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Cited by 114Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeural dynamics and brain function

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Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation

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Vandael, David, Borges-Merjane, Carolina, Zhang, Xiaomin, Jonas, Peter·2020·Neuron
DOI 10.1016/j.neuron.2020.05.013PMC PMC7427323
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Abstract

Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and "flash and freeze" electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural "pool engrams." Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network.

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Graphical abstract CC BY-NC-ND · PubMed Central
Figure 1 SB Activity in GCs in Awake Behaving Mice during Spatial Navigation (A) Schematic illustration of the in vivo recording configuration. Mice were running on a linear belt. The belt surface had three partitions with different textures, providing tactile cues for spatial orientation. (B) Left: light micrographs of two recorded neurons, superimposed with reconstruction. Somatodendritic morphology unequivocally identified the recorded neurons as dentate gyrus GCs. Dotted lines represent GC layer (GCL) boundaries and the hippocampal fissure, respectively. Right: current-clamp recording from the two GCs shown on the left. Top trace: intracellular membrane potential. Center trace: extracellular LFP. Bottom trace: velocity of the animal. The recorded GCs generated SBs with 18 and 26 APs, respectively. (C) Histogram of ISIs. The black line represents fit with the sum of three log-normal distributions; colored lines indicate individual components. Inset: histogram of log-likelihood ratios (LLRs) for fits with three and two Gaussian functions from 1,000 bootstrap replications. The vertical red line indicates the measured LLR. (D) Histogram of the number of APs per SB. (E) Histogram of SB duration. (F) Summary bar graph of SB frequency during running versus immobile periods and during theta versus non-theta periods. SB frequency is significantly higher during running periods. ∗∗p < 0.01. Boxes indicate mean values, and error bars denote SEM. (G) Proportion of GCs showing SBs plotted against cell body location along the axis from the inner to the outer GC layer (left) and the axis from the upper to the lower blade (right). Note that GCs with SBs were observed in all parts of the dentate gyrus. (H) Left: summary pie chart of the proportion of GCs that generated SBs. The total sample was comprised of 43 active GCs that generated APs during the recording period (5–30 min). Center: summary pie chart of the proportion of events (blue, single APs; green, bursts; red, SBs) in the total GC population. Right: summary pie chart of the proportion of APs (blue, APs occurring in isolation; green, APs contained in bursts; red, APs contained in SBs) in the total GC population. Note that the majority of spikes are contained in SBs.
Figure 1 SB Activity in GCs in Awake Behaving Mice during Spatial Navigation (A) Schematic illustration of the in vivo recording configuration. Mice were running on a linear belt. The belt surface had three partitions with different textures, providing tactile cues for spatial orientation. (B) Left: light micrographs of two recorded neurons, superimposed with reconstruction. Somatodendritic morphology unequivocally identified the recorded neurons as dentate gyrus GCs. Dotted lines represent GC layer (GCL) boundaries and the hippocampal fissure, respectively. Right: current-clamp recording from the two GCs shown on the left. Top trace: intracellular membrane potential. Center trace: extracellular LFP. Bottom trace: velocity of the animal. The recorded GCs generated SBs with 18 and 26 APs, respectively. (C) Histogram of ISIs. The black line represents