Long-term potentiation induced by temporary block of glycolysis in CA1 hippocampal neurons

This thesis focuses on the effects of temporary block of glycolysis by the competitive antimetabolite 2-deoxy-D-glucose (2-DG) on neuronal activity in the CA1 region of rat hippocampal slices. The overall aim was to investigate how synaptic transmission is suppressed when metabolism is greatly reduced by the replacement of glucose by 2-DG to provide some insight into the cellular mechanisms underlying these depressant effects. Experiments were carried out on hippocampal slices kept submerged and constantly superfused with oxygenated saline at 33--34°C. Block of glycolysis was induced by replacement of glucose by equimolar concentrations of 2-DG. Changes in synaptic efficacy and postsynaptic cell membrane properties were assessed in the initial slopes of EPSPs recorded by extra/intra or whole-cell patch recordings.The most striking observation of 2-DG induced glycolysis block is the consistent and sustained potentiation of CA1 synaptic transmission named as "2-DG LTP". Although in some respects 2-DG LTP is similar to conventional tetanic LTP, this novel type of LTP is unique in most of its features.Another finding is the reversible depression of synaptic function by 2-DG application. Adenosine receptor antagonists strongly delay or reduce this depression. In contrast, glyburide, a blocker of KATP channels, does not prevent the suppression of neuronal depression induced by 2-DG. In keeping with this only adenosine receptor blockers, but not glyburide, effectively attenuate 2-DG induced postsynaptic hyperpolarization.The evidence presented in this thesis indicates that, increased adenosine release as the result of 2-DG-induced energy deprivation, is a major cause of reversible loss of synaptic transmission and drop in membrane resistance. In addition, 2-DG LTP brings in a new concept that the regulation of glycolytic pathway plays an important role in modulation of neuronal synaptic plasticity that may contribute to learning and memory