and postsynaptic sites to this depression by comparing AMPA- and NMDA-receptor-mediated responses. Equal depression of the two receptor components would indicate involvement of presynaptic mechanisms, while differences in depression would indicate involvement of postsynaptic mechanisms. Pharmacologically isolated AMPA- and NMDA-receptor-mediated currents were recorded using the whole-cell patch-clamp technique in acute thalamic slices. Both the AMPA and the NMDA components showed pronounced depression when retinal afferents were activated by paired pulses. The depression decayed within 5 s. The AMPA component was more strongly depressed than the NMDA component at paired-pulse intervals ranging from 20 to 200 ms, suggesting the involvement of postsynaptic mechanisms. For intervals of 500 ms and longer, the depression of the two components was identical, suggesting the involvement of purely presynaptic mechanisms. The degree of depression measured without the use of pharmacological tools produced similar results, thus excluding the involvement of presynaptic ionotropic glutamate receptors. Cyclothiazide, a blocker of AMPA-receptor desensitisation, reduced the difference in depression between the two components, suggesting that desensitisation of the AMPA receptors is a postsynaptic mechanism that contributes to the difference in depression between the AMPA and the NMDA components.
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PMID:AMPA and NMDA currents show different short-term depression in the dorsal lateral geniculate nucleus of the rat. 1209 54

We have studied the effects of tetanic stimulation of the corticostriatal pathway on the amplitude of striatal excitatory synaptic potentials. Recordings were obtained from a corticostriatal slice preparation by utilizing both extracellular and intracellular techniques. Under the control condition (1.2 mM external Mg2+), excitatory postsynaptic potentials (EPSPs) evoked by cortical stimulation were reversibly blocked by 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of dl-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) ionotropic glutamate receptors, while they were not affected by 30 - 50 microM 2-amino-5-phosphonovalerate (APV), an antagonist of N-methyl-d-aspartate (NMDA) glutamate receptors. In the presence of 1.2 mM external Mg2+, tetanic activation of cortical inputs produced long-term depression (LTD) of both extracellularly and intracellularly recorded synaptic potentials. When Mg2+ was removed from the external medium, EPSP amplitude and duration increased. In Mg2+-free medium, cortically evoked EPSPs revealed an APV-sensitive component; in this condition tetanic stimulation produced long-term potentiation (LTP) of synaptic transmission. Incubation of the slices in 30 - 50 microM APV blocked striatal LTP, while it did not affect LTD. In Mg2+-free medium, incubation of the slices in 10 microM CNQX did not block the expression of striatal LTP. Intrinsic membrane properties (membrane potential, input resistance and firing pattern) of striatal neurons were altered neither by tetanic stimuli inducing LTD and LTP, nor by removal of Mg2+ from the external medium. These findings show that repetitive activation of cortical inputs can induce long-term changes of synaptic transmission in the striatum. Under control conditions NMDA receptor channels are inactivated by the voltage-dependent Mg2+ block and repetitive cortical stimulation induces LTD which does not require activation of NMDA channels. Removal of external Mg2+ deinactivates these channels and reveals a component of the EPSP which is potentiated by repetitive activation. Since the striatum has been involved in memory and in the storage of motor skills, LTD and LTP of synaptic transmission in this structure may provide the cellular substrate for motor learning and underlie the physiopathology of some movement disorders.
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PMID:Long-term Potentiation in the Striatum is Unmasked by Removing the Voltage-dependent Magnesium Block of NMDA Receptor Channels. 1210 28

Studies of ionotropic receptors indicate that glutamate (Glu) neurotransmission plays a role in sleep. Here, we show for the first time that metabotropic 2/3 Glu (mGlu2/3) receptors play an active or permissive role in the control of REM sleep. The potent, selective, and systemically active mGlu2/3 receptor agonist LY379268 was administered systemically in doses of 1.0 and 0.25 mg/kg sc. The drug produced a dose-dependent suppression of rapid eye movement (REM) sleep and fast (10-50 Hz) EEG in non-rapid eye movement (NREM) sleep. The 1.0-mg/kg effect on REM sleep was remarkably powerful: REM sleep was totally suppressed in the 6-h postinjection and reduced by 80% in the next 6 h. NREM duration was unchanged during the REM suppression in spite of the strong and unusual depression of EEG power in fast NREM frequencies. These sleep and EEG effects were unaccompanied by motor or behavioral abnormalities. We hypothesize that the REM and the fast EEG suppression were both caused by a depression of brain arousal levels by LY379268. If correct, depressing arousal by reducing excitatory neurotransmission with an mGlu2/3 receptor agonist produces electrophysiological effects that differ drastically from those produced by depressing arousal by enhancing neural inhibition with GABAergic drugs. This different approach to modifying the excitation/inhibition balance in the brain might yield novel therapeutic actions.
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PMID:The selective group mGlu2/3 receptor agonist LY379268 suppresses REM sleep and fast EEG in the rat. 1211 2

Many behaviorally relevant sounds, including language, are composed of brief, rapid, repetitive acoustic features. Recent studies suggest that abnormalities in producing and understanding spoken language are correlated with abnormal neural responsiveness to such auditory stimuli at higher auditory levels [Tallal et al., Science 271 (1996) 81-84; Wright et al., Nature 387 (1997) 176-178; Nagarajan et al., Proc. Natl. Acad. Sci. USA 96 (1999) 6483-6488] and with abnormal anatomical features in the auditory thalamus [Galaburda et al., Proc. Natl. Acad. Sci. USA 91 (1994) 8010-8013]. To begin to understand potential mechanisms for normal and abnormal transfer of sensory information to the cortex, we recorded the intracellular responses of medial geniculate body thalamocortical neurons in a rat brain slice preparation. Inferior colliculus or corticothalamic axons were excited by pairs or trains of electrical stimuli. Neurons receiving only excitatory collicular input had tufted dendritic morphology and displayed strong paired-pulse depression of their large, short-latency excitatory postsynaptic potentials. In contrast, geniculate neurons receiving excitatory and inhibitory collicular inputs could have stellate or tufted morphology and displayed much weaker depression or even paired-pulse facilitation of their smaller, longer-latency excitatory postsynaptic potentials. Depression was not blocked by ionotropic glutamate, GABA(A) or GABA(B) receptor antagonists. Facilitation was unaffected by GABA(A) receptor antagonists but was diminished by N-methyl-D-aspartate (NMDA) receptor blockade. Similar stimulation of the corticothalamic input always elicited paired-pulse facilitation. The NMDA-independent facilitation of the second cortical excitatory postsynaptic potential lasted longer and was more pronounced than that seen for the excitatory collicular inputs. Paired-pulse stimulation of isolated collicular inhibitory postsynaptic potentials generated little change in the second GABA(A) potential amplitude measured from the resting potential, but the GABA(B) amplitude was sensitive to the interstimulus interval. Train stimuli applied to collicular or cortical inputs generated intra-train responses that were often predicted by their paired-pulse behavior. Long-lasting responses following train stimulation of the collicular inputs were uncommon. In contrast, corticothalamic inputs often generated long-lasting depolarizing responses that were dependent on activation of a metabotropic glutamate receptor. Our results demonstrate that during repetitive afferent firing there are input-specific mechanisms controlling synaptic strength and membrane potential over short and long time scales. Furthermore, they suggest that there may be two classes of excitatory collicular input to medial geniculate neurons and a single class of small-terminal corticothalamic inputs, each of which has distinct features.
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PMID:Effects of paired-pulse and repetitive stimulation on neurons in the rat medial geniculate body. 1218

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