Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons
- Janelia Research Campus, Howard Hughes Medical Institute, United States
- Northwestern University, United States
Figures
Figure 1 with 1 supplement
Reducing Nav channel availability with 20 nM TTX does not affect synaptic transmission at PP → CA1tuft synapses.
(A) Experimental configuration showing somatic whole-cell recording with presynaptic stimulation of the perforant pathway (PP), 10 µM TTX locally applied to the soma, and bath application of 20 nM …
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Figure 1—source data 1
Source data for Figure 1.
- https://doi.org/10.7554/eLife.06414.004
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Figure 1—source data 2
Source data for Figure 1—figure supplement 1.
- https://doi.org/10.7554/eLife.06414.005
Figure 1—figure supplement 1
Effects of reducing Nav channel availability with 20 nM TTX on somatic action potentials.
(A) Left, experimental configuration showing somatic whole-cell recording. Right, representative traces of somatically recorded voltage in response to a current step (100 ms) at the level of action …
Figure 2 with 4 supplements
Reducing Nav channel availability with 20 nM TTX inhibits postsynaptic dSpikes evoked by presynaptic TBS of PP → CA1tuft synapses.
(A) Left, experimental configuration showing dendritic whole-cell recording with presynaptic stimulation of the PP. Right, traces of dendritically recorded voltage in response to a single burst of …
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Figure 2—source data 1
Source data of Figure 2.
- https://doi.org/10.7554/eLife.06414.008
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Figure 2—source data 2
Source data of Figure 2—figure supplement 1–4.
- https://doi.org/10.7554/eLife.06414.009
Figure 2—figure supplement 1
Peak amplitude and the first temporal derivative of dendritically recorded voltage in response to TBS plotted as a function of stimulus position in TBS.
(A) Additional analysis of the experiments in Figure 2A, showing peak amplitude of dendritically recorded voltage (V) in response to presynaptic TBS plotted as a function of stimulus position (Stim. …
Figure 2—figure supplement 2
Distinguishing between bAPs and large dSpikes in dendritic recordings.
(A) Analysis of the onset kinetics of large-amplitude dendritic events. A1. Left, experimental configuration showing dendritic whole-cell recording with presynaptic stimulation of the PP. Right, …
Figure 2—figure supplement 3
Voltage and the first temporal derivative of voltage of the clearest small dSpikes (spikelets).
Traces of dendritically recorded voltage (V) and the first temporal derivative of voltage (dV/dt) in response to a single presynaptic burst of the PP for the events above the upper bound of the 99% …
Figure 2—figure supplement 4
Small dSpikes (spikelets) identified by a second method.
(A) Alternative analysis of the experiments in Figure 2B, showing notched box plots of peak first temporal derivative of dendritically recorded voltage (dV/dt), normalized to the median value for …
Figure 3
TBS-induced PP → CA1tuft LTP is blocked by reducing Nav channel availability with 20 nM TTX.
(A) Left, experimental configuration showing somatic whole-cell recording with presynaptic stimulation of the PP. Right, representative trace of somatically recorded voltage in response to …
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Figure 3—source data 1
Source data of Figure 3.
- https://doi.org/10.7554/eLife.06414.015
Figure 4 with 1 supplement
NMDAR and L-Cav channels mediate TBS-induced LTP at PP → CA1tuft synapses.
(A–D) Representative time course of EPSP amplitude before and after TBSx3+Current was delivered (arrows) in 50 µM AP5 (A), 10 µM nimodipine (B), 50 µM AP5 and 10 µM nimodipine (C), or 50 µM Ni2+ (D).…
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Figure 4—source data 1
Source data of Figure 4.
- https://doi.org/10.7554/eLife.06414.017
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Figure 4—source data 2
Source data of Figure 4—figure supplement 1.
- https://doi.org/10.7554/eLife.06414.018
Figure 4—figure supplement 1
L-Cav channels are not required for synaptic transmission before or after the induction of PP → CA1tuft LTP.
