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)

S100 beta, a calcium binding astrocytic brain protein, influences hippocampal long-term potentiation (LTP) and depression (LTD), synaptic processes suggested to play role in spatial (contextual) learning and memory. In the present study we trained S100 beta transgenic and wild-type control mice in a nonspatial version of the Morris water maze, the visible platform task, and analyzed retention of memory over periods of 18 h, several days, and weeks. The results show that acquisition and retention were not altered in the S100 beta transgenic mice compared to control. However, a single alteration of an environmental stimulus, water temperature, significantly worsened the performance of transgenic mice. This impairment lasted for two consecutive trials separated by a 2-week intertrial interval, suggesting a temporary disturbance associated with memory processes. We discuss the possibility that these results are compatible with normal cortical but abnormal hippocampal functioning in the S100 beta transgenic mice.
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PMID:Memory and the effect of cold shock in the water maze in S100 beta transgenic mice. 884 Sep 25

Long-term potentiation (LTP) is probably the most widely studied form of synaptic plasticity in the mammalian central nervous system. In the early descriptions, the term referred to a sustained increase in synaptic response following a brief high-frequency electrical tetanus. Apparently unique properties of the phenomenon triggered considerable excitement in the field: for many, LTP offered the promise of a potential substrate for learning and/or memory. In the more than 20 years since LTP was first discovered, investigators motivated by this promise have described a vast array of molecules and processes that may be involved in LTP induction and maintenance. And yet, the mechanisms by which LTP occurs have not been resolved. Instead, the compiled results have uncovered layer upon layer of intricacy, including multiple LTP forms and multiple molecular cascades involved in LTP expression. The generally stated thesis that LTP equates to learning and/or memory at a synaptic level has not faced a serious challenge despite the fact that workers in the field have not provided an unambiguous correlation of LTP with either. A number of investigators have now shifted their attention to a newer form of synaptic modification, long-term depression (LTP). Whatever studies of LTD reveal, it is clear that the fundamental questions about LTP remain unanswered: what is it really and what, if anything, is it used for? In this review, we summarize the data concerning putative LTP mechanisms and the evidence for LTP's role in learning and memory. We show that extant models are not sufficient to account for the various forms of LTP and that the experimental evidence does not justify the view that LTP equates to learning and memory. Instead, we suggest that LTP can be related to other forms of synaptic modification, e.g., LTD and kindling, in a neuroplasticity/pathology continuum of events. In particular, we suggest that neurotransmitter receptor regulation may be a key element leading to synaptic modification: in the adult nervous system, homeostatic receptor regulation normally compensates for alterations in synaptic input, while in the developing nervous system a form of 'homeodynamic' receptor regulation prevails. Our model proposes that homeodynamic receptor regulation leading to an LTP-like effect triggers, or acts in concert with, synaptogenesis to allow young neurons to modify response characteristics in response to altered input. In contrast, some forms of LTP in adult neurons may represent a 'failed' form of receptor regulation whose final outcome is neural death. The model suggests a series of experimentally verifiable hypotheses.
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PMID:An alternative to the LTP orthodoxy: a plasticity-pathology continuum model. 887 85

The neostriatum is the entryway into the basal ganglia and is the site of many of the neurological defects involving basal ganglia function. Thus, it is important to understand the regulation of synaptic transmission at afferent synapses innervating the neostriatum. Cortical glutamatergic and nigral dopaminergic afferent input impinge on neurons in the neostriatum, providing the most significant afferent inputs to this structure. Our understanding of the mechanisms involved in transmission and modulation of transmission at these synapses has greatly increased. It is now apparent that the corticostriatal glutamatergic inputs produce rapid depolarization of striatal neurons via activation of ionotropic AMPA-type glutamate receptors. In addition, transmission is modulated by a number of presynaptic, G-protein-coupled receptors but, surprisingly, relatively little evidence of postsynaptic modulation has been observed. Corticostriatal synapses also express certain forms of plasticity, most notably short- and long- term synaptic depression (STI) and LTD, respectively). It appears that LTD may involve convergent actions of glutamate and dopamine. Striatal LTD may have important roles in information storage and motor set selection in the striatum. However, some aspects of synaptic transmission in the striatum remain unclear. In particular, the exact physiological roles of dopaminergic nigrostriatal input and the role of NMDA-type glutamate receptors are not well understood. In addition, intrastriatal synaptic connections have received relatively little attention as compared with extrinsic input to the neostriatum. Future studies will need to focus on elucidating these aspects of neostriatal function.
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PMID:Synaptic transmission and modulation in the neostriatum. 889 45

