UMLS:C0011570 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

1. We studied the transient suppression of evoked GABAA ergic inhibitory postsynaptic currents (eIPSCs) that follows brief membrane depolarization in rat CA1 hippocampal pyramidal cells, a process called depolarization-induced suppression of inhibition (DSI). We used whole-cell patch electrodes filled with a CsCl-based solution to voltage clamp the currents. All experiments were done in the presence of 50 microM 2-amino-5-phosphonovaleric acid (APV) and 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) to block ionotropic glutamate-induced currents and polysynaptic transmission in the slice preparation. 2. Substituting strontium (Sr2+) for extracellular calcium (Ca2+) led to the appearance of numerous 'asynchronous' small IPSCs following an eIPSC. These asynchronous IPSCs were indistinguishable from TTX-insensitive quantal IPSCs. 3. Although somewhat less effective than Ca2+, Sr2+ was capable of supporting DSI, and both asynchronous and synchronous IPSCs were blocked by the DSI process. 4. During DSI, quantal content of eIPSCs, but not quantal size, was significantly reduced. 5. Sr2+ converted paired-pulse depression (PPD) of eIPSCs to a paired-pulse facilitation (PPF), presumably by altering the probability of release at inhibitory nerve terminals. DSI had no effect on either PPD or PPF. 6. The results show that Sr2+ induces asynchronous release of GABA as it does of other neurotransmitters and changes the probability of release at GABAA ergic terminals as well. Most importantly, the results support the hypothesis that, despite being induced postsynaptically, DSI is expressed presynaptically as a decrease in GABA release, possibly by acting at a site other than the Ca(2+)-dependent release step.
...
PMID:Sr2+ supports depolarization-induced suppression of inhibition and provides new evidence for a presynaptic expression mechanism in rat hippocampal slices. 942 74

gamma-Aminobutyric acid-B(GABAB) receptor-dependent and -independent components of paired-pulse depression (PPD) were investigated in the rat CA3 hippocampal region. Intracellular and whole cell recordings of CA3 pyramidal neurons were performed on hippocampal slices obtained from neonatal (5-7 day old) and adult (27-34 day old) rats. Electrical stimulation in the hilus evoked monosynaptic GABAA postsynaptic currents (eIPSCs) isolated in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and D(-)2-amino-5-phosphovaleric acid (-AP5, 50 microM) with 2(triethylamino)-N-(2,6-dimethylphenyl) acetamine (QX314) filled electrodes. In adult CA3 pyramidal neurons, when a pair of identical stimuli was applied at interstimulus intervals (ISIs) ranging from 50 to 1,500 ms the amplitude of the second eIPSC was depressed when compared with the first eIPSC. This paired-pulse depression (PPD) was partially blocked by P-3-aminoprophyl -P-diethoxymethylphosphoric acid (CGP35348, 0.5 mM), a selective GABAB receptor antagonist. In neonates, PPD was restricted to ISIs shorter than 200 ms and was not affected by CGP35348. The GABAB receptor agonist baclofen reduced the amplitude of eIPSCs in a dose-dependent manner with the same efficiency in both adults and neonates. Increasing the probability of transmitter release with high Ca2+ (4 mM)/low Mg2+ (0.3 mM) external solution revealed PPD in neonatal CA3 pyramidal neurons that was 1) partially prevented by CGP35348, 2) independent of the membrane holding potential of the recorded cell, and 3) not resulting from a change in the reversal potential of GABAA eIPSCs. In adults the GABA uptake blocker tiagabine (20 microM) increased the duration of eIPSCs and the magnitude of GABAB receptor-dependent PPD. In neonates, tiagabine also increased duration of eIPSCs but to a lesser extent than in adult and did not reveal a GABAB receptor-dependent PPD. These results demonstrate that although GABAB receptor-dependent and -independent mechanisms of presynaptic inhibition are present onGABAergic terminals and functional, they do not operate at the level of monosynaptic GABAergic synaptic transmission at early stages of development. Absence of presynaptic autoinhibition of GABA release seems to be due to the small amount of transmitter that can access presynaptic regulatory sites.
...
PMID:Ontogenesis of presynaptic GABAB receptor-mediated inhibition in the CA3 region of the rat hippocampus. 949 15