fit with the sum of three log-normal distributions; colored lines indicate individual components. Inset: histogram of log-likelihood ratios (LLRs) for fits with three and two Gaussian functions from 1,000 bootstrap replications. The vertical red line indicates the measured LLR. (D) Histogram of the number of APs per SB. (E) Histogram of SB duration. (F) Summary bar graph of SB frequency during running versus immobile periods and during theta versus non-theta periods. SB frequency is significantly higher during running periods. ∗∗p < 0.01. Boxes indicate mean values, and error bars denote SEM. (G) Proportion of GCs showing SBs plotted against cell body location along the axis from the inner to the outer GC layer (left) and the axis from the upper to the lower blade (right). Note that GCs with SBs were observed in all parts of the dentate gyrus. (H) Left: summary pie chart of the proportion of GCs that generated SBs. The total sample was comprised of 43 active GCs that generated APs during the recording period (5–30 min). Center: summary pie chart of the proportion of events (blue, single APs; green, bursts; red, SBs) in the total GC population. Right: summary pie chart of the proportion of APs (blue, APs occurring in isolation; green, APs contained in bursts; red, APs contained in SBs) in the total GC population. Note that the majority of spikes are contained in SBs.CC BY-NC-ND · PubMed Central
Figure 2 A Highly Sensitive Induction Mechanism of Hippocampal Mossy Fiber PTP (A) Left: schematic illustration of the paired recording configuration (cell-attached recording from a presynaptic terminal, whole-cell recording from a postsynaptic CA3 pyramidal neuron). Center: representative differential interference contrast videomicrograph of a mossy fiber terminal-CA3 pyramidal neuron pair. The light-yellow area represents the 2D projection of the soma and proximal dendrite of the postsynaptic CA3 pyramidal neuron. Right: Neurolucida reconstruction of a mossy fiber terminal-CA3 pyramidal neuron pair. The mossy fiber terminal and axon are depicted in white, and the pyramidal neuron is shown in yellow. The inset shows an adjacent non-recorded terminal at higher magnification. Note that mossy fiber terminals were more than 100 μm apart; thus, transmitter release originates from the recorded presynaptic terminal. (B) Average EPSCs before (black traces) and 20 s after (red traces) HFS with different numbers of stimuli, as indicated (HFS3APs, HFS9APs, HFS18APs, HFS36APs, and HFS72APs), all at a frequency of 100 Hz. (C) Plot of average EPSC peak amplitude (top) and postsynaptic series resistance (bottom) against experimental time. Red and gray lines indicate running averages. Vertical dashed lines indicate time points of HFS. Data are from 9 pairs. (D) Summary bar graph showing the effect of high-frequency stimulation with the indicated number of APs on the amplitude of unitary mossy fiber EPSCs. (E) Plot of PTP against number of stimuli (log scale). Data points represent the mean value of PTP. Red curve, Hill function fit to the data points. Half-maximal PTP was reached with n50 = 10.8 APs. (F) The PTP induction curve overlaps with the natural GC activity. Red curve, Hill function fit to the PTP induction data and normalized to maximum; black curve, inverted cumulative distribution of the number of APs per SB from in vivo recordings; light blue area, region of overlap between the two curves. (G) Histogram of the predicted PTP arising from SBs with different numbers of APs measured in vivo. (H) Left: EPSCs during an SB with 10 APs (SB10APs, top) and 24 APs (SB24APs, bottom). Right: EPSCs evoked by single stimuli before (control) and 20 s after SB10APs and SB24APs (post-SB). (I) Summary bar graph showing the effect of SB10APs and SB24APs (9 pairs). In (D) and (I), boxes indicate mean values, error bars denote SEM, and circles show data from individual experiments. ∗p < 0.05, ∗∗p < 0.01.
