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At least 1,621 records · Page 90Linked to original sources

PubMed2004

Calcium-binding protein Caldendrin and CaMKII are localized in spinules of the carp retina.

Calcium-binding proteins translate the influx of Ca(2+) at excitatory synapses into spatiotemporal signals that regulate a variety of processes underlying synaptic plasticity. In the fish retina, the synaptic connectivity between photoreceptors and horizontal cells undergoes a remarkable plasticity, triggered by the ambient light conditions. With increasing light, the synaptic dendrites of horizontal cells form numerous spinules that are dissolved during dark adaptation. The dynamic regulation of this process is calcium-dependent and involves the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), but astonishingly its principal regulator Calmodulin (CaM) could not be localized to spinules. Here, we show that antibodies directed against Caldendrin (CaBP1), a member of the EF-hand calcium-binding protein family, strongly label the terminal dendrites of horizontal cells invaginating cone pedicles. Double-labeling experiments revealed that this label is closely associated with label for CaMKII. This association was confirmed at the ultrastructural level. Caldendrin immunoreactivity and CaMKII immunoreactivity are both present in horizontal cell dendrites flanking the synaptic ribbon within the cone pedicle and in particular in spinules formed by these terminals. Comparison of light- and dark-adapted retinas revealed a shift of the membrane-associated label for Caldendrin from the terminal dendrites into the spinules during light adaptation. These results suggest that Caldendrin is involved in the dynamic regulation of spinules and confirms the assumed potential of Caldendrin as a neural calcium sensor for synaptic plasticity.

Animals↗

PubMed2003

Maturation of long-term potentiation induction rules in rodent hippocampus: role of GABAergic inhibition.

The induction rules of synaptic plasticity are important for the functional operation of a neural network. We asked whether such synaptic plasticity rules change during development from juvenile to adult animals. Using perforated patch and whole-cell recordings from CA1 pyramidal cells in hippocampal slices, we demonstrate here that the postsynaptic requirements for induction of associative long-term potentiation (LTP) shift gradually. Presynaptic stimulation paired with single postsynaptic action potentials became progressively less effective at inducing LTP with advancing developmental age until, in adult hippocampus, postsynaptic bursts of action potentials were necessary to induce synaptic potentiation. This developmental change might be accounted for by changes in GABA(A) receptor-mediated inhibition known to occur in the hippocampus during this postnatal period, because blocking GABA(A) receptor-mediated inhibition re-established the effectiveness of single postsynaptic action potentials at inducing LTP in adult hippocampus. These data reveal a gradual shift in the induction rules for LTP, explained by a maturational change in GABAergic inhibition, and could have implications for our understanding of the role of inhibition in information processing in the brain.

Action Potentials↗

PubMed2002

Specific plasticity of parallel fiber/Purkinje cell spine synapses by motor skill learning.

New synapse formation may underlie learning and memory. To examine specific synaptic plasticity by motor learning, we conducted quantitative analysis of synapses between parallel fibers and Purkinje cell dendritic spines in cerebella of rats trained to complete various obstacle courses. Synapses between parallel fibers and Purkinje cell spines were classified into single synapse boutons, multiple synapse boutons, and multiple synapse spines by their different contact features. Acrobat-trained animals had more single and multiple synaptic boutons, without change of multiple synapse spines, than motor control animals. These results may suggest that motor learning induces specific synaptogenesis and Purkinje cell spines are primary sites in motor learning-dependent cerebellar synaptic plasticity.

Animals↗

PubMed2005

Presynaptic calcium stores and synaptic transmission.

Following the gradual recognition of the importance of intracellular calcium stores for somatodendritic signaling in the mammalian brain, recent reports have also indicated a significant role of presynaptic calcium stores. Ryanodine-sensitive stores generate local, random calcium signals that shape spontaneous transmitter release. They amplify spike-driven calcium signals in presynaptic terminals, and consequently enhance the efficacy of transmitter release. They appear to be recruited by an association with certain types of calcium-permeant ion channels, and they induce specific forms of synaptic plasticity. Recent research also indicates a role of inositoltrisphosphate-sensitive presynaptic calcium stores in synaptic plasticity.

Animals↗

PubMed2003

Regulation of kainate receptors by protein kinase C and metabotropic glutamate receptors.

Kainate receptors have recently been shown to be involved in synaptic transmission, to regulate transmitter release and to mediate synaptic plasticity in different regions of the CNS. However, very little is known about endogenous mechanisms that can control native kainate receptor signalling. In this study we have found that GluR5-containing kainate receptor-mediated actions can be modulated by activation of protein kinase C (PKC) but not protein kinase A (PKA). However, both PKA and PKC directly phosphorylate the GluR5 subunit of kainate receptors. Metabotropic glutamate (mGlu) receptors are well known to be involved in synaptic transmission, regulation of transmitter release and synaptic plasticity in a variety of brain regions. We now demonstrate that kainate receptor signalling is enhanced by activation of group I mGlu receptors, in a PKC-dependent manner. These data demonstrate for the first time that kainate receptor function can be modulated by activation of metabotropic glutamate receptors and have implications for understanding mechanisms of synaptic transmission, plasticity and disorders such as epilepsy.

