Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although much is known about the induction of synaptic plasticity, the persistence of memories suggests the importance of understanding factors that maintain synaptic strength and prevent unwanted synaptic changes. Here we present evidence that recurrent inhibitory connections in the CA1 region of hippocampus may contribute to this task by modulating the relative ability to induce long-term potentiation and depression (LTP and LTD). Bath application of the gamma-aminobutyric acid (GABA) type A agonist muscimol to hippocampal slices increased the range of frequencies that produce LTD, whereas in the presence of the GABA type A antagonist picrotoxin LTD was induced only at very low stimulation frequencies (0.25-0.5 Hz). Because one source of GABAergic input to CA1 pyramidal cells is via recurrent inhibition, we tested the prediction that elevated postsynaptic spike activity would increase feedback GABA inhibition and favor the induction of LTD. By using an induction stimulation of 8 Hz, which alone produced no net change in synaptic strength, we found that stimulation presented during antidromic activation of pyramidal cell spikes induced LTD. This effect was blocked by picrotoxin. The influence of recurrent inhibition on LTP and LTD displays properties that may decrease the potential for self-reinforcing, runaway changes in synapse strength. A mechanism of this sort may help maintain patterns of synaptic strengths despite the ongoing opportunities for plasticity produced by synapse activation.
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PMID:Inhibitory control of LTP and LTD: stability of synapse strength. 1020 Jan 91

The distribution of the P2X2 receptor subunit of the adenosine 5'-triphosphate (ATP)-gated ion channels was examined in the adult rat central nervous system (CNS) by using P2X2 receptor-specific antisera and riboprobe-based in situ hybridisation. P2X2 receptor mRNA expression matched the P2X2 receptor protein localisation. An extensive expression pattern was observed, including: olfactory bulb, cerebral cortex, hippocampus, habenula, thalamic and subthalamic nuclei, caudate putamen, posteromedial amygdalo-hippocampal and amygdalo-cortical nuclei, substantia nigra pars compacta, ventromedial and arcuate hypothalamic nuclei, supraoptic nucleus, tuberomammillary nucleus, mesencephalic trigeminal nucleus, dorsal raphe, locus coeruleus, medial parabrachial nucleus, tegmental areas, pontine nuclei, red nucleus, lateral superior olive, cochlear nuclei, spinal trigeminal nuclei, cranial motor nuclei, ventrolateral medulla, area postrema, nucleus of solitary tract, and cerebellar cortex. In the spinal cord, P2X2 receptor expression was highest in the dorsal horn, with significant neuronal labeling in the ventral horn and intermediolateral cell column. The identification of extensive P2X2 receptor immunoreactivity and mRNA distribution within the CNS demonstrated here provides a basis for the P2X receptor antagonist pharmacology reported in electrophysiological studies. These data support the role for extracellular ATP acting as a fast neurotransmitter at pre- and postsynaptic sites in processes such as sensory transmission, sensory-motor integration, motor and autonomic control, and in neuronal phenomena such as long-term potentiation (LTP) and depression (LTD). Additionally, labelling of neuroglia and fibre tracts supports a diverse role for extracellular ATP in CNS homeostasis.
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PMID:Distribution of the P2X2 receptor subunit of the ATP-gated ion channels in the rat central nervous system. 1021 85

We examined the effect of stimulus interruption on dual component field EPSPs in the hippocampal CA1 region. Resuming test stimulation at 0.1 Hz after 10-60 min silent periods led to an increase of the response followed by a decline, involving AMPA and NMDA components to a similar extent. Similar changes were seen when stimulation was initially applied to a naive pathway or the stimulus strength was increased during an experiment. The potentiation of the AMPA response was largely blocked by prior application of the NMDA antagonist AP5 while application of this drug immediately after the initial potentiation prevented the following decline. The results demonstrate that NMDA-dependent potentiation and depression, possibly equivalent to LTP and LTD, can both be induced by the same, very low, test stimulus frequency. Furthermore, the depression appeared to have a longer time window for its induction than the potentiation.
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PMID:Potentiation and depression following stimulus interruption in young rat hippocampi. 1032 60

