Article Figures & Data
Figures
- Figure 1.
Increased excitability, but reduced facilitation, at mossy fibers of presymptomatic and symptomatic SynTKO mice. a, Excitability was increased in brain slices from presymptomatic SynTKO mice (red, 37 slices from 13 animals) compared with WT mice (blue, 31 slices from 12 animals). Pooled fEPSP amplitudes (mV) were plotted against pooled PFV amplitudes (mV) and fitted with a simple linear regression. The slopes of the linear regressions were significantly different (p < 0.0001, tested with a two-tailed ANCOVA). The 95% confident bands are shown as dotted lines around the fit. The black arrows indicate the data points corresponding to the example traces shown in the inset. Inset, Example traces from WT (blue) and SynTKO (red) slices with similar PFV amplitudes. Note the difference in the corresponding fEPSP amplitude. b, c, Frequency facilitation is reduced in presymptomatic SynTKO (red) compared with WT (blue) slices. b, Averaged normalized fEPSP amplitudes ± SEM from all WT (blue, 31 slices from 12 animals) and SynTKO (red, 27 slices from 9 animals) recordings plotted against the number of stimuli. Stimuli 1–10 were given with a frequency of 0.05 Hz, Stimuli 11–30 with 1 Hz, and Stimuli 31–41 with a frequency of 0.05 Hz again. Both time and the interaction between genotype and time were significantly different in a mixed-effect model (p < 0.0001; p < 0.001). Post hoc Sidak’s test for multiple comparisons revealed no significant differences. Right, Example fEPSP amplitudes from WT (blue) and SynTKO (red) recordings at the 20th 1 Hz stimulus. Respective baseline fEPSP amplitudes are shown in black. c, fEPSP amplitudes at the 20th stimulus at 1 Hz for individual WT (blue dots; 31 slices from 12 animals) and SynTKO (red dots; 27 slices from 9 animals) recordings. Median values ± interquartile ranges are shown in black. Facilitation was significantly different (p = 0.0089; Mann–Whitney U test). d, PPR for presymptomatic SynTKO and age-matched control animals. Dots represent PPR from individual recordings from WT (blue dots, 31 slices from 12 animals) and SynTKO (red dots, 34 slices from 12 animals) slices, calculated as the ratio of second to first fEPSP amplitude. The interstimulus interval was 50 ms. Median values ± interquartile ranges are depicted in black. Ranks were compared in a Mann–Whitney U test and were not significantly different (p = 0.133). e, Excitability was increased in recordings from symptomatic SynTKO mice (red; 18 slices from 5 animals) compared with WT mice (blue; 17 slices from 4 animals). Pooled fEPSP amplitudes (mV) were plotted against pooled PFV amplitudes (mV) and fitted with a simple linear regression. The slopes of the linear regressions were significantly different (p < 0.0001, tested with a two-tailed ANCOVA). The 95% confidence bands are shown as dotted lines around the fit. Inset, Example traces from WT (blue) and SynTKO (red) animals with similar PFV amplitudes. Note the difference in the corresponding fEPSP amplitude. f, g, Frequency facilitation was reduced in symptomatic SynTKO (red) compared with WT (blue) animals. f, Averaged normalized fEPSP amplitudes ± SEM from all WT (blue; 17 slices from 4 animals) and SynTKO (red; 19 slices from 5 animals) recordings plotted against the number of stimuli. Stimuli 1–10 were given with a frequency of 0.05 Hz, Stimuli 11–30 with 1 Hz, and Stimuli 31–41 with a frequency of 0.05 Hz again. Both time and the interaction between genotype and time were significantly different in a mixed-effect model (p < 0.0001). Post hoc Sidak’s test for multiple comparisons revealed significant differences (p < 0.05) for two time points. Right, Example fEPSP amplitudes from WT (blue) and SynTKO (red) animals at the 20th 1 Hz stimulus. Respective baseline fEPSP amplitudes are shown in gray. g, fEPSP amplitudes at the 20th stimulus at 1 Hz for individual WT (blue dots, 17 slices from 4 animals) and SynTKO (red dots, 19 slices from 5 animals) recordings. Median values ± interquartile ranges are shown in black. Facilitation was significantly different (p = 0.0009; tested with Mann–Whitney U test). h, PPR for symptomatic SynTKO and age-matched control animals. Top, Example traces for a paired-pulse from WT (dark blue) and SynTKO (dark red) recordings, respectively. Bottom, Dots represent PPR from individual recordings from WT (dark blue dots, 17 slices from 4 animals) and SynTKO (dark red dots, 19 slices from 5 animals) slices, calculated as the ratio of second to first fEPSP amplitude. The interstimulus interval was 50 ms. Median values ± interquartile ranges are depicted in black. Ranks were compared in a Mann–Whitney U test and were significantly different (p = 0.0325).