Animals↗

PubMed2000

Molecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II.

Synaptic plasticity is thought to be a key process for learning, memory and other cognitive functions of the nervous system. The initial events of plasticity require the conversion of brief electrical signals into alterations of the biochemical properties of synapses that last for much longer than the initial stimuli. Here we show that a regulator of synaptic plasticity, calcium/calmodulin-dependent protein kinase IIalpha (CaMKII), sequentially translocates to postsynaptic sites, undergoes autophosphorylation and gets trapped for several minutes until its dissociation is induced by secondary autophosphorylation and phosphatase 1 action. Once dissociated, CaMKII shows facilitated translocation for several minutes. This suggests that trapping of CaMKII by its targets and priming of CaMKII translocation may function as biochemical memory mechanisms that change the signaling capacity of synapses.

Aniline Compounds↗

PubMed2004

Impaired synaptic scaling in mouse hippocampal neurones expressing NMDA receptors with reduced calcium permeability.

NMDA receptors (NMDARs) play a crucial role for the acquisition of functional AMPARs during Hebbian synaptic plasticity at cortical and hippocampal synapses over a short timescale of seconds to minutes. In contrast, homeostatic synaptic plasticity can occur over longer timescales of hours to days. The induction mechanisms of this activity-dependent synaptic scaling are poorly understood but are assumed to be independent of NMDAR signalling in the cortex. Here we investigated in the hippocampus a potential role of NMDAR-mediated Ca(2+) influx for synaptic scaling of AMPA currents by genetic means. The Ca(2+) permeability of NMDARs was reduced by selective postnatal expression in principal neurones of mouse forebrain half of the NR1 subunits with an amino acid substitution at the critical channel site (N598R). This genetic manipulation did not reduce the total charge transfer via NMDARs in nucleated patches (somatic) and at synaptic sites. In contrast, the current amplitude and the charge carried through AMPARs were substantially reduced at somatic and synaptic sites in juvenile and adult mutants, indicating persistent downscaling of AMPA responses. Smaller and less frequent AMPA miniature currents in the mutant demonstrated a postsynaptic locus of this down-regulation. Afferent innervation and release probability were unchanged at CA3-to-CA1 synapses of mutants, as judged from input-output and minimal stimulation experiments. Our results indicate that NMDAR-mediated Ca(2+) signalling is important for synaptic scaling of AMPA currents in the hippocampus in vivo.

Aging↗

PubMed2003

Synaptic augmentation contributes to environment-driven regulation of the aplysia siphon-withdrawal reflex.

This research shows that short-term synaptic plasticity can play a critical role in shaping the behavioral response to environmental change. In Aplysia, exposure to turbulent environments produces a stable reduction in the duration of the siphon-withdrawal reflex (SWR) and the responsiveness of siphon motor neurons. Recovery takes >1 min after a brief (10 sec-5 min) exposure but <1 min after a long (10 min) exposure. Here we demonstrate that (1) in-turbulence and post-turbulence phases of regulation depend on different cellular processes and (2) the post-turbulence phase of regulation is mediated by augmentation (AUG), an activity-dependent form of short-term synaptic plasticity. In reduced preparations (tail, siphon, and CNS), we show that treatment with 100 microm d-tubocurarine has no effect on in-turbulence regulation but blocks up to 90% of post-turbulence regulation, indicating that these phases of regulation are mediated by distinct cellular process. We then show that (1) turbulence induces activity in L30 inhibitory interneurons, (2) this activation produces AUG that lasts 1 min after a brief exposure to turbulence, and (3) manipulations that attenuate L30 AUG also attenuate regulation after brief turbulence. We also found that long (10 min) exposures to turbulence do not produce a post-turbulence phase of regulation because L30 activity declines over the course of a long turbulence exposure, leading to the decay of AUG before turbulence offset. Our results demonstrate a specific behavioral function of AUG and show how interactions between cellular processes can confer temporal sensitivity in the network regulation of behavior.

Animals↗

PubMed2005

Botulinum toxin: from spasticity reliever to a neuromotor re-learning tool.

Botulinum toxin is becoming increasingly popular as the drug of choice for relief of spasticity in a wide range of conditions, from stroke to strabismus to vaginismus. Besides this role as spasticity reliever, several recent clinical reports claim that in stroke, cerebral palsy, spinal cord injury (SCI), and dystonias, BoTx brings about significant improvement in function--attributed to synaptic plasticity of the muscular afferents. The authors' research had shown that BoTx also generates synaptic plasticity in spinal alpha-motoneurons-interneurons. The article describes how BoTx facilitates relearning by Hebbian and Contrastive Hebbian modes and how it can be used as a neuro-relearning tool to enhance and hasten motor recovery in the aforementioned disorders.

