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Synaptic Efficacy (synaptic + efficacy)
Selected AbstractsControl of the triceps surae during the postural sway of quiet standingACTA PHYSIOLOGICA, Issue 3 2007C. D. Tokuno Abstract Aim:, The present study investigated how the triceps surae are controlled at the spinal level during the naturally occurring postural sway of quiet standing. Methods:, Subjects stood on a force platform as electrical stimuli were applied to the posterior tibial nerve when the center of pressure (COP) was either 1.6 standard deviations anterior (COPant) or posterior (COPpost) to the mean baseline COP signal. Peak-to-peak amplitudes of the H-reflex and M-wave from the soleus (SOL) and medial gastrocnemius (MG) muscles were recorded to assess the efficacy of the Ia pathway. Results:, A significant increase in the Hmax : Mmax ratio for both the SOL (12 ± 6%) and MG (23 ± 6%) was observed during the COPant as compared to the COPpost condition. The source of the modulation between COP conditions cannot be determined from this study. However, the observed changes in the synaptic efficacy of the Ia pathway are unlikely to be simply a result of an altered level of background electromyographic activity in the triceps surae. This was indicated by the lack of differences observed in the Hmax : Mmax ratio when subjects stood without postural sway (via the use of a tilt table) at two levels of background activity. Conclusions:, It is suggested that the phase-dependent modulation of the triceps surae H-reflexes during the postural sway of quiet standing functions to maintain upright stance and may explain the results from previous studies, which, until now, had not taken the influence of postural sway on the H-reflex into consideration. [source] Efficient copackaging and cotransport yields postsynaptic colocalization of neuromodulators associated with synaptic plasticityDEVELOPMENTAL NEUROBIOLOGY, Issue 10 2008J.E. Lochner Abstract Recent data suggest that tissue plasminogen activator (tPA) influences long-term plasticity at hippocampal synapses by converting plasminogen into plasmin, which then generates mature brain-derived neurotrophic factor (mBDNF) from its precursor, proBDNF. Motivated by this hypothesis, we used fluorescent chimeras, expressed in hippocampal neurons, to elucidate (1) mechanisms underlying plasminogen secretion from hippocampal neurons, (2) if tPA, plasminogen, and proBDNF are copackaged and cotransported in hippocampal neurons, especially within dendritic spines, and (3) mechanisms mediating the transport of these neuromodulators to sites of release. We find that plasminogen chimeras traffic through the regulated secretory pathway of hippocampal neurons in dense-core granules (DCGs) and that tPA, plasminogen, and proBDNF chimeras are extensively copackaged in DCGs throughout hippocampal neurons. We also find that 80% of spines that contain DCGs contain chimeras of these neuromodulators in the same DCG. Finally, we demonstrate, for the first time, that neuromodulators undergo cotransport along dendrites in rapidly mobile DCGs, indicating that neuromodulators can be efficiently recruited into active spines. These results support the hypothesis that tPA mediates synaptic activation of BDNF by demonstrating that tPA, plasminogen, and proBDNF colocalize in DCGs in spines, where these neuromodulators can undergo activity-dependent release and then interact and/or mediate changes that influence synaptic efficacy. The results also raise the possibility that frequency-dependent changes in extents of neuromodulator release from DCGs influence the direction of plasticity at hippocampal synapses by altering the relative proportions of two proteins, mBDNF and proBDNF, that exert opposing effects on synaptic efficacy. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] GABAergic modulation of primary gustatory afferent synaptic efficacyDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2002Andrew A. Sharp Abstract Modulation of synaptic transmission at the primary sensory afferent synapse is well documented for the somatosensory and olfactory systems. The present study was undertaken to test whether GABA impacts on transmission of gustatory information at the primary afferent synapse. In goldfish, the vagal gustatory input terminates in a laminated structure, the vagal lobes, whose sensory layers are homologous to the mammalian nucleus of the solitary tract. We relied on immunoreactivity for the