- Figure 2.
Faster depression during high-frequency stimulation in SynTKO mice.
High-frequency stimulation comprised four trains of 125 pulses at 25 Hz with an interval of 20 s between the first stimuli of consecutive trains. a, Top, Example traces show fEPSP amplitudes of mossy fibers from WT (blue) and SynTKO (red) slices in response to the first 10 stimuli of the first high-frequency stimulation train. Bottom, Normalized averaged fEPSP amplitudes plotted against the number of stimuli of the first high-frequency stimulation train for WT (blue, 11 slices from 5 animals) and SynTKO (red, 12 slices from 6 animals) recordings. A mixed-effect model revealed no significant difference between genotypes (p = 0.59), but significant differences (p < 0.0001) for the factor time (stimulus). A post hoc Sidak’s test for multiple comparisons revealed no significant differences for single time points. b, Top, Example traces show fEPSP amplitudes of WT (blue) and SynTKO (red) animals in response to the first 10 stimuli of the fourth high-frequency stimulation train. Bottom, Normalized averaged fEPSP amplitudes plotted against number of stimuli of the first high-frequency stimulation train for WT (blue, 11 slices from 5 animals) and SynTKO (red, 12 slices from 6 animals) animals. The factor time (stimulus) was significantly different in a mixed-effect model (p < 0.0001), while the genotype and the interaction of both were not (p = 0.22 and p > 0.99). A post hoc Sidak’s test for multiple comparisons revealed no significant differences for single time points. c, Normalized fEPSP amplitudes at the 25th and 125th stimulus of the first stimulation train for individual WT (blue dots, 11 slices from 5 animals) and SynTKO (red dots, 12 slices from 6 animals) recordings. Median values ± interquartile ranges are shown in black. Ranks were not significantly different for either 25th (p = 0.695; Mann–Whitney U test) or 125th stimulus (p = 0.74, Mann–Whitney U test). d, Normalized fEPSP amplitudes at the 25th and 125th stimulus of the fourth stimulation train for individual WT (blue dots, 11 slices from 5 animals) and SynTKO (red dots, 12 slices from 6 animals) recordings. Median values ± interquartile ranges are shown in black. Ranks were significantly different at the 125th stimulus (p = 0.032; Mann–Whitney U test), but not at the 25th stimulus (p = 0.88; Mann–Whitney U test). e, The loss of fibers during high-frequency stimulation is not substantial and similar for SynTKO and WT mice. Exemplary traces from high-frequency stimulation trains for WT (blue) and SynTKO (red) animals. The 10th PFV and fEPSP from the first and fourth stimulation train are depicted, respectively. Dotted lines indicate the peaks of the PFV. Note that although the PFV is smaller for SynTKO (due to technical reasons in response to the high excitability), the size is relatively consistent throughout the trains. f, Averaged PFV (mV) taken from 10–15 pulses from the first and fourth stimulation train, respectively, for recordings from WT (blue, 11 slices from 5 animals) and SynTKO (red, 12 slices from 6 animals) slices. Average values from the same recording are connected. Median values and interquartile ranges are depicted in black. Ranks between first and fourth stimulation train were not significantly different for neither WT (p = 0.36) nor SynTKO (p = 0.08) recordings, compared in a Wilcoxon test. g, The relative loss of fibers was similar for WT and SynTKO recordings. Averaged ratios between fourth and first train PFV sizes are depicted for both WT (blue, 11 slices from 5 animals) and SynTKO (red, 12 slices from 6 animals) animals. Median values and interquartile ranges are depicted in black. Ranks were not significantly different (p = 0.24) in a Mann–Whitney U test.
