Date of Award
Doctor of Philosophy (PhD)
Dr. Ronald J. Racine
Information is believed to be stored in the brain by constructing new neural circuits, and these circuits are shaped by changes in the strength of the synaptic connections between the neurons making up the circuit. According to most theories of memory, new circuits can be formed by either increasing or decreasing the strength of synaptic connections. Bidirectional modifications in synaptic efficacy are also central components in recent computer simulations of learning and memory. While long-term potentiation (LTP) has been the focus of extensive research into the mechanisms underlying information storage in the mammalian brain, long-term depression (LTD) and depotentiation, its depressive counterparts, have not. Furthermore, most of the LTD research has involved the used of anaesthetized animals and in vitro slice preparations, making it more difficult to determine the role of this synaptic phenomenon in learning and memory in the intact behaving animal.
This thesis provides the first detailed examination of: 1) the induction and decay of both LTD and depotentiation in the neocortex of the awake, freely moving animals; 2) the effects of N-methyl D-Aspartate receptor (NDMAR) blockade on the induction of LTD, LTP, and depotentiation (NMDA receptor activation is known to play a major role in most forms of LTP); and 3) the interactions between these synaptic phenomena.
LTD was expressed as a significant reduction in the amplitude of both short- and long-latency field potential components. Depotentiation was expressed as a long lasting decrease in the amplitude of a previously enhanced late component. LTD was found to be greater in magnitude and longer lasting when the conditioning stimulation was repeated. However, unlike LTP induction, the conditioning stimulation was equally effective whether spaced over hours or days.
NMDA receptor antagonism blocked LTP induction and instead produced a depression effect similar to LTD. Unlike LTP, LTD and depotentiation were found to be NMDAR-independent in the neocortex of the freely moving rat.
LTP and LTD are both reversible phenomena and LTD-inducing stimulation can modulate the effects of LTP-inducing stimulation. LTD-inducing stimulation, when delivered following to LTP-inducing stimulation, attenuates the induction rate for potentiation. LTD and depotentiation may play important roles in the ongoing experience-induced modification of neuronal connectivity. Furthermore, these results are consistent with the hypothesis that potentiation and depression reflect the physiological instantiation of a bidirectional learning rule.
Froc, David John, "Neocortical Long-Term Depression and Depotentiation in the Adult, Freely Moving Rat" (2002). Open Access Dissertations and Theses. Paper 981.