Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Target 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 577 records · Page 32Linked to original sources
PubMed2006

Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain.

Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons. To identify which adult neural circuits can be modulated by Reelin-mediated signaling, we systematically mapped the distribution of Reelin in adult rat brain using sensitive immunolabeling techniques. Results show that the distribution of intracellular and secreted Reelin is both very widespread and specific. Some interneuron and projection neuron populations in the cerebral cortex contain Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these cells are preferentially located in striosomes. Some thalamic nuclei contain Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic thalamic interneurons. High local concentrations of extracellular Reelin selectively outline several dendrite spine-rich neuropils. Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal ('perforant') path, the lateral olfactory tract or the parallel fiber system of the cerebellum. A preferential secretion of Reelin in these neuropils is consistent with reports of rapid, activity-induced structural changes in adult brain circuits.

Animals↗
PubMed2002

Plastic biochannel hybridization devices: a new concept for microfluidic DNA arrays.

Conventional DNA hybridization assay kinetics depends solely on the diffusion of target to surface-bound probes, causing long hybridization times. In this study, we examined the possibilities of accelerating the hybridization process by using microfluidic channels ("biochannels") made of polycarbonate, optionally with an integrated pump. We produced two different devices to study these effects: first, hybridization kinetics was investigated by using an eSensor electrochemical DNA detection platform allowing kinetic measurements in homogenous solution. We fabricated an integrated cartridge for the chip comprising the channel network and a micropump for the oscillation of the hybridization mixture to further overcome diffusion limitations. As a model assay, we used an assay for the detection of single-nucleotide polymorphisms in the HFE-H gene. Second, based on the biochannel approach, we constructed a plastic microfluidic chip with a network of channels for optical detection of fluorescent-labeled targets. An assay for the simultaneous detection of four pathogenic bacteria surrogate strains from multiple samples was developed for this device. We observed high initial hybridization velocities and a fast attainment of equilibrium for the biochannel with integrated pump. Experimental results were compared with predictions generated by computer simulations.

Computer Simulation↗
PubMed2003

Intrinsic differences in sensitivity to 5-HT between high- and low-output terminals innervating the same target.

The differential action of neuromodulators on synapses of various efficacy provides additional fine tuning of synaptic regulation beyond frequency induced plasticity. We used the well-characterized high- and low-output motor nerve terminals, of the tonic and phasic neuromuscular junctions (NMJs) in the walking leg extensor muscle of the crayfish, to investigate differential actions of serotonin (5-HT) since both terminals innervate the same target. The excitatory postsynaptic potentials of the tonic NMJ are enhanced to a greater extent than for the phasic NMJs during exposure to 5-HT (100 nM). Macropatch current recordings at identified sites along the motor nerve terminals and quantal analysis indicate that mean quantal content is substantially increased by 5-HT. The overall probability of vesicular release increases to a greater extent at tonic terminals than at phasic terminals when exposed to 100 nM 5-HT. Measures in the area (i.e. charge) of spontaneous quantal currents indicate no difference in postsynaptic receptivity to the glutamatergic synaptic transmission upon exposure to 5-HT. The results provide new details concerning differential modulation of low- and high-output synapses present on the same target tissue.

Animals↗
PubMed2003

It could be habit forming: drugs of abuse and striatal synaptic plasticity.

Drug addiction can take control of the brain and behavior, activating behavioral patterns that are directed excessively and compulsively toward drug usage. Such patterns often involve the development of repetitive and nearly automatic behaviors that we call habits. The striatum, a subcortical brain region important for proper motor function as well as for the formation of behavioral habits, is a major target for drugs of abuse. Here, we review recent studies of long-term synaptic plasticity in the striatum, emphasizing that drugs of abuse can exert pronounced influences on these processes, both in the striatum and in the dopaminergic midbrain. Synaptic plasticity in the ventral striatum appears to play a prominent role in early stages of drug use, whereas dopamine- and endocannabinoid-dependent synaptic plasticity in the dorsal striatum could contribute to the formation of persistent drug-related habits when casual drug use progresses towards compulsive drug use and addiction.

Animals↗
PubMed2002

Inhibition in the propagation of fast electrons in plastic foams by resistive electric fields.

The propagation of relativistic electrons in foam and solid density targets has been studied by means of K-alpha spectroscopy. Experimental results point out the role of self-generated electric fields in propagation and the role of heating of matter induced by the passage of fast electrons. A simple analytical formulation has been given and Spitzer conductivity has been shown to be fairly compatible with experimental results.

