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At least 1,729 records · Page 96Linked to original sources
PubMed2005

Enriched environment induces cellular plasticity in the adult substantia nigra and improves motor behavior function in the 6-OHDA rat model of Parkinson's disease.

The adult substantia nigra bears the capacity to generate new neural cells throughout adulthood. The mechanisms of cellular plasticity in this brain region remain unknown. In the adult dentate gyrus, dopamine was suggested to be one of the key players in neurogenesis. We therefore investigated nigral cellular plasticity in the 6-OHDA rat model of Parkinson's disease. The absolute numbers of newborn cells in the SN were not affected by dopamine depletion. Interestingly, we found a specific downregulation of generation of newborn nigral astrocytic cells. As enriched environment with physical activity are robust inducers of neuro- and gliogenesis in the adult DG, we investigated the role of these physiological stimuli in nigral cellular plasticity and in motor behavior of 6-OHDA lesioned rats. We describe a significant increase in numbers of newborn NG2-positive and GFAP-positive cells in the SN. Moreover, 6-OHDA lesioned animals living in enriched environment with physical activity for 7 weeks showed improved motor behavior compared to controls under standard conditions. Thus, physiological neurogenic and gliogenic stimuli induce significant microenvironmental changes in the adult SN and improve motor behavior in the 6-OHDA lesion model of PD.

Adrenergic Agents↗
PubMed2004

The role of protein phosphatase-1 in the modulation of synaptic and structural plasticity.

Synaptic plasticity is a phenomenon contributing to changes in the efficacy of neuronal transmission. These changes are widely believed to be a major cellular basis for learning and memory. Protein phosphorylation is a key biochemical process involved in synaptic plasticity that operates through a tight balance between the action of protein kinases and protein phosphatases (PPs). Although the majority of research in this field has concentrated primarily on protein kinases, the significant role of PPs is becoming increasingly apparent. This review examines one such phosphatase, PP1, and highlights recent advances in the understanding of its intervention in synaptic and structural plasticity and the mechanisms of learning and memory.

Animals↗
PubMed2006

Rehabilitation plasticity: influence of hearing aid fitting on frequency discrimination performance near the hearing-loss cut-off.

Several studies have already demonstrated that patients with steeply sloping hearing loss of cochlear origin exhibit an improvement in frequency discrimination performance at or around the cut-off frequency. This enhancement cannot be explained in terms of peripheral mechanisms and should rather be interpreted in terms of central reorganization: i.e., injury-induced cortical plasticity. However, the reversibility and time course of such reorganization has not yet been described. The main goal of the present study was therefore to investigate the occurrence of rehabilitation plasticity associated with hearing-aid fitting in human subjects. Nine subjects with steeply sloping hearing loss and who were candidates for auditory rehabilitation were tested. Discrimination-limen-for-frequency (DLF) enhancement was investigated at the frequency with the best DLF (bDLF) for each individual subject before and during auditory rehabilitation (at 1 month, 3 months and 6 months). From 1 month on, frequency discrimination performance decreased significantly at the bDLF frequency, while remaining stable at other frequencies. This normalization may reflect a new central reorganization reversing the initial injury-induced changes in the cortical map. A correlation between subject's age and alteration in DLF at 1 month was also found, suggesting that plasticity operates faster in younger patients.

Adult↗
PubMed2004

Characterization and drug-permeation profiles of microporous and dense cellulose acetate membranes: influence of plasticizer and pore forming agent.

