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

To elucidate a role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in induction of long-term potentiation (LTP), KN-62, a selective inhibitor for CaMKII, was injected into layer 2/3 neurons of sliced visual cortex obtained from young rats. Tetanic stimulation (5 Hz, 1 min) applied to the white matter after the KN-62 injection induced long-term depression (LTD) of excitatory postsynaptic potentials (EPSPs) evoked by test stimulation of the white matter in 9 of the 14 cells tested. However, EPSPs evoked by test stimulation of the non-tetanized site were not changed, indicating that the induction of LTD was input-specific. Simultaneously, recorded field potentials which were derived from neurons with intact CaMKII showed LTP. These results suggest that postsynaptic CaMKII plays a role in the induction of LTP/LTD in visual cortex.
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PMID:Long-term depression is induced in Ca2+/calmodulin kinase-inhibited visual cortex neurons. 132 Apr 22

Long-term potentiation of synaptic efficacy following tetanic synaptic inputs was described originally in the hippocampus, and it has been studied extensively based on the hypothesis that it represents a synaptic model of learning and memory in the brain. In the cerebral neocortex, studies on LTP have burgeoned later, and have progressed less rapidly than those in the hippocampus. Recently, however, experimental data describing the phenomenology and the mechanisms underlying LTP have accumulated in the neocortex, particularly in the visual, somatosensory, and motor cortices. In the developing visual cortex, LTP has been induced by afferent tetanic stimulation at relatively low frequencies, for long duration. Thus, particular attention has been given to parameters of the tetanus optimal for the induction of cortical LTP, and the differences between these and those effective in inducing hippocampal LTP have been reviewed. In the motor cortex, the associative LTP following combined activation of separate sites as well as homosynaptic LTP following activation of single pathways have been reported and these types of synaptic plasticity have been suggested as being a basis for a certain type of motor learning. Long-lasting depression (LTD) of synaptic efficacy also has been reported in the developing visual cortex and suggested as a neural basis for experience-dependent modifications of visual cortical neurons. LTD has been found in other areas of the neocortex as well, although the probability of its induction is relatively low and its functional significance is not yet clear. Among the possible mechanisms for the induction of LTP and LTD, those including the involvement of NMDA receptors, protein kinase C, Ca2+/calmodulin-dependent kinase II, and membrane-associated cytoskeletal proteins have been reviewed, although the results obtained so far are only fragmentary and are premature for definitive conclusions to be drawn.
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PMID:Long-term potentiation and depression in the cerebral neocortex. 196 84

Much has been learned about the activity-dependent synaptic modifications (long-term potentiation and long-term depression) that are thought to underlie memory storage, but the mechanism by which these modifications are stored remains unclear. A good candidate for the storage mechanism is Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) because it is localized at synapses, and its known autophosphorylation properties enable it to undergo long-term modification. In this review, John Lisman describes recent tests of the role of CaM kinase II in long-term potentiation. Experiments show that activity of CaM kinase II is increased for long periods of time after induction of long-term potentiation, that enhanced activity mimics long-term potentiation, and that enzyme activity is necessary for induction of long-term potentiation. The crucial question remaining is whether persistent enzyme activity is necessary to maintain stored information. Related issues concerning the mechanism by which synapses are weakened and the role of gene expression and structural changes are also discussed.
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PMID:The CaM kinase II hypothesis for the storage of synaptic memory. 753 Aug 78

To investigate the function of the autophosphorylated form of CaMKII in synaptic plasticity, we generated transgenic mice that express a kinase that is Ca2+ independent as a result of a point mutation of Thr-286 to aspartate, which mimics autophosphorylation. Mice expressing the mutant form of the kinase show an increased level of Ca(2+)-independent CaMKII activity similar to that seen following LTP. The mice nevertheless exhibit normal LTP in response to stimulation at 100 Hz. However, at lower frequencies, in the range of 1-10 Hz, there is a systematic shift in the size and direction of the resulting synaptic change in the transgenic animals that favors LTD. The regulation of this frequency-response function by Ca(2+)-independent CaMKII activity seems to account for two previously unexplained synaptic phenomena, the relative loss of LTD in adult animals compared with juveniles and the enhanced capability for depression of facilitated synapses.
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PMID:CaMKII regulates the frequency-response function of hippocampal synapses for the production of both LTD and LTP. 778 Oct 66

Both CA1 and dentate gyrus regions of the hippocampal slice exhibit an irreversible loss of synaptic transmission after exposure to in vitro ischemic conditions (buffer without oxygen and glucose). However, after shorter durations of ischemia (8-10 min) the CA1 region shows an irreversible loss of synaptic responses, whereas the dentate gyrus region completely recovers synaptic responses upon reoxygenation. To determine biochemical mechanisms underlying this differential susceptibility, we have examined changes in Ca2+/calmodulin-dependent protein kinase II (CaM-KII) and cyclic AMP-dependent protein kinase activities in homogenates from CA1 and dentate gyrus regions of the hippocampal slice after increasing durations of in vitro ischemia. Time-dependent changes in CaM-KII activities were correlated with changes in electrophysiological responses. CA1 homogenates from slices exposed to 1 min of ischemia showed significant increases in CaM-KII activity, whereas there was no significant change in kinase activity in dentate homogenates after 1 min of ischemia. However, after longer durations of ischemia (5, 10, and 20 min) we found a time-dependent reduction in CaM-KII activity in both CA1 and dentate gyrus regions, whereas no change was detected in cyclic AMP-dependent protein kinase activity. Irreversible depression of CaM-KII activity was seen at shorter durations of ischemia (10 min) in the CA1 region than in dentate region (20 min), which correlated with irreversible effects on synaptic responses. Immunoblot analysis showed that the decrease in CaM-KII activity was not due to degradation of CaM-KII protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activity of Ca2+/calmodulin-dependent protein kinase II following ischemia: a comparison between CA1 and dentate gyrus in a hippocampal slice model. 796 41

