Fig. 2

Dysfunction of basal neuronal activity. a–f Spontaneous synchronous neuronal firing in hippocampal CA1 (a, b), ventral medial hypothalamus (VMH; c, d), and basolateral amygdala (BLA; e, f) at the pre-clinical stage (a, c, e) and at clinical onset (b, d, f) measured by MEA (left panels of a, c, e; black dots are electrodes with the regions of interest marked by the dotted box). Raster plots (middle panels) present the neuronal firing (black dash) and burst (red line) with the quantification of burst rate (scatterplot on the right), comparing uninfected controls (UN) and infected mice (INF). See supplementary file 2 for representative burst traces. g–i Relative oscillatory powers of delta and gamma oscillations in UN versus INF at the pre-clinical stage and clinical onset in the CA1 (g), VMH (h), and BLA (i). Upper panels are representative traces of local field potentials (LFP; light blue) and delta waves from UN (dark blue) and INF (red). See supplementary file 3 for delta and gamma peak frequency. j–l Calcium flux analysis in the three limbic regions (hippocampus, hypothalamus, amygdala) at the pre-clinical stage and clinical onset (n = 3 per group). m–o Input–output curves measuring the magnitude of field excitatory post-synaptic potential (fEPSP) responses to increasing strength of stimuli to assess the impact of prion disease on the strength of synaptic transmission in the three limbic regions (CA1, VMH, BLA) at the pre-clinical stage (left panels; n = 8 for UN; n = 4 for IN) and clinical onset (right panels; n = 8 for UN; n = 4 for IN). Representative traces of fEPSPs are presented in each plot (vertical bars represent 100 µV and horizontal bars show 10 ms). Data were analyzed by unpaired Student’s t test (a–i) and Two-way ANOVA (assuming sphericity) with repeated measures and Sidak corrections for multiple comparisons. Data (biological replicates) are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001