The use of pore forming agents and plasticizers are efficient ways to obtain membranes for controlled drug permeation through polymeric membranes. The challenge of the present study was to combine these two strategies to obtain cellulose acetate (CA) membranes, where poly(caprolactone triol) (PCL-T) was used as a plasticizer and water, dissolved in a casting solution, was used as a pore forming agent. First, the influence of water on membrane morphology, porosity and the permeation coefficient of a model drug (paracetamol) was analyzed. The influence of different amounts of PCL-T on the permeation coefficient of the CA membranes was then evaluated. Finally, both strategies were combined to obtain porous CA/PCL-T membranes. The membrane microstructure was analyzed using scanning electron microscopy (SEM), the CA crystallinity was determined via differential scanning calorimetry (DSC), and membrane permeability was investigated using paracetamol. The addition of water, a non-solvent, during the membrane casting process was found to be a simple and effective way to change membrane porosity and consequently the drug-permeation profile. When small quantities of non-solvent were used to obtain low porosity membranes, the presence of a plasticizer agent could be used to better modulate drug permeation. Combining the addition of PCL-T with the use of a non-solvent resulted in a series of CA membranes with paracetamol-permeation coefficient values in the range of ca. 10(-7) to 10(-5) cm s(-1).

Cellulose↗
PubMed2006

Quantitative estimation of film forming polymer-plasticizer interactions by the Lorentz-Lorenz Law.

Molar refraction as well as refractive index has many uses. Beyond confirming the identity and purity of a compound, determination of molecular structure and molecular weight, molar refraction is also used in other estimation schemes, such as in critical properties, surface tension, solubility parameter, molecular polarizability, dipole moment, etc. In the present study molar refraction values of polymer dispersions were determined for the quantitative estimation of film forming polymer-plasticizer interactions. Information can be obtained concerning the extent of interaction between the polymer and the plasticizer from the calculation of molar refraction values of film forming polymer dispersions containing plasticizer.

Chemistry, Pharmaceutical↗
PubMed2006

Extractables/leachables from plastic tubing used in product manufacturing.

While the ability of packaging systems to contribute leached substances to finished drug products is well established, increasing interest is being focused on the potential contamination of drug substances by plastic materials encountered during their production. The direct contact of such plastic parts (such as tubing, gaskets, filters and temporary storage containers) with the drug substance at some point in its production raises the possibility that plastic-related contaminants (leachables) may be present in the finished drug product. In this study, eight tubing materials potentially encountered in pharmaceutical production facilities, including six silicone materials and two Santoprene materials, were characterized for their extractable substances by static extraction coupled with comprehensive chemical characterization of the resulting extracts. Based on the extractables profiles thus generated, target leachables were identified for each tubing material. The accumulation of these target leachables was studied by subjecting the tubing to dynamic flow, simulated use extractions. The primary organic extractables from the silicone tubing were a homologous series of silicone oligomers, with most of the tubings demonstrating a unique distribution of oligomers. Several of the silicone tubings also possessed extractable dioctyl phthalate and dioctyl adipate. The primary organic extractables from the Santoprene-type tubing included a number of phthalates, a series of alkyl phenols and decomposition products of Irganox-type antioxidants. Inorganic extractables associated with many of the tubings included Ca, Mg, Zn and B. In general, the levels of targeted leachables extracted from the tubing materials under simulated use (flow) conditions was much smaller than the total amount of these leachables in the tubing.

Drug Contamination↗
PubMed2004

Plastic substrates based separation channels in electromigration techniques.

Three types of plastic materials (polyester, polyurethane and polymethylmethacrylate) were tested as materials for manufacturing separation columns (polyester and polyurethane capillaries were used) or separation channels (polymethylmethacrylate) in the chip format. A set of 11 fluorescein isothiocyanate amino acid derivatives was used as the test mixture. Using alpha-cyclodextrin additive to the background electrolyte in the case of the chip separation was also tested. The main problem with all plastic separation media was the selectivity of the separation. The best results, practically identical with bare fused silica capillary, were obtained with the polymethylmethacrylate chip, provided that alpha-cyclodextrin in a concentration 40 mmol/l was added to the background electrolyte. An important observation was that in SDS containing background electrolyte all the plastic materials used exhibited a distinct electroosmotic flow, which was ascribe to the sorption of the negatively charged constituents of the background electrolyte to the capillary wall. Regarding the order in which the individual components of the test mixture were brought to the detector only a single change was observed. Histidine migrated in the polystyrene and polymethylmethacrylate separation channels more slowly than in the bare silica or polyurethane based capillaries.

Electrophoresis, Capillary↗
PubMed2004

A computer model of field potential responses for the study of short-term plasticity in hippocampus.

