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

The phenomenon of paired-pulse facilitation (PPF) was exploited to investigate the role of presynaptic mechanisms in the induction and maintenance of long-term synaptic plasticity in the neocortex. Long-term potentiation (LTP) and depression (LTD) were induced without afferent activation by applying tetani of intracellular pulses. Our results show that synaptic modifications closely resembling LTP and LTD can be induced by postsynaptic activation alone. The polarity of these synaptic modifications depends on initial properties of the input, as indicated by a correlation between initial PPF ratio and post-tetanic amplitude changes: inputs exhibiting strong PPF, which might be associated with low release probability tend to be potentiated, while inputs with small PPF are more likely to show depression. Maintenance of both LTP and LTD involve presynaptic mechanisms, as indicated by changes in PPF ratios and in failure rate after LTP or LTD induction. Presynaptic mechanisms could include changes in release probability and/or in the number of active release sites. Because induction was postsynaptic, this supports the notion of a retrograde signal. The relative contribution of pre- and postsynaptic mechanisms in the maintenance of long-term synaptic modifications depends on the initial state of the synaptic input and on LTP magnitude. PPF changes were especially pronounced in inputs which had initially high PPF and underwent strong potentiation. Since LTP and LTD are associated with changes of PPF ratios these synaptic modifications do not only alter the gain but also the temporal properties of synaptic transmission. Because of the LTP associated reduction of PPF, potentiated inputs profit less from temporal summation, favouring transmission of synchronized, low frequency activity.
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PMID:Relations between long-term synaptic modifications and paired-pulse interactions in the rat neocortex. 928 20

In this review, we attempt to cover the descriptive, biochemical and molecular biological work that has contributed to our current knowledge about RC3/neurogranin function and its role in dendritic spine development, long-term potentiation, long-term depression, learning, and memory. Based on the data reviewed here, we propose that RC3, GAP-43, and the small cerebellum-enriched peptide, PEP-19, belong to a protein family that we have named the calpacitins. Membership in this family is based on sequence homology and, we believe, a common biochemical function. We propose a model wherein RC3 and GAP-43 regulate calmodulin availability in dendritic spines and axons, respectively, and calmodulin regulates their ability to amplify the mobilization of Ca2+ in response to metabotropic glutamate receptor stimulation. PEP-19 may serve a similar function in the cerebellum, although biochemical characterization of this molecule has lagged behind that of RC3 and GAP-43. We suggest that these molecules release CaM rapidly in response to large influxes of Ca2+ and slowly in response to small increases. This nonlinear response is analogous to the behavior of a capacitor, hence the name calpacitin. Since CaM regulates the ability of RC3 to amplify the effects of metabotropic glutamate receptor agonists, this activity must, necessarily, exhibit nonlinear kinetics as well. The capacitance of the system is regulated by phosphorylation by protein kinase C, which abrogates interactions between calmodulin and RC3 or GAP-43. We further propose that the ratio of phosphorylated to unphosphorylated RC3 determines the sliding LTP/LTD threshold in concept with Ca2+/ calmodulin-dependent kinase II. Finally, we suggest that the close association between RC3 and a subset of mitochondria serves to couple energy production with the synthetic events that accompany dendritic spine development and remodeling.
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PMID:RC3/neurogranin, a postsynaptic calpacitin for setting the response threshold to calcium influxes. 939 8

Developing sensory systems are sculpted by an activity-dependent strengthening and weakening of connections. Long-term potentiation (LTP) and depression (LTD) in vitro have been proposed to model this experience-dependent circuit refinement. We directly compared LTP and LTD induction in vitro with plasticity in vivo in the developing visual cortex of a mouse mutant of protein kinase A (PKA), a key enzyme implicated in the plasticity of a diverse array of systems. In mice lacking the RIbeta regulatory subunit of PKA, we observed three abnormalities of synaptic plasticity in layer II/III of visual cortex in vitro. These included an absence of (1) extracellularly recorded LTP, (2) depotentiation or LTD, and (3) paired-pulse facilitation. Potentiation was induced, however, by pairing low-frequency stimulation with direct depolarization of individual mutant pyramidal cells. Together these findings suggest that the LTP defect in slices lacking PKA RIbeta lies in the transmission of sufficient net excitation through the cortical circuit. Nonetheless, functional development and plasticity of visual cortical responses in vivo after monocular deprivation did not differ from normal. Moreover, the loss of all responsiveness to stimulation of the originally deprived eye in most cortical cells could be restored by reverse suture of eyelids during the critical period in both wild-type and mutant mice. Such an activity-dependent increase in response would seem to require a mechanism like potentiation in vivo. Thus, the RIbeta isoform of PKA is not essential for ocular dominance plasticity, which can proceed despite defects in several common in vitro models of neural plasticity.
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PMID:Comparison of plasticity in vivo and in vitro in the developing visual cortex of normal and protein kinase A RIbeta-deficient mice. 948 97