Journal Article↗
PubMed2005

Development of respiratory control: evolving concepts and perspectives.

The mechanisms underlying respiratory system immaturity in newborns have been investigated, both in vivo and in vitro, in humans and in animals. Immaturity affects breathing rhythmicity and its modulation by suprapontine influences and by afferents from central and peripheral chemoreceptors. Recent research has moved from bedside tools to sophisticated technologies, bringing new insights into the plasticity and genetics of respiratory control development. Genetic research has benefited from investigations of newborn mice having targeted deletions of genes involved in respiratory control. Genetic variability may govern the normal programming of development and the processes underlying adaptation to homeostasis disturbances induced by prenatal and postnatal insults. Studies of plasticity have emphasized the role of neurotrophic factors. Improvements in our understanding of the mechanistic effects of these factors should lead to new neuroprotective strategies for infants at risk for early respiratory control disturbances, such as apnoeas of prematurity, sudden infant death syndrome and congenital central hypoventilation syndrome.

Animals↗
PubMed2004

Role of Cdk5 in drug abuse and plasticity.

Neuronal plasticity serves as the basis for learning and memory in the adult brain. Contextual, motor, and reward-based learning are important in reinforcing survival behavior in animals. Most psychostimulant drugs of abuse target the dopaminergic reward system of the brain. Drugs of abuse cause long-standing cellular and molecular neuroadaptations in the brain. The neuronal protein kinase Cdk5 is emerging as an important player in the cellular and physiological responses to drugs of abuse. Substantial evidence indicates that Cdk5 controls dopamine neurotransmission through regulation of the protein phosphatase-1 inhibitor, DARPP-32. Furthermore, the morphological changes associated with chronic cocaine exposure are dependent on Cdk5. Thus, Cdk5 mediates cellular responses to psychostimulant drug-induced changes in dopamine signal transduction and cytoskeletal reorganization. In this regard, Cdk5, through its targeting of various substrates, integrates a number of intracellular pathways that are targeted by psychostimulant drugs. These studies and the emerging role of Cdk5 in various forms of neuronal plasticity are reviewed.

Animals↗
PubMed1995

Targeted neocortical cell death in adult mice guides migration and differentiation of transplanted embryonic neurons.

Local expression of cellular and molecular signals is required for normal neuronal migration and differentiation during neocortical development and during periods of plasticity in the adult brain. We have previously shown that neonatal and juvenile mice that induction of apoptotic degeneration in neocortical pyramidal neurons by targeted photolysis provides an altered environment that directs migration and differentiation of transplanted embryonic neurons. Here we employ the same paradigm in adult mice to test whether targeted photolysis induces the reexpression in the mature brain of developmental signals that control migration, differentiation and integration of embryonic neurons. We examined both the time course of migration and the morphologic and immunocytochemical differentiation of embryonic neurons transplanted into regions of targeted photolytic cell death. Pyramidal neurons in neocortical lamina II/III underwent photolytically induced apoptosis after retrograde incorporation of the photoactive chromophore chlorine e6 and transdural exposure to 674 nm near-infrared laser energy. Embryonic day 17 neocortical neurons were prelabeled with fluorescent nanospheres and the lipophilic dye PKH26, transplanted into regions of ongoing neuronal degeneration in adult mice, and examined histologically and immunocytochemically. Transplanted neurons began migration into regions of neuronal death within 3 d and differentiated into large pyramidal neurons similar to those degenerating. In contrast, neurons transplanted into intact cortex did not migrate, and they differentiate into small presumptive interneurons. Migration up to 430 microM in experimental mice was complete by 2 weeks; approximately 45% of the donor neurons migrated greater than 3 SDs beyond the mean for neurons transplanted into intact neocortex of age-matched adult hosts. Following migration, dendrites and axons of many donor neurons were properly oriented toward the pial surface and corpus callosum, indicating integration into the host parenchyma. Neurofilament and neuron-specific enolase staining further support appropriate differentiation and integration. These results indicate that signals guiding neuronal migration and differentiation in neocortex are reexpressed in adult mice well beyond the period of corticogenesis within regions of targeted photolytic cell death. Elucidating the molecular mechanisms underlying these events by comparison with adjacent unperturbed regions will contribute to efforts toward future therapeutic transplantation and control over endogenous plasticity.

Animals↗
PubMed2002

Photoperiod and androgens act independently to induce spinal nucleus of the bulbocavernosus neuromuscular plasticity in the Siberian hamster, Phodopus sungorus.

