Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “synaptic plasticity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,387 records · Page 77Linked to original sources
PubMed1997

Developmental changes of glutamate receptors in the rat cerebral cortex and hippocampus.

We studied the immunohistochemical localization of the glutamate receptors (GluR-1, -2, and -3,) in the developing rat cerebral cortex and hippocampus using antibodies to GluR1 and to an epitope common to GluR2 and GluR3 (GluR2/3) subunits. In the cerebral cortex, GluR1 immunoreactivity appeared in the neurons from postnatal day (PND) 0, increased with maturation, was highest at PND 10, decreased until PND 30, and thereafter remained at the same level as on PND 0. GluR2/3 immunoreactivity appeared earlier in scattered neurons on embryonal day (ED) 18, increased with maturation and reached a peak between PND 10 and PND 15, after which the immunoreactivity gradually decreased and reached a plateau at PND 30. For both GluR1 and GluR2/3, some of the pyramidal neurons showed intense staining. In the pyramidal layers of the hippocampus, GluR1 and GluR2/3 immunoreactivity was found in all the pyramidal neurons of the CA1-4 area from ED 20. In the dentate gyrus of the hippocampus, GluR1 and GluR2/3 immunoreactivity was found in the neurons of the granule cells after PND 0. Immunoreactivity in the neurons of the subiculum was found after PND 5 and that of the polymorphic cell layers was found after PND 15-20. Our results indicate that the development of glutamate receptor subunits in the rat cerebral cortex and hippocampus is expressed in different spatial patterns and distinct temporal patterns throughout development and is scheduled during the early postnatal period, when synaptic plasticity or synaptic connection occurs in these regions.

Animals↗
PubMed1991

Microencephaly reduces the phosphorylation of the PKC substrate B-50/GAP43 in rat cortex and hippocampus.

The administration of the antimitotic agent methylazoxymethanol (MAM) to rats at day 15 of gestation results in a consistent loss of intrinsic neurons primarily in cortex and hippocampus. These animals when adult, show a cognitive impairment, if tested in specific behavioural tasks. B-50/GAP43 is a neuronal phosphoprotein, specific substrate for protein kinase C (PKC) and involved in the development and plasticity of synaptic connections. Since B-50/GAP43 has been implicated in functional modulation of synapses and in the molecular mechanism underlying cognitive processes, we studied the phosphorylation of B-50 in cortex and hippocampus of control and MAM-treated rats. Here we report that B-50 in MAM-treated rats shows a marked reduction in the phosphate incorporation in the areas affected by the prenatal treatment. In situ hybridization studies demonstrate that the mRNA levels for B-50 are not altered in MAM-treated rats and that the relative amount of the protein, as revealed by Western blot analysis, is also not affected in microencephalic rats. These results suggest that microencephalic animals might represent a useful experimental model to study biochemical correlates of cognitive impairment and synaptic plasticity.

Animals↗
PubMed1996

Memory, sleep, and dynamic stabilization of neural circuitry: evolutionary perspectives.

Some aspects of the evolution of mechanisms for enhancement and maintenance of synaptic efficacy are treated. After the origin of use-dependent synaptic plasticity, frequent synaptic activation (dynamic stabilization, DS) probably prolonged transient efficacy enhancements induced by single activations. In many "primitive" invertebrates inhabiting essentially unvarying aqueous environments, DS of synapses occurs primarily in the course of frequent functional use. In advanced locomoting ectotherms encountering highly varied environments, DS is thought to occur both through frequent functional use and by spontaneous "non-utilitarian" activations that occur primarily during rest. Non-utilitarian activations are induced by endogenous oscillatory neuronal activity, the need for which might have been one of the sources of selective pressure for the evolution of neurons with oscillatory firing capacities. As non-sleeping animals evolved increasingly complex brains, ever greater amounts of circuitry encoding inherited and experiential information (memories) required maintenance. The selective pressure for the evolution of sleep may have been the need to depress perception and processing of sensory inputs to minimize interference with DS of this circuitry. As the higher body temperatures and metabolic rates of endothermy evolved, mere skeletal muscle hypotonia evidently did not suffice to prevent sleep-disrupting skeletal muscle contractions during DS of motor circuitry. Selection against sleep disruption may have led to the evolution of further decreases in muscle tone, paralleling the increase in metabolic rate, and culminating in the postural atonia of REM (rapid eye movement) sleep. Phasic variations in heart and respiratory rates during REM sleep may result from superposition of activations accomplishing non-utilitarian DS of redundant and modulatory motor circuitry on the rhythmic autonomic control mechanisms. Accompanying non-utilitarian DS of circuitry during sleep, authentic and variously modified information encoded in the circuitry achieves the level of unconscious awareness as dreams and other sleep mentation.