- Figure 3.
SynTKO mossy fibers display reduced post-tetanic potentiation but increased long-term potentiation. a, Post-tetanic potentiation is decreased in SynTKO mossy fibers. Normalized averaged fEPSP amplitudes plotted against time (min) from WT (blue, 15 slices from 6 animals) and SynTKO (red, 23 slices from 9 animals) recordings. This plot is a partial zoom-in from the plot shown in c (9–13 min). Mean values ± SEM are shown. The arrow indicates the time point of high-frequency stimulation (4 times 125 pulses at 25 Hz). Stimulation before and after was at 0.05 Hz. Statistics for dataset as reported in c. b, Scatterplots for individual fEPSP amplitudes for WT (blue) and SynTKO (red) recordings for the 1st, 3rd, and 10th stimulus after high-frequency stimulation, respectively. Median values ± interquartile ranges are shown in black. The significance was tested with a Kruskal–Wallis test and a post hoc Dunn’s correction for multiple comparisons. The Kruskal–Wallis test revealed significant differences between ranks with p < 0.0001. Multiple comparisons revealed significant differences for the 1st (p = 0.0003) and 10th (p = 0.0002) time point. c, LTP is increased in SynTKO animals after 30 min. Top, Example traces of fEPSP amplitudes 30 min after high-frequency stimulation for mossy fibers from WT (blue, left) and TKO (red, right) mice compared with baseline fEPSP amplitude (gray) and response to 1 µM DCG-IV (black). Bottom, Normalized averaged fEPSP amplitudes plotted over time (min) from WT (blue, 15 slices from 6 animals) and SynTKO (red, 23 slices from 9 animals) recordings. Mean values ± SEM are shown. The arrow indicates the high-frequency stimulation (4 times 125 pulses at 25 Hz). Stimulation frequency before (baseline) and after (LTP recording) was 0.05 Hz. At the end of the recording, 1 µM DCG-IV was washed in to ensure mossy fiber specificity. The last 10 fEPSP amplitudes during DCG-IV wash-in are shown at the end of the recording. A mixed-effect model revealed significant differences for the genotype (p = 0.005), time (p < 0.0001), and the interaction of both (p < 0.0001). A post hoc Sidak’s test for multiple comparisons revealed significant differences for the first sweep after high-frequency stimulation (p = 0.0125) and Sweeps 38 (p < 0.05) and Sweeps 40–54 (p < 0.05; ∼14–18 min), as well as for Sweeps 61, 67, and 94 (p < 0.05; ∼20, 22, and 32 min). d, Dots indicate averaged fEPSP amplitudes from individual WT (blue) and SynTKO (red) recordings. Amplitudes were averaged over the last 10 min of the LTP recording; from 20 to 30 min after high-frequency stimulation. Median values ± interquartile ranges are shown in black. Ranks were significantly different with p < 0.0001 (Mann–Whitney U test).
- Figure 4.
Synaptic vesicles are more dispersed in mossy fiber boutons from SynTKO mice. a, In mossy fiber boutons, synaptic vesicles are more dispersed, and their density is reduced. Example images from TEM showing mossy fiber boutons from WT (left) and SynTKO (right) animals. Top, Raw TEM images of mossy fiber boutons in stratum lucidum. Middle, An automated tool (eImbrosci et al., 2022) was used to detect vesicles. Mossy fiber boutons were extracted from the raw image, and the center of detected vesicles is marked with a white dot. Blue and red boxes show the region for the zoom-ins in WT and SynTKO, respectively. Bottom, Zoom-ins, as marked in the middle pictures. High-magnification images of mossy fiber boutons from a WT and a SynTKO animal, respectively. Note the reduced abundance of synaptic vesicles in the SynTKO bouton. b, Partial 3D reconstruction of hippocampal mossy fiber boutons from a WT (top) and a SynTKO animal (bottom) for visualization purposes only. Vesicles are shown in blue and red, respectively, the presynaptic mossy fiber membrane is shown in light blue, and postsynaptic spines are shown in green. c, The number of synaptic vesicles per cubic micrometer is reduced in SynTKO animals. Dots represent the number of vesicles in individual mossy fiber boutons from three WT (blue, 18 boutons) and three SynTKO (red, 16 boutons) animals. Median values and interquartile ranges are shown in black. A generalized linear mixed model revealed significant differences between genotypes with p = 0.0015. d, The MNND is increased between synaptic vesicles in SynTKO compared with those in WT boutons. The scatterplot shows average MNND (nm) for individual mossy fiber boutons from three WT (blue, 18 boutons) and three SynTKO (red, 16 boutons) animals. Genotypes were significantly different in a generalized linear mixed model with p = 0.0015. Median values are shown in black with interquartile ranges.
