Figure 2

CD treatment reduces excitatory synaptic transmission. (A) Hippocampal slices prepared from mice fed with KD or CD displayed reduced basal synaptic transmission compared to control SD fed animals (SD controls, n = 14; CD, n = 7; KD, n = 6; p < 0.001). Calibration bars: 10 ms, 0.5 mV. (B) Analysis of blood ketone bodies concentrations revealed a significant increase in both β-hydroxybutyrate (βHB; p < 0.001) and acetoacetate (ACA; p < 0.001) in the KD group only (n = 10). Markers of glycolysis (glucose, p < 0.01; lactate, p < 0.05; pyruvate, p < 0.05) were also significantly reduced in mice supplied with KD, indicating that this diet only induces high level of ketosis. The only change triggered by CD was a significant reduction in lactate (p < 0.05). (C) Analysis of the fibre volley amplitude as a function of stimulation intensity revealed a significant reduction in presynaptic excitability of CD and KD fed mice as compared to controls fed SD (CD: p < 0.001, KD: p < 0.01). (D) CD and KD dietary treatment also resulted in a clear enhancement of paired-pulse facilitation (SD, n = 5; KD, n = 6, p < 0.05; CD, n = 7, p < 0.001), which indicates a decreased probability of release. Example traces show facilitation at 50 ms ISI. Calibration bars: 10 ms, 0.5 mV. (E) The low-affinity competitive antagonist γ-d-glutamylglycine (γ-DGG), at a non-saturating concentration (0.5 mM) at which its potency depends on glutamate concentration decreased neurotransmission to a greater extent in CD and KD fed mice compared to SD controls (SD, n = 9; KD, n = 6, p < 0.001; CD, n = 7, p < 0.05), indicating lower glutamate synaptic concentrations in the KD and CD groups. Calibration bars: 10 ms, 0.5 mV. *p < 0.05, **p < 0.01, ***p < 0.001.