In the Siberian hamster, Phodopus sungorus, short-day photoperiods induce the winter phenotype, which in males includes a decrease in the production of androgens and changes in physiology to inhibit reproduction. Motoneurones of the spinal nucleus of the bulbocavernosus (SNB) and their target muscles, the bulbocavernosus and the levator ani, a neuromuscular system involved in male copulation, also display seasonal plasticity in P. sungorus. It is not known whether the plasticity seen in the SNB system of gonadally intact hamsters is due to the effects of photoperiod per se, or to the photoperiod-induced changes in androgen production. To answer this question, we castrated adult male hamsters from long days and then implanted them with capsules containing either testosterone or blanks. Half of the hamsters from each hormone condition were moved into short photoperiod (8 : 16 h light/dark cycle) while the rest were maintained under long-day conditions (15 : 9 h light/dark cycle). After 15 weeks, many measures of the SNB system, such as somata size and weight of target muscles, responded only to androgen, not to photoperiod. However, there were effects of photoperiod on the neuromuscular junctions (NMJs) that were independent of androgen status. For example, the number of synaptic zones per NMJ and the area of the NMJs were significantly increased by short days and/or testosterone treatment. The two factors exerted an additive, rather than an interactive, effect on these measures. Another striated muscle, the extensor digitorum longus, which is present in both sexes and plays no specialized role in reproduction, displayed neither an effect of androgen nor of photoperiod on fibre size or NMJ structure. These results suggest that, in addition to androgenic effects on SNB plasticity, there is also an androgen-independent effect of photoperiod on the SNB neuromuscular system.

Androgens↗
PubMed1999

BDNF stimulates expression, activity and release of tissue-type plasminogen activator in mouse cortical neurons.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal development and synaptic plasticity. Although the physiological effects of BDNF have been examined in detail, target proteins which mediate its actions remain largely unknown. Here, we report that BDNF stimulates the expression of tissue-type plasminogen activator (tPA) in primary cultures of cortical neurons in a time- and concentration-dependent manner. Among the other members of the neurotrophin family, neurotrophin-4 (NT-4) and to a lesser extent neurotrophin-3 (NT-3) also increased tPA mRNA expression, while nerve growth factor (NGF) was devoid of any effect. Induction of tPA expression by BDNF is accompanied by an increase in the proteolytic activity of tPA associated with cortical neurons and a release of tPA into the extracellular space. Release of tPA induced by BDNF depends on extracellular Ca2+ since it is markedly reduced in the presence of ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). Up-regulation of tPA expression by BDNF is followed by the induction of plasminogen activator inhibitor 2 (PAI-2), an inhibitor of tPA. Together these results suggest that activation of tPA by BDNF may contribute to structural changes associated with neuronal development or synaptic plasticity.

Animals↗
PubMed2002

Loss and sprouting of nitric oxide synthase neurons in the human epileptic hippocampus.

PURPOSE: Nitric oxide (NO) has been implicated in a variety of functions, including the control of synaptic plasticity and sensory signaling. Current evidence suggests that this unconventional neurotransmitter mediates N-methyl-d-aspartate (NMDA) receptor-linked excitotoxicity. This study describes the expression of neuronal NO synthase (nNOS) immunoreactivity (IR) in hippocampi from patients with temporal lobe epilepsy (TLE). METHODS: Hippocampi from patients with clinical symptoms, neuroimaging, and EEG typical of hippocampal sclerosis (HS; n = 22) were compared with those from patients with neocortical temporal lesions (NONHS; n = 4) and autopsy (AUT; n = 18) patients for total cells, and nNOS-IR neuron and puncta densities. RESULTS: Compared with AUT, HS hippocampi had significantly less nNOS-IR neuron densities in the fascia dentata (FD); hilus, and CA4, CA3, CA2, and CA1 subfields. HS hippocampi had significantly greater nNOS-IR puncta densities in the FD, as compared with AUT and NONHS. CONCLUSIONS: Our results show that hippocampi from TLE patients exhibit a loss of nNOS-IR neurons and an abnormal FD innervation. The release of NO can influence the dynamics of ionic channels and neurotransmitter release, thus affecting neuronal membrane potential. Because the NOergic transmission does not obey the topographic constraints imposed on conventional transmitters, target cells can be stimulated even in regions with severe deafferentation. The plastic changes described here may contribute to abnormal hippocampal excitability.

Epilepsy, Temporal Lobe↗
PubMed2006

Group I metabotropic glutamate receptors activate the p70S6 kinase via both mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK 1/2) signaling pathways in rat striatal and hippocampal synaptoneurosomes.