The functional organization and synaptic physiology of olfactory bulb glomeruli were studied in rat in vitro slice preparations stained with the voltage-sensitive dye RH-155. Optical signals were recorded with a 100-element photodiode array at high temporal resolution. Pharmacological and ionic manipulations were used to investigate synaptic responses to stimulation of the olfactory nerve layer (ONL). ONL stimulation evoked a sodium-mediated compound action potential that propagated across the ONL and invaded individual glomeruli. This presynaptic volley evoked calcium-dependent synaptic responses the amplitudes of which were largest within the glomerular layer (GL); smaller amplitude responses were recorded in deeper layers of the olfactory bulb. Synaptic responses in the GL were attenuated by the non-NMDA ionotropic glutamate receptor antagonist CNQX; the residual component was suppressed by the NMDA glutamate receptor antagonist AP-5. The GABAA receptor antagonist bicuculline methiodide had little effect, whereas the GABAB receptor agonist baclofen dramatically attenuated ONL-evoked synaptic responses. The effects of baclofen were reversed by the GABAB receptor antagonist CGP35348. Paired-pulse depression of ONL-evoked synaptic responses in the GL was partially reversed by CGP35348. These findings suggest that olfactory nerve axons release glutamate to activate both NMDA and non-NMDA receptors on GL neurons, that GABAA receptor-mediated inhibition has little effect on these responses, and that GABAB receptor-mediated inhibition may act presynaptically on olfactory nerve axons to modulate their inputs to olfactory bulb neurons.
...
PMID:Functional organization of rat olfactory bulb glomeruli revealed by optical imaging. 950 19

In the hippocampus there are two distinct forms of long-term depression (LTD) of excitatory synaptic transmission. In the CA1 region, prolonged low-frequency stimulation induces LTD by activating postsynaptic NMDA receptors, which causes a moderate rise in Ca2+ concentrations. In mossy fiber synapses of the CA3 region, similar low-frequency stimulation also gives rise to LTD. However, this form of LTD (mossy fiber LTD) does not require activation of NMDA receptors, but is mediated by activation of presynaptic metabotropic glutamate receptors. Induction of mossy fiber LTD is not dependent on postsynaptic depolarization or activation of postsynaptic ionotropic glutamate receptors, thus it is likely to be mediated by purely presynaptic mechanisms. This conclusion is confirmed by the analysis of mutant mice lacking presynaptic mGluR2, in which mossy fiber LTD is almost absent. Since long-term potentiation at mossy fiber synapses is also induced presynaptically, the synaptic efficacy may be regulated through common mechanisms bidirectionally, which may contribute to neural information processing in the hippocampus.
...
PMID:Two forms of hippocampal long-term depression, the counterpart of long-term potentiation. 954 31

Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)-Purkinje cell (PC) synapses in the cerebellum has been the first established example of enduring decrease of synaptic efficacy in the central nervous system. This review focuses on the underlying cellular and molecular mechanisms. Thus, at the level of the postsynaptic membranes of PCs, induction of LTD requires concommitent activation of voltage-gated calcium channels (VGCCs) and of ionotropic and metabotopic glutamate receptors, of the alpha-amino-3 hydroxy-5-methyl-isoxalone-4-propionate (AMPA) and mGluR1 alpha types respectively. Subsequent intracellular cascades involve production of nitric oxide from arginine and of cGMP, activation of phospholipase A2 and of several protein kinases including protein kinase C and tyrosine kinases. Activation of protein kinase G and of phosphatases are also likely to be involved in LTD induction. In contrast, there are still uncertainties concerning a major role of release of calcium from internal stores in LTD induction. Finally protein synthesis is required for a late phase of LTD to occur. All available experimental evidence points towards a postsynaptic site for LTD expression. In particular, electrophysiological data demonstrate a genuine modification of the functional properties of AMPA receptors of PCs during LTD, and immunocytochemical evidence suggests that this might result from a phosphorylation of these receptors.
...
PMID:Long-term depression of synaptic transmission in the cerebellum: cellular and molecular mechanisms revisited. 960 1

