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dc.contributor.authorKwon, Hyungbae
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 69-07, Section: B, page: 4006.;Advisors: Pablo E. Castillo.
dc.description.abstractThe mossy fiber to CA3 pyramidal cell synapse (mf-CA3) provides a major source of excitation to the hippocampus. It shows unique robust facilitation, and in a long-term manner, mf-CA3 synapse is well recognized for showing a presynaptic, NMDA receptor-independent form of long-term potentiation (LTP) which is expressed as a long-lasting increase of transmitter release. Thus, it is plausible that any transient or prolonged changes in synaptic efficacy at this synapse may have profound effects on information processing by hippocampal networks.;At the mf-CA3 synapse, two types of glutamatergic autoreceptors have been identified; transmitter release is reportedly suppressed by metabotropic glutamate receptors (mGluRs) and augmented by kainate receptors (KARs). Here, we show that during low-frequency mossy fiber stimulation, endogenous glutamate acting through presynaptic mGluRs substantially suppresses transmitter release. However, using similar recording conditions, we find that presynaptic KARs are insufficient to facilitate transmitter release over a wide range of mossy fiber stimulus frequencies. Furthermore, we report that actions generally attributed to presynaptic KARs are likely due to activation of recurrent CA3 network activity. Thus, negative feedback via presynaptic mGluRs is the dominant mode of glutamatergic autoregulation at the mf-CA3 synapse.;We also show that in addition to the "classical" LTP, mf-CA3 synapses can undergo a form of LTP characterized by a selective enhancement of NMDA receptor-mediated transmission. This potentiation requires coactivation of NMDA and mGlu5 receptors, and a postsynaptic calcium rise. Unlike classical LTP, expression of this novel mossy fiber LTP is due to a PKC-dependent recruitment of NMDA receptors specifically to the mf-CA3 synapse via a SNARE-dependent process. Having two mechanistically different forms of LTP may allow mf-CA3 synapses to respond with more flexibility to the changing demands of the hippocampal network.;We report here that the NMDAR-mfLTP speeds up spike onset and increases firing rate in CA3 pyramidal cells induced by physiologically relevant patterns of synaptic activity. Therefore, dynamic modulation of NMDAR-mediated transmission may participate in long-term modification of the CA3 network known to be critical to spatial memory formation.
dc.publisherProQuest Dissertations & Theses
dc.titleSynaptic plasticity at hippocampal mossy fiber to CA3 pyramidal cell synapses

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