GABA-transporter, GAT-1, to determine the distribution of GABAergic synapses in the vagal lobe. Immunocytochemistry showed dense, punctate GAT-1 immunoreactivity coincident with the layers of termination of primary afferent fibers. The laminar nature and polarized dendritic structure of the vagal lobe make it amenable to an in vitro slice preparation to study early synaptic events in the transmission of gustatory input. Electrical stimulation of the gustatory nerves in vitro produces synaptic field potentials (fEPSPs) predominantly mediated by ionotropic glutamate receptors. Bath application of either the GABAA receptor agonist muscimol or the GABAB receptor agonist baclofen caused a nearly complete suppression of the primary fEPSP. Coapplication of the appropriate GABAA or GABAB receptor antagonist bicuculline or CGP-55845 significantly reversed the effects of the agonists. These data indicate that GABAergic terminals situated in proximity to primary gustatory afferent terminals can modulate primary afferent input via both GABAA and GABAB receptors. The mechanism of action of GABAB receptors suggests a presynaptic locus of action for that receptor. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 133,143, 2002 [source] N -methyl- d -aspartate receptor- and metabotropic glutamate receptor-dependent long-term depression are differentially regulated by the ubiquitin-proteasome systemEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009Ami Citri Abstract Long-term depression (LTD) in CA1 pyramidal neurons can be induced by activation of either N -methyl- d -aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs), both of which elicit changes in synaptic efficacy through ,-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) endocytosis. To address the role of the ubiquitin-proteasome system in regulating AMPAR endocytosis during these forms of LTD, we examined the effects of pharmacological inhibitors of proteasomal degradation and protein ubiquitination on endocytosis of glutamate receptor 1 (GluR1) -containing AMPARs in dissociated rat hippocampal cultures as well as LTD of excitatory synaptic responses in acute rat hippocampal slices. Our findings suggest that the contribution of the ubiquitin-proteasome system to NMDAR-induced vs. mGluR-induced AMPAR endocytosis and the consequent LTD differs significantly. NMDAR-induced AMPAR endocytosis and LTD occur independently of proteasome function but appear to depend, at least in part, on ubiquitination. In contrast, mGluR-induced AMPAR endocytosis and LTD are enhanced by inhibition of proteasomal degradation, as well as by the inhibitor of protein ubiquitination. Furthermore, the decay of mGluR-induced membrane depolarization and Erk activation is delayed following inhibition of either ubiquitination or proteasomal degradation. These results suggest that, although NMDAR-dependent LTD may utilize ubiquitin as a signal for AMPAR endocytosis, mGluR-induced signaling and LTD are limited by a feedback mechanism that involves the ubiquitin-proteasome system. [source] Stabilizing effects of extracellular ATP on synaptic efficacy and plasticity in hippocampal pyramidal neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Eduardo D. Martín Abstract The role of adenosine triphosphate (ATP) as a neurotransmitter and extracellular diffusible messenger has recently received considerable attention because of its possible participation in the regulation of synaptic plasticity. However, the possible contribution of extracellular ATP in maintaining and regulating synaptic efficacy during intracellular ATP depletion is understudied. We tested the effects of extracellular ATP on excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by Schaffer collateral stimulation. In the absence of intracellular ATP, EPSC rundown was neutralized when a low concentration of ATP (1 µm) was added to the extracellular solution. Adenosine and ATP analogues did not prevent the EPSC rundown. The P2 antagonists piridoxal-5,-phosphate-azophenyl 2,,4,-disulphonate (PPADS) and reactive blue-2, and the P1 adenosine receptor antagonist 8-cyclopentyltheophylline (CPT) had no detectable effects in cells depleted of ATP. However, the protective action of extracellular ATP on synaptic efficacy was blocked by extracellular application of the protein kinase inhibitors K252b and staurosporine. In contrast, K252b and staurosporine per se did not interfere with synaptic transmission in ATP loaded cells. Without intracellular