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Results for “synaptic plasticity”

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At least 1,009 records · Page 56Linked to original sources
PubMed1996

The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.

We have produced a mouse strain in which the deletion of the NMDAR1 gene is restricted to the CA1 pyramidal cells of the hippocampus by using a new and general method that allows CA1-restricted gene knockout. The mutant mice grow into adulthood without obvious abnormalities. Adult mice lack NMDA receptor-mediated synaptic currents and long-term potentiation in the CA1 synapses and exhibit impaired spatial memory but unimpaired nonspatial learning. Our results strongly suggest that activity-dependent modifications of CA1 synapses, mediated by NMDA receptors, play an essential role in the acquisition of spatial memories.

Animals↗
PubMed2004

Receptor trafficking and synaptic plasticity.

Long-term potentiation and long-term depression are processes that have been widely studied to understand the molecular basis of information storage in the brain. Glutamate receptors are required for the induction and expression of these forms of plasticity, and GABA (gamma-aminobutyric acid) receptors are involved in their modulation. Recent insights into how these receptors are rapidly moved into and out of synaptic membranes has profound implications for our understanding of the mechanisms of long-term potentiation and long-term depression.

Animals↗
PubMedDate not supplied

Study of synaptic plasticity via random graphs.

The dynamical random graphs associated with a certain class of biological neural networks are introduced and studied. We describe the phase diagram revealing the parameters of a single neuron and of the synaptic strengths which allow formation of the stable strongly connected large groups of neurons. It is shown that the cycles are the most stable structures when the Hebb rule is implemented into the dynamics of the network of excitatory neurons. We discuss the role of cycles for the synchronization of the neuronal activity.

Neural Networks, Computer↗
PubMed2004

Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway.

The requirement for transcription during long-lasting plasticity indicates that signals generated at the synapse must be transported to the nucleus. We have investigated whether the classical active nuclear import pathway mediates intracellular retrograde signal transport in Aplysia sensory neurons and rodent hippocampal neurons. We found that importins localize to distal neuronal processes, including synaptic compartments, where they are well positioned to mediate synapse to nucleus signaling. In Aplysia, stimuli known to produce long-lasting but not short-lasting facilitation triggered importin nuclear translocation. In hippocampal neurons, NMDA receptor activation but not depolarization induced importin nuclear translocation. We further showed that LTP-inducing stimuli recruited active nuclear import in hippocampal slices. Together with our finding that long-term facilitation of Aplysia sensory-motor synapses required active nuclear import, our results indicate that regulation of the active nuclear import pathway plays a critical role in transporting synaptically generated signals into the nucleus during learning-related forms of plasticity.

Active Transport, Cell Nucleus↗
PubMed1996

Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity.

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.

Action Potentials↗
PubMed2003

Integrin requirement for hippocampal synaptic plasticity and spatial memory.

The establishment of memory requires coordinated signaling between presynaptic and postsynaptic terminals in the CNS. The integrins make up a large family of cell adhesion receptors that are known to mediate bidirectional signaling between cells or between cells and their external environment. We show here that many different integrins, including alpha3 and alpha5, are expressed broadly in the adult mouse brain and are associated with synapses. Mice with genetically reduced expression of alpha3 integrin fail to maintain long-term potentiation (LTP) generated in hippocampal CA1 neurons. Mice with reduced expression of the alpha3 and alpha5 integrins exhibit a defect in paired-pulse facilitation. Mice with reduced expression of alpha3, alpha5, and alpha8 are defective in hippocampal LTP and spatial memory in the water maze but have normal fear conditioning. These results demonstrate that several different integrins are involved in physiological plasticity and provide the first evidence of their requirement for behavioral plasticity in vertebrates.

Animals↗
PubMed1992

Calcium-ganglioside interactions and synaptic plasticity: effect of calcium on specific ganglioside/peptide (valinomycin, gramicidin A)-complexes in mixed mono- and bilayers.

A controlled exchange of calcium between the extracellular space (mM Ca2+) and the neuroplasm (microM Ca2+) is considered to be an essential prerequisite for almost every stage of neuronal activity. Our research interest is focused on those compounds, which due to their physico-chemical properties and localization within the synaptic membrane might fulfill the task as neuromodulators for functional synaptic proteins. Because of this specific binding properties towards calcium and their peculiar interactions with calcium in model systems gangliosides (amphiphilic sialic acid containing glycosphingolipids) are favorite candidates for a functional involvement in synaptic transmission of information. In this study we used monolayers to investigate the molecular packing and surface potential at the air/water interface, the interaction of gangliosides with the depsipeptide valinomycin (= monovalent ion carrier), and its influenceability by calcium. Furthermore we looked at calcium effects on the single channel conductance and mean channel life-time of the monovalent ion channel gramicidin A in mixed PC/ganglioside bilayers. In pure ganglioside monolayers the addition of 0.01 mM Ca2+ induces monolayer condensation, a rise in collapse pressure (= higher film stability), a shift of phase transition (= change of conformation), and a more negative head group potential (change of electric properties). In mixed ganglioside-valinomycin monolayers the addition of Ca2+ causes phase separation and/or aggregate formation between the ganglioside and the peptide. Single channel conductance fluctuations as well as mean channel life-time were analyzed for gramicidin A incorporated into binary mixed black lipid membranes of negatively charged gangliosides (GM1, GD1a, GT1b, GMix) and neutral lecithin (DOPC) in different molar ratios. At monovalent electrolyte concentrations up to < 250 mM CsCl the single channel conductance was significantly larger in the negatively charged mixed DOPC/ganglioside membranes than in the neutral DOPC membrane. Additionally, in the presence of gangliosides the mean channel life-time is increased. The addition of calcium (0.05 mM) induced a reduction of single channel conductance of gramicidin A in DOPC- and mixed DOPC/ganglioside membranes. These physico-chemical data in connection with new electromicroscopical evidences for a precise localization of calcium, a calcium pump (Ca(2+)-ATPase), a clustered arrangement of gangliosides in synaptic terminals, and biochemical results with regard to activatory nature of exogenous gangliosides for neuronal protein phosphorylation and ATPases, support the hypothesis of a modulatory function of gangliosides in synaptic transmission.