- Figure 5.
Increased active zone density in mossy fiber boutons of SynTKO mice. a, Example images from TEM showing mossy fiber boutons from WT (left) and SynTKO (right) animals in control (top) and FSK (bottom) condition. Black asterisks indicate the active zones. b, Example partial 3D reconstructions of mossy fiber boutons from untreated (top) and FSK-treated (bottom) SynTKO mice. Active zones with docked vesicles are shown in red (SynTKO) and yellow (SynTKO + FSK), respectively. Synaptic vesicles, mitochondria, and presynaptic membrane are shown in light blue; the postsynaptic membrane is shown in green. c, Single active zones were reconstructed from serial sections of TEM images. Left, An example stack of serial sections for one active zone, indicated by yellow lines at the active zone boundaries. Right, 3D reconstructions of single active zones from untreated (red) and FSK-treated (yellow) SynTKO mice, in side and top view, respectively. The yellow active zone corresponds to the serial images to the left. d, Complexity of boutons [measured as perimeter/area (µm-1)] plotted for individual mossy fiber boutons from untreated WT (blue dots, 17 boutons from 3 animals) and untreated SynTKO slices (red dots, 16 boutons from 3 animals) as well as for FSK-treated WT (green dots, 16 boutons from 3 animals) and FSK-treated SynTKO slices (yellow dots, 18 boutons from 3 animals). Median values are shown in black with interquartile ranges. A hypothesis test between generalized linear mixed models revealed no significant differences (p = 0.3972). e, The number of active zones per cubic micrometer plotted for individual mossy fiber boutons from untreated WT (blue dots, 17 boutons from 3 animals) and untreated SynTKO slices (red dots, 16 boutons from 3 animals) as well as for FSK-treated WT (green dots, 16 boutons from 3 animals) and FSK-treated SynTKO slices (yellow dots, 18 boutons from 3 animals). Median values are shown in black with interquartile ranges. A hypothesis test between nested generalized linear mixed models revealed significant differences (p = 0.04). A post hoc test (marginal contrasts analysis with p value adjustment) revealed significant differences between WT and SynTKO (p = 0.0359), WT and WT + FSK (p = 0.05), SynTKO and SynTKO + FSK (p = 0.005), and WT + FSK and SynTKO + FSK (p = 0.005), but no significant difference between WT + FSK and SynTKO (p = 0.772). f, The mean active zone area (µm2) per bouton for individual mossy fiber boutons from untreated WT (blue dots, 17 boutons from 3 animals) and untreated SynTKO slices (red dots, 16 boutons from 3 animals) as well as for FSK-treated WT (green dots, 16 boutons from 3 animals) and FSK-treated SynTKO slices (yellow dots, 18 boutons from 3 animals). Median values and interquartile ranges are shown in black. A hypothesis test between generalized linear mixed models revealed no significant differences (p = 0.8112). g, The number of docked synaptic vesicles per cubic micrometer plotted for individual mossy fiber boutons from untreated WT (blue dots, 17 boutons from 3 animals) and untreated SynTKO slices (red dots, 16 boutons from 3 animals) as well as for FSK-treated WT (green dots, 16 boutons from 3 animals) and FSK-treated SynTKO slices (yellow dots, 18 boutons from 3 animals). Median values are shown in black with interquartile ranges. A hypothesis test between generalized linear mixed models revealed significant differences for FSK treatment (p = 0.0002). A post hoc test (marginal contrasts analysis with p value adjustment) revealed significant differences between SynTKO and SynTKO + FSK (p = 0.0009).