ATP, bath-applied caffeine induced a transient (< 35 min) EPSC potentiation that was transformed into a persistent long-term potentiation (> 80 min) when 1 µm ATP was added extracellularly. An increased probability of transmitter release paralleled the long-term potentiation induced by caffeine, suggesting that it originated presynaptically. Therefore, we conclude that extracellular ATP may operate to maintain and regulate synaptic efficacy and plasticity in conditions of abnormal intracellular ATP depletion by phosphorylation of a surface protein substrate via activation of ecto-protein kinases. [source] Group I metabotropic glutamate receptors regulate the frequency,response function of hippocampal CA1 synapses for the induction of LTP and LTDEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2004Els J. M. Van Dam Abstract Synaptically released glutamate binds to ionotropic or metabotropic glutamate receptors. Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors and can be divided into three subclasses (Group I,III) depending on their pharmacology and coupling to signal transduction cascades. Group I mGluRs are coupled to phospholipase C and are implicated in several important physiological processes, including activity-dependent synaptic plasticity, but their exact role in synaptic plasticity remains unclear. Synaptic plasticity can manifest itself as an increase or decrease of synaptic efficacy, referred to as long-term potentiation (LTP) and long-term depression (LTD). The likelihood, degree and direction of the change in synaptic efficacy depends on the history of the synapse and is referred to as ,metaplasticity'. We provide direct experimental evidence for an involvement of group I mGluRs in metaplasticity in CA1 hippocampal synapses. Bath application of a low concentration of the specific group I agonist 3,5-dihydroxyphenylglycine (DHPG), which does not affect basal synaptic transmission, resulted in a leftward shift of the frequency,response function for the induction of LTD and LTP in naïve synapses. DHPG resulted in the induction of LTP at frequencies which induced LTD in control slices. These alterations in the induction of LTD and LTP resemble the metaplastic changes observed in previously depressed synapses. In addition, in the presence of DHPG additional potentiation could be induced after LTP had apparently been saturated. These findings provide strong evidence for an involvement of group I mGluRs in the regulation of metaplasticity in the CA1 field of the hippocampus. [source] Activity-dependent modulation of GABAergic synapses in developing rat spinal networks in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002Marcelo Rosato-Siri Abstract The role of activity-dependent plasticity in modulating inhibitory synapses was investigated in embryonic rat spinal cord slice cultures, by chronic exposure to non-NMDA receptor blockers. GABAergic synaptic efficacy in control and chronic-treated cultures was investigated by patch-recordings from visually identified spinal interneurons. In both culture groups proximal stimulation induced the appearance of postsynaptic currents (PSCs), which were fully antagonized by 20 µM bicuculline application and reverse polarity at potential values close to those reported for spontaneous GABAergic PSCs. In chronically treated cells GABAergic evoked PSCs displayed a larger failure rate and a smaller coefficient of variation of mean PSC amplitude, when compared to controls. As opposed to controls, chronic GABAergic evoked PSCs did not facilitate upon paired-pulse stimulation. Facilitation at chronic synapses was observed when extracellular calcium levels were decreased below physiological values (< 2 mM). Kainate was used to disclose any functional differences between control and treated slices. In accordance with the presynaptic action of kainate, the application of this drug along with GYKI, an AMPA receptor selective antagonist, changed, with analogous potency, short-term plasticity of GABAergic synapses from control and treated cultures. Nevertheless, in chronic cultures, the downstream effects of such activation unmasked short-term depression. Ultrastructural analysis of synapses in chronically treated cultures showed a reduction both in symmetric synapses and in the number of vesicles at symmetric terminals. Thus, based on electrophysiological and ultrastructural data, it could be suggested that during the development of spinal circuits, GABAergic synapses are modulated by glutamatergic