Synaptic plasticity at excitatory glutamatergic synapses is believed to be instrumental in the maturation of neuronal networks. Using whole-cell patch-clamp recordings, we have studied the mechanisms of induction and expression of long-term depression at excitatory GABAergic synapses in the neonatal rat hippocampus (LTD(GABA-A)). We report that the induction of LTD(GABA-A) requires a GABA(A) receptor-mediated membrane depolarization, which is necessary to remove the Mg(2+) block from postsynaptic NMDA receptors. LTD(GABA-A) is associated with an increase in the coefficient of variation of evoked GABA(A) receptor-mediated synaptic currents and a decrease in the frequency, but not amplitude, of Sr(2+)-induced asynchronous GABA(A) quantal events. We conclude that LTD(GABA-A) induction requires the activation of both GABA(A) and NMDA postsynaptic receptors and that its expression is likely presynaptic.
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PMID:Mechanisms of induction and expression of long-term depression at GABAergic synapses in the neonatal rat hippocampus. 1046 Feb 63

Thalamocortical synaptic transmission in the rat's primary somatosensory (S1) cortex is modified by sensory experience during a critical period early in life. Despite the importance of such plasticity for the maturation of thalamocortical circuits, the synaptic basis of this plasticity is unknown. Here, we review evidence suggesting that long-term potentiation and depression (LTP and LTD) of thalamocortical synaptic transmission may be involved in this plasticity. In an in vitro slice preparation, thalamocortical synaptic responses exhibit N-methyl-D-aspartate (NMDA) receptor-dependent LTP and LTD during a developmental period similar to the critical period in vivo. The inability to induce LTP and LTD after the critical period may result in part from a developmental reduction in the duration of NMDA receptor currents. In addition, during the critical period many thalamocortical synapses exhibit NMDA receptor currents but no detectable AMPA receptor currents, and thus may be functionally silent at resting membrane potentials. LTP converts silent synapses to functional ones by causing the rapid appearance of AMPA currents. These observations suggest that thalamocortical synapses may be formed as silent synapses which are subsequently made functional by LTP. LTP and LTD may then regulate the efficacy of these functional synapses and thereby contribute to experience-dependent changes in S1 thalamocortical circuits.
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PMID:Synaptic plasticity at thalamocortical synapses in developing rat somatosensory cortex: LTP, LTD, and silent synapses. 1050 96

1. The authors have recently reported a new protocol for inducing long-term depression through activation of GABAA receptors in the hippocampal slices. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone. It was also shown that glutamate receptor activity is not involved in the induction of this novel type of long-term depression. Brain derived neurotrophic factor is a member of the neurotrophins family widely expressed in the central nervous system. There is increasing evidence that indicate an important role for brain-derived neurotrophic factor in synaptic plasticity. It has been reported that brain-derived neurotrophic factor level is downregulated by GABA system. The present study investigated a possible relation between muscimol-induced long-term depression and brain-derived neurotrophic factor level. 2. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibers in stratum radiatum. 3. It was observed that brain-derived neurotrophic factor at concentration that did not have any effect itself on the population spike, prevents the induction of long-term depression by muscimol. In addition to this, K-252a an inhibitor of Trk type kinase blocked the prevention of muscimol-induced LTD by brain-derived neurotrophic factor. 4. The results suggest that there is an interaction between muscimol-induced long-term depression and brain-derived neurotrophic factor and may explain the post receptor mechanism of muscimol-induced long-term depression through a bilateral relation between GABAA activity and brain-derived neurotrophic factor.
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PMID:Prevention of muscimol-induced long-term depression by brain-derived neurotrophic factor. 1058 43

Depotentiation comprises a reversal of tetanization-induced long-term potentiation (LTP) which occurs following low-frequency stimulation (LFS) in the hippocampus in vivo. Although depotentiation has been consistently demonstrated in the CA1 region, no positive reports of the existence of depotentiation in the dentate gyrus in vivo have occurred. This study therefore investigated whether depotentiation is possible in the dentate gyrus in vivo. We found that depotentiation can be induced, but it is very tightly dependent on the interval between tetanization and LFS. Thus, LFS given 2 or 5 min following tetanization produced significant depotentiation, whereas LFS given 10-30 min following tetanization had no significant effect on the expression of LTP. Depotentiation occurred in two phases: a transient depression of evoked responses to below pre-tetanization values, which occurred in the first 60 min following LFS, and a recovery of this response to a stable level of synaptic transmission which comprised a significant reduction in the magnitude of LTP. Group 2 metabotropic glutamate receptors (mGluRs) play an important role in the expression of long-term depression in vivo. We therefore investigated whether group 2 mGluRs contribute to depotentiation. The group 2 antagonist (2S)-alpha-ethylglutamic acid (EGLU) inhibited the early transient depression at a concentration which inhibits LTD in vivo, but did not block the expression of depotentiation. EGLU also inhibited the transient depression induced by 5 Hz given alone. Increasing the concentration of EGLU prevented depotentiation, however. The group 2 agonist (S)-4-carboxy-3-hydroxyphenyl- glycine (4C3HPG) inhibited LTP and enhanced depotentiation. These data suggest a role for group 2 mGluRs in depotentiation.
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PMID:Time-dependent induction of depotentiation in the dentate gyrus of freely moving rats: involvement of group 2 metabotropic glutamate receptors. 1058 75