1. Long-term potentiation (LTP) and depression (LTD) were investigated at synapses formed by pairs of monosynaptically connected CA3 pyramidal cells in rat hippocampal slice cultures. 2. An N-methyl-D-aspartate (NMDA) receptor-mediated component of the unitary EPSP, elicited at the resting membrane potential in response to single action potentials in an individual CA3 cell, could be isolated pharmacologically. 3. Associative LTP was induced when single presynaptic action potentials were repeatedly paired with 240 ms postsynaptic depolarizing pulses that evoked five to twelve action potentials or with single postsynaptic action potentials evoked near the peak of the unitary EPSP. LTP induction was prevented by an NMDA receptor antagonist. 4. Associative LTD was induced when single presynaptic action potentials were repeatedly elicited with a certain delay after either 240 ms postsynaptic depolarizing pulses or single postsynaptic action potentials. The time window within which presynaptic activity had to occur for LTD induction was dependent on the amount of postsynaptic depolarization. LTD was induced if single pre- and postsynaptic action potentials occurred synchronously. 5. Homosynaptic LTD was induced by 3 Hz tetanization of the presynaptic neuron for 3 min and was blocked by an NMDA receptor antagonist. 6. Depotentiation was produced with stimulation protocols that elicit either homosynaptic or associative LTD. 7. Recurrent excitatory synapses between CA3 cells display associative potentiation and depression. The sign of the change in synaptic strength is a function of the relative timing of pre- and postsynaptic action potentials.
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PMID:Long-term synaptic plasticity between pairs of individual CA3 pyramidal cells in rat hippocampal slice cultures. 949 Aug 45

Information is stored in neural circuits through long-lasting changes in synaptic strengths. Most studies of information storage have focused on mechanisms such as long-term potentiation and depression (LTP and LTD), in which synaptic strengths change in a synapse-specific manner. In contrast, little attention has been paid to mechanisms that regulate the total synaptic strength of a neuron. Here we describe a new form of synaptic plasticity that increases or decreases the strength of all of a neuron's synaptic inputs as a function of activity. Chronic blockade of cortical culture activity increased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) without changing their kinetics. Conversely, blocking GABA (gamma-aminobutyric acid)-mediated inhibition initially raised firing rates, but over a 48-hour period mESPC amplitudes decreased and firing rates returned to close to control values. These changes were at least partly due to postsynaptic alterations in the response to glutamate, and apparently affected each synapse in proportion to its initial strength. Such 'synaptic scaling' may help to ensure that firing rates do not become saturated during developmental changes in the number and strength of synaptic inputs, as well as stabilizing synaptic strengths during Hebbian modification and facilitating competition between synapses.
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PMID:Activity-dependent scaling of quantal amplitude in neocortical neurons. 949 34

Learning and memory are exquisitely sensitive to behavioral stress, but the underlying mechanisms are still poorly understood. Because activity-dependent persistent changes in synaptic strength are believed to mediate memory processes in brain areas such as the hippocampus we have examined the means by which stress affects synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats. Inescapable behavioral stress (placement on an elevated platform for 30 min) switched the direction of plasticity, favoring low frequency stimulation-induced decreases in synaptic transmission (long-term depression, LTD), and opposing the induction of long-term potentiation by high frequency stimulation. We have discovered that glucocorticoid receptor activation mediates these effects of stress on LTD and long-term potentiation in a protein synthesis-dependent manner because they were prevented by the glucocorticoid receptor antagonist RU 38486 and the protein synthesis inhibitor emetine. Consistent with this, the ability of exogenously applied corticosterone in non-stressed rats to mimic the effects of stress on synaptic plasticity was also blocked by these agents. The enablement of low frequency stimulation-induced LTD by both stress and exogenous corticosterone was also blocked by the transcription inhibitor actinomycin D. Thus, naturally occurring synaptic plasticity is liable to be reversed in stressful situations via glucocorticoid receptor activation and mechanisms dependent on the synthesis of new protein and RNA. This indicates that the modulation of hippocampus-mediated learning by acute inescapable stress requires glucocorticoid receptor-dependent initiation of transcription and translation.
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PMID:Glucocorticoid receptor and protein/RNA synthesis-dependent mechanisms underlie the control of synaptic plasticity by stress. 950 Dec 41