transmission, and thus implying that excitatory transmission regulates the strength of GABAergic synapses. [source] GDNF enhances the synaptic efficacy of dopaminergic neurons in cultureEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2000Marie-Josée Bourque Abstract Glial cell line-derived neurotrophic factor (GDNF) is known to promote the survival and differentiation of dopaminergic neurons of the midbrain. GDNF also causes an enhancement of dopamine release by a mechanism which is presently unclear. Using isolated dopaminergic neurons of the rat ventral tegmental area in culture, we have tested the hypothesis that GDNF regulates the establishment and functional properties of synaptic terminals. Previous studies have shown that single dopaminergic neurons in culture can co-release glutamate in addition to dopamine, leading to the generation of a fast excitatory autaptic current via glutamate receptors. Using excitatory autaptic currents as an assay for the activity of synapses established by identified dopaminergic neurons, we found that chronically applied GDNF produced a threefold increase in the amplitude of excitatory autaptic currents. This action was specific for dopaminergic neurons because GDNF had no such effect on ventral tegmental area GABAergic neurons. The enhancement of excitatory autaptic current amplitude caused by GDNF was accompanied by an increase in the frequency of spontaneous miniature excitatory autaptic currents. These observations confirmed a presynaptic locus of change. We identified synaptic terminals by using synapsin-1 immunofluorescence. In single tyrosine hydroxylase-positive neurons, the number of synapsin-positive puncta which represent putative synaptic terminals was found to be approximately doubled in GDNF-treated cells at 5, 10 and 15 days in culture. The number of such morphologically identified terminals in isolated GABAergic neurons was unchanged by GDNF. These results suggest that one mechanism through which GDNF may enhance dopamine release is through promoting the establishment of new functional synaptic terminals. [source] Plasticity of perisynaptic astroglia during synaptogenesis in the mature rat hippocampusGLIA, Issue 1 2007Mark R. Witcher Abstract Astroglia are integral components of synapse formation and maturation during development. Less is known about how astroglia might influence synaptogenesis in the mature brain. Preparation of mature hippocampal slices results in synapse loss followed by recuperative synaptogenesis during subsequent maintenance in vitro. Hence, this model system was used to discern whether perisynaptic astroglial processes are similarly plastic, associating more or less with recently formed synapses in mature brain slices. Perisynaptic astroglia was quantified through serial section electron microscopy in perfusion-fixed or sliced hippocampus from adult male Long-Evans rats that were 65,75 days old. Fewer synapses had perisynaptic astroglia in the recovered hippocampal slices (42.4% ± 3.4%) than in the intact hippocampus (62.2% ± 2.6%), yet synapses were larger when perisynaptic astroglia was present (0.055 ± 0.003 ,m2) than when it was absent (0.036 ± 0.004 ,m2) in both conditions. Importantly, the length of the synaptic perimeter surrounded by perisynaptic astroglia and the distance between neighboring synapses was not proportional to synapse size. Instead, larger synapses had longer astroglia-free perimeters where substances could escape from or enter into the synaptic clefts. Thus, smaller presumably newer synapses as well as established larger synapses have equal access to extracellular glutamate and secreted astroglial factors, which may facilitate recuperative synaptogenesis. These findings suggest that as synapses enlarge and release more neurotransmitter, they attract astroglial processes to a discrete portion of their perimeters, further enhancing synaptic efficacy without limiting the potential for cross talk with neighboring synapses in the mature rat hippocampus. © 2006 Wiley-Liss, Inc. [source] Tyrosine phosphorylation of the GluR2 subunit is required for long-term depression of synaptic efficacy in young animals in vivoHIPPOCAMPUS, Issue 8 2007Christopher J. Fox Abstract The study of the intracellular mechanics that underlay changes in synaptic efficacy is a rapidly evolving field of research. It is currently believed that NMDA receptors play a significant role in the induction of synaptic plasticity, whereas AMPA receptors play a