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Results for “synaptic plasticity”

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At least 1,081 records · Page 60Linked to original sources
PubMed1990

Synaptic plasticity in rat medial prefrontal cortex under chronic haloperidol treatment produced behavioral sensitization.

Morphometric analysis of the population of synapses in medial prefrontal cortex (layer VI) of rat treated daily with haloperidol in a dose of 1.0 mg/kg during 3 weeks was performed on the electronmicroscopic level. The density of synapses on dendritic shafts increased on 29% and on the head of spine it increased on 20%. Nearly all the parameters measured in axo-spinous synapses were significantly decreased (area of presynaptic terminal, summarized area of mitochondriae per terminal, number of synaptic vesicles near the active zone, area of postsynaptic spine). There were no differences between the parameters of axo-dendritic synapses in control and haloperidol-treated rats. The data suggest that haloperidol might have induced the formation of the new synapses and may have changed the efficacy of the synaptic transmission in axo-spinous synapses on the head of spine.

Animals↗
PubMed1999

Priming stimulation in the basolateral amygdala modulates synaptic plasticity in the rat dentate gyrus.

We investigated the effects of basolateral amygdala (BLA) priming on long-term potentiation (LTP) in the dentate gyrus (DG). In the control animals, the induction of high-frequency stimulation (HFS) to the perforant path (PP) resulted in hippocampal LTP at all the time intervals tested. A priming stimulation to the BLA prior to the application of HFS to the PP resulted in the enhancement of the excitatory post-synaptic potential (EPSP)-LTP and population spike (PS)-LTP in the DG from 90-min post-HFS onwards. These findings suggest that the amygdala has a potential role in the modulation of some aspects of memory that are mediated by the hippocampus.

Action Potentials↗
PubMed2006

MuSK expressed in the brain mediates cholinergic responses, synaptic plasticity, and memory formation.

Muscle-specific tyrosine kinase receptor (MuSK) has been believed to be mainly expressed and functional in muscle, in which it mediates the formation of neuromuscular junctions. Here we show that MuSK is expressed in the brain, particularly in neurons, as well as in non-neuronal tissues. We also provide evidence that MuSK expression in the hippocampus is required for memory consolidation, because temporally restricted knockdown after training impairs memory retention. Hippocampal disruption of MuSK also prevents the learning-dependent induction of both cAMP response element binding protein (CREB) phosphorylation and CCAAT enhancer binding protein beta (C/EBPbeta) expression, suggesting that the role of MuSK during memory consolidation critically involves the CREB-C/EBP pathway. Furthermore, we found that MuSK also plays an important role in mediating hippocampal oscillatory activity in the theta frequency as well as in the induction and maintenance of long-term potentiation, two synaptic responses that correlate with memory formation. We conclude that MuSK plays an important role in brain functions, including memory formation. Therefore, its expression and role are broader than what was believed previously.

Acetylcholine↗
PubMed2002

Calcium dynamics in spines: link to synaptic plasticity.

Dendritic spines are morphologically and functionally heterogeneous. Here, we use two-photon imaging of layer V pyramidal neurons in slices from mouse visual cortex to characterize differences in spine calcium dynamics between individual spines. By measuring action potential-evoked [Cell transients in spines, we find different calcium dynamics in spines from proximal apical and distal apical dendrites. Using a mathematical multi-compartmental model, we demonstrate that these differences are even more pronounced in the absence of exogenous calcium buffers. We also find that these different calcium dynamics cause different susceptibility to synaptic depression in proximal and distal apical synapses, and that modifying calcium decay kinetics in spines changes the expression of long-term depression. We conclude that the location of the spine determines its time window of calcium compartmentalization and degree of calcium-dependent synaptic plasty. Our results highlight the precision of the design of neocortical neurons.

Action Potentials↗
PubMed2004

Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders.