1. CB-1 cannabinoid receptors are strongly expressed in the molecular layer of the cerebellar cortex. We have analysed, in patch-clamped Purkinje cells (PCs) in rat cerebellar slices, the effect of the selective CB-1 agonists WIN55,212-2 and CP55,940 and of the selective CB-1 antagonist SR141716-A on excitatory synaptic transmission and synaptic plasticity. 2. Bath application of both agonists markedly depressed parallel fibre (PF) EPSCs. This effect was reversed by SR141716-A. In contrast, responses of PCs to ionophoretic application of glutamate were not affected by WIN55, 212-2. 3. The coefficient of variation and the paired-pulse facilitation of these PF-mediated EPSCs increased in the presence of WIN55,212-2. 4. WIN55,212-2 decreased the frequency of miniature EPSCs and of asynchronous synaptic events evoked in the presence of strontium in the bath, but did not affect their amplitude. 5. WIN55, 212-2 did not change the excitability of PFs. 6. WIN55,212-2 impaired long-term depression induced by pairing protocols in PCs. This effect was antagonized by SR141716-A. The same impairment of LTD was produced by 2-chloroadenosine, a compound that decreases the probability of release of glutamate at PF-PC synapses. 7. The present study demonstrates that cannabinoids inhibit synaptic transmission at PF-PC synapses by decreasing the probability of release of glutamate, and thereby impair LTD. These two effects might represent a plausible cellular mechanism underlying cerebellar dysfunction caused by cannabinoids.
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PMID:Cannabinoids decrease excitatory synaptic transmission and impair long-term depression in rat cerebellar Purkinje cells. 966 Aug 99

1. During block of gamma-aminobutyric acid-A-mediated inhibition, low-frequency stimulation (2 Hz, 900 pulses) to Schaffer collateral-CA1 neuron synapses of adult rat hippocampus induced an N-methyl-D-aspartate receptor-independent, postsynaptic Ca2+-dependent depression of synaptic strength (long-term depression; LTD). 2. Ratio imaging with fura-2 revealed moderate dendritic [Ca2+] increases (approximately 500 nM) during only the initial approximately 30 s of the 7.5 min stimulation period. Conditioning for 30 s was, however, insufficient to induce LTD. 3. The [Ca2+] changes were insensitive to the metabotropic glutamate receptor (mGluR) antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). MCPG, however, completely blocked LTD when present during conditioning. 4. The [Ca2+] changes were abolished by postsynaptic hyperpolarization (-110 mV at the soma). Hyperpolarizing neurons to -110 mV during conditioning significantly attenuated LTD induction. 5. LTD induction was also blocked by the postsynaptic presence of the protein kinase C inhibitor peptide PKC(19-36). 6. These results suggest that LTD induction in adult hippocampus by prolonged low-frequency stimulation depends on both a rapid Ca2+ influx through voltage-sensitive channels and synaptic stimulation of mGluRs which may be coupled to phospholipase C.
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PMID:Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long-term depression in adult rat hippocampus. 971 58

Long-term potentiation and depression (LTP and LTD) in excitatory synapses can coexist, the former being triggered by stimuli that produce strong postsynaptic excitation and the latter by stimuli that produce weaker postsynaptic excitation. It has not been determined whether these properties also apply to LTP and LTD in the inhibitory synapses between Purkinje neurons and the neurons of the deep cerebellar nuclei (DCN), a site that has been implicated in certain types of motor learning. DCN cells exhibit a prominent rebound depolarization (RD) and associated spike burst upon release from hyperpolarization. In these cells, LTP can be elicited by short, high-frequency trains of inhibitory postsynaptic potentials (IPSPs), which reliably evoke an RD. LTD is induced if the same protocol is applied with conditions where the amount of postsynaptic excitation is reduced. The polarity of the change in synaptic strength is correlated with the amount of RD-evoked spike firing during the induction protocol. Thus, some important computational principles that govern the induction of use-dependent change in excitatory synaptic efficacy also apply to inhibitory synapses.
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PMID:Polarity of long-term synaptic gain change is related to postsynaptic spike firing at a cerebellar inhibitory synapse. 980 48

We have used confocal microscopy to monitor synaptically evoked Ca2+ transients in the dendritic spines of hippocampal pyramidal cells. Individual spines respond to single afferent stimuli (<0.1 Hz) with Ca2+ transients or failures, reflecting the probability of transmitter release at the activated synapse. Both AMPA and NMDA glutamate receptor antagonists block the synaptically evoked Ca2+ transients; the block by AMPA antagonists is relieved by low Mg2+. The Ca2+ transients are mainly due to the release of calcium from internal stores, since they are abolished by antagonists of calcium-induced calcium release (CICR); CICR antagonists, however, do not depress spine Ca2+ transients generated by backpropagating action potentials. These results have implications for synaptic plasticity, since they show that synaptic stimulation can activate NMDA receptors, evoking substantial Ca2+ release from the internal stores in spines without inducing long-term potentiation (LTP) or depression (LTD).
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PMID:Single synaptic events evoke NMDA receptor-mediated release of calcium from internal stores in hippocampal dendritic spines. 1002 94


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