Figure 2 A Highly Sensitive Induction Mechanism of Hippocampal Mossy Fiber PTP (A) Left: schematic illustration of the paired recording configuration (cell-attached recording from a presynaptic terminal, whole-cell recording from a postsynaptic CA3 pyramidal neuron). Center: representative differential interference contrast videomicrograph of a mossy fiber terminal-CA3 pyramidal neuron pair. The light-yellow area represents the 2D projection of the soma and proximal dendrite of the postsynaptic CA3 pyramidal neuron. Right: Neurolucida reconstruction of a mossy fiber terminal-CA3 pyramidal neuron pair. The mossy fiber terminal and axon are depicted in white, and the pyramidal neuron is shown in yellow. The inset shows an adjacent non-recorded terminal at higher magnification. Note that mossy fiber terminals were more than 100 μm apart; thus, transmitter release originates from the recorded presynaptic terminal. (B) Average EPSCs before (black traces) and 20 s after (red traces) HFS with different numbers of stimuli, as indicated (HFS3APs, HFS9APs, HFS18APs, HFS36APs, and HFS72APs), all at a frequency of 100 Hz. (C) Plot of average EPSC peak amplitude (top) and postsynaptic series resistance (bottom) against experimental time. Red and gray lines indicate running averages. Vertical dashed lines indicate time points of HFS. Data are from 9 pairs. (D) Summary bar graph showing the effect of high-frequency stimulation with the indicated number of APs on the amplitude of unitary mossy fiber EPSCs. (E) Plot of PTP against number of stimuli (log scale). Data points represent the mean value of PTP. Red curve, Hill function fit to the data points. Half-maximal PTP was reached with n50 = 10.8 APs. (F) The PTP induction curve overlaps with the natural GC activity. Red curve, Hill function fit to the PTP induction data and normalized to maximum; black curve, inverted cumulative distribution of the number of APs per SB from in vivo recordings; light blue area, region of overlap between the two curves. (G) Histogram of the predicted PTP arising from SBs with different numbers of APs measured in vivo. (H) Left: EPSCs during an SB with 10 APs (SB10APs, top) and 24 APs (SB24APs, bottom). Right: EPSCs evoked by single stimuli before (control) and 20 s after SB10APs and SB24APs (post-SB). (I) Summary bar graph showing the effect of SB10APs and SB24APs (9 pairs). In (D) and (I), boxes indicate mean values, error bars denote SEM, and circles show data from individual experiments. ∗p < 0.05, ∗∗p < 0.01.CC BY-NC-ND · PubMed Central
Figure 3 PTP of Mossy Fiber Unitary EPSCs Is Primarily Generated by an Increase in the Size of the RRP (A) EPSCs evoked by a test train of 10 stimuli at 50 Hz (black), EPSCs during HFS100APs (blue), and EPSCs evoked by a test train of 10 stimuli at 50 Hz 20 s after HFS100APs (red). (B) Plot of average EPSC peak amplitude (top) and postsynaptic series resistance (bottom) against experimental time. The red line represents an exponential function fit to the data points, and gray line represents running average. The vertical dashed line indicates time point of HFS100APs. Data are from 12 pairs. (C) Summary of the paired-pulse ratio (EPSC2/EPSC1) before (black) and after HFS100APs (red). Note that the ratio was only slightly reduced after HFS100APs (p = 0.158). (D) Cumulative EPSC peak amplitude during a train with 10 stimuli at 50 Hz before (black) and 20 s after application of HFS100APs (red). Data points during the last 3–5 stimuli (at time points ≥ 100–140 ms) were fit by linear regression. Note that PTP markedly increased the size of the RRP (represented by the intersection of the regression line with the ordinate). (E–G) Summary bar graphs of RRP (E), Pr (F), and refilling rate (G) estimated by the 10-AP paradigm before (black) and 20 s after HFS100APs (red). Bars represent mean values, error bars indicate SEM, and circles show data from individual experiments; data points from the same experiment are connected by lines. Note that PTP is caused by a preferential increase in RRP. (H) Plot of RRP against experimental time.