The amygdala is involved in the associative processes for both appetitive and aversive emotions, and its function is modulated by stress hormones. The neuropeptide corticotrophin releasing factor (CRF) is released during stress and has been linked to many stress-related behavioral, autonomic, and endocrine responses. In the present study, nonanxiety-inducing doses of a potent CRF type 1 and 2 receptor agonist, urocortin (Ucn), was infused locally into the basolateral amygdala (BLA) of rats. After 5 daily injections of Ucn, the animals developed anxiety-like responses in behavioral tests. Intravenous administration of the anxiogenic agent sodium lactate elicited robust increases in blood pressure, respiratory rate, and heart rate. Furthermore, in the absence of any additional Ucn treatment, these behavioral and autonomic responses persisted for >30 d. Whole-cell patch-clamp recordings from BLA neurons of these hyper-reactive animals revealed a pronounced reduction in both spontaneous and stimulation-evoked IPSPs, leading to a hyperexcitability of the BLA network. This Ucn-induced plasticity appears to be dependent on NMDA receptor and subsequent calcium-calmodulin-dependent protein kinase II (CaMKII) activation, because it is blocked by pretreatment with NMDA receptor antagonists and by coadministration of CaMKII inhibitors. Our results show for the first time a stress peptide-induced behavioral syndrome that can be correlated with cellular mechanisms of neural plasticity, a novel mechanism that may explain the etiological role of stress in several chronic psychiatric and medical disorders.

Affective Symptoms↗
PubMed2006

MMP-2, VCAM-1 and NCAM-1 expression in the brain of rats with experimental autoimmune encephalomyelitis as a trigger mechanism for synaptic plasticity and pathology.

The neural cell adhesion molecules (NCAMs), and vascular cell adhesion molecules (VCAMs) that regulate cell-to-extracellular matrix adhesion, and matrix metalloproteinases (MMPs), modulating the extracellular matrix (ECM), are considered to play an important role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Clinical signs appearance and significant increases of MMP-2 expression in CA1 and CA3 subdomains of the hippocampus and around the central canal of the cervical spinal cord, with the clusters of VCAM-1(+) immunoreactive cells localized in the choroid plexus epithelium and hypothalamo-hypophyses portal vessel system indicate an inflammation in acute EAE. Decreased NCAM-1 expression in CA1 and CA3 fields of the hippocampus, and in a lesser degree in the basal ganglia, limbic structure and cervical spinal cord, support the concept that the demyelinating neuroinflammatory damage in an autoimmune brain affect synaptic organization of the brain, altering the balance between extracellular proteases and cell adhesion molecules which appears to be critical for both the brain plasticity and autoimmune processes.

Animals↗
PubMed2006

Spinal motoneuron synaptic plasticity during the course of an animal model of multiple sclerosis.

During the course of experimental autoimmune encephalomyelitis, a massive loss of motor and sensitive function occurs, which has been classically attributed to the demyelination process. In rats, the clinical signs disappear within 5 days following complete tetraplegia, indicating that demyelination might not be the only cause for the rapid evolution of the disease. The present work investigated the occurrence of experimental autoimmune encephalomyelitis-induced changes of the synaptic covering of spinal motoneurons during exacerbation and after remission. The terminals were typed with transmission electron microscopy as C-, F- and S-type. Immunohistochemical analysis of synaptophysin, glial fibrillary acidic protein and the microglia/macrophage marker F4/80 were also used in order to draw a correlation between the synaptic changes and the glial reaction. The ultrastructural analysis showed that, during exacerbation, there was a strong retraction of both F- and S-type terminals. In this sense, both the covering as well as the length of the remaining terminals suffered great reductions. However, the retracted terminals rapidly returned to apposition, although the mean length remained shorter. A certain level of sprouting may have occurred as, after remission, the number of F-terminals was greater than in the control group. The immunohistochemical analysis showed that the peak of synaptic loss was coincident with an increased macro- and microglial reaction. Our results suggest that the major changes occurring in the spinal cord network during the time course of the disease may contribute significantly to the origin of the clinical signs as well as help to explain their rapid recovery.

Animals↗
PubMed1995

Subcortical modulation of synaptic plasticity in the hippocampus.

A two-stage model of memory trace formation in the hippocampus considers exploratory behavior associated with theta activity and consumatory behaviors or immobility associated with the occurrence of synchronous pyramidal cell discharges. Threshold, frequency and extent of CA3 bursts differ between differently performing strains of mice and are subject to subcortical modulation. Mechanisms for such actions are described: interference with potassium and other cation channels through second messengers and a direct action of histamine on the NMDA receptor channel. Furthermore long-lasting potentiations of synaptic transmission and excitability following brief exposures of hippocampal slices to histamine, noradrenaline, and serotonin are mediated by cyclic AMP and presumably protein kinase A.

Animals↗
PubMed1999

Facilitated NMDA receptor-mediated synaptic plasticity in the hippocampal CA1 area of dystrophin-deficient mice.