Summary of effects of 10 µM nimodipine (Nimo) on somatically recorded voltage or current in response to single-shock stimulation of the PP before (A, B) or after (C, D) the induction of PP → CA1tuft …
Figure 5
Reducing Nav channel availability reduces the slow synaptic depolarization in distal apical trunk in response to TBS significantly less than blocking NMDAR channels.
(A) Differential effects of 20 nM TTX and 50 µM AP5 on dendritically recorded voltage in response to presynaptic TBS. A1, Left, experimental configuration showing dendritic whole-cell recording with …
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Figure 5—source data 1
Source data of Figure 5.
- https://doi.org/10.7554/eLife.06414.021
Figure 6
Brief synaptic stimuli are sufficient for the induction of PP → CA1tuft LTP.
(A) Top left, experimental configuration showing somatic whole-cell recording with presynaptic stimulation of the PP. Bottom right, representative trace of somatically recorded voltage in response …
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Figure 6—source data 1
Source data of Figure 6.
- https://doi.org/10.7554/eLife.06414.023
Figure 7 with 1 supplement
Reducing Nav channel availability reduces the calcium influx in distal apical tuft dendrites in response to high-frequency burst stimulation significantly less than blocking NMDAR channels.
(A) Bottom, experimental configuration showing somatic whole-cell recording with presynaptic stimulation of the PP, with a representative Z-stack image of a neuron (filled with 50 µM AF-594) on …
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Figure 7—source data 1
Source data of Figure 7.
- https://doi.org/10.7554/eLife.06414.025
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Figure 7—source data 2
Source data of Figure 7—figure supplement 1.
- https://doi.org/10.7554/eLife.06414.026
Figure 7—figure supplement 1
Stability of two-photon calcium imaging over long recording durations.
(A) Experimental configuration showing somatic whole-cell recording with presynaptic stimulation of the PP, with a representative Z-stack image of a neuron (filled with 50 µM AF-594). The box …
Figure 8 with 1 supplement
Computational modeling reveals a large, rapid, Na-dSpike-mediated calcium current through NMDAR and L-Cav channels.
(A) Left, Z-stack image of a neuron (filled with 50 µM AF-594). Right, morphology of the model neuron. Red dots indicate the locations of simulated synapses. Arrow indicates the imaged compartment …
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Figure 8—source data 1
Source data of Figure 8.
- https://doi.org/10.7554/eLife.06414.029
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Figure 8—source data 2
Source data of Figure 8—figure supplement 1.
- https://doi.org/10.7554/eLife.06414.030
Figure 8—figure supplement 1
Minimal effect of blocking L-Cav channels on the calcium influx in distal apical tuft dendrites is consistent with the prediction of the model.
(A) Left, experimental configuration showing somatic whole-cell recording with presynaptic stimulation of the PP, with a representative Z-stack image of a neuron (filled with 50 µM AF-594) on which …
Figure 9
TBS-induced PP → CA1tuft LTP is blocked by intracellular calcium buffering with a high concentration of BAPTA, but not a low concentration of BAPTA or low or high EGTA.
(A–D) Representative time course of EPSP amplitude before and after TBSx3+Current was delivered (arrows) from cells buffered with 0.5 mM EGTA (A), 0.5 mM BAPTA (B), 10 mM EGTA (C), or 10 mM BAPTA (D)…
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Figure 9—source data 1
Source data of Figure 9.
- https://doi.org/10.7554/eLife.06414.033
Figure 10
Proposed model for the critical role of Na-dSpikes in the induction of PP → CA1tuft LTP.
(A) Synaptic membrane potential and calcium currents in response to a high-frequency burst activation of glutamatergic synapses (re-plotted from Figure 8D). (1) AMPA-/NMDA-EPSP, (2) Na-dSpike, (3) IC…
Author response image 1
Dye saturation does not occur under our experimental conditions. Top. Summary of peak ∆G/R from dendritic shaft in response to different stimulation patterns. Only the experiments in which TBS of …
Author response image 2
Relationship between dendritic calcium responses in control condition and normalized drug effects on the responses. Summary of effects of different pharmacological agents on ∆G/R (normalized to …