Figure 3 PTP of Mossy Fiber Unitary EPSCs Is Primarily Generated by an Increase in the Size of the RRP (A) EPSCs evoked by a test train of 10 stimuli at 50 Hz (black), EPSCs during HFS100APs (blue), and EPSCs evoked by a test train of 10 stimuli at 50 Hz 20 s after HFS100APs (red). (B) Plot of average EPSC peak amplitude (top) and postsynaptic series resistance (bottom) against experimental time. The red line represents an exponential function fit to the data points, and gray line represents running average. The vertical dashed line indicates time point of HFS100APs. Data are from 12 pairs. (C) Summary of the paired-pulse ratio (EPSC2/EPSC1) before (black) and after HFS100APs (red). Note that the ratio was only slightly reduced after HFS100APs (p = 0.158). (D) Cumulative EPSC peak amplitude during a train with 10 stimuli at 50 Hz before (black) and 20 s after application of HFS100APs (red). Data points during the last 3–5 stimuli (at time points ≥ 100–140 ms) were fit by linear regression. Note that PTP markedly increased the size of the RRP (represented by the intersection of the regression line with the ordinate). (E–G) Summary bar graphs of RRP (E), Pr (F), and refilling rate (G) estimated by the 10-AP paradigm before (black) and 20 s after HFS100APs (red). Bars represent mean values, error bars indicate SEM, and circles show data from individual experiments; data points from the same experiment are connected by lines. Note that PTP is caused by a preferential increase in RRP. (H) Plot of RRP against experimental time.CC BY-NC-ND · PubMed Central
Figure 4 Increase in Q Contributes Only Minimally to Mossy Fiber PTP (A) Schematic illustration of the experimental approach to measure mEPSCs generated by a single presynaptic mossy fiber terminal. (1) The synapse was first examined in the paired recording configuration, with the presynaptic terminal in the tight-seal, cell-attached configuration. (2) To induce PTP, the presynaptic terminal was then stimulated using HFS100APs (100 stimuli at 100 Hz). (3) To enable recording of mEPSCs, TTX and TEA were applied immediately after HFS100APs, and a transition was made from bouton-attached to whole-bouton configuration. (4) mEPSCs were evoked by depolarization of the presynaptic terminal with 4-s pulses from −70 mV to −10 mV. The first depolarizing pulse was applied ∼20 s after HFS. The effect of TTX was verified by the absence of Na+ inward currents in the presynaptic terminals. (B) Traces of mEPSCs evoked by 4-s depolarizations after HFS100APs (left) and under control conditions (right). The insets show mEPSCs at an expanded timescale after detection and alignment to the onset time point; the white curve represents the average. (C) Histograms of mEPSC peak amplitude in the same paired recordings as shown in (B). The inset shows an overlay of the corresponding cumulative distributions. (D) Summary bar graph of the peak amplitude of mEPSCs evoked by 4-s pulses under control conditions (black) and after HFS100APs (red). Note that the mean value was significantly higher (left), whereas median values were not significantly different (right), indicating a change in the shape of the distribution and a preferential increase in the proportion of large mEPSCs. Data are from 7 pairs. Boxes indicate mean values, and error bars denote SEM. ∗p < 0.05, ∗∗p < 0.01.
Figure 4 Increase in Q Contributes Only Minimally to Mossy Fiber PTP (A) Schematic illustration of the experimental approach to measure mEPSCs generated by a single presynaptic mossy fiber terminal. (1) The synapse was first examined in the paired recording configuration, with the presynaptic terminal in the tight-seal, cell-attached configuration. (2) To induce PTP, the presynaptic terminal was then stimulated using HFS100APs (100 stimuli at 100 Hz). (3) To enable recording of mEPSCs, TTX and TEA were applied immediately after HFS100APs, and a transition was made from bouton-attached to whole-bouton configuration. (4) mEPSCs were evoked by depolarization of the presynaptic terminal with 4-s pulses from −70 mV to −10 mV. The first depolarizing pulse was applied ∼20 s after HFS. The effect of TTX was verified by the absence of Na+ inward currents in the presynaptic terminals. (B) Traces of mEPSCs evoked by 4-s depolarizations