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UBC Theses and Dissertations

Long-term potentiation and discrimination learning Skelton, Ronald William


Recent electrophysiological studies have shown that electrical brain stimulation (EBS) can produce lasting increases in synaptic efficacy, defined as the quantitative relationship between pre- and postsynaptic activity. However, the behavioural significance of this long-term potentiation (LTP) has yet to be demonstrated clearly. The principal objective of this thesis was to determine whether increased synaptic efficacy, produced by high-frequency EBS, enhances behavioural responses to a fixed amount of presynaptic activity. Following identification of EBS parameters capable of monitoring synaptic efficacy for long periods without producing LTP, a paradigm was developed in which a single-pulse of EBS in the perforant path (PP) acquired stimulus control over the temporal pattern of operant responses. In this paradigm, postsynaptic evoked potentials in the dentate gyrus (DG) produced by the PP EBS were used to monitor synaptic efficacy on every trial of conditioning and also to measure one component of the neural activity generated by the EBS stimulus controlling the operant responses. In Experiment 3, high-frequency stimulation of the PP produced- LTP at the PP-DG synaptic interface and facilitated subsequent acquisition of stimulus control by the single pulse PP EBS. This effect could not have been due to sensitization or to the stimulus properties of the high-frequency trains. The final experiment confirmed the importance of the EBS-evoked activity in the DG to the stimulus control by the PP EBS. The rate of acquisition was directly related to the magnitude of the evoked potentials and two-stage bilateral lesions of the PP in a specific sequence reduced the probability of behavioural responses to the EBS. Taken together, these results indicate that the behavioural consequence of excitatory neural activity can be enhanced by an increase in synaptic efficacy. As such, they provide considerable support for the validity of LTP as a model of neural changes subserving learning and for physiological theories of memory based on modifications in the- strength of synaptic connections.

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