Animals↗
PubMed2005

Antipsychotic drugs elevate mRNA levels of presynaptic proteins in the frontal cortex of the rat.

BACKGROUND: Molecular adaptations are believed to contribute to the mechanism of action of antipsychotic drugs (APDs). We attempted to establish common gene regulation patterns induced by chronic treatment with APDs. METHODS: Gene expression analysis was performed with the Affymetrix U34A array in the frontal cortex (FC) and the striatum of rats chronically treated with two concentrations of either clozapine or haloperidol. Key data were verified with real-time quantitative polymerase chain reaction. RESULTS: Many genes in the FC affected by APD-treatment contribute to similar functions. mRNAs coding for synaptic vesicle docking- and microtubule-associated proteins were upregulated; mRNAs for serine-threonine protein phosphatases were downregulated, whereas the serine-threonine kinases protein kinase A, protein kinase C, and calcium/calmodulin kinase II alpha and IV were upregulated, indicating increased potential for protein phosphorylation. In the striatum, altered gene expression was less focused on genes of particular function or location, and the high concentration of haloperidol had a different gene expression profile than any of the other APD treatments. CONCLUSION: We found an increase in the transcription of genes coding for proteins involved in synaptic plasticity and synaptic activity in the FC. We furthermore found that the gene expression profile of APDs is different between FC and striatum.

Animals↗
PubMed2003

Neural mechanisms of reward-related motor learning.

The analysis of the neural mechanisms responsible for reward-related learning has benefited from recent studies of the effects of dopamine on synaptic plasticity. Dopamine-dependent synaptic plasticity may lead to strengthening of selected inputs on the basis of an activity-dependent conjunction of sensory afferent activity, motor output activity, and temporally related firing of dopamine cells. Such plasticity may provide a link between the reward-related firing of dopamine cells and the acquisition of changes in striatal cell activity during learning. This learning mechanism may play a special role in the translation of reward signals into context-dependent response probability or directional bias in movement responses.

Animals↗
PubMed2005

Synaptic protein degradation by the ubiquitin proteasome system.

Synaptic plasticity -- the modulation of synaptic strength between a presynaptic terminal and a postsynaptic dendrite -- is thought to be a mechanism that underlies learning and memory. It has become increasingly clear that regulated protein synthesis is an important mechanism used to regulate the protein content of synapses that results in changes in synaptic strength. Recent experiments have highlighted a role for the opposing process, that is, regulated protein degradation via the ubiquitin-proteasome system, in synaptic plasticity. These recent findings raise exciting questions as to how proteasomal activity can regulate synapses over different temporal and spatial scales.

Animals↗
PubMed1998

Synaptic density of the prefrontal cortex regulated by dopamine instead of serotonin in rats.

Recent findings indicate that monoamine contributes to synaptic plasticity. We examined the synaptic density of the prefrontal cortex and parietal cortex of rats using dopamine (DA) antagonists and agonists, as well as serotonin (5-HT) depleters and found a reduction in synaptic density in the prefrontal cortex lamina V-VI at a maximum of 20% with administration of a D1 antagonist (SCH23390) and at a maximum of 30% with a D2 antagonist (YM09151). Further, with the administration of D1+D2 antagonists there was a 27% decrease in synaptic density, which was a larger reduction than the total of the single dosages of each DA antagonist at equal levels. Increase in synaptic density was seen at a maximum of 8.5% with dosage of a D1 agonist (SKF38390) and 14.5% with dosage of a D2 agonist (PPHT). The dosage of D1+D2 agonists showed a 27.1% increase in synaptic density. There was no change in synaptic density of the parietal cortex with either DA antagonist or agonist administration. Administration of 5-HT depleter pCPA resulted in a 13.8% reduction of synaptic density in the parietal cortex, though there was no change identified in the synaptic density in the prefrontal cortex. Based on these results, it was suggested that the area of the brain with affected synaptic plasticity could differ, depending on the type of monoamine.