Tables
Section/topic Item number Checklist item Reported on page number General 1 The terms sex/gender used appropriately Does not apply Title 2a Title specifies the sex of animals or any cells, tissues, and other material derived from these 1 2b In applied sciences (technology, engineering, etc.), the title indicates if the study model was based on one sex/gender or the application was considered for the use of one specific sex/gender Does not apply Abstract 3a Abstract specifies sex of animals or any cells, tissues, and other material derived from these 4 3b In applied sciences (technology, engineering, etc.), the abstract indicates if the study model was based on one sex/gender or the application was considered for the use of one specific sex/gender Does not apply Introduction 4a If relevant, previous studies that show presence or lack of sex or gender differences or similarities are cited Does not apply 4b Mention of whether sex/gender might be an important variant and if differences might be expected Not performed Materials and Methods 5a In cell biological, molecular biological, or biochemical experiments, the origin and sex chromosome constitutions of cells or tissue cultures are stated. If unknown, the reasons are stated Does not apply 5b For studies testing devices or technology, explanation of whether the product will be applied or used by all genders and if it has been tested with a user's gender in mind Does not apply 5c If relevant, description of how sex/gender was considered in the design Does not apply 5d For in vivo and in vitro studies using primary cultures of cells, or cell lines from humans or animals, or ex vivo studies with tissues from humans or animals, the sex of the subjects or source donors is stated (except for immortalized cell lines, which are highly transformed) 7 Results 6 For studies using animal models, present a sex breakdown of the animalsa Does not apply Discussion 7 If relevant, potential implications of sex/gender on the study results and analyses, including the extent to which the findings can be generalized to all sexes/genders in a population 28 Adapted from Heidari et al. (2016).
↵a These points extend beyond the original SAGER table.
Item Item number Recommendation Reported in section Study design 1 a. For each experiment, provide brief details of study design including: the groups being compared, including control groups. If no control group has been used, the rationale should be stated Materials and Methods, Study design and Results b. The experimental unit (e.g., a single animal, litter, or cage of animals) Materials and Methods, Study design and Table 5 Sample size 2 a. Specify the exact number of experimental units allocated to each group and the total number in each experiment. Also indicate the total number of animals used Materials and Methods, Study design and Table 5 b. Explain how the sample size was decided. Provide details of any a priori sample size calculation, if done Materials and Methods, Study design Inclusion and exclusion criteria 3 a. Describe any criteria used for including and excluding animals (or experimental units) during the experiment and data points during the analysis. Specify if these criteria were established a priori. If no criteria were set, state this explicitly Materials and Methods, Field recordings b. For each experimental group, report any animals, experimental units, or data points not included in the analysis and explain why. If there were no exclusions, state so Materials and Methods, Tables 5 and 6 c. For each analysis, report the exact value of n in each experimental group. Materials and Methods, Study design and Table 5 Randomization 4 a. State whether randomization was used to allocate experimental units to control and treatment groups. If done, provide the method used to generate the randomization sequence Materials and Methods, Study design b. Describe the strategy used to minimize potential confounders such as the order of treatments and measurements or animal/cage location. If confounders were not controlled, state this explicitly Materials and Methods, Study design Blinding 5 Describe who was aware of the group allocation at the different stages of the experiment (during the allocation, the conduct of the experiment, the outcome assessment, and the data analysis) Materials and Methods, Study design Outcome measures 6 a. Clearly define all outcome measures assessed (e.g., cell death, molecular markers, or behavioral changes) Results; Materials and Methods, TEM and Table 5 b. For hypothesis-testing studies, specify the primary outcome measure, i.e., the outcome measure that was used to determine the sample size Does not apply Statistical methods 7 a. Provide details of the statistical methods used for each analysis, including the software used Materials and Methods, Statistics b. Describe any methods used to assess whether the data met the assumptions of the statistical approach and what was done if the assumptions were not met Materials and Methods, Statistics Experimental animals 8 a. Provide species-appropriate details of the animals used, including species, strain and substrain, sex, age or developmental stage, and, if relevant, weight Materials and Methods, Study design and key resources table b. Provide further relevant information on the provenance of animals, health/immune status, genetic modification status, genotype, and any previous procedures Materials and Methods, Study design; Results; Discussion Experimental procedures 9 a. For each experimental group, including controls, describe the procedures in enough detail to allow others to replicate them, including: what was done, how it was done, and what was used Materials and Methods b. When and how often Materials and Methods, TEM, Table 5 c. Where (including detail of any acclimatization periods) Materials and Methods, Acute slice preparation, Field recordings, and TEM d. Why (provide rationale for procedures) Introduction; Results; Discussion; Materials and Methods Results 10 a. For each experiment conducted, including independent replications, report the summary/descriptive statistics for each experimental group, with a measure of variability where applicable (e.g., mean and SD or median and range) Results, text and figure legends b. If applicable, the effect size with a confidence interval Does not apply Adapted from Percie du Sert et al. (2020).
