Date of Award
Doctor of Philosophy (PhD)
Ronald J. Racine
Long-term potentiation (LTP) is a lasting enhancement of synaptic transmission following high frequency electrical stimulation. It has been widely studied as a memory model, primarily because it has associative properties and is long-lasting. If LTP reflects a mechanism for information storage, then it should be readily induced within structures believed to encode long-term memory. The neocortex, however, has proven resistant to LTP induction. Most of our knowledge about neocortical LTP has come from anaesthetized and in vitro slice preparations. If LTP is to be considered seriously as a memory model, then it must be demonstrated in awake animals and shown to last for periods longer than a few hours. This thesis provides the first parametric analysis of neocortical neocortical LTP in the freely moving rat including: (i) the variables governing the induction and decay of LTP; (ii) the critical role played by the NMDA receptor in LTP induction; (iii) GABAergic and cholinergic modulation of LTP and; (iv) the effects of maximal electroconvulsive shock on the induction of LTP. Neocortical potentiation resulted in robust changes in an early and two late components of the evoked EPSPs, as well as the superimposed population spikes. Stronger potentiation effects were obtained by increasing the number of trains delivered/session, the number of stimulation sessions, the pulse intensity of the trains, or the interval between train delivery. Moreover, the delivery of either 1 train/day, or very low intensity trains, resulted in LTP. An NMDA antagonist blocked potentiation and unmasked a long-term depression effect. GABAergic agonism or cholinergic antagonism retarded the development of LTP while cholinergic agonism enhanced LTP of a polysynaptic component. GABAergic antagonism slowed the development of LTP. Maximal electroconvulsive shock (MES) resulted in a blockade of LTP induction that was dependent on the interval between the trains and the MES stimulation. These results are discussed relative to in vitro data and considered in the context of the different information processing features of the neocortical and hippocampal learning systems.
Trepel, Christopher, "Neocortical long-term potentiation in the adult, freely moving rat" (1997). Open Access Dissertations and Theses. Paper 3371.