Home About us Contact
|
Home About us Contact | ||
|
|
||
Hippocampal Synapses (hippocampal + synapsis)
Selected AbstractsEfficient 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] 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] Evidence that caspase-1 is a negative regulator of AMPA receptor-mediated long-term potentiation at hippocampal synapsesJOURNAL OF NEUROCHEMISTRY, Issue 4 2006Chengbiao Lu Abstract Best known for their pivotal role in a form of programmed cell death called apoptosis, caspases may also function in more subtle physiological processes. Caspases are present in synapses and dendrites of neurons where they can be activated in response to glutamate receptor stimulation and calcium influx. Here we tested the hypothesis that caspase-1 plays a role in modulating long-term potentiation (LTP) at hippocampal synapses. We provide evidence that caspase-1 plays a role in regulating ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated calcium influx and synaptic plasticity in the hippocampus. LTP of excitatory postsynaptic potentials at CA1 synapses was significantly enhanced when hippocampal slices were treated with either a pan-caspase inhibitor or a selective inhibitor of caspase-1, but not by an inhibitor of caspase-6. Inhibition of caspase-1 significantly enhanced the AMPA current-mediated component of LTP without affecting the N -methyl- d -aspartate current-mediated component. Calcium responses to AMPA were enhanced in hippocampal neurons treated with a caspase-1 inhibitor suggesting that caspase-1 normally functions to reduce AMPA receptor-mediated calcium influx. These findings suggest that, by selectively reducing AMPA currents and calcium influx, caspase-1 functions as a negative regulator of LTP at hippocampal synapses. [source] | ||||||||||