Item Item number Recommendation Reported in section Abstract 11 Provide an accurate summary of the research objectives, animal species, strain and sex, key methods, principal findings, and study conclusions Abstract Background 12 a. Include sufficient scientific background to understand the rationale and context for the study, and explain the experimental approach Introduction; Results; Discussion b. Explain how the animal species and model used address the scientific objectives and, where appropriate, the relevance to human biology Introduction; Results; Discussion Objectives 13 Clearly describe the research question, research objectives, and, where appropriate, specific hypotheses being tested Abstract; Introduction; Results; Discussion Ethical statement 14 Provide the name of the ethical review committee or equivalent that has approved the use of animals in this study and any relevant license or protocol numbers (if applicable). If ethical approval was not sought or granted, provide a justification Materials and Methods, Ethics statement Housing and husbandry 15 Provide details of housing and husbandry conditions, including any environmental enrichment Materials and Methods, Acute slice preparation Animal care and monitoring 16 a. Describe any interventions or steps taken in the experimental protocols to reduce pain, suffering, and distress Materials and Methods, Acute slice preparation b. Report any expected or unexpected adverse events Does not apply c. Describe the humane endpoints established for the study, the signs that were monitored, and the frequency of monitoring. If the study did not have humane endpoints, state this Not performed Interpretation/scientific implications 17 a. Interpret the results, taking into account the study objectives and hypotheses, current theory, and other relevant studies in the literature Discussion b. Comment on the study limitations including potential sources of bias, limitations of the animal model, and imprecision associated with the results Discussion Generalizability/translation 18 Comment on whether, and how, the findings of this study are likely to generalize to other species or experimental conditions, including any relevance to human biology (where appropriate) Discussion Protocol registration 19 Provide a statement indicating whether a protocol (including the research question, key design features, and analysis plan) was prepared before the study and if and where this protocol was registered Not performed Data access 20 Provide a statement describing if and where study data are available Data Availability Declaration of interests 21 a. Declare any potential conflicts of interest, including financial and non-financial. If none exist, this should be stated Conflict of interest statement b. List all funding sources (including grant identifier) and the role of the funder(s) in the design, analysis, and reporting of the study Acknowledgments Adapted from Percie du Sert et al. (2020).
- Table 4.
Statistical comparison for experimental values between two cohorts of presymptomatic SynTKO animals
Experiment Measure Presynaptic SynTKO
animals from ItalyPresynaptic SynTKO
animals from BerlinInput–output Slope of simple linear regression 1.341 0.833 Ranges of 95% confidence band 0.5494–2.134 0.09287–1.573 p value slopes (ANCOVA) 0.69 1 Hz facilitation Median 4.440 5.955 Interquartile range 3.760–6.260 3.753–11.41 p value (Mann–Whitney U test) 0.3473 PPR Median 3.557 4.545 Interquartile ranges 2.299–4.260 2.568–6.035 p value (Mann–Whitney U test) 0.0899 PTP (norm. fEPSP) Median 3.469 4.116 Interquartile ranges 2.118–4.589 3.374–7.144 p value (Mann–Whitney U test) 0.1151 LTP after 30 min (norm. fEPSP) Median 245.2 228.8 Interquartile ranges 198.3–302.9 182.5–384.4 p value (Mann–Whitney U test) 0.8793 - Table 5.
