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Title: Mossy fibre plasticity
Author: Sherwood , James Lawrence
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2007
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This study used extracellular field potential recordings (fEPSP) to investigate the role of kainate receptors (containing GLUK5) in short- and long-term potentiation (S-/L-TP) in the mossy fibre (MF) pathway. In vitro, the role of GLUK5 in synaptic plasticity is dependent on extracellular calcium concentration. So the physiological importance was investigated in vivo. In a single experiment GLUK5 selective antagonist, LY382884 (10, i.v.), attenuated STP. Notwithstanding, there is continued controversy regarding the role of GLUK5 in MF synaptic plasticity. Using GLUK5 selective antagonists, LY382884 and ACET, the method of hippocampal slice preparation is identified as deterministic. In parasagittal slices prepared in standard aCSF (PsH), STP, measured as ratio of 1st and 5th pulse (P5:P1) evoked at 25Hz, was antagonised by 10uM LY382884; NMDAR independent L TP, evoked by 100 pulses at 100Hz in 50uM AP5, was reversibly antagonised by 50nM ACET. Transverse hippocampal slices prepared in standard aCSF were not viable. In transverse slices prepared in high sucrose aCSF (TH), 10uM LY382884 had no effect on P5:P1-25Hz or P5:P1-50Hz; furthermore 100nM ACET had no effect on P5:P1-50Hz, or on the induction of NMDAR independent LTP. The depression of transmission by Group II mGluR agonists is reportedly a characteristic MF property. In PsH, DCG-IV had no effect on MF fEPSP but depressed P5:Pt-25Hz. In TH, DCG-IV and LY395756 (mGlu2 selective agonist) transiently depressed MF fEPSP. This was attenuated by a Group U competitive antagonist L Y341495. DCG-IV and LY395756 induced a concentration dependent long-term depression (LTD). While 100nM L Y341495 had no effect on OCGI-IV L TO, 300nM transiently reversed L Y395756 L TO. In conclusion, the pharmacology of synaptic plasticity in vitro is critically dependent on slice preparation; preliminary data suggest that GLUK5 receptors contribute to MF plasticity in vivo. Disparity in EC50 values for DCG-IV and L Y395756 induced depression suggests the possible involvement of mGlu3.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available