Figure 4

Synaptic plasticity and altered synapse morphology in Mcoln1 ^−/− mice. (A). Basal synaptic transmission: the synaptic input–output curve shows fEPSP slopes as a function of fiber-volley amplitudes for wild-type (n = 24 slices, 6 mice) and Mcoln1 ^−/− (n = 26 slices, 6 mice). The lines represent linear regression of the data; p = 0.08. (B). The paired-pulse facilitation (PPF) is enhanced in Mcoln1 ^−/− mice. The facilitation ratio is shown as a function of interpulse interval (ISI) for wild-type (n = 29 slices, 6 mice) and Mcoln1 ^−/− (n = 31 slices, 6 mice) slices. *, p < 0.05. (C). Increased LTP in Mcoln1 ^−/− mice. LTP was induced in control (n = 18 slices, 6 mice) and Mcoln1 ^−/− slices (n = 16 slices, 6 mice) with 4 tetanic trains (100 Hz, 1 s) separated by 5 min each. *, p < 0.05. fEPSP recordings were filtered at 1 kHz, digitized at 20 kHz, and analyzed using pClamp10 (Axon Instruments). (D). Electron micrographs of CA1 stratum radiatum: white arrowheads indicate examples of PSDs in macular excitatory (glutamatergic) synapses included in the analysisin (E); black arrows show post-synaptic densities of active zones in the perforated excitatory synapses omitted from the analysis. Mth, mitochondria; gl, process of a glial cell; sp – dendritic spine. (E). PSD length quantification in 4 control and 4 Mcoln1 ^−/− mice, total number of 433 control and 402 Mcoln1 ^−/− synapses. Data presented as median values with interquartile range, *, p (clustered rank-sum test) <0.05. (F). Synapse density quantification. Each data point represents the average number of synapses per μm² per mouse; line bars represent average value per genotype group and SEM; p (Student's t-test) >0.05. (G). Volume of mitochondria: total number of 1262 control and 1196 Mcoln1 ^−/− mitochondria measured (n = 4 mice per genotype); n.s., p (clustered rank-sum test) > 0.05.