Animals↗
PubMed2004

The role of actin in the regulation of dendritic spine morphology and bidirectional synaptic plasticity.

Dendritic spines, which are the preferred site of excitatory synapses in the mammalian CNS, are actin-rich structures. We hypothesized that dynamic regulation of actin in spines would differentially affects processes that lead to potentiation vs depression of synaptic efficacy. Here, we report that the expression of long-term depression of excitatory synaptic transmission persists in the presence of actin polymerization in rat hippocampal slices. We observe that the reversal of LTD, de-depression, by high-frequency stimulation was completely blocked. Using electron microscopy, dramatic changes in dendritic spine morphology which accompany the sustained, irreversible depression of excitatory synaptic transmission were observed.

Actins↗
PubMed2006

RGS2 determines short-term synaptic plasticity in hippocampal neurons by regulating Gi/o-mediated inhibition of presynaptic Ca2+ channels.

RGS2, one of the small members of the regulator of G protein signaling (RGS) family, is highly expressed in brain and regulates G(i/o) as well as G(q)-coupled receptor pathways. RGS2 modulates anxiety, aggression, and blood pressure in mice, suggesting that RGS2 regulates synaptic circuits underlying animal physiology and behavior. How RGS2 in brain influences synaptic activity is unknown. We therefore analyzed the synaptic function of RGS2 in hippocampal neurons by comparing electrophysiological recordings from RGS2 knockout and wild-type mice. Our study provides a general mechanism of the action of the RGS family containing RGS2 by demonstrating that RGS2 increases synaptic vesicle release by downregulating the G(i/o)-mediated presynaptic Ca(2+) channel inhibition and therefore provides an explanation of how regulation of RGS2 expression can modulate the function of neuronal circuits underlying behavior.

Animals↗
PubMed2002

IP3-dependent calcium-induced calcium release mediates bidirectional calcium waves in neurones: functional implications for synaptic plasticity.

IP(3)-dependent calcium-induced calcium release (ICICR) is a general mechanism of calcium release that occurs in pyramidal neurones of hippocampus, the neocortex and in Purkinje cells of the cerebellar cortex. When ICICR is initiated synaptically in dendrites of neurones from brain slices, calcium waves can propagate bidirectionally to the soma and distal dendrites. ICICR relies on the coincidence of a calcium influx triggered by the backpropagation of action potentials and the activation of cholinergic, serotoninergic or glutamatergic metabotropic receptors. The involvement of IP(3) receptors (IP(3)R) in ICICR is clearly established. In contrast, ryanodine receptors (RyR) do not seem necessary for the triggering and propagation of calcium waves, but ICICR depends on calcium stores sensitive to ryanodine. Thus, the role of RyR remains to be established. ICICR provides a mechanism for global calcium signalling in neurones that may be involved in the reinforcement of Hebbian plasticity, heterosynaptic plasticity and cell death.

Animals↗
PubMed1980

Mathematical models of synaptic plasticity: I. Posttetanic potentiation.

A mathematical model of post-tetanic potentiation is proposed. The model uses differential equations and is based upon physiological postulates of the electrical, metabolic, and neuroendocrine activities that are related to synaptic connectivity. These activities may modify some important parameters in synaptic function. In the proposed model these parameters are restricted to the presynapse in view of the physiological evidence indicating that posttetanic potentiation is probably due to presynaptic mechanisms. The model takes into consideration the size of the transmitter pool available for release, the mobilization of transmitter from and to this pool, and the fraction of transmitter released. Based upon the above postulates, we have simulated different phases of the phenomenon of posttetanic potentiation, and we have presented the results of several preparations in which this event has been studied. This work represents a successful attempt to reproduce the dynamics of posttetanic potentiation based upon physiological results with a mathematical model.

Calcium↗
PubMed2006

Androgen modulation of hippocampal synaptic plasticity.