1. Activity-dependent plasticity of GABAergic synaptic transmission was investigated in neonatal rat hippocampal slices obtained between postnatal day (P) 2-10 using intracellular recording techniques. In all experiments, AMPA receptors were blocked by continual application of CNQX (10 microM). 2. Between P2 and P4, tetanic stimulation (TS) evoked NMDA receptor-dependent long-term depression of monosynaptic GABAA EPSPS (LTDGABAA). In contrast, when NMDA receptors were blocked by D-AP5 (50 microM), the same TS evoke long-term potentiation of GABAA EPSPS (LTPGABAA). 3. Between P6 and P10, TS failed to produce either LTP or LTD or hyperpolarizing monosynaptic GABAA IPSPS under the same recording conditions. However, when GABAergic potentials were rendered depolarizing (KCl-filled electrode) Ts induced either LTPGABAA or LTDGABAA in the presence or absence of D-AP5, respectively. 4. Both LTPGABAA and LTDGABAA were specific to the conditioned pathway and could be sequentially expressed at the same synapses. Potentiation of GABAergic synaptic efficacy was induced more easily following previous induction of LTDGABAA than in naive slices. 5. In conclusion, early in development, bidirectional synaptic plasticity is expressed by GABAA receptors and the activation (or not) of NMDA receptors determines the induction of either LTPGABAA or LTDGABAA.
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PMID:Bidirectional plasticity expressed by GABAergic synapses in the neonatal rat hippocampus. 891 Feb 30

There are still no clear biophysical models for Associative Long-Term Potentiation (LTP) and Depression (LTD) in the hippocampus, where two populations of synapses targeted to the same receptive field are involved. Here we propose a model that allows an interpretation of the experiments in terms of the molecular processes that may be involved in associative memory. The model suggests that retrograde messengers could have a critical role in the induction and maintenance of associative LTP and LTD, by controlling the coupling between the two populations of synapses.
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PMID:Possible roles of retrograde messengers on LTP, LTD, and associative memory. 897 Dec 4

Individual GABAergic interneurons in hippocampus can powerfully inhibit more than a thousand excitatory pyramidal neurons. Therefore, control of interneuron excitability provides control over hippocampal networks. We have identified a novel mechanism in hippocampus that weakens excitatory synapses onto GABAergic interneurons. Following stimulation that elicits long-term potentiation at neighboring synapses onto excitatory cells, excitatory synapses onto inhibitory interneurons undergo a long-term synaptic depression (interneuron LTD; iLTD). Unlike most other forms of hippocampal synaptic plasticity, iLTD is not synapse specific: stimulation of an afferent pathway triggers depression not only of activated synapses but also of inactive excitatory synapses onto the same interneuron. These results suggest that high frequency afferent activity increases hippocampal excitability through a dual mechanism, simultaneously potentiating synapses onto excitatory neurons and depressing synapses onto inhibitory neurons.
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PMID:Hippocampal interneurons express a novel form of synaptic plasticity. 905 99

Heterosynaptic long-term depression (hetLTD) at one input can be induced by applying a conditioning stimulus to an adjacent set of synapses. In hippocampal CA1 pyramidal cells, our results suggest that hetLTD is triggered by an extracellular diffusible factor that is released following tetanic activation of NMDA receptors. This hetLTD occludes with homosynaptic LTD suggesting common underlying mechanisms.
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PMID:Heterosynaptic long-term depression in the hippocampus. 911 60

