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Title: The role of Galanin in synaptic transmission and plasticity in the CA1 area of the rodent hippocampus
Author: Coumis, U.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Long-term potentiation (LTP) has been widely recognised as a model of the synaptic changes that may underlie learning and memory in vertebrates. It may be predicted that the physiological action of galanin at the cellular level would be to depress LTP, thereby causing an impairment in mnemonic processes mediated by the hippocampus. Experiments were designed to address three aspects of this hypothesis, namely (1) characterisation of the effect of galanin agonists and antagonists on synaptic transmission and plasticity in the CA1 area of rodent hippocampus and (2) investigation of glutamatergic synaptic plasticity in galanin knockout mice and their wild-type littermates. Exogenous galanin induced a does-dependent increase in the slope of baseline fEPSPs, which appeared to be dependent on the pathways from CA3 to CA1 being intact, but it did not have any effect on paired-pulse facilitation ratios. In CA3 hemisected hippocampal slices the aforementioned effect did not occur. The effect of galanin on LTP and long-term depression (LTD) of glutamate mediated synaptic transmission in apical and basal dendrites of CA1 pyramidal neurones were investigated using both intracellular and extracellular recording techniques in vitro. LTP induced in either apical or basal dendrites of CA1 pyramidal neurones by different paradigms was significantly inhibited by galanin. Galanin also inhibited LTP in hippocampal slices prepared form wild-type mice. This effect was reversible by the known galanin antagonist, galantide (M15). Galanin did not affect isolated pure NMDA receptor-mediated postsynaptic potentials or the loss of spike frequency adaptation and increase in input resistance evoked by metabotropic glutamate receptor activation indicating that its inhibition of LTP was downstream of these receptors. Galanin applied had no effect the expression of LTP indicating that galanin may inhibit LTP by interfering with kinase activity necessary for the induction of LTP e.g. protein kinase C. Galanin did not affect the induction of LTD. Subsequent studies in the galanin-null transgenic mice yielded no effect on synaptic strength or paired pulse facilitation ratios. Galanin seems to have inhibitory modulatory effect on excitatory neurotransmitters such as glutamate in the hippocampus, thereby delaying the neurodegenerative effect of age. The research described in this thesis is deemed of importance in biomedical research of drug therapy for protection against neurodegenerative disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available