after HFS100APs (left) and under control conditions (right). The insets show mEPSCs at an expanded timescale after detection and alignment to the onset time point; the white curve represents the average. (C) Histograms of mEPSC peak amplitude in the same paired recordings as shown in (B). The inset shows an overlay of the corresponding cumulative distributions. (D) Summary bar graph of the peak amplitude of mEPSCs evoked by 4-s pulses under control conditions (black) and after HFS100APs (red). Note that the mean value was significantly higher (left), whereas median values were not significantly different (right), indicating a change in the shape of the distribution and a preferential increase in the proportion of large mEPSCs. Data are from 7 pairs. Boxes indicate mean values, and error bars denote SEM. ∗p < 0.05, ∗∗p < 0.01.CC BY-NC-ND · PubMed Central
Figure 5 Functional EM Analysis Reveals an Increase in the Number of Docked Vesicles during PTP (A) Left: schematic illustration of “flash and freeze” experiments at hippocampal mossy fiber synapses. Thin hippocampal slices were embedded in a sandwich between two sapphire blades, hippocampal GCs were stimulated by light pulses, and slices were subjected to high-pressure freezing at defined time intervals for subsequent EM analysis (Borges-Merjane et al., 2020). (B) Example transmission EM (TEM) micrographs of active zones of hippocampal mossy fiber synapses in control slices (left), slices frozen immediately after stimulation with 100 light pulses (center), and slices frozen 20 s after stimulation (right). Images were taken from the mossy fiber tract in the stratum lucidum of the CA3 region, primarily CA3b and CA3c. White bars indicate postsynaptic densities. (C–E) Scatterplot (C), cumulative distributions (D), and histograms (E) of the number of docked vesicles per 100 nm of active zone profile length for a non-light stimulated control (black), slices frozen immediately after HFS100APs stimulation at 20 Hz (blue), and slices frozen after HFS100APs stimulation + 20 s recovery time (red). Bars show mean and standard deviation. Each data point in (C) represents an active-zone profile. Note that the number of docked vesicles increased 20 s after HFS, indicating “overfilling” of the docked vesicle pool. (F–H) Similar plots as shown in (C)–(E) but for diameter of docked vesicles. The diameter of docked vesicles was slightly but significantly larger in the HFS100APs stimulation + 20 s recovery time in comparison with control experiments. Each data point in (F) represents a docked synaptic vesicle. Data for the HFS100APs stimulation (blue) include measurements taken from a previous study (Borges-Merjane et al., 2020). In (C) and (F), boxes indicate mean values, and error bars denote standard deviation. ∗∗p < 0.01, ∗∗∗∗p < 0.0001.
Figure 5 Functional EM Analysis Reveals an Increase in the Number of Docked Vesicles during PTP (A) Left: schematic illustration of “flash and freeze” experiments at hippocampal mossy fiber synapses. Thin hippocampal slices were embedded in a sandwich between two sapphire blades, hippocampal GCs were stimulated by light pulses, and slices were subjected to high-pressure freezing at defined time intervals for subsequent EM analysis (Borges-Merjane et al., 2020). (B) Example transmission EM (TEM) micrographs of active zones of hippocampal mossy fiber synapses in control slices (left), slices frozen immediately after stimulation with 100 light pulses (center), and slices frozen 20 s after stimulation (right). Images were taken from the mossy fiber tract in the stratum lucidum of the CA3 region, primarily CA3b and CA3c. White bars indicate postsynaptic densities. (C–E) Scatterplot (C), cumulative distributions (D), and histograms (E) of the number of docked vesicles per 100 nm of active zone profile length for a non-light stimulated control (black), slices frozen immediately after HFS100APs stimulation at 20 Hz (blue), and slices frozen after HFS100APs stimulation + 20 s recovery time (red). Bars show mean and standard deviation. Each data point in (C) represents an active-zone profile. Note that the number of docked vesicles increased 20 s after HFS, indicating “overfilling” of the docked vesicle pool. (F–H) Similar plots as shown in (C)–(E) but for diameter of docked vesicles. The diameter of docked vesicles was slightly but significantly larger in the HFS100APs stimulation + 20 s recovery time in comparison with control experiments. Each data point in (F) represents a docked synaptic vesicle. Data for the HFS100APs stimulation (blue) include measurements taken from a previous study (Borges-Merjane et al., 2020). In (C) and (F), boxes indicate mean values, and error bars denote standard deviation. ∗∗p < 0.01, ∗∗∗∗p < 0.0001.CC BY-NC-ND · PubMed Central