Overview of slice and animal numbers for different experimental groups for field recordings
s = number of slices
a = number of animals
C57BL/6J
(4–6 weeks)Synapsin TKO (4–6 weeks) C57BL/6J
(17–19 weeks)Synapsin TKO
(18–19 weeks)From Italy
(4–5 weeks)From Berlin
(4–6 weeks)Recorded s = 67 s = 39 s = 18 s = 29 s = 24 a = 12 a = 9 a = 7 a = 5 a = 5 Included s = 31 s = 24 s = 14 s = 17 s = 19 a = 12 a = 9 a = 4 a = 4 a = 5 Input–output ratio s = 31 s = 23 s = 14 s = 17 s = 18 a = 12 a = 9 a = 4 a = 4 a = 5 PPR s = 31 s = 20 s = 14 s = 17 s = 19 a = 12 a = 8 a = 4 a = 4 a = 5 1 Hz facilitation s = 31 s = 15 s = 12 s = 17 s = 19 a = 12 a = 5 a = 4 a = 4 a = 5 25 Hz stimulation s = 11 s = 4 s = 8 a = 5 a = 3 a = 3 PTP + LTP s = 15 s = 13 s = 10 a = 6 a = 6 a = 3 Note: all numbers reported for individual experiments are only from the included subset of recordings.
Excluded recordings C57BL/6J
(4–6 weeks)Synapsin TKO (4–6 weeks) C57BL/6J
(17–19 weeks)Synapsin TKO
(18–19 weeks)Baseline fEPSP <50 µV 4 2 2 2 DCG-IV effect <75% 27 14 11 4 Other reasons 6 2 0 1 Total number 36 19 12 5 Note that several reasons can apply to the same recording.
Train Measure WT animals SynTKO animals First train 25th stimulus Median 3.704 3.653 Interquartile range [1.873; 7.935] [2.426; 7.092] p value (Mann–Whitney U test) p = 0.695 First train 125th stimulus Median 1.243 0.7514 Interquartile ranges [0.473; 2.332] [0.4997; 1.650] p value (Mann–Whitney U test) p = 0.74 Fourth train 25th stimulus Median 3.176 1.61 Interquartile ranges [1.039; 3.77] [0.75; 4.314] p value (Mann–Whitney U test) p = 0.88 Fourth train 125th stimulus Median 0.687 0.3714 Interquartile ranges [0.501; 1.987] [0.049; 0.72] p value (Mann–Whitney U test) p = 0.032 Amplitudes were measured in both genotypes in the first and fourth train of 125 pulses at 25 Hz (Fig. 2) at the 25th and 125th stimulus, and their ranks were compared in Mann–Whitney U tests.
- Table 8.
Overview of functional and structural changes in glutamatergic synapses of synapsin KOs
Genotype Syn I KO Syn II KO Syn III KO SynDKO SynTKO References Excitability ↑ ↑ (↑) Boido et al., 2010; Farisello et al., 2013; Matos et al., 2019
(this work)
Frequency facilitation ↓ = ↓ (↓) Owe et al., 2009; Nikolaev and Heggelund, 2015
(this work)
Depression =↑ =↑ ↓ ↑ ↑ (↑) Rosahl et al., 1995; Feng et al., 2002; Gitler et al., 2004; J. Sun et al., 2006; Vasileva et al., 2012; Farisello et al., 2013
(this work)
PTP =↓ =↓ ↓ ↓ (↓) Rosahl et al., 1993, 1995; Spillane et al., 1995; Kielland et al., 2006; Valente et al., 2012; Farisello et al., 2013; Nikolaev and Heggelund, 2015; Cheng et al., 2018
(this work)
LTP = = (↑) Rosahl et al., 1993, 1995; Spillane et al., 1995; Takei et al., 1995
(this work)
Density of synaptic vesicles ↓ = ↓ ↓(↓) Li et al., 1995; Pieribone et al., 1995; Rosahl et al., 1995; Takei et al., 1995; Feng et al., 2002; Gitler et al., 2004; Siksou et al., 2007; Owe et al., 2009; Vasileva et al., 2012
(this work)
Arrows indicate an increase or decrease of the properties listed in the first column, while equal signs indicate no changes. Bold symbols indicate that previous work also considered the hippocampal mossy fiber bouton. References are marked accordingly. Arrows in brackets refer to the findings of this study.
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