Activity-dependent synaptic plasticity has important implications for network function. The previously developed model of the hippocampal CA1 area, which contained pyramidal cells (PC) and two types of interneurons involved in feed-forward and recurrent inhibition, respectively, and received synaptic inputs from CA3 neurons via the Schaffer collaterals, was enhanced by incorporating dynamic synaptic connections capable of changing their weights depending on presynaptic activation history. The model output was presented as field potentials, which were compared with those derived experimentally. The parameters of Schaffer collateral-PC excitatory model synapse were determined, with which the model successfully reproduced the complicated dynamics of train-stimulation sequential potentiation/depression observed in experimentally recorded field responses. It was found that the model better reproduces the time course of experimental field potentials if the inhibitory synapses on PC are also made dynamic, with expressed properties of frequency-dependent depression. This finding supports experimental evidence that these synapses are subject to activity-dependent depression. The model field potentials in response to various randomly generated and real (derived from recorded CA3 unit activity) long stimulating trains were calculated, illustrating that short-term plasticity with the observed characteristics could play specific roles in frequency processing in hippocampus and thus providing a new tool for the theoretical study of activity-dependent synaptic plasticity.

Animals↗
PubMed2004

Acute exposure to CXC chemokine ligand 10, but not its chronic astroglial production, alters synaptic plasticity in mouse hippocampal slices.

Brain levels of CXC chemokine ligand 10 (CXCL10) are elevated in a number of neuropathological conditions. To determine its impact on neuronal function, we measured synaptic transmission and plasticity in hippocampal slices prepared from transgenic (TG) mice with chronic astroglial production of CXCL10. We also tested the acute effect of recombinant CXCL10 applied to slices from normal C57Bl/6J mice, CXCL10 TG mice and CXCR3 knock out (KO) mice. Chronic production of CXCL10 did not alter synaptic plasticity. By contrast, exogenous CXCL10 (10 ng/ml) significantly inhibited long-term potentiation (LTP) in slices from normal C57Bl/6J mice and CXCL10 TG. The effect was probably receptor-mediated because CXCL10-induced inhibition of LTP was not observed in CXCR3 KO mice. Our findings suggest that acute exposure to CXCL10 alters synaptic plasticity via CXCR3 in mouse hippocampus.

Animals↗
PubMed2006

More than a sidekick: glia and homeostatic synaptic plasticity.

Homeostatic synaptic plasticity is thought to have a crucial role in stabilizing the activity of neurons and networks, but the mechanisms are poorly understood. In a recent study, Stellwagen and Malenka have shown that synaptic scaling can be induced by activity-dependent changes in release of the cytokine tumor necrosis factor-alpha (TNF-alpha) and, surprisingly, that the source of TNF-alpha is glia rather than neurons. In addition to provide insight into the mechanisms of homeostatic plasticity, these data argue for the first time for an equal partnership between glial cells and neurons in the generation of an important form of synaptic plasticity.

Animals↗
PubMed2003

The influence of developmental periods of sodium valproate exposure on synaptic plasticity in the CA1 region of rat hippocampus.

The effects of chronic sodium valproate (VPA) exposure during different developmental periods on synaptic plasticity were studied in the hippocampal CA1 area. Rats were exposed to VPA (300 mg/kg per day, intraperitoneal) over different developmental intervals: (1). prenatal exposure (PR group); (2). from parturition to weaning (PW group); (3). from pregnancy day 1 to weaning (PRW group). At postnatal day 22-28, field excitatory postsynaptic potentials were recorded in the CA1 area of hippocampal slices. We found that VPA exposure in the PR and PRW groups significantly impaired long-term potentiation (LTP), long-term depression (LTD) and paired-pulse facilitation (PPF). However, exposure during lactation (PW group) only impaired LTP and had no significant effect on LTD and PPF. These results suggested that VPA exposure during lactation had the least deficits on synaptic plasticity, while VPA exposure in the PR and PRW groups seriously impaired synaptic plasticity and should be avoided.