Group I metabotropic glutamate receptors (mGluRs) have been demonstrated to play a role in synaptic plasticity via a rapamycin-sensitive mRNA translation signaling pathway. Various growth factors can stimulate this pathway, leading to the phosphorylation and activation of mammalian target of rapamycin (mTOR), a serine/threonine protein kinase that modulates the activity of several translation regulatory factors, such as p70S6 kinase. However, little is known about the cellular and molecular mechanisms that bring the plastic changes of synaptic transmission after stimulation of group I mGluRs. Here, we investigated the role of the mTOR-p70S6K and the ERK1/2-p70S6K pathways in rat striatal and hippocampal synaptoneurosomes after group I mGluR stimulation. Our findings show that (S)-3,5-dihydroxyphenylglycine (DHPG) increases significantly the activation of mTOR and p70S6K (Thr389, controlled by mTOR) in both brain areas. The mTOR activation is dose-dependent and requires the stimulation of mGluR1 subtype receptors as for the p70S6K activation observed in striatum and hippocampus. In addition, the p70S6K (Thr421/Ser424) activation via the ERK1/2 activation is increased and involved also mGluR1 receptors. These results demonstrate that group I mGluRs are coupled to mTOR-p70S6K and ERK1/2-p70S6K pathways in striatal and hippocampal synaptoneurosomes. The translational factor p70S6K could be involved in the group I mGluRs-modulated synaptic efficacy.

Animals↗
PubMed2002

Modulation of synaptic plasticity by stress and antidepressants.

Recent preclinical and clinical studies have shown that mechanisms underlying neuronal plasticity and survival are involved in both the outcome of stressful experiences and the action of antidepressants. Whereas most antidepressants predominantly affect the brain levels of monoamine neurotransmitters, it is increasingly appreciated that they also modulate neurotransmission at synapses using the neurotransmitter glutamate (the most abundant in the brain). In the hippocampus, a main area of the limbic system involved in cognitive functions as well as attention and affect, specific molecules enriched at glutamatergic synapses mediate major changes in synaptic plasticity induced by stress paradigms or antidepressant treatments. We analyze here the modifications induced by stress or antidepressants in the strength of synaptic transmission in hippocampus, and the molecular modifications induced by antidepressants in two main mediators of synaptic plasticity: the N-methyl-D-aspartate (NMDA) receptor complex for glutamate and the Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). Both stress and antidepressants induce alterations in long-term potentiation of hippocampal glutamatergic synapses, which may be partly accounted for by the influence of environmental or drug-induced stimulation of monoaminergic pathways projecting to the hippocampus. In the course of antidepressant treatments significant changes have been described in both the NMDA receptor and CaM kinase II, which may account for the physiological changes observed. A central role in these synaptic changes is exerted by brain-derived neurotrophic factor (BDNF), which modulates both synaptic plasticity and its molecular mediators, as well as inducing morphological synaptic changes. The role of these molecular effectors in synaptic plasticity is discussed in relation to the action of antidepressants and the search for new molecular targets of drug action in the therapy of mood disorders.

Animals↗
PubMed2006

Mitochondrial regulation of neuronal plasticity.

The structure and function of neurons is dynamic during development and in adaptive responses of the adult nervous system to environmental demands. The mechanisms that regulate neuronal plasticity are poorly understood, but are believed to involve neurotransmitter and neurotrophic factor signaling pathways. In the present article, I review emerging evidence that mitochondria play important roles in regulating developmental and adult neuroplasticity. In neurons, mitochondria are located in axons, dendrites, growth cones and pre- and post-synaptic terminals where their movements and functions are regulated by local signals such as neurotrophic factors and calcium influx. Mitochondria play important roles in fundamental developmental processes including the establishment of axonal polarity and the regulation of neurite outgrowth, and are also involved in synaptic plasticity in the mature nervous system. Abnormalities in mitochondria are associated with neurodegenerative and psychiatric disorders, suggesting a therapeutic potential for approaches that target mitochondrial mechanisms.

Aging↗
PubMed2006

Roles of glutamate receptors and the mammalian target of rapamycin (mTOR) signaling pathway in activity-dependent dendritic protein synthesis in hippocampal neurons.