Figure 6 Pool Refilling Rate during HFS100APs Predicts the Magnitude of PTP (A–C) The PKA blocker H-89 (10 μM) inhibits PTP and pool refilling. (A) Unitary EPSCs evoked by a train of 10 stimuli in the presynaptic terminal before application of H-89 (black), in the presence of H-89 before HFS100APs (green), and in the presence of H-89 after HFS100APs (red). (B) Left: plot of EPSC1 against experimental time. H-89 was applied during the horizontal green continuous line, and HFS100APs was applied at the time point indicated by the vertical black dashed line. Note that H-89 reduced EPSC1 peak amplitude and suppressed the induction of PTP after subsequent HFS100APs. Right: summary bar graph. Data are from 7 pairs. (C) Left: unitary EPSCs evoked by HFS100APs under control conditions (black) and in the presence of H-89 (green). Right: plot of cumulative EPSC peak amplitude (100 stimuli, 100 Hz in presynaptic cell-attached stimulation) under control conditions (black) and in the presence of H-89 (green). (D) Similar plots as shown in (C), but with the actin polymerization blockers latrunculin B (20 μM) and cytochalasin D (10 μM). Traces from different pairs; same control trace shown in (C, left) and (D, left). (E) Comparison of RRP (left), Pr (center), and refilling rate (right) under control conditions (black), in the presence of H-89 (green), and in the presence of latrunculin B and cytochalasin D. RRP and Pr were unchanged, whereas the refilling rate was significantly reduced by H-89 and the actin polymerization blockers. (F) Unitary EPSCs evoked by a train of 10 stimuli in the presynaptic terminal in the presence of latrunculin B and cytochalasin D before (orange) and after (red) HFS100APs. (G) Plot of EPSC1 against experimental time. Latrunculin B and cytochalasin D were applied during the horizontal orange continuous line, and HFS100APs was applied at the time point indicated by the vertical black dashed line. Actin polymerization blockers reduce synaptic transmission and inhibit PTP. (H) Summary bar graph of the effects of H-89 and latrunculin B and cytochalasin D on PTP. (I) Scatterplot of the magnitude of PTP against the refilling rate during HFS100APs. Black, control data; green, data in the presence of H-89; orange, data in the presence of latrunculin B and cytochalasin D. The line represents linear regression to the data points (Spearman rank correlation coefficient ρ = 0.61, p = 0.0005, 28 pairs). In (B), right, (E), and (H), boxes indicate mean values, error bars denote SEM, circles show data from individual experiments, and data from the same experiment are connected by lines. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
Figure 6 Pool Refilling Rate during HFS100APs Predicts the Magnitude of PTP (A–C) The PKA blocker H-89 (10 μM) inhibits PTP and pool refilling. (A) Unitary EPSCs evoked by a train of 10 stimuli in the presynaptic terminal before application of H-89 (black), in the presence of H-89 before HFS100APs (green), and in the presence of H-89 after HFS100APs (red). (B) Left: plot of EPSC1 against experimental time. H-89 was applied during the horizontal green continuous line, and HFS100APs was applied at the time point indicated by the vertical black dashed line. Note that H-89 reduced EPSC1 peak amplitude and suppressed the induction of PTP after subsequent HFS100APs. Right: summary bar graph. Data are from 7 pairs. (C) Left: unitary EPSCs evoked by HFS100APs under control conditions (black) and in the presence of H-89 (green). Right: plot of cumulative EPSC peak amplitude (100 stimuli, 100 Hz in presynaptic cell-attached stimulation) under control conditions (black) and in the presence of H-89 (green). (D) Similar plots as shown in (C), but with the actin polymerization