Animals↗
PubMed2001

Barrel cortex critical period plasticity is independent of changes in NMDA receptor subunit composition.

The regulation of NMDA receptor (NMDAR) subunit composition and expression during development is thought to control the process of thalamocortical afferent innervation, segregation, and plasticity. Thalamocortical synaptic plasticity in the mouse is dependent on NMDARs containing the NR2B subunit, which are the dominant form during the "critical period" window for plasticity. Near the end of the critical period there is a gradual increase in the contribution of NR2A subunits that happens in parallel to changes in NMDAR-mediated current kinetics. However, no extension of the critical period occurs in NR2A knockout mice, despite the fact that NMDA subunit composition and current kinetics remain immature past the end of the critical period. These data suggest that regulation of NMDAR subunit composition is not essential for closing the critical period plasticity window in mouse somatosensory barrel cortex.

Animals↗
PubMed2007

Differential roles of Rap1 and Rap2 small GTPases in neurite retraction and synapse elimination in hippocampal spiny neurons.

The Rap family of small GTPases is implicated in the mechanisms of synaptic plasticity, particularly synaptic depression. Here we studied the role of Rap in neuronal morphogenesis and synaptic transmission in cultured neurons. Constitutively active Rap2 expressed in hippocampal pyramidal neurons caused decreased length and complexity of both axonal and dendritic branches. In addition, Rap2 caused loss of dendritic spines and spiny synapses, and an increase in filopodia-like protrusions and shaft synapses. These Rap2 morphological effects were absent in aspiny interneurons. In contrast, constitutively active Rap1 had no significant effect on axon or dendrite morphology. Dominant-negative Rap mutants increased dendrite length, indicating that endogenous Rap restrains dendritic outgrowth. The amplitude and frequency of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-mediated miniature excitatory postsynaptic currents (mEPSCs) decreased in hippocampal neurons transfected with active Rap1 or Rap2, associated with reduced surface and total levels of AMPA receptor subunit GluR2. Finally, increasing synaptic activity with GABA(A) receptor antagonists counteracted Rap2's inhibitory effect on dendrite growth, and masked the effects of Rap1 and Rap2 on AMPA-mediated mEPSCs. Rap1 and Rap2 thus have overlapping but distinct actions that potentially link the inhibition of synaptic transmission with the retraction of axons and dendrites.

Action Potentials↗
PubMed1986

Neuronal experience modifies synaptic long-term facilitation.

In a crayfish phasic neuromuscular junction, we have demonstrated low-frequency depression (LFD), high-frequency depression (HFD), and long-term facilitation (LTF) in response to different regimens of stimulation. Chronic stimulation of the phasic axon supplying the closer muscle of the claw in Procambarus clarkii resulted in diminished expression of HFD and LTF. Conversely, when impulse production in the phasic motoneuron was reduced by claw immobilization, both HFD and LTF were enhanced. LFD was insensitive to these manipulations. These results provide further evidence for long-term adaptation of the phasic neuromuscular junction to ongoing levels of impulse activity and illustrate the importance of a neuron's past history for synaptic plasticity. The ability of the neuron to adjust its short-term plasticity in response to altered experience constitutes an adaptive response that could be of general significance.

Adaptation, Physiological↗
PubMed2004

Cellular mechanisms of neuronal population oscillations in the hippocampus in vitro.

A variety of population oscillations, at frequencies approximately 5 Hz up to 200 Hz and above, can be induced in hippocampal slices either by (a) manipulation of the ionic environment, or (b) by stimulation of metabotropic receptors; brief oscillations can even occur spontaneously. In this review, we consider in vitro theta (4-12 Hz), gamma/beta (15-70 Hz), and very fast oscillations (VFO) (>70 Hz). Many in vitro oscillations are gated by synaptic inhibition but are influenced by electrical coupling as well; one type depends solely on electrical coupling. For some oscillations dependent upon inhibition, the detailed firing patterns of interneurons can influence long-range synchronization. Two sorts of electrical coupling are important in modulating or generating various in vitro oscillations: (a) between interneurons, primarily between dendrites; and (b) between axons of pyramidal neurons. VFO can exist in isolation or can act as generators of gamma frequency oscillations. Oscillations at gamma frequencies and below probably create conditions under which synaptic plasticity can occur, between selected neurons-even those separated by significant axonal conduction delays.