The principal role of ionotropic glutamate receptors in the transmission and processing of information in the auditory pathway has been investigated extensively. In contrast, little is known about the functional contribution of the G-protein-coupled metabotropic glutamate receptors (mGluRs), although their anatomic location suggests that they exercise a significant influence on auditory processing. To investigate this issue, sound-evoked responses were obtained from single auditory neurons in the cochlear nuclear complex of anesthetized cats and gerbils, and metabotropic ligands were administered locally through microionophoretic pipettes. In general, microionophoresis of the mGluR agonists, (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S,1'S, 2'S)-2-(carboxycyclopropyl)glycine, initially produced a gradual increase in spontaneous and sound-evoked discharge rates. However, activation and recovery times were significantly longer than those observed for ionotropic agonists, such as N-methyl--aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, consistent with the recruitment of a second-messenger system. The efficacy of mGluR agonists was diminished after administration of the mGluR antagonist, (+)-alpha-methyl-4-carboxyphenylglycine, consistent with a selective action at metabotropic recognition sites. In contrast, two distinct changes were observed after the mGluR agonist had been discontinued for several minutes. Approximately 50% of neurons exhibited a chronic depression of sound-evoked discharge rate reminiscent of long-term depression, a cellular property observed in other systems. Approximately 30% of neurons exhibited a long-lasting enhancement of the sound-evoked response similar to the cellular phenomenon of long-term potentiation. These findings suggest that mGluR activation has a profound influence on the gain of primary afferent driven activity in the caudal cochlear nucleus.
...
PMID:Metabotropic glutamate receptor activation modulates sound level processing in the cochlear nucleus. 965 42

1. Using an in vitro slice preparation of the rat dorsal lateral geniculate nucleus (dLGN), the properties of retinogeniculate and corticothalamic inputs to thalamocortical (TC) neurones were examined in the absence of GABAergic inhibition. 2. The retinogeniculate EPSP evoked at low frequency (>= 0.1 Hz) consisted of one or two fast-rising (0.8 +/- 0.1 ms), large-amplitude (10.3 +/- 1.6 mV) unitary events, while the corticothalamic EPSP had a graded relationship with stimulus intensity, owing to its slower-rising (2.9 +/- 0.4 ms), smaller-amplitude (1.3 +/- 0.3 mV) estimated unitary components. 3. The retinogeniculate EPSP exhibited a paired-pulse depression of 60.3 +/- 5.6 % at 10 Hz, while the corticothalamic EPSP exhibited a paired-pulse facilitation of > 150 %. This frequency-dependent depression of the retinogeniculate EPSP was maximal after the second stimulus, while the frequency-dependent facilitation of the corticothalamic EPSP was maximal after the fourth or fifth stimulus, at interstimulus frequencies of 1-10 Hz. 4. There was a short-term enhancement of the >= 0.1 Hz corticothalamic EPSP (64.6 +/- 9.2 %), but not the retinogeniculate EPSP, following trains of stimuli at 50 Hz. 5. The >= 0.1 Hz corticothalamic EPSP was markedly depressed by the non-NMDA antagonist 1-(4-amino-phenyl)-4-methyl-7,8-methylene-dioxy-5H-2, 3-benzodiazepine (GYKI 52466), but only modestly by the NMDA antagonist 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ((RS)-CPP), and completely blocked by the co-application of GYKI 52466, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), (RS)-CPP and (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (MK-801). Likewise, the corticothalamic responses to trains of stimuli (1-500 Hz) were greatly reduced by this combination of ionotropic glutamate receptor antagonists. 6. In the presence of GYKI 52466, CNQX, (RS)-CPP and MK-801, residual corticothalamic responses and slow EPSPs, with a time to peak of 2-10 s, could be generated following trains of five to fifty stimuli. Neither of these responses were occluded by 1S,3R-1-aminocyclopentane-1, 3-dicarboxylic acid (1S,3R-ACPD), suggesting they are not mediated via group I and II metabotropic glutamate receptors.
...
PMID:Characterization of sensory and corticothalamic excitatory inputs to rat thalamocortical neurones in vitro. 966 Aug 97