blockers latrunculin B (20 μM) and cytochalasin D (10 μM). Traces from different pairs; same control trace shown in (C, left) and (D, left). (E) Comparison of RRP (left), Pr (center), and refilling rate (right) under control conditions (black), in the presence of H-89 (green), and in the presence of latrunculin B and cytochalasin D. RRP and Pr were unchanged, whereas the refilling rate was significantly reduced by H-89 and the actin polymerization blockers. (F) Unitary EPSCs evoked by a train of 10 stimuli in the presynaptic terminal in the presence of latrunculin B and cytochalasin D before (orange) and after (red) HFS100APs. (G) Plot of EPSC1 against experimental time. Latrunculin B and cytochalasin D were applied during the horizontal orange continuous line, and HFS100APs was applied at the time point indicated by the vertical black dashed line. Actin polymerization blockers reduce synaptic transmission and inhibit PTP. (H) Summary bar graph of the effects of H-89 and latrunculin B and cytochalasin D on PTP. (I) Scatterplot of the magnitude of PTP against the refilling rate during HFS100APs. Black, control data; green, data in the presence of H-89; orange, data in the presence of latrunculin B and cytochalasin D. The line represents linear regression to the data points (Spearman rank correlation coefficient ρ = 0.61, p = 0.0005, 28 pairs). In (B), right, (E), and (H), boxes indicate mean values, error bars denote SEM, circles show data from individual experiments, and data from the same experiment are connected by lines. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.CC BY-NC-ND · PubMed Central
Figure 7 Long SB-Spike and SB-Burst Intervals and Extended Time Course of PTP in the Absence of Activity (A) Left: rasterplot analysis of activity following SBs in GCs in vivo. Points represent activity events (blue, single APs; green, bursts; red, SBs). Events were sorted according to the time point of the last event. Note that the activity extended over several seconds in a subset of events. Inset: summary pie chart of the percentage of SB-single spike (light blue), SB-burst (green), and SB-SB sequences (yellow). (B and C) Cumulative distributions of latencies between SBs and the first event (B) and last event (C) for all events (black), spikes (blue), and bursts (green). In total, data represent 167 SBs. (D and E) Similar analysis as shown in (B) and (C) but for the mean latencies in individual GCs. Note that the SB-last event latency covers and occasionally exceeds the time window of PTP. In total, data were obtained from 20 GCs in vivo. (F) Absence of stimulation extends the time period of PTP. Red, plot of EPSC peak amplitude against experimental time during the standard stimulation paradigm (test stimulation once every 20 s, followed by HFS100APs, followed by test stimulation once every 20 s); orange, plot of EPSC peak amplitude against time during a stimulation paradigm with a 3- to 4-min delay period. The inset shows test stimulation, and the vertical dashed line indicates HFS100APs. Note that PTP was significantly larger in the delay protocol than expected for a process that exponentially decays after HFS100APs. Thus, the time course of PTP was extended in the absence of activity. Data were from 9 pairs (20 s) and 6 pairs (3–4 min). (G) Comparison of PTP after HFS100APs, with 20-s delay, 1- to 2-min delay, and 3- to 4-min delay. Data were from 9 pairs (20 s), 6 pairs (1–2 min), and 6 pairs (3–4 min). In (F and G), PTP was quantified from the amplitudes of the first three EPSCs. (H and I) Similar plots as in (G) but for RRP (H) and Pr (I). Note that, after a delay, PTP was generated by a selective increase in RRP. (G–I) Boxes indicate mean values, and error bars denote SEM. ∗p < 0.05, ∗∗p < 0.01. (J) Pool engrams may allow prolonged storage and efficient readout of information in hippocampal circuits. Natural GC activity (SBs) increases the docked vesicle pool, leading to a structural “pool engram.” In the absence of activity (“delay”), the pool engram is long lasting. APs or bursts can lead to readout of information after a delay. The lifetime of the pool engram is limited by the readout (right top) or by the rates of spontaneous release and vesicle undocking (right bottom; Murthy and Stevens, 1999).