This review briefly summarizes recent developments in our understanding of the role of androgens in maintaining normal hippocampal structure. Studies in rats and vervet monkeys have demonstrated that removal of the testes reduces the density of synaptic contacts on dendritic spines of cornu ammonis 1 (CA1) pyramidal neurons. This effect is rapidly reversed by treatment with either testosterone or the non-aromatizable androgen dihydrotestosterone, suggesting that maintenance of normal synaptic density is androgen-dependent, via a mechanism that does not require intermediate estrogen biosynthesis. Similar effects of these androgens are observed in ovariectomized female rats, except that in the female the actions of testosterone include a substantial contribution from estrogen formation. The ability to stimulate hippocampal spine synapse density is not directly related to systemic androgenic potency: thus, weak androgens such as dehydroepiandrosterone exert effects that are comparable to those of dihydrotestosterone; while partial agonist responses are observed after injection of the synthetic antiandrogen, flutamide. These data provide a morphological counterpart to observations that androgens enhance cognitive function and mood state, suggesting that these effects may result at least in part from hippocampal neurotrophic responses. The unusual specificity of these responses raises the possibility that effects of androgens on the brain may be mediated via different mechanisms than the masculinizing actions of these steroids in non-neural androgen target organs.

Androgens↗
PubMed1993

Cytosolic Ca2+ gradients, Ca2+ binding proteins and synaptic plasticity.

Trains of spikes encoded by presynaptic neurons are decoded into rises in cytosolic Ca2+ concentration both in presynaptic terminals and in postsynaptic dendrites. Intracellular [Ca2+] rises trigger neurotransmitter release and also induce short- and long-term modifications of synaptic efficacy. These modifications can be potentiation or depression depending on the intensity of stimuli. A dynamic mechanism, "dynamic decoding", is proposed to understand the multiplicity of the functions of Ca2+, based on recent knowledge of Ca2+ binding proteins and of the dynamics of Ca2+ signaling. The dynamic model is in many ways superior to static models, and may be applied to various neuronal functions including the induction of long-term plasticity in cerebral cortex.

Animals↗
PubMed2000

Decoding temporal information: A model based on short-term synaptic plasticity.

In the current paper it is proposed that short-term plasticity and dynamic changes in the balance of excitatory-inhibitory interactions may underlie the decoding of temporal information, that is, the generation of temporally selective neurons. Our initial approach was to simulate excitatory-inhibitory disynaptic circuits. Such circuits were composed of a single excitatory and inhibitory neuron and incorporated short-term plasticity of EPSPs and IPSPs and slow IPSPs. We first showed that it is possible to tune cells to respond selectively to different intervals by changing the synaptic weights of different synapses in parallel. In other words, temporal tuning can rely on long-term changes in synaptic strength and does not require changes in the time constants of the temporal properties. When the units studied in disynaptic circuits were incorporated into a larger single-layer network, the units exhibited a broad range of temporal selectivity ranging from no interval tuning to interval-selective tuning. The variability in temporal tuning relied on the variability of synaptic strengths. The network as a whole contained a robust population code for a wide range of intervals. Importantly, the same network was able to discriminate simple temporal sequences. These results argue that neural circuits are intrinsically able to process temporal information on the time scale of tens to hundreds of milliseconds and that specialized mechanisms, such as delay lines or oscillators, may not be necessary.

Computer Simulation↗
PubMed2001

Modification of AMPA receptor clustering regulates cerebellar synaptic plasticity.

Cerebellar long-term depression (LTD) induced at parallel fiber-Purkinje neuron synapses is proposed to underlie certain types of motor learning. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors, which mediate chemical transmission in these synapses, are clustered on the postsynaptic membrane. By increasing local density of the receptors, clustering is believed to increase synaptic efficacy. This article focuses on molecular mechanisms regulating the synaptic AMPA receptor clustering in Purkinje cells, which could underlie the expression of cerebellar LTD. Synaptic AMPA receptor clusters in dendritic spines of Purkinje cells are disrupted upon protein kinase C (PKC)-mediated phosphorylation of serine 880 in the C-terminal domain of GluR2. Phosphorylation of this residue causes significant reduction in the affinity of GluR2 C-terminal tail for glutamate receptor interacting protein (GRIP), a molecule known to be crucial for AMPA receptor clustering. Consequently, AMPA receptors on the synaptic membrane are destabilized and internalized by endocytosis. Based on these findings, a model for the expression of cerebellar LTD is proposed, in which a decrease in the number of postsynaptic AMPA receptors, initiated by phosphorylation of GluR2 serine 880, is the major mechanism underlying cerebellar LTD.

Animals↗
PubMed1989

Perforated synapses on double-headed dendritic spines: a possible structural substrate of synaptic plasticity.

Examination of axospinous synapses in serial sections obtained from the middle molecular layer of the rat dentate gyrus has revealed that some of them involve double-headed dendritic spines. Each spine head is apposed by a separate axon terminal with which it always forms a perforated synaptic contact distinguished by a discontinuous postsynaptic density. The number of perforated synapses on double-headed spines was estimated as a synapse-to-neuron ratio with the aid of the disector technique and found to be significantly increased in rats kindled via medial perforant path stimulation. These results support the notion that perforated synapses involving double-headed dendritic spines represent a structural modification related to enhanced synaptic efficacy.

Animals↗