Animals↗
PubMed2005

Rapid eye movement sleep deprivation revives a form of developmentally regulated synaptic plasticity in the visual cortex of post-critical period rats.

The critical period for observing a developmentally regulated form of synaptic plasticity in the visual cortex of young rats normally ends at about postnatal day 30. This developmentally regulated form of in vitro long-term potentiation (LTP) can be reliably induced in layers II-III by aiming high frequency, theta burst stimulation (TBS) at the white matter situated directly below visual cortex (LTPWM-III). Previous work has demonstrated that suppression of sensory activation of visual cortex, achieved by rearing young rats in total darkness from birth, delays termination of the critical period for inducing LTPWM-III. Subsequent data also demonstrated that when rapid eye movement sleep (REMS) is suppressed, thereby reducing REMS cortical activation, just prior to the end of the critical period, termination of this developmental phase is delayed, and LTPWM-III can still be reliably produced in the usual post-critical period. Here, we report that for approximately 3 weeks immediately following the usual end of the critical period, suppression of REMS disrupts the maturational processes that close the critical period, and LTPWM-III is readily induced in brain slices taken from these somewhat older animals. Insofar as in vitro LTP is a model for the cellular and molecular changes that underlie developmental synaptic plasticity, these results suggest that mechanisms of synaptic plasticity, which participate in brain development and perhaps also in learning and memory processes, remain susceptible to the effects of REMS deprivation during the general period of adolescence in the rat.

Animals↗
PubMed2006

Optical coherence tomography reveals in vivo cortical plasticity of adult mice in response to peripheral neuropathic pain.

We examined neural plasticity in mice in vivo using optical coherence tomography (OCT) of primary somatosensory (S1) and motor (M1) cortices of mice under the influence of sciatic nerve chronic constriction injury (CCI), a model of neuropathic pain widely utilized in rats. The OCT system used in this study provided cross-sectional images of the cortical tissue of mice up to a depth of about 1mm with longitudinal resolution up to 11 microm. This is the first study to evaluate neural plasticity in vivo using OCT. CCI mice exhibited cold allodynia and spontaneous pain behaviors, which are signs of neuropathic pain, 30 days after sciatic nerve ligation, when OCT observation of S1 and M1 cortices was carried out. The scattering intensity of near-infrared light within the hind paw area of S1 and M1 regions in the contralateral hemisphere was significantly higher than in the ipsilateral hemisphere. These CCI-induced increases in scattering intensity within cortical regions associated with the hind paw probably reflect elevated neural activity associated with neuropathic pain. Synapses and mitochondria are believed to have high light scattering coefficients, since they contain remarkably high concentrations of proteins and complicated membrane structure. Number densities of mitochondria and synapses are known to increase in parallel with increases in neural activity. Our findings thus suggest that neuropathic pain gives rise to neural plasticity within the hind paw area of S1 and M1 contralateral to the ligated sciatic nerve.

Animals↗
PubMed2004

Age-related effects of Ginkgo biloba extract on synaptic plasticity and excitability.

EGb 761 is a standardized extract from the Ginkgo biloba leaf and is purported to improve age-related memory impairment. The acute and chronic effect of EGb 761 on synaptic transmission and plasticity in hippocampal slices from young adult (8-12 weeks) and aged (18-24 months) C57Bl/6 mice was tested because hippocampal plasticity is believed to be a key component of memory. Acutely applied EGb 761 significantly increased neuronal excitability in slices from aged mice by reducing the population spike threshold and increased the early phase of long-term potentiation, though there was no effect in slices from young adults. In chronically treated mice fed for 30 days with an EGb 761-supplemented diet, EGb 761 significantly increased the population spike threshold and long-term potentiation in slices from aged animals, but had no effect on slices from young adults. The rapid effects of EGb 761 on plasticity indicate a direct interaction with the glutamatergic system and raise interesting implications with respect to a mechanism explaining its effect on cognitive enhancement in human subjects experiencing dementia.

Aging↗
PubMed2004

Spike timing-dependent plasticity of neural circuits.