Long-term potentiation (LTP) and depression (LTD) were investigated in hippocampus of a genetic model of Down syndrome, the segmental trisomy (Ts65Dn) mouse. Field excitatory postsynaptic potentials were recorded from hippocampal slices and LTP and LTD evoked sequentially. LTP decreased whereas LTD increased significantly in Ts65Dn compared with control hippocampus.
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PMID:Increased synaptic depression in the Ts65Dn mouse, a model for mental retardation in Down syndrome. 1060 87

We have previously shown that the two types of adrenal steroid receptors, mineralocorticoid MR. and glucocorticoid GR. produce opposite effects on long-term potentiation LTP. in the dentate gyrus in vivo. and CA1 hippocampal field in vitro. More specifically, MR activation enhanced and prolonged LTP, whereas GR activation suppressed LTP in these areas and also produced a long-term depression LTD. of the synaptic response. In the present experiment we investigated acute effects of MR and GR activation on LTP induction in the mossy fiber and commissural associational input to the CA3 hippocampal field, since the mechanisms underlying LTP induction in these two pathways differ, the former being N-methyl-D-aspartate receptor NMDAR. independent while the latter being NMDAR-dependent. Rats were either adrenalectomized ADX or adrenally intact. ADX animals were acutely injected with either the specific MR agonist, aldosterone, the specific GR agonist RU 28362 or vehicle. One hour following the injection, the animals were prepared for electrophysiological recording stimulation. Field potential recordings were performed in the radiatum or laconosum moleculare layers of the CA3 field, with stimulation of either the mossy fibers or the commissural associational input from the contralateral hemisphere. We also replicated our previous findings by recording in the dentate gyrus with stimulation of the medial perforant pathway, in the same animals. As observed in our previous study in the dentate gyrus, we found an enhancement and a suppression of LTP with MR and GR activation, respectively. Similarly, for the commissural associational input to CA3, MR activation enhanced LTP, while GR activation reduced it. In contrast, for the mossy fiber input to CA3, neither MR nor GR activation significantly affected LTP induction. These results indicate that adrenal steroids may modulate LTP induction in the hippocampus via an interaction with glutamatergic NMDAR.
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PMID:Effects of mineralocorticoid and glucocorticoid receptors on long-term potentiation in the CA3 hippocampal field. 1064 45

Although synaptic transmission is an important means of communication between neurons, neurons themselves and neurons and glia also communicate by extrasynaptic "volume" transmission, which is mediated by diffusion in the extracellular space (ECS). The ECS of the central nervous system (CNS) is the microenvironment of neurons and glial cells. The composition and size of ECS change dynamically during neuronal activity as well as during pathological states. Following their release, a number of neuroactive substances, including ions, mediators, metabolites and neurotransmitters, diffuse via the ECS to targets distant from their release sites. Glial cells affect the composition and volume of the ECS and therefore also extracellular diffusion, particularly during development, aging and pathological states such as ischemia, injury, X-irradiation, gliosis, demyelination and often in grafted tissue. Recent studies also indicate that diffusion in the ECS is affected by ECS volume inhomogeneities, which are the result of a more compacted space in certain regions, e.g. in the vicinity of oligodendrocytes. Besides glial cells, the extracellular matrix also changes ECS geometry and forms diffusion barriers, which may also result in diffusion anisotropy. Glial cells therefore play an important role in extrasynaptic transmission, for example in functions such as vigilance, sleep, depression, chronic pain, LTP, LTD, memory formation and other plastic changes in the CNS. In turn, ECS diffusion parameters affect neuron-glia communication, ionic homeostasis and movement and/or accumulation of neuroactive substances in the brain.
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PMID:Glial cells and volume transmission in the CNS. 1073 7


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