Local protein synthesis in neuronal dendrites is critical for synaptic plasticity. However, the signaling cascades that couple synaptic activation to dendritic protein synthesis remain elusive. The purpose of this study is to determine the role of glutamate receptors and the mammalian target of rapamycin (mTOR) signaling in regulating dendritic protein synthesis in live neurons. We first characterized the involvement of various subtypes of glutamate receptors and the mTOR kinase in regulating dendritic synthesis of a green fluorescent protein (GFP) reporter controlled by alphaCaMKII 5' and 3' untranslated regions in cultured hippocampal neurons. Specific antagonists of N-methyl-d-aspartic acid (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and metabotropic glutamate receptors abolished glutamate-induced dendritic GFP synthesis, whereas agonists of NMDA and metabotropic but not AMPA glutamate receptors activated GFP synthesis in dendrites. Inhibitions of the mTOR signaling, as well as its upstream activators, phosphatidylinositol 3-kinase and AKT, blocked NMDA receptor-dependent dendritic GFP synthesis. Conversely, activation of mTOR signaling stimulated dendritic GFP synthesis. In addition, we also found that inhibition of the mTOR kinase blocked dendritic synthesis of the endogenous alphaCaMKII and MAP2 proteins induced by tetanic stimulations in hippocampal slices. These results identify critical roles of NMDA receptors and the mTOR signaling pathway for control of synaptic activity-induced dendritic protein synthesis in hippocampal neurons.

Animals↗
PubMed1993

Somatic gene therapy in otolaryngology-head and neck surgery.

The initial clinical trials of somatic gene therapy have demonstrated that gene transfer can be performed safely in a clinical setting and with public acceptance. These trials have focused attention on the broad applications of this technology in routine medical and surgical practice. This article reviews the reasons why somatic gene therapy could lead to significant improvements in clinical practice as well as specific therapies in otolaryngology-head and neck surgery. Early applications include the treatment of inherited diseases such as cystic fibrosis, new approaches for treating malignancies, new methods for enhancing tissue repair, and regeneration after plastic and reconstructive surgery, and the potential for using the thyroid as a target for somatic gene therapy. The following review will illustrate how somatic gene therapy may have a significant impact not only on the treatment of rare genetic diseases but on managing the common problems encountered by physicians and patients in daily practice.

Bone Transplantation↗
PubMed1981

Factors regulating growth of catecholamine-containing nerves, as revealed by transplantation and explantation studies.

Intraocular grafting of various types of neuron and target tissue shows that peripheral and central noradrenergic neurons may substitute morphologically and functionally for each other in certain, but not all, target tissues. The morphology of growing adrenergic nerve terminals, their patterning, and the number of fibres are completely determined by the target tissues. Thus, the sympathetic adrenergic neuron of an adult organism is a highly plastic unit which may, for instance, double or even triple its terminal field in response to new demands from the environment. Several differences exist between central and peripheral adrenergic nerves: locus coeruleus will not innervate heart grafts; sympathetic fibres will not innervate the spinal cord; and central adrenergic neurons are not sensitive to nerve growth factor (NGF). Chromaffin cells can be made to innervate peripheral and central targets. No NGF is detected in normal adult iris. The iris responds to grafting, explantation, and to sensory or sympathetic denervation with rapid production of NGF as shown by bioassays on chick embryonic ganglia. This iris also contains a potent stimulatory factor for the ciliary ganglion. Trauma to the iris or to the anterior eye chamber may cause it to become hyperinnervated. Heavy metals have characteristic and different effects on the sympathetic nerves of the iris: lead and manganese causes hyperinnervation; cadmium does not change the number of nerves; while mercury causes severe terminal degeneration followed by regeneration.

Animals↗
PubMed2003

Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA receptors.

Activity-dependent targeting of NMDA receptors (NMDARs) is a key feature of synapse formation and plasticity. Although mechanisms for rapid trafficking of glutamate receptors have been identified, the molecular events underlying chronic accumulation or loss of synaptic NMDARs have remained unclear. Here we demonstrate that activity controls NMDAR synaptic accumulation by regulating forward trafficking at the endoplasmic reticulum (ER). ER export is accelerated by the alternatively spliced C2' domain of the NR1 subunit and slowed by the C2 splice cassette. This mRNA splicing event at the C2/C2' site is activity dependent, with C2' variants predominating upon activity blockade and C2 variants abundant with increased activity. The switch to C2' accelerates NMDAR forward trafficking by enhancing recruitment of nascent NMDARs to ER exit sites via binding of a divaline motif within C2' to COPII coats. These results define a novel pathway underlying activity-dependent targeting of glutamate receptors, providing an unexpected mechanistic link between activity, mRNA splicing, and membrane trafficking during excitatory synapse modification.

6-Cyano-7-nitroquinoxaline-2,3-dione↗