Figure 7 Long SB-Spike and SB-Burst Intervals and Extended Time Course of PTP in the Absence of Activity (A) Left: rasterplot analysis of activity following SBs in GCs in vivo. Points represent activity events (blue, single APs; green, bursts; red, SBs). Events were sorted according to the time point of the last event. Note that the activity extended over several seconds in a subset of events. Inset: summary pie chart of the percentage of SB-single spike (light blue), SB-burst (green), and SB-SB sequences (yellow). (B and C) Cumulative distributions of latencies between SBs and the first event (B) and last event (C) for all events (black), spikes (blue), and bursts (green). In total, data represent 167 SBs. (D and E) Similar analysis as shown in (B) and (C) but for the mean latencies in individual GCs. Note that the SB-last event latency covers and occasionally exceeds the time window of PTP. In total, data were obtained from 20 GCs in vivo. (F) Absence of stimulation extends the time period of PTP. Red, plot of EPSC peak amplitude against experimental time during the standard stimulation paradigm (test stimulation once every 20 s, followed by HFS100APs, followed by test stimulation once every 20 s); orange, plot of EPSC peak amplitude against time during a stimulation paradigm with a 3- to 4-min delay period. The inset shows test stimulation, and the vertical dashed line indicates HFS100APs. Note that PTP was significantly larger in the delay protocol than expected for a process that exponentially decays after HFS100APs. Thus, the time course of PTP was extended in the absence of activity. Data were from 9 pairs (20 s) and 6 pairs (3–4 min). (G) Comparison of PTP after HFS100APs, with 20-s delay, 1- to 2-min delay, and 3- to 4-min delay. Data were from 9 pairs (20 s), 6 pairs (1–2 min), and 6 pairs (3–4 min). In (F and G), PTP was quantified from the amplitudes of the first three EPSCs. (H and I) Similar plots as in (G) but for RRP (H) and Pr (I). Note that, after a delay, PTP was generated by a selective increase in RRP. (G–I) Boxes indicate mean values, and error bars denote SEM. ∗p < 0.05, ∗∗p < 0.01. (J) Pool engrams may allow prolonged storage and efficient readout of information in hippocampal circuits. Natural GC activity (SBs) increases the docked vesicle pool, leading to a structural “pool engram.” In the absence of activity (“delay”), the pool engram is long lasting. APs or bursts can lead to readout of information after a delay. The lifetime of the pool engram is limited by the readout (right top) or by the rates of spontaneous release and vesicle undocking (right bottom; Murthy and Stevens, 1999).CC BY-NC-ND · PubMed Central

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Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

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Metadata

Authors
Vandael, D., Borges-Merjane, C., Zhang, X., & Jonas, P.
Affiliations
Institute of Science and Technology Austria (AT)
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2020-08
Volume
107
Issue
3
Pages
509-521.e7
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2020.05.013
PMC
PMC7427323
OpenAlex
W3032084133
Cited by
114
References
80
Citations by year
2026: 16 · 2025: 13 · 2024: 17 · 2023: 24 · 2022: 15 · 2021: 23 · 2020: 6
FWCI
7.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Horizon 2020 (692692)
  • European Research Council
  • Austrian Science Fund (V 739-B27, Z 312-B27)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
post-tetanic potentiation, short-term plasticity, mossy fiber synapses, hippocampus, CA3 pyramidal cells, granule cells, synaptic vesicle pools, readily releasable pool, docked vesicles, short-term memory, synaptic plasticity, presynaptic activity
MeSH terms
Action Potentials, Animals, Memory, Short-Term, Microscopy, Electron, Neuronal Plasticity, Synapses, Synaptic Vesicles, Pyramidal Cells, Patch-Clamp Techniques, Dentate Gyrus, Mossy Fibers, Hippocampal, Mice, Rats, Synaptic Potentials, CA3 Region, Hippocampal

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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