significant role in its expression. For AMPA receptors, it has been shown that tyrosine phosphorylation of the GluR2 carboxyl termini is required for the expression of long-term depression of synaptic efficacy (LTD) in vitro (Ahmadian et al. (2004) EMBO J 23:1040,1050). In the present study, we sought to determine whether similar mechanisms are involved in vivo, where different stimulation parameters are required for the induction of LTD. We initially used a paired-burst (PB) paradigm that reliably induces LTD in vivo. In these animals we were able to prevent the induction and expression of PB-LTD by administering a peptide (GluR-3Y) that acted as a competitive inhibitor of tyrosine phosphorylation. In a separate set of animals, we exposed animals to brief periods of stress (S) before using low-frequency stimuli to induce LTD (S-LTD). Again, GluR2,3Y blocked both the induction and expression of S-LTD. In contrast, an inert version of the peptide, with alanine replacing the three tyrosine residues, did not inhibit LTD induction. In addition, we demonstrated that GluR2,3Y did not affect the induction of long-term potentiation in vivo. These findings support the hypothesis that tyrosine phosphorylation and AMPA receptor endocytosis are necessary steps for the induction and maintenance of two forms of LTD in the CA1 region. © 2007 Wiley-Liss, Inc. [source] Transforming growth factor-,2 modulates synaptic efficacy and plasticity and induces phosphorylation of CREB in hippocampal neuronsHIPPOCAMPUS, Issue 1 2007Teruyuki Fukushima Abstract Transforming growth factor-,s (TGF-,s) are widely expressed and play roles as multifunctional growth factors and regulators of key events in development, disease, and repair. However, it is not known whether TGF-,s affect the plasticity of hippocampal neurons. As a first step to address this issue, we examined whether TGF-,2 modulated the electrophysiological and biochemical properties of cultured hippocampal neurons. We found that prolonged 24 h treatment with TGF-,2 induced facilitation of evoked postsynaptic currents (ePSCs). This facilitation was associated with a decrease in short-term synaptic depression of ePSCs and increases in both the amplitude and frequency of spontaneous miniature postsynaptic currents (mPSCs). The long-term changes of ePSCs and mPSCs may be associated with cAMP response element-binding protein (CREB), which has been previously implicated in long-term potentiation. Immunofluorescence techniques and Western blot analysis both revealed that TGF-,2 enhanced the phosphorylation of CREB. Together, these results suggest that TGF-,2 may play a role in the cascade of events underlying long-term synaptic facilitation in hippocampus, and that CREB may be an important mediator of these effects. © 2006 Wiley-Liss, Inc. [source] Corticosterone shifts different forms of synaptic potentiation in opposite directionsHIPPOCAMPUS, Issue 6 2005Harm J. Krugers Abstract Calcium entering the cell via different routes, e.g.,N -methyl- D -aspartate (NMDA) receptors or voltage-dependent calcium channels (VDCCs), plays a pivotal role in hippocampal synaptic potentiation. Since corticosteroid hormones have been reported to enhance calcium influx through VDCCs, one may predict that these hormones facilitate hippocampal synaptic efficacy. Surprisingly, though, stress and corticosteroids have so far been found to reduce synaptic potentiation. Here, we addressed this apparent paradox and examined synaptic potentiation in the CA1 area of hippocampal slices from mice with low basal corticosterone levels 1,4 h after a brief in vitro administration of corticosterone. Nifedipine and APV were used to isolate NMDA receptor-mediated and VDCC-mediated long-term potentiations (LTPs), respectively. We report that corticosterone facilitates synaptic potentiation that depends on activation of VDCCs while impairing synaptic plasticity that is mediated by NMDA receptor activation. The glucocorticoid-receptor (GR) antagonist RU 38486 blocked both the effects of corticosterone. These results indicate that the net effect of corticosteroid hormones on synaptic plasticity is determined by the balance between different types of potentiation, a balance that may be region specific and depends on the experimental conditions. We speculate that these opposite effects on synaptic efficacy are involved in the bidirectional modulation of cognitive performance by corticosteroid hormones. © 2005 Wiley-Liss, Inc. [source] Hierarchical model