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Title: Synaptic plasticity of the hippocampal mossy fibres in vivo
Author: Wallis , James
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2013
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Hippocampal mossy fibres (MFs) have been studied intensely in vitro. While many properties of the MFs are well characterised, other findings are debated, particularly in relation to MF long-term potentiation (MF-L TP). MF-L TP is widely accepted as being expressed presynaptically in vitro; however, the induction mechanisms remain unclear. Although kainate receptors (KARs) are generally considered to have a role in MF-L TP induction, the identity of the subtype is debated. Furthermore, the contribution of metabotropic glutamate receptors (mGlu receptors) in this form of plasticity is also controversial. The MFs also exhibit unusual short-term plasticity, including frequency facilitation (FF) which is observed to variable extents in vitro and in conscious rats. An aim of this study was to circumvent the methodological variations, which can affect experimental outcomes in vitro. This was achieved by assessing MF synaptic plasticity in vivo, in anaesthetised rats. A slow-onset MF-L TP was reliably induced and saturated by one train of tetanisation at 100 Hz. MF field excitatory postsynaptic potentials (fEPSPs) were depressed by a group II mGlu receptor agonist, DCG-IV. MF-L TP was also shown to be inducible independently of NMDAR activation. The slow-onset profile of MF-L TP was further investigated and found to be unaffected by altering anaesthetic and tetanisation parameters. Depression, as opposed to facilitation, of the MF fEPSPs occurred in anaesthetised rats during increased frequencies of stimulation. However, facilitation of the fEPSPs was noted in the hippocampus, most likely at the associational/commissural pathway following contralateral or ipsilateral stimulation. MF-L TP persisted in the presence of KAR antagonists or mGlu receptor antagonists. However, MF-L TP was abolished by intrahippocampal co-injection of a KAR antagonist with specific mGlu receptor antagonists. Use of group I mGlu receptor antagonists indicated roles for both mGlu1 and mGlu5 receptors. This study suggests that KARs and mGlu receptors play interchangeable roles in the induction of MF-LTP in vivo.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available