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Title: An electrophysiological study of the actions of substance P and b-amyloid on synaptic transmission in the rat hippocampus
Author: Wease, Kerrie Nicola
ISNI:       0000 0001 3564 7806
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2003
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The fragment b-amyloid (25-35) has sequence similarity with the tachykinin family.  It was therefore suggested that amyloid peptides might produce their effects via the tachykinin receptors.  The actions of tachykinin agonist and b-amyloid fragments on synaptic transmission in the rat hippocampus were explored using extracellular and whole cell patch clamp recording techniques.  Using extracellular recording techniques we examined the effect of substance P on population spikes and in particular on paired pulse depression (PPD) within the CA1 region of the hippocampus. Slices, which gave PPD on onset, showed marked changes in the amplitude of population spike on the application of substance P.  Substance P (8mm) produced a two-fold decrease in PPD with the second population spike increasing in amplitude.  However, substance P had little or no effect on the amplitude of the first population spike.  The use of various tachykinin receptor agonists revealed that only NK-1 receptor agonists could significantly increase the amplitude of the second population spike.  Further to this, the NK-1 receptor antagonist SR140333 blocked the action of substance P.  Therefore, it was concluded that substance P acting via the NK-1 receptor could decrease the degree of paired pulse depression observed, thereby increasing the amplitude of the second population spike. Application of b-amyloid (1-40)(5mm) produced a similar effect to substance P, having no effect on PS1, but reducing the amount of PPD.  However, the application of the neurotoxic fragment b-amyloid (25-35)(5, 10mm) which contains the sequence found in tachykinins, caused no reduction in the PPD.  The results demonstrated that the action of b-amyloid may depend on the length of the fragment used. Whole cell patch clamp recording revealed that substance P had no consistent effect on the passive membrane properties of the cells recorded from.  Substance P increased the amplitude of pharmacologically isolated NMDA receptor mediated EPSPs and pharmacologically isolated GABAA receptor mediated IPSPs.  These effects are not easily reconciled with the results obtained using extracellular recordings.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Electrophysiology