The contribution of the cytoskeletal membrane-associated protein dystrophin in glutamatergic transmission and related plasticity was investigated in the hippocampal CA1 area of wild-type and dystrophin-deficient (mdx) mice, using extracellular recordings in the ex vivo slice preparation. Presynaptic fiber volleys and field excitatory postsynaptic potentials (fEPSPs) mediated through N-methyl-D-Aspartate receptors (NMDAr) or non-NMDAr were compared in both strains. Comparable synaptic responses were observed in wild-type and mdx mice, suggesting that basal glutamatergic transmission is not altered in the mutants. By contrast, the synaptic strengthening induced by a conditioning stimulation of either 10, 30, or 100 Hz was significantly greater in mdx mice during the first minutes posttetanus. Because the posttetanic potentiation induced in the presence of the NMDAr antagonist D-APV was not affected in the mutants, a critical role of NMDAr in this increase was suggested. The magnitude of the potentiation induced by a 30 Hz stimulation in mdx mice was normalized as compared to wild-type mice by increasing the extracellular magnesium concentration from 1.5 to 3 mM. Moreover, the transitory depression of fEPSPs induced by bath-applied NMDA (50 microM for 30s) was more sensitive to an increased extracellular magnesium concentration in wild-type than in mdx mice. Our results suggest that the absence of dystrophin may facilitate NMDAr activation in the CA1 hippocampal subfield of mdx mice, which may be partly due to a reduction of the voltage-dependent block of this receptor by magnesium.

Animals↗
PubMed2006

Two-photon imaging of synaptic plasticity and pathology in the living mouse brain.

Two-photon microscopy (TPM) has become an increasingly important tool for imaging the structure and function of brain cells in living animals. TPM imaging studies of neuronal structures over intervals ranging from seconds to years have begun to provide important insights into the structural plasticity of synapses and the modulating effects of experience in the intact brain. TPM has also started to reveal how neuronal connections are altered in animal models of neurodegeneration, acute brain injury, and cerebrovascular disease. Here, we review some of these studies with special emphasis on the degree of structural dynamism of postsynaptic dendritic spines in the adult mouse brain as well as synaptic pathology in mouse models of Alzheimer's disease and cerebral ischemia. We also discuss technical considerations that are critical for the acquisition and interpretation of data from TPM in vivo.

Absorptiometry, Photon↗
PubMed2004

Hepatocyte growth factor as an enhancer of nmda currents and synaptic plasticity in the hippocampus.

Hepatocyte growth factor (HGF) promotes the survival and migration of immature neurons, but its role in the mature brain has remained elusive. In the hippocampus of juvenile rats, we found that the HGF receptor c-Met was expressed in neurons. Furthermore, it was highly Tyr-phosphorylated, more so than in the liver under normal conditions, suggesting that the receptor is activated and that HGF may act continuously in the intact brain. Exogenously applied HGF enhanced synaptic long-term potentiation (LTP) in the CA1 region of hippocampus, but did not affect long-term depression. We further found that HGF augmented N-methyl-D-aspartate receptor-mediated currents in both slices and dissociated neurons. This augmentation is likely to underlie the enhancement of LTP. Considering that the expression of both HGF and c-Met are known to be induced by ischemic stimuli, this modulation would provide a novel understanding of a neuronal regulatory systems shared with pathogenic ischemic states.

Animals↗
PubMed2002

Distance-dependent Ni(2+)-sensitivity of synaptic plasticity in apical dendrites of hippocampal CA1 pyramidal cells.

Low concentration of Ni(2+), a T- and R-type voltage-dependent calcium channel (VDCC) blocker, is known to inhibit the induction of long-term potentiation (LTP) in the hippocampal CA1 pyramidal cells. These VDCCs are distributed more abundantly at the distal area of the apical dendrite than at the proximal dendritic area or soma. Therefore we investigated the relationship between the Ni(2+)-sensitivity of LTP induction and the synaptic location along the apical dendrite. Field potential recordings revealed that 25 microM Ni(2+) hardly influenced LTP at the proximal dendritic area (50 microM distant from the somata). In contrast, the same concentration of Ni(2+) inhibited the LTP induction mildly at the middle dendritic area (150 microM) and strongly at the distal dendritic area (250 microM). Ni(2+) did not significantly affect either the synaptic transmission at the distal dendrite or the burst-firing ability at the soma. However, synaptically evoked population spikes recorded near the somata were slightly reduced by Ni(2+) application, probably owing to occlusion of dendritic excitatory postsynaptic potential (EPSP) amplification. Even when the stimulating intensity was strengthened sufficiently to overcome such a reduction in spike generation during LTP induction, the magnitude of distal LTP was not significantly recovered from the Ni(2+)-dependent inhibition. These results suggest that Ni(2+) may inhibit the induction of distal LTP directly by blocking calcium influx through T- and/or R-type VDCCs. The differentially distributed calcium channels may play a critical role in the induction of LTP at dendritic synapses of the hippocampal pyramidal cells.