Action Potentials↗
PubMed1976

[Ultrastructural variations of synapses in the normal human cerebral cortex].

The numerous synapses in the normal human brain cortex display various aspects. The authors have also observed some electronic type synapses which are more numerous around the pericaryons. The cortical synapses are classed according to their synaptic vesicle richness : synapses with very few vesicles, synapses very rich in vesicles and synapses with a middling vesicular density. With the help of observations on these aspects and on variations of the synaptic cleft and that of the postsynaptic density, the authors advance an hypothesis on synaptic plasticity, the synaptic structures going from a simple intercellular contact (probably non functional) to a completly formed synapse and vice versa.

Adolescent↗
PubMed2000

Protective role of estrogen in the neurodegenerative disorders.

Estrogen is an anabolic hormone of gonadal cells and it also modulates the growth and differentiation of non-gonadal cells like neuron/glia and protects them against the injury. The anabolic or protective actions of estrogen on the neuronal cells are mediated by the modulation of intracellular factors such as insulin like growth factor (IGF-I), tyrosine kinase A (Trk A), nerve growth factors (NGF) etc. It also modulates the action of neurotrophins which in turn regulate the synaptogenesis, synaptic plasticity and synaptic functions. By these actions estrogen prevents or slows down the neurodegenerative process.

Estrogens↗
PubMed2003

Ischemic insults derepress the gene silencer REST in neurons destined to die.

A subset of genes implicated in genetic and acquired neurological disorders encode proteins essential to neural patterning and neurogenesis. The gene silencing transcription factor neuronal repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) plays a critical role in elaboration of the neuronal phenotype. In neural progenitor and non-neural cells, REST acts by repression of a subset of neural genes important to synaptic plasticity and synaptic remodeling, including the AMPA receptor (AMPAR) subunit GluR2. Here we show that global ischemia triggers REST mRNA and protein expression. REST suppresses GluR2 promoter activity and gene expression in neurons destined to die. Because the GluR2 subunit governs AMPAR Ca2+ permeability, these changes are expected to have profound effects on neuronal survival. In keeping with this concept, acute knockdown of the REST gene by antisense administration prevents GluR2 suppression and rescues post-ischemic neurons from ischemia-induced cell death in an in vitro model. To our knowledge, our study represents the first example of ischemia-induced induction of a master transcriptional regulator gene and its protein expression critical to neural differentiation and patterning in adult neurons. Derepression of REST is likely to be an important mechanism of insult-induced neuronal death.

Animals↗
PubMed1995

Cloning and characterization of two related serotonergic receptors from the brain and the reproductive system of Aplysia that activate phospholipase C.

Serotonin (5-HT) plays important roles in various behavioral and physiological processes in Aplysia californica. These include feeding, locomotion, circadian rhythm, learning and memory, synaptic plasticity, and synaptic growth. Serotonin modulates these various functions by interacting with different 5-HT receptor subtypes that are coupled to various second-messenger systems. We report here the isolation and characterization of the first two serotonergic receptors from Aplysia californica, Ap5-HTB1 and Ap5-HTB2, using a strategy based on the amino acid sequence homology among G-protein-coupled biogenic amine receptors. Ap5-HTB1 and Ap5-HTB2 are both intronless and highly homologous to each other, sharing 79.5% sequence identity at the amino acid level. Sequence comparison reveals that these receptors are 33.1 to 23.3% identical to the following 5-HT receptors: 5-HTdro1 > 5-HT6 > 5-HTlym > mouse 5-HT1B > 5-HTdro2A > mouse 5-HT7 > rat 5-HT2A. Both Ap5-HTB1 and Ap5-HTB2 encode functional 5-HT receptors. When expressed in cultured cells, these receptors stimulate phospholipase C in response to 5-HT in a dose-dependent manner. This stimulation can be blocked by specific 5-HT receptor antagonists. Using RT-PCR and Western blot analysis, we have detected these receptors in the CNS (Ap5-HTB2) and in the reproductive system (Ap5-HTB1). The nucleotide sequences of Ap5-HTB1 and Ap5-HTB2 were submitted to GenBank; the accession numbers are L43557 and L43558, respectively.