Anti-Dyskinesia Agents↗

PubMed1992

Cerebellar long-term potentiation under suppressed postsynaptic Ca2+ activity.

To study the roles of postsynaptic Ca2+ activity in cerebellar synaptic plasticity, we used a patch-recording technique in Purkinje cell dendrites. While the combination of parallel fibre stimulation and 8-bromo cyclic guanosine monophosphate (Br-cGMP) application produced long-term depression (LTD) of the parallel fibre/Purkinje cell transmission, the same stimuli evoked long-term potentiation (LTP) during postsynaptic injection of Ethyleneglycol-bis-(beta-amino-ethylether)-N, N, N', N'-tetraacetate (EGTA). Furthermore, in the presence of alpha-aminobutyric acid (GABA), parallel fibre stimulation plus Br-cGMP produced LTP of extracellular K+ increases following parallel fibre stimulation. These results suggest that postsynaptic Ca2+ activity in Purkinje cells is negatively correlated to the direction of plastic changes and that the Ca2+ changes and cGMP play distinct roles in cerebellar synaptic plasticity.

Animals↗

PubMedDate not supplied

[The effect of the transmembrane potential level on the dynamic extinction of the amplitude of the synaptic reactions in the snail under potential-fixation conditions].

The goal of this work was to describe a contribution of postsynaptic membrane in synaptic plasticity. To solve this problem the influence of the level of transmembrane potential on the dynamics of transmembrane synaptic current amplitude was studied during rhythmical stimulation of the nerve. It was shown that with increase of transmembrane potential value the slope of the function of transmembrane current decrease became steeper. It was also shown that with higher stimulation frequency the influence of transmembrane holding potential upon the dynamics of synaptic reaction increased. The data obtained can be considered as an evidence to the contribution of postsynaptic membrane in synaptic plasticity.

Animals↗

PubMed2004

Brain-derived neurotrophic factor.

Since the purification of BDNF in 1982, a great deal of evidence has mounted for its central roles in brain development, physiology, and pathology. Aside from its importance in neural development and cell survival, BDNF appears essential to molecular mechanisms of synaptic plasticity. Basic activity-related changes in the central nervous system are thought to depend on BDNF modification of synaptic transmission, especially in the hippocampus and neocortex. Pathologic levels of BDNF-dependent synaptic plasticity may contribute to conditions such as epilepsy and chronic pain sensitization, whereas application of the trophic properties of BDNF may lead to novel therapeutic options in neurodegenerative diseases and perhaps even in neuropsychiatric disorders.

Animals↗

PubMed2006

The proteomes of neurotransmitter receptor complexes form modular networks with distributed functionality underlying plasticity and behaviour.

Neuronal synapses play fundamental roles in information processing, behaviour and disease. Neurotransmitter receptor complexes, such as the mammalian N-methyl-D-aspartate receptor complex (NRC/MASC) comprising 186 proteins, are major components of the synapse proteome. Here we investigate the organisation and function of NRC/MASC using a systems biology approach. Systematic annotation showed that the complex contained proteins implicated in a wide range of cognitive processes, synaptic plasticity and psychiatric diseases. Protein domains were evolutionarily conserved from yeast, but enriched with signalling domains associated with the emergence of multicellularity. Mapping of protein-protein interactions to create a network representation of the complex revealed that simple principles underlie the functional organisation of both proteins and their clusters, with modularity reflecting functional specialisation. The known functional roles of NRC/MASC proteins suggest the complex co-ordinates signalling to diverse effector pathways underlying neuronal plasticity. Importantly, using quantitative data from synaptic plasticity experiments, our model correctly predicts robustness to mutations and drug interference. These studies of synapse proteome organisation suggest that molecular networks with simple design principles underpin synaptic signalling properties with important roles in physiology, behaviour and disease.

Animals↗

PubMed2003

NMDA receptors contribute to synaptic transmission in anterior cingulate cortex of adult mice.

Glutamatergic synapses are common excitatory chemical connections in mammalian central nervous system. At these synapses, most of baseline synaptic transmission is mediated by glutamate AMPA receptors. NMDA receptors that are sensitive to voltage-dependent magnesium blockade selectively contribute to activity-dependent synaptic plasticity. However, inhibition of NMDA receptors by systemic or local administration of NMDA receptor antagonists produced significant effects on different physiological functions that are not believed to depend on NMDA receptor related synaptic plasticity. Here we show that NMDA receptors contribute to synaptic responses in the anterior cingulate cortex (ACC), a region important for cognitive and other brain functions. The contribution of NMDA receptors became more prominent when synapses are stimulated at higher frequencies. Furthermore, at temperatures more close to physiological brain temperatures, more NMDA receptor mediated responses were recorded as compared to the room temperature. These data suggest a new function for NMDA receptors in the ACC as important postsynaptic receptors involved in synaptic transmission, in particular when cells are firing at high frequencies.

