The properties of long-term potentiation at SC-CA1/ TA-CA1 hippocampal synaptic pathways depends upon their input pathway activation patterns

Abstract

Long-term potentiation (LTP) has been considered as a cellular mechanism of memory. Since the Schaffer collateral (SC) and temporoammonic (TA) inputs to CA1 are distinct synaptic pathways that could mediate different cognitive functions, this study was therefore aimed to separately study and compare the properties of LTP of these two synaptic pathways. In the current study we used slice electrophysiological methods to compare various properties of these two synaptic pathways in response to single, paired pulse stimulation, and to three standard protocols for inducing LTP: the high frequency electrical stimulation (HFS), theta-burst (TBS), and primed burst (PBs) stimulation. We found that the SC-CA1 synapses could produce bigger maximum synaptic responses than TA-CA1 synapses. In addition, we showed that paired-pulse ratios of the SC-CA1 synapses were higher than TA-CA1 synapses at certain inter-pulses intervals. Finally, we showed a higher LTP% was induced by PBs or TBS at the SC-CA1 synapse than the TA-CA1 synapse. Briefly, our findings suggest the differential basal synaptic transmission, paired-pulse evoked synaptic responses, and LTP exhibition of the hippocampal SC-CA1/ TA-CA1 synaptic pathways, which may rely on spontaneous and evoked activity pattern at the local circuit level.

Keywords: Activation pattern; Field potentials; Hippocampus; Plasticity; Synaptic transmission.

Fig. 1

Drawing of the hippocampal slice preparation depicting the cut site to remove area CA3 and dentate gyrus, and electrode positions for recording of SC-CA1 and TA-CA1 synaptic responses. A. For Schaffer collaterals field potentials recording, stimulating electrode (stim) and recording electrode (rec) sites were shown. B. For field potentials recording from TA-CA1 synapses, stimulating electrode (stim) was placed on the perforant pathway and recording electrode (rec) was located on the stratum lacunosome-molecular in CA1. C To verify the correct isolation of the temporoammonic pathway, stimulating electrode was placed on the perforant pathway and recording electrode was placed on stratum radiatum in CA1. The waveform in this section represents an evoked fEPSP from the current sources following the temporoammonic pathway stimulation. The traces on the right show the fEPSPs that were recorded in each configuration.The green color () is used to show SC-CA1 pathway and response, the pink color () is used to show TA-CA1 pathway and response, and the blue cell represents a pyramidal cell in CA1 area.

Fig. 2

SC-CA1 synapses could produce bigger maximum synaptic responses than TA-CA1 synapses. Input/output curves for the SC-CA1 (A) TA-CA1 (B) synaptic pathways. The insets show superimposed field EPSPs at different stimulation intensities for SC-CA1 (n = 17) and TA-CA1 (n = 16) synaptic responses. The mean value of test pulse intensity (C) and the mean value of maximum intensity (D) at hippocampal TA-CA1 input were significantly larger than those of hippocampal SC-CA1 input. The mean value of test pulse response (E) and the mean value of maximum response (F) were smaller at hippocampal TA-CA1 synapses. Data presented as mean ± SEM. * **P < 0.001, unpaired t-test.

Fig. 3

Paired-pulse ratios of SC-CA1 synapses were higher than TA-CA1 synapses at certain inter-pulses intervals. The mean values of paired pulse ratio at 10, 20, 80, 200 and 300 ms IPIs for these two synaptic pathways are shown (A). A reduced level of excitation-to-inhibition at TA-CA1 input (n = 11) was observed as compared to SC-CA1 input (n = 18). The chart at left shows the mean values of the paired pulse ratio vs IPIs plot and the right chart shows the mean values of AUC for the two synaptic pathways (B). Representative waveforms at three different IPIs for these two synaptic pathways are shown (C). Data presented as mean ± SEM. * P < 0.05, * **P < 0.001, unpaired t-test. P1, the first fEPSP; P2, the second fEPSP.

Fig. 4

LTP induction by HFS, PBs and TBS at SC-CA1 and TA-CA synaptic pathways. The arrows indicate the application of different protocols: HFS (A), PBs (B) and TBS (C). The insets for each part show bar charts of normalized fEPSP slopes at the last 10 min of 1 h after LTP induction (marked by number 2) compared to 10 min baseline before applying tetanic stimulation (marked by number 1) and representative superimposed waveforms at baseline (red traces) and during 50–60 min after tetanus application (blue traces). Data presented as mean ± SEM. * P < 0.05, * *P < 0.01, * **P < 0.001unpaired t-test. For all groups n = 8, except for HFS (n = 9) and TBS (n = 7) attempts for TA-CA1 synaptic pathways.

Fig. 5

Primed burst stimulation (PBs) was able to reliably induce persistent LTP at TA-CA1 synapses as compared to theta-burst stimulation (TBS). The potentiation extent (%) caused by each individual protocol was the same in the two synaptic pathways. The percentage of potentiation induced by each individual protocol was not significantly different between the two synaptic pathways (A). The total pulse number used in each individual protocol is differentially depicted for each synaptic response (B). For PBs and TBS equal pulse numbers were used in the two synaptic pathways. PBs with half of the total number of pulses was able to reliably induce persistent LTP of fEPSP at TA-CA1 synapses as compared to TBS. But for HFS total pulse numbers in TA-CA1 synapse was fourfold.