of the population dynamics of hippocampal dentate granule cellsHIPPOCAMPUS, Issue 5 2002G.A. Chauvet Abstract A hierarchical modeling approach is used as the basis for a mathematical representation of the population activity of hippocampal dentate granule cells. Using neural field equations, the variation in time and space of dentate granule cell activity is derived from the summed synaptic potential and summed action potential responses of a population of granule cells evoked by monosynaptic excitatory input from entorhinal cortical afferents. In this formulation of the problem, we have considered a two-level hierarchy: the synapses of entorhinal cortical axons define the first level of organization, and dentate granule cells, which include these synapses, define the second, higher level of organization. The model is specified by two state field variables, for membrane potential and for synaptic efficacy, respectively, with both evolving according to different time scales. The two state field variables introduce new parameters, physiological and anatomical, which characterize the dentate from the point of view of neuronal and synaptic populations: (1) a set of geometrical constraints corresponding to the morphological properties of granule cells and anatomical characteristics of entorhinal-dentate connections; and (2) a set of neuronal parameters corresponding to physiological mechanisms. Assuming no interaction between granule cells, i.e., neither ephaptic nor synaptic coupling, the model is shown to be mathematically tractable and allows solution of the field equations leading to the determination of activity. This treatment leads to the definition of two state variables, volume of stimulated synapses and firing time, which describe observed activity. Numerical simulations are used to investigate the populational characterization of the dentate by individual parameters: (1) the relationship between the conditions of stimulation of active perforant path fibers, e.g., stimulating intensity, and activity in the granule cell layer; and (2) the influence of geometry on the generation of activity, i.e., the influence of neuron density and synaptic density-connectivity. As an example application of the model, the granule cell population spike is reconstructed and compared with experimental data. Hippocampus 2002;12:698,712. © 2002 Wiley-Liss, Inc. [source] MRNA differential display identification of thyroid hormone-responsive protein (THRP) gene in association with early phase of long-term potentiationHIPPOCAMPUS, Issue 6 2001Y.P. Tang Abstract The process of long-term potentiation (LTP) consists of the early induction and late maintenance phases. Few studies have examined the cellular mechanisms underlying these two phases; their respective mRNA expression profiles have not yet been elucidated. Here we used the technique of PCR differential display to identify genes that are differentially expressed between the early and late phases of LTP in vivo. Our results indicated that the cDNA fragment corresponding to one mRNA with preferentially increased expression during the early, but not late, phase of LTP encodes the rat thyroid hormone-responsive protein (THRP) gene. In situ hybridization analysis confirmed the results obtained from the PCR differential display. Prior NMDA receptor blockade with MK801 prevented induction of LTP and decreased THRP mRNA expression in the dentate gyrus, as assayed by quantitative RT-PCR analysis. THRP antisense oligonucleotide treatment before tetanic stimulation also prevented induction of LTP. However, when THRP antisense oligonucleotide was administered after induction of LTP, it did not affect expression and maintenance of LTP. THRP is known to be responsive to thyroid hormone. Our results indicate that direct thyroid hormone (T3) injection into the dentate gyrus produces a long-lasting enhancement of synaptic efficacy of these neurons. T3 injection also markedly increased THRP mRNA expression in the dentate gyrus. Taken together, our results suggest that THRP mRNA expression plays an important role in the early phase, but not the late phase, of LTP and that both THRP and thyroid hormone are involved in synaptic plasticity in hippocampal neurons. Hippocampus 2001;11:637,646. © 2001 Wiley-Liss, Inc. [source] Metabotropic Glutamate Receptors: Gatekeepers of HomeostasisJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2010J. B. Kuzmiski The capacity to appropriately respond to physiological challenges