Animals↗
PubMed1999

Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning.

Gene-targeted mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A-/- mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca2+ transients, Ca2+-dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A-/- mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.

Action Potentials↗
PubMed2005

Hippocampal synthesis of estrogens and androgens which are paracrine modulators of synaptic plasticity: synaptocrinology.

Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone and 17beta-estradiol. Both estrogens and androgens are synthesized in male hippocampus. These brain steroids are synthesized by cytochrome P450s (P450scc, P45017alpha and P450arom), hydroxysteroid dehydrogenases and reductases from endogenous cholesterol. The expression levels of enzymes are as low as 1/300-1/1000 of those in endocrine organs. Synthesis is dependent on the acute Ca(2+) influx upon neuron-neuron communication via NMDA receptors. Estradiol is particularly important because estradiol rapidly modulates neuronal synaptic transmission such as long-term potentiation via synaptic estrogen receptors. Xenoestrogens may also act via estrogen-driven signaling pathways.

Androgens↗
PubMed2004

Bidirectional modification of presynaptic neuronal excitability accompanying spike timing-dependent synaptic plasticity.

Correlated pre- and postsynaptic activity that induces long-term potentiation is known to induce a persistent enhancement of the intrinsic excitability of the presynaptic neuron. Here we report that, associated with the induction of long-term depression in hippocampal cultures and in somatosensory cortical slices, there is also a persistent reduction in the excitability of the presynaptic neuron. This reduction requires postsynaptic Ca(2+) elevation and presynaptic PKA- and PKC-dependent modification of slow-inactivating K(+) channels. The bidirectional changes in neuronal excitability and synaptic efficacy exhibit identical requirements for the temporal order of pre- and postsynaptic activation but reflect two distinct aspects of activity-induced modification of neural circuits.

Animals↗
PubMed1996

Diversity of glutamate receptors in neocortical neurons: implications for synaptic plasticity.

The biochemical and functional characteristics of the AMPA subtype of the glutamate receptors expressed by pyramidal and non-pyramidal neurons of the neocortex have been studied in acute slices by means of single-cell RT-PCR and fast applications of glutamate on outside-out patches. Our results suggest that the predominant expression of the flop splice variants of the GluR1-4 AMPA subunits contributes to the faster desensitization of these receptors in non-pyramidal neurons compared to pyramidal cells where flip variants of GluR1-4 are dominant. Alternative splicing of AMPA receptors may therefore play an important role in regulating synaptic function in a cell-type specific manner.

Alternative Splicing↗
PubMed1996

Neuropeptide localization in varicosities of Aplysia sensory neurons is regulated by target and neuromodulators evoking long-term synaptic plasticity.

The synapses between the sensory neuron (SN) and motor neuron of Aplysia undergo long-term functional and structural modulation with appropriate behavioral training or with applications of specific neuromodulators. Expression of molecules within the presynaptic terminals may be regulated in parallel with the changes evoked by the neuromodulators. We examined with immunocytochemical methods whether the level of sensorin, the SN-specific neuropeptide, is modulated in SN varicosities by the location of interaction with the target motor cell L7 and by applications of either 5-HT that evoke long-term facilitation or FMRFamide that evoke long-term depression of Aplysia sensorimotor connections in vitro. A significantly higher proportion of SN varicosities are sensorin positive when they are in contact with the proximal axons of L7 compared to varicosities of the same SNs in contact with distal L7 neurites. Both 5-HT and FMRFamide evoked changes in the efficacy and structure of sensorimotor connections that are accompanied by changes in the frequency of sensorin-positive varicosities contacting the axons of L7. More preexisting SN varicosities are stained after 5-HT, and fewer preexisting SN varicosities are stained after FMRFamide. These results suggest that the postsynaptic target and the neuromodulators not only regulate overall structure but also regulate the level of SN neuropeptide at synaptic sites.

Animals↗