Animals↗

PubMed2002

Early chronic aluminium exposure impairs long-term potentiation and depression to the rat dentate gyrus in vivo.

As an important neurotoxin, aluminium can cause cognitive dysfunctions and mental diseases. Previous studies have reported that aluminium impaired long-term potentiation (LTP) in vivo and in vitro. Here, we utilise two models of synaptic plasticity, LTP and long-term depression (LTD) to study the effects of aluminium on synaptic plasticity in vivo. Neonatal Wistar rats were chronically exposed to aluminium from birth to weaning via the milk of dams fed with 0.3% aluminium chloride solution. Excitatory postsynaptic potential (EPSP) and population spikes (PS) were recorded from the dentate gyrus (DG) of adult rats by electrically stimulating the perforant path. THE FOLLOWING RESULTS WERE OBTAINED: (1) The input/output function indicated that, as compared to controls, aluminium increased the baseline amplitude of the PS, but decreased the baseline slope of EPSP. (2) Aluminium significantly prevented LTD in PS (controls: 77.36+/-6.7%, n=7; aluminium-exposed: 102.01+/-9.1%, n=7; P<0.05) and decreased the LTD amplitude in EPSP (controls: 76.61+/-4.1%, n=7; aluminium-exposed: 94.31+/-7.9% n=7, P<0.05). (3) Aluminium reduced the amplitude of LTP in both PS (controls: 190+/-16.1%, n=7; aluminium-exposed: 135+/-9.7%, n=7; P<0.05) and EPSP (control: 132+/-9.3%, n=7; aluminium-exposed: 115+/-10.6%, n=7; P<0.05). As for LTD and LTP, PS was impaired more seriously than EPSP in aluminium-exposed rats. (4) Aluminium exposure decreased the paired-pulse facilitation (PPF) of PS at 30-150 ms interpulse interval (IPI), and reduced 93.5% of PPF at 80 ms IPI in PS (controls: 243.4+/-39.8%, n=7; aluminium-exposed: 149.9+/-12.3%, n=7). There was no significant difference in EPSP of PPF. From these results we conclude that aluminium exposure in neonatal rats thus reduces the amplitude of LTP and PPF and blocks the induction of LTD in the DG. We suggest that aluminium affects both presynaptic and postsynaptic mechanisms of synaptic transmission.

Aluminum↗

PubMed1997

No changes in cerebrospinal fluid levels of nitrite, nitrate and cyclic GMP with aging. Short communication.

Nitric oxide (NO) is a free radical gas that plays a role in various signal transduction processes. NO has been proposed to have a function in the mechanism of synaptic plasticity, including long-term potentiation and memory formation in vivo. Because a failure in synaptic plasticity is considered to be involved in aging-associated brain dysfunction, NO production in the brain may be altered by aging. In the present study, we measured the levels of NO metabolites, nitrite and nitrate, and cyclic GMP in the cerebrospinal fluid (CSF) of human subjects without neurological or psychiatric disorders. There were no age-related changes in the CSF levels of either nitrite, nitrate or cyclic GMP. These results suggest that NO production in the brain may be maintained during the aging process.

Adult↗

PubMed2004

Molecular mechanisms underlying emotional learning and memory in the lateral amygdala.

Fear conditioning is a valuable behavioral paradigm for studying the neural basis of emotional learning and memory. The lateral nucleus of the amygdala (LA) is a crucial site of neural changes that occur during fear conditioning. Pharmacological manipulations of the LA, strategically timed with respect to training and testing, have shed light on the molecular events that mediate the acquisition of fear associations and the formation and maintenance of long-term memories of those associations. Similar mechanisms have been found to underlie long-term potentiation (LTP) in LA, an artificial means of inducing synaptic plasticity and a physiological model of learning and memory. Thus, LTP-like changes in synaptic plasticity may underlie fear conditioning. Given that the neural circuit underlying fear conditioning has been implicated in emotional disorders in humans, the molecular mechanisms of fear conditioning are potential targets for psychotherapeutic drug development.

Amygdala↗

PubMed2000

The role of short-term synaptic dynamics in motor control.

During the past few years, much attention has been given to the role of short-term synaptic plasticity, in particular depression and facilitation, in sculpting network activity. A recent study shows that synaptic depression in rhythmic motor networks could switch the control of network frequency from intrinsic neuronal properties to the synaptic dynamics. Short-term synaptic plasticity is also involved in the stabilization and reconfiguration of motor circuits and in the initiation, maintenance and modulation of motor programs.

Animals↗