or perturbations in homeostasis is a requisite for survival. It is becoming increasingly clear that long-lasting alterations in synaptic efficacy are a fundamental mechanism for modifying neuroendocrine and autonomic output. We review recent advances in our understanding of plasticity at glutamate synapses onto magnocellular neurones (MNCs) in the paraventricular and supraoptic nuclei of the hypothalamus, with a focus on the contributions of metabotropic glutamate receptors (mGluRs) to long-lasting modifications in synaptic efficacy. Special attention is paid to the role of presynaptic mGluRs as gatekeepers for metaplasticity and regulation of body fluid homeostasis. The work highlighted here provides insight into the synaptic mechanisms that couple MNC activity to physiological states. [source] Tibolone Rapidly Attenuates the GABAB Response in Hypothalamic NeuronesJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2008J. Qiu Tibolone is primarily used for the treatment of climacteric symptoms. Tibolone is rapidly converted into three major metabolites: 3,- and 3,-hydroxy (OH)-tibolone, which have oestrogenic effects, and the ,4-isomer (,4-tibolone), which has progestogenic and androgenic effects. Because tibolone is effective in treating climacteric symptoms, the effects on the brain may be explained by the oestrogenic activity of tibolone. Using whole-cell patch clamp recording, we found previously that 17,-oestradiol (E2) rapidly altered ,-aminobutyric acid (GABA) neurotransmission in hypothalamic neurones through a membrane oestrogen receptor (mER). E2 reduced the potency of the GABAB receptor agonist baclofen to activate G-protein-coupled, inwardly rectifying K+ (GIRK) channels in hypothalamic neurones. Therefore, we hypothesised that tibolone may have some rapid effects through the mER and sought to elucidate the signalling pathway of tibolone's action using selective inhibitors and whole cell recording in ovariectomised female guinea pigs and mice. A sub-population of neurones was identified post hoc as pro-opiomelanocortin (POMC) neurones by immunocytochemical staining. Similar to E2, we have found that tibolone and its active metabolite 3,OH-tibolone rapidly reduced the potency of the GABAB receptor agonist baclofen to activate GIRK channels in POMC neurones. The effects were blocked by the ER antagonist ICI 182 780. Other metabolites of tibolone (3,OH-tibolone and ,4-tibolone) had no effect. Furthermore, tibolone (and 3,OH-tibolone) was fully efficacious in ER, knockout (KO) and ER,KO mice to attenuate GABAB responses. The effects of tibolone were blocked by phospholipase C inhibitor U73122. However, in contrast to E2, the effects of tibolone were not blocked by protein kinase C inhibitors or protein kinase A inhibitors. It appears that tibolone (and 3,OH-tibolone) activates phospholipase C leading to phosphatidylinositol bisphosphate metabolism and direct alteration of GIRK channel function. Therefore, tibolone may enhance synaptic efficacy through the Gq signalling pathways of mER in brain circuits that are critical for maintaining homeostatic functions. [source] Functional Consequences of Morphological Neuroglial Changes in the Magnocellular Nuclei of the HypothalamusJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2002S. H. R. OlietArticle first published online: 8 APR 200 Abstract The supraoptic and paraventricular nuclei of the hypothalamus undergo reversible anatomical changes under conditions of intense neurohypophysial hormone secretion, such as lactation, parturition and chronic dehydration. This morphological remodelling includes a reduction in astrocytic coverage of neurones resulting in an increase in the number and extent of directly juxtaposed somatic and dendritic surfaces. There is a growing body of evidence indicating that such anatomical plasticity is of functional significance. Astrocytic-dependent clearance of electrolytes and neurotransmitters from the extracellular space appears to be altered under conditions where glial coverage of magnocellular neurones is reduced. Glutamate, for example, has been found to accumulate in the extracellular space in the supraoptic nucleus of lactating animals and cause a modulation of synaptic efficacy. On the other hand, the range of action of substances released from astrocytes and acting on adjacent magnocellular neurones is expected to be limited during such anatomical remodelling. It thus appears that the structural plasticity of the magnocellular nuclei