Fig. 2.

Confronting mathematical model and experimental data delineates the energetic needs of synaptic plasticity. (A) In the model (Materials and Methods and SI Appendix, Supplementary Information for the Mathematical Model, Supplementary Methods and Materials, and SI Appendix, Table S2), the synaptic weight is gated by both neuronal calcium (potentiation) and ATP (depression); VGCC, voltage-gated calcium channel; VGSC, voltage-gated sodium channel; EAAT2, excitatory amino acid transporter-2; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid. (B) Time course of the synaptic weight in the model (lines) fitted to 5-TBS (n = 7) and STDP (n = 14; 50 pairings at 0.5 Hz; spike timing = 10 ms) experiments (circles). (C) Model prediction for the evolution of neuronal concentrations and synaptic weight with 5-TBS (red) or STDP (black). (D) TBS-LTP expression depending on glucose concentration ([Glucose]_c) as predicted by the model. Experimentally, 5-TBS induced LTP (P = 0.0299, n = 8) at a high glucose concentration (25 mM), and this LTP was not impaired by LDH inhibition (i-oxamate; P = 0.0044, n = 6). (E) 5-TBS–LTP expression with hexokinase inhibition (i-mannoheptulose; P = 0.0230, n = 7). (F) Fifty pairings at 0.5 Hz induced STDP-LTP with i-mannoheptulose (P = 0.0210, n = 7). (G) One hundred pairings at 1 Hz induced STDP-LTP with i-mannoheptulose (P = 0.0436, n = 6). When neuronal glycolysis and lactate conversion into pyruvate were inhibited with coapplied i-mannoheptulose and i-oxamate, 100 pairings did not induce plasticity (P = 0.5297, n = 6). Representative traces show 15 EPSCs averaged during baseline (gray) and 45 min (red) after protocols (arrows). All data are represented as mean ± SEM (except in B where SEM was omitted for clarity); *, P < 0.05; ns, not significant by two tailed t test. See SI Appendix, Table S3 for detailed data and statistics.