Amino Acid Sequence↗
PubMed1998

Cloning and functional expression of an Aplysia 5-HT receptor negatively coupled to adenylate cyclase.

Serotonin (5-HT) is involved in the control of various behaviors in Aplysia californica, including reproduction, feeding, locomotion, circadian rhythm, synaptic plasticity, and synaptic growth. The large variety of functions of 5-HT is mediated by different receptor subtypes that are coupled to different second-messenger systems. Here, we report the cloning of a cDNA coding for an Aplysia G-protein-coupled 5-HT receptor (5-HTap1). Its deduced amino acid sequence resembles those of the 5-HT1 receptor subfamily. When expressed in stable cell lines, 5-HTap1 exhibits high-affinity binding for the serotonergic radioligand [N-methyl-3H]lysergic acid diethylamide. This binding is competed by several 5-HT agonists and antagonists, and the pharmacological profile of inhibition has some similarities with those of 5-HT1 and 5-HT7 receptors. Application of 5-HT or its agonists 5-carboxamidotryptamine maleate and (+/-)-8-hydroxy-2-(di-n-propyl-amino) tetralin hydrobromide on cells transformed with 5-HTap1 produced a dose-dependent inhibition of forskolin-stimulated cAMP accumulation. 5-HTap1 is thus negatively coupled to adenylate cyclase. The production of antiserum against the 5-HTap1 receptor allowed us to examine its expression in animal tissues. The receptor protein is detected in every tissue examined, although it seems only weakly expressed in some samples. The receptor is also found in every ganglia of the nervous system, both in the sheath and in the neurons. 5-HTap1 mRNA is absent from the sheath, indicating that the protein observed there is probably located on the nerve terminals.

Adenylyl Cyclase Inhibitors↗
PubMed1994

Neurochemical aspects of hippocampal and cortical Pb2+ neurotoxicity.

The amino acid glutamate is the neurotransmitter used by most excitatory synapses in the mammalian brain. Glutamatergic synapses in the hippocampus and cerebral cortex play an important role in synaptic plasticity. In the developing brain, the interaction of neurotoxins with presynaptic and/or postsynaptic sites on glutamatergic neurons could alter synaptic plasticity. Recent studies have shown that chronic lead (Pb2+) exposure may impair neuronal process underlying synaptic plasticity via a direct interaction with the N-Methyl-D-Aspartate (NMDA) glutamate receptor subtype. The NMDA receptor-ion channel complex regulates calcium influx and is involved in the initiation of changes in synaptic plasticity. In vitro and in vivo neurochemical studies have found that Pb2+ has a marked inhibitory effect on the activation of the NMDA receptor-ion channel complex. Evidence indicates that the inhibitory effect of Pb2+ on the NMDA receptor complex may be mediated by its interaction with a zinc regulatory site on the receptor complex. The ability of Pb2+ to inhibit NMDA receptor-ion channel function was shown to be age-dependent and brain region-specific. The age-dependent effects of Pb2+ on the NMDA receptor complex may help explain the selective toxicity of this heavy metal in the developing brain.

Age Factors↗
PubMed2003

[Analysis of signal transduction pathways in cerebellar long-term depression by use of kinetic simulations].

It is essential to analyze molecular basis of synaptic plasticity systematically for understanding our psychological processes and psychological disorders. Recent progress identified many signaling molecules responsible for the regulation of synaptic plasticity. However, because multiple molecular signal transduction molecules and pathways are involved, the systematic relationship between synaptic plasticity and the currently known signal transduction pathways remains obscure. To address this issue, we here focused on cerebellar long-term depression (LTD), one of the well known synaptic plasticity. We took advantage of a simulation model for cerebellar LTD based on biochemical reactions, kinetics, and explored the behaviors of complex signal transduction pathways involved in cerebellar LTD.

Cerebellar Cortex↗