does affect neuroglial interactions, inducing significant changes in signal transmission and processing. [source] Environmental enrichment stimulates progenitor cell proliferation in the amygdalaJOURNAL OF NEUROSCIENCE RESEARCH, Issue 16 2009Hiroaki Okuda Abstract Enriched environments enhance hippocampal neurogenesis, synaptic efficacy, and learning and memory functions. Recent studies have demonstrated that enriched environments can restore learning behavior and long-term memory after significant brain atrophy and neural loss. Emotional and anxiety-related behaviors were also improved by enriched stimuli, but the effect of enriched environments on the amygdala, one of the major emotion-related structures in the central nervous system, remains largely unknown. In this study, we have focused on the effects of an enriched environment on cell proliferation and differentiation in the murine amygdala. The enriched environment increased bromodeoxyuridine (BrdU)-positive (newborn) cell numbers in the amygdala, almost all of which, immediately after a 1-week period of enrichment, expressed the oligodendrocyte progenitor marker Olig2. Furthermore, enriched stimuli significantly suppressed cell death in the amygdala. Some of the BrdU-positive cells in mice exposed to the enriched environment, but none in animals housed in the standard environment, later differentiated into astrocytes. Our findings, taken together with previous behavioral studies, suggest that progenitor proliferation and differentiation in the amygdala may contribute to the beneficial aspects of environmental enrichment such as anxiolytic effects. © 2009 Wiley-Liss, Inc. [source] Activation of M2 muscarinic receptors leads to sustained suppression of hippocampal transmission in the medial prefrontal cortexTHE JOURNAL OF PHYSIOLOGY, Issue 21 2009Lang Wang Cholinergic innervation of the prefrontal cortex is critically involved in arousal, learning and memory. Dysfunction of muscarinic acetylcholine receptors and their downstream signalling pathways has been identified in mental retardation. To assess the role played by the muscarinic receptors at the hippocampal,frontal cortex synapses, an important relay in information storage, we used a newly developed frontal slice preparation in which hippocampal afferent fibres are preserved. Transient activation of muscarinic receptors by carbachol results in a long-lasting depression of synaptic efficacy at the hippocampal but not cortical pathways or local circuitry. On the basis of a combination of electrophysiological, pharmacological and anatomical results, this input-specific muscarinic modulation can be partially attributed to the M2 subtype of muscarinic receptors, possibly through a combination of pre- and postsynaptic mechanisms. [source] Postnatal development of synaptic transmission in local networks of L5A pyramidal neurons in rat somatosensory cortexTHE JOURNAL OF PHYSIOLOGY, Issue 1 2007Andreas Frick The probability of synaptic transmitter release determines the spread of excitation and the possible range of computations at unitary connections. To investigate whether synaptic properties between neocortical pyramidal neurons change during the assembly period of cortical circuits, whole-cell voltage recordings were made simultaneously from two layer 5A (L5A) pyramidal neurons within the cortical columns of rat barrel cortex. We found that synaptic transmission between L5A pyramidal neurons is very reliable between 2 and 3 weeks of postnatal development with a mean unitary EPSP amplitude of ,1.2 mV, but becomes less efficient and fails more frequently in the more mature cortex of ,4 weeks of age with a mean unitary EPSP amplitude of 0.65 mV. Coefficient of variation and failure rate increase as the unitary EPSP amplitude decreases during development. The paired-pulse ratio (PPR) of synaptic efficacy at 10 Hz changes from 0.7 to 1.04. Despite the overall increase in PPR, short-term plasticity displays a large variability at 4 weeks, ranging from strong depression to strong facilitation (PPR, range 0.6,2.1), suggesting the potential for use-dependent modifications at this intracortical synapse. In conclusion, the transmitter release probability at the L5A,L5A connection is developmentally regulated in such a way that in juvenile animals excitation by single action potentials is efficiently transmitted, whereas in the more mature cortex synapses might be endowed with a diversity of filtering characteristics. [source] | ||||||||||