Recent findings of spike timing-dependent plasticity (STDP) have stimulated much interest among experimentalists and theorists. Beyond the traditional correlation-based Hebbian plasticity, STDP opens up new avenues for understanding information coding and circuit plasticity that depend on the precise timing of neuronal spikes. Here we summarize experimental characterization of STDP at various synapses, the underlying cellular mechanisms, and the associated changes in neuronal excitability and dendritic integration. We also describe STDP in the context of complex spike patterns and its dependence on the dendritic location of the synapse. Finally, we discuss timing-dependent modification of neuronal receptive fields and human visual perception and the computational significance of STDP as a synaptic learning rule.

Action Potentials↗
PubMed2004

The AMPA receptor subunits GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain.

Ca(2+)-permeable AMPA receptors are densely expressed in the spinal dorsal horn, but their functional significance in pain processing is not understood. By disrupting the genes encoding GluR-A or GluR-B, we generated mice exhibiting increased or decreased numbers of Ca(2+)-permeable AMPA receptors, respectively. Here, we demonstrate that AMPA receptors are critical determinants of nociceptive plasticity and inflammatory pain. A reduction in the number of Ca(2+)-permeable AMPA receptors and density of AMPA channel currents in spinal neurons of GluR-A-deficient mice is accompanied by a loss of nociceptive plasticity in vitro and a reduction in acute inflammatory hyperalgesia in vivo. In contrast, an increase in spinal Ca(2+)-permeable AMPA receptors in GluR-B-deficient mice facilitated nociceptive plasticity and enhanced long-lasting inflammatory hyperalgesia. Thus, AMPA receptors are not mere determinants of fast synaptic transmission underlying basal pain sensitivity as previously thought, but are critically involved in activity-dependent changes in synaptic processing of nociceptive inputs.

Animals↗
PubMed2005

mGluR7 is a metaplastic switch controlling bidirectional plasticity of feedforward inhibition.

Plasticity of feedforward inhibition in the hippocampal mossy fiber (MF) pathway can dramatically influence dentate gyrus-CA3 dialog. Interestingly, MF inputs to CA3 stratum lucidum interneurons (SLINs) undergo long-term depression (LTD) following high-frequency stimulation (HFS), in contrast to MF-pyramid (PYR) synapses, where long-term potentiation (LTP) occurs. Furthermore, activity-induced potentiation of MF-SLIN transmission has not previously been observed. Here we report that metabotropic glutamate receptor subtype 7 (mGluR7) is a metaplastic switch at MF-SLIN synapses, whose activation and surface expression governs the direction of plasticity. In naive slices, mGluR7 activation during HFS generates MF-SLIN LTD, depressing presynaptic release through a PKC-dependent mechanism. Following agonist exposure, mGluR7 undergoes internalization, unmasking the ability of MF-SLIN synapses to undergo presynaptic potentiation in response to the same HFS that induces LTD in naive slices. Thus, selective mGluR7 targeting to MF terminals contacting SLINs and not PYRs provides cell target-specific plasticity and bidirectional control of feedforward inhibition.

Animals↗
PubMed2005

Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF.

A recently described form of synaptic plasticity results in dynamic changes in the calcium permeability of synaptic AMPA receptors. Since the AMPA receptor GluR2 subunit confers calcium permeability, this plasticity is thought to occur through the dynamic exchange of synaptic GluR2-lacking and GluR2-containing receptors. To investigate the molecular mechanisms underlying this calcium-permeable AMPA receptor plasticity (CARP), we examined whether AMPA receptor exchange was mediated by subunit-specific protein-protein interactions. We found that two GluR2-interacting proteins, the PDZ domain-containing Protein interacting with C kinase (PICK1) and N-ethylmaleimide sensitive fusion protein (NSF), are specifically required for CARP. Furthermore, PICK1, but not NSF, regulates the formation of extrasynaptic plasma membrane pools of GluR2-containing receptors that may be laterally mobilized into synapses during CARP. These results demonstrate that PICK1 and NSF dynamically regulate the synaptic delivery of GluR2-containing receptors during CARP and thus regulate the calcium permeability of AMPA receptors at excitatory synapses.

Animals↗