In the past decade there have been advances in understanding the cellular mechanisms of the long-term depression (LTD) of synaptic transmission at parallel fiber-Purkinje cell synapses in the cerebellum. This review first summarizes current views on mechanisms involved in LTD induction, from activation of voltage-gated Ca2+ channels, of ionotropic (AMPA) and metabotropic (mGluRI) glutamate receptors, to stimulation of protein kinase C and nitric oxide formation. Second, we will focus on recent findings that point towards the involvement of Ca2+ release from internal stores in LTD induction, localize the sources and targets of nitric oxide and indicate a postsynaptic site for LTD expression. Finally, a role for LTD in motor learning is now well supported by recent experiments on transgenic mice.
...
PMID:Cellular mechanisms of cerebellar LTD. 973 48

In young rats, low frequency (1-2 Hz) stimulation of the Schaffer collaterals for 15 min induces in the CA1 area of the hippocampus a homosynaptic and N-methyl-D-aspartate receptor-dependent form of long-term depression (LTD) of synaptic efficacy. In the adults, while a similar stimulation paradigm is able to depress previously potentiated synapses, it leads to conflicting results when applied to naive synapses. In the present experiments, different stimulation paradigms have been used to induce LTD in the CA1 area of the adult rat hippocampus in vitro. Thus, stimulation of the afferent pathway at frequencies higher than those used to produce LTD in young animals (5-10 Hz, for 15 min) reliably induced a homosynaptic form of LTD. This form of LTD was associated with a significant increase in paired-pulse facilitation ratio and was insensitive to ionotropic (CNQX, 10 microM and CPP, 20 microM) and metabotropic (S-MCPG, 1 mM) glutamate receptors antagonists, suggesting a presynaptic mechanism for both LTD induction and expression. In conclusion, our experiments clearly show that LTD is not a purely developmental phenomenon but is present also in mature rats, which possess the whole machinery for LTD induction and this will greatly enhance the flexibility and the storing capacity of neuronal circuits.
...
PMID:A novel form of long-term depression in the CA1 area of the adult rat hippocampus independent of glutamate receptors activation. 975 65

Functional interaction between ionotropic and metabotropic glutamate receptors (iGluR and mGluR respectively) was studied in cerebellar granule cell cultures using quisqualate (QA), the most potent agonist of phosphoinositide hydrolysis coupled mGluR, and N-methyl-D-aspartate (NMDA) or kainate (KA) that activate different classes of iGluR. Two h exposure to NMDA or KA resulted in a marked reduction (about 75%) of QA-evoked PI hydrolysis. The efficacy of the two agonists was about the same, but the potencies were different (IC50 for NMDA about 35 microM and for KA about 70 microM). NMDA-induced depression of QA-stimulated PI hydrolysis was relatively long lasting but reversible. Recovery required protein synthesis. In nominally Ca2+-free medium both NMDA and KA failed to attenuate QA-stimulated PI hydrolysis. The effect of NMDA was prevented by the NMDA receptor antagonist MK801, but not by the wide spectrum protein kinase inhibitor staurosporin nor by the nitric oxide synthase inhibitor N omega-nitro-L-arginine. Cycloheximide and concanavalin A were also ineffective. The effect of KA was prevented by the selective non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX). Voltage sensitive Ca2+ channel antagonists together with MK801 did not counteract the inhibition by KA of the QA response. Both NMDA and KA attenuated PI hydrolysis evoked by the muscarinic receptor agonist carbachol (about 30%), indicating that the activation of iGluRs exerts a relatively general inhibitory effect on the function of different PLC-coupled metabotropic receptors. Consistent with this observation is that treatments either with KA and NMDA induced an inhibition (about 30%) of NaF-stimulated PI hydrolysis which occurs through the direct activation of G proteins. Our observations show that ionotropic glutamate receptor stimulation induces a long lasting suppression of QA-evoked PI breakdown through a Ca2+ dependent mechanism which seems to involve receptor coupled transduction systems downstream from mGluR. Such a Ca2+-dependent cross-talk involving ionotropic and metabotropic receptors may play a role in certain events of synaptic plasticity.
...
PMID:Calcium influx via ionotropic glutamate receptors causes long lasting inhibition of metabotropic glutamate receptor-coupled phosphoinositide hydrolysis. 975 22

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>