Stimulation of synaptoneurosome suspensions by the neurotransmitter glutamate gives rise to rapid loading of ribosomes onto mRNA and increased incorporation of amino acids into trichloroacetic acid-precipitable polypeptides. Metabotropic glutamate receptors (mGluRs) are responsible for this effect. Although simultaneous Ca2+ entry and mGluR stimulation do not change the response, entry of Ca2+ 30 s or 3 min before mGluR stimulation markedly depresses the polyribosomal loading. Either NMDA or ionophore (A23187) produces the depression. A calmodulin antagonist, W7, alleviates the effect, suggesting that inactivation of phospholipase A2 by calcium-calmodulin-dependent kinase II is partially responsible for the phenomenon. Thus, interaction between different classes of glutamate receptors affects the control of protein translation at the synapse. This effect may partially explain recent observations of negative interactions between receptor classes in induction of long-term potentiation.
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PMID:Calcium ion impedes translation initiation at the synapse. 852 53

Phosphorylation of the transcription factor CREB is thought to be important in processes underlying long-term memory. It is unclear whether CREB phosphorylation can carry information about the sign of changes in synaptic strength, whether CREB pathways are equally activated in neurons receiving or providing synaptic input, or how synapse-to-nucleus communication is mediated. We found that Ca(2+)-dependent nuclear CREB phosphorylation was rapidly evoked by synaptic stimuli including, but not limited to, those that induced potentiation and depression of synaptic strength. In striking contrast, high frequency action potential firing alone failed to trigger CREB phosphorylation. Activation of a submembranous Ca2+ sensor, just beneath sites of Ca2+ entry, appears critical for triggering nuclear CREB phosphorylation via calmodulin and a Ca2+/calmodulin-dependent protein kinase.
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PMID:Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity. 856 94

1. Extracellular bath application of the selective Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor KN-62 to hippocampal slices in vitro blocked the induction of long-term depression (LTD) by low-frequency Schaffer collateral stimulation (1 Hz/15 min) of the same concentration as has been shown previously to prevent induction of long-term potentiation (LTP) at these synapses. 2. In contrast, postsynaptic intracellular infusion of KN-62 into single CA1 pyramidal neurons did not prevent induction of LTD, although it was quite effective in blocking LTP. 3. We conclude that there is a presynaptic CaMKII that must be activated to induce LTD, whereas postsynaptic CaMKII stimulation is needed to evoke LTP. 4. Bath application of KN-62 also blocked depotentiation by low-frequency stimuli of previously induced LTP, suggesting that induction of depotentiation and de novo LTD may require the same CaMKII-dependent mechanisms.
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PMID:Distinct synaptic loci of Ca2+/calmodulin-dependent protein kinase II necessary for long-term potentiation and depression. 889 Mar 20

Plasticity was studied in the barrel cortex of rats and mice. Vibrissae deprivation in adult and adolescent animals caused changes in the response properties of cortical neurons to stimulation of spared and deprived vibrissae. Plasticity involved both potentiation of spared vibrissae responses and depression of deprived vibrissae responses in layer II/III of the cortex. Vibrissae response potentiation was found to require alpha CaMKII in adult cortex. Vibrissae response depression was not found to occur in adult cortex but was found in adolescent animals for the principal vibrissa. Preliminary results suggested that vibrissae response depression exhibits both hetero- and homosynaptic components.
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PMID:Mechanisms underlying experience-dependent potentiation and depression of vibrissae responses in barrel cortex. 911 80

Long-term depression (LTD) of synaptic strength is induced by glutamate-triggered increases in postsynaptic [Ca2+], through either influx or release from intracellular stores. Induction of LTD has also been reported to require release of Ca2+ from presynaptic stores and activation of presynaptic Ca2+/calmodulin-dependent protein kinase II. This finding leads to the hypothesis that the intercellular messenger nitric oxide (NO) may be a means by which postsynaptic Ca2+ triggers changes expressing LTD in presynaptic terminals. We report that bath application of the oxadiazoloquinoxalone derivative ODQ (4 microM), a selective inhibitor of NO-sensitive guanylyl cyclase (NOGC), markedly attenuated (90%) the magnitude of LTD induced by low-frequency stimulation (LFS; 1 Hz/15 min) of Schaffer collateral-CA1 synapses in hippocampal slices in vitro. Both the NO donor S-nitroso-N-acetylpenicillamine (100 microM) and the membrane-permeant cyclic guanine 3',5'-monophosphate (cGMP) analogue 8-(-4-chlorophenylthio) guanosine (8-pCPT)-cGMP (50 microM) enhanced the magnitude of LTD, which is consistent with he hypothesis that activation of NOGC plays a role in the induction of LTD. Nicotinamide (20 mM), an inhibitor of NO-activated ADP ribosyltransferase, did not impair the induction of LTD. In contrast to de novo LTD, the reversal of long-term potentiation by LFS (depotentiation) was only partially blocked (55%) by ODQ, and heterosynaptic LTD was not impaired at all, suggesting that there are both NOGC-dependent and -independent forms of LTD. Because postsynaptic intracellular infusion of ODQ (500 microM) failed to block the induction of LTD, we conclude that activation of presynaptic NOGC is a necessary step in the induction of an NOGC-dependent component of LTD.
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PMID:Nitric-oxide-guanylyl-cyclase-dependent and -independent components of multiple forms of long-term synaptic depression. 922 26


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