Immunocytochemical investigation of metabotrop glutamate receptor la in the cerebellar cortex of rat revealed a presence of this receptor in all cortical inhibitory nerve cells (Purkinje, basket, stellate, Lugaro and Golgi). In addition to the previously described localization of this receptor in Purkinje dendritic spines supplied by parallel and climbing fibres and considered to be responsible for cerebellar long-term depression, we have observed metabotropic glutamate receptor la immunopositivity also in the synapses between parallel fibres and dendrites of basket, stellate and Golgi neurons. The postsynaptic receptor was also present occasionally in inhibitory synapses between stellate cell axons and Purkinje cells as well as between Purkinje axon collaterals and Lugaro cell dendrites. The possibility, that mGluR1a receptors in basket, Golgi and stellate cells might directly or indirectly contribute to cerebellar LTD, is discussed.
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PMID:Immunocytochemical localization of mGluR1a metabotropic glutamate receptor in inhibitory interneurons of the cerebellar cortex. 912 90

The effects of bath application of the metabotropic glutamate receptor (mGluR) agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, 10 microM) were studied at the Schaffer collateral-CA1 synapse in hippocampal slices from rats of 8-33 days postnatal age. In immature animals (8-12 days) ACPD induced a biphasic response characterized by an acute decrease in field EPSP slope (approximately 50-60% of baseline) in the presence of the agonist, followed by long-term depression (LTD, approximately 75-80% of baseline) after washout. In animals older than 20 days, ACPD induced a slow onset potentiation or minimal change. Both the acute depression and LTD were blocked by the mGluR antagonist alpha-methyl-4-carboxyphenyl glycine (MCPG). ACPD-induced LTD was blocked by the N-methyl-D-aspartate receptor (NMDAR) antagonists D(-)-2-amino-5 phosphopentanoic acid (AP5) and dizocilpine maleate (MK-801), and by ethanol. Glutamic pyruvic transaminase, an enzyme that selectively metabolizes endogenous extracellular glutamate, also blocked LTD suggesting that the requisite NMDA currents were tonically activated by extracellular rather than synaptically released glutamate. ACPD-induced LTD was blocked by staurosporine, indicating a requirement for serinethreonine kinase activation, and was unaffected by the L-type voltage sensitive calcium channel blocker nitrendipine and the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT). Because mGluR-mediated LTD was observed only in immature CA1, mGluRs may play a role in hippocampal development, perhaps by contributing to synapse pruning in a temporally restricted fashion.
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PMID:Metabotropic glutamate receptor mediated long-term depression in developing hippocampus. 922 11

Temporary block of glycolysis by 2-deoxy-D-glucose (2-DG) reversibly suppresses synaptic transmission in the CA1 region of hippocampal slices. Recovery of responses is followed by a sustained potentiation of field excitatory postsynaptic potentials (EPSPs) (2-DG-LTP). To investigate the mechanisms involved in this type of LTP, we studied the effects of 2-DG on membrane properties of CA1 neurons (in slices from Sprague-Dawley rats), recorded with sharp intracellular electrodes containing 3 M KCl, as well as patch electrodes, filled mainly with 150 mM KMeSO4 and Hepes. The predominant change produced by 15- to 20-min applications of 2-DG (10 mM, replacing glucose) was hyperpolarization (-5.6 +/- 1.1 mV for 18 intracellular recordings and -7.2 +/- 0.80 mV for 17 whole-cell recordings) accompanied by a fall in resistance (-33 +/- 2.5% for 14 intracellular recordings and -11.6 +/- 7.1% for 15 whole-cell recordings). Virtually identical hyperpolarizations were recorded in the presence of 20 microM glyburide (-5.5 +/- 1.5 mV, n = 6), but they were abolished by adenosine antagonists 8-(p-sulfophenyl)theophylline (8-SPT) and 8-cyclopentyl-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX) (2.8 +/- 1.6 and 4.0 +/- 1.7 mV, respectively; n = 5 for both). It was concluded that the hyperpolarization is most likely caused by an increase in K+ conductance, activated by a 2-DG-induced rise in adenosine release. After such applications of 2-DG, a sustained potentiation of EPSPs (similar to the 2-DG-LTP of field EPSPs) was evident in five neurons recorded with intracellular electrodes but not in any of nine whole-cell recordings, where it was replaced by sustained, LTD-like depression. We conclude that a factor essential for 2-DG-LTP induction is lost during whole-cell recording.
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PMID:2-Deoxy-D-glucose-induced changes in membrane potential, input resistance, and excitatory postsynaptic potentials of CA1 hippocampal neurons. 925 Mar 70


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