Long-term potentiation in hippocampal slices induced by temporary suppression of glycolysis

Abstract

1. Temporary suppression of glycolysis by 2-deoxy-D-glucose (2-DG)-long enough to abolish CA1 population spikes (PSs) and reduce field excitatory postsynaptic potentials (EPSPs) by two-thirds-is followed by a sustained rebound of EPSPs and PSs (both up by 70-150%). 2. Post 2-DG long-term potentiation (2-DG-LTP) is prevented by block of N-methyl-D-aspartate (NMDA) receptors (NMDARs). Though 2-DG-LTP is normally expressed by other receptors, in presence of picrotoxin 2-DG causes similar LTP of NMDAR-mediated EPSPs. 3. Stimulation at 1 s-1 fully depotentiates 2-DG-LTP. 4. Unlike tetanic LTP, 2-DG-LTP is not pathway-specific, is not occluded by a preceding tetanic LTP (or vice versa) and is insensitive to block of NO synthesis. 5. Hypoglycemic states may have long-lasting after-effects on cerebral synaptic function.

Ischemia induces short‐ and long‐term remodeling of synaptic activity in the hippocampus

“…Interestingly, hypoglycemic episodes may also have per se long-lasting effects on synaptic function. Temporary suppression of glycolysis by 2-deoxy-D-glucose (2-DG), long enough to abolish CA1 population spikes and reduce field EPSPs, is followed by a sustained increase of EPSP amplitude [30]. This pathological LTP is prevented by NMDA receptors antagonists, and is not pathway-specific.…”

Nampt is required for long-term depression and the function of GluN2B subunit-containing NMDA receptors

“…While P30 CamKIIαNampt −/− mice exhibit relatively normal CA1 population spikes and fEPSPs, other conditions involving energy deprivation, such as hypoglycemia [72, 81], anoxia [31, 33], or ischemia [60, 87] are associated with reduced or abolished population spikes and fEPSPs. Similarly, CamKIIαNampt −/− mice exhibit normal LTP, whereas hypoglycemia [37], anoxia [33], ischemia [13, 87], or pharmacological glycolytic blockade [34] can abolish LTP.…”

“…Consolidation of hippocampal-dependent memory has been linked to N-methyl-D-aspartate receptor (NMDAR) dependent LTD in CA1 [7, 25, 91]. NMDAR activation modulates induction of LTP and LTD [94] and occurs during conditions of energy deprivation, such as hypoxia and hypoglycemia [13, 14, 26, 31, 81]. NMDARs are tetrameric receptors consisting of two obligatory NR1 (GluN1) subunits and two regulatory subunits, usually a combination of GluN2A (NR2A) and GluN2B (NR2B) [94].…”

IDDM, Counterregulation, and the Brain

“…After less-profound hypoglycemia, these same compounds could also alter signaling in the brain through such learninglike mechanisms as long-term potentiation. Inhibition of glycolysis and cellular glucopenia have been shown to induce such long-term potentiation (18,19).…”