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A divergence appears only at weak stimulations (below 10−3 µM/s) where the rising time of RP at soma is shorter than that of SP (Fig. 4C).
Therefore, NMDARs contributed neither to the firing mode nor to the temporal precision of PP inputs in DGCs from chronic epileptic rats when PP-EPSPs were evoked by weak stimulations.
To examine the EPSP spike coupling, weak stimulations were used (see methods) in order to evoke small EPSPs (∼5 mV) at around −50 mV (threshold holding potential), a potential at which EPSPs triggered cell firing in single-spike mode (Fig. 1 A ) in about 50% of the trials (see Table 1) both in DGCs from control and epileptic rats.
Weak stimulations of PP evoked AMPAR-mediated EPSPs (amplitude ∼3 5 mV, see Methods) that triggered cell firing in single-spike mode with a high temporal precision both in DGCs from control and epileptic rats (mean SD = 3.5 ± 0.3 ms, n = 38 cells from control rats; mean SD = 3.1 ± 0.3 ms, n = 23 cells from epileptic rats; P > 0.05; Fig. 6 A, B, D ).
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Whereas one might expect only the strongly stimulated synapse to undergo LTP (since weak stimulation alone is insufficient to induce LTP at either synapse), both synapses will in fact undergo LTP.
For the first time, we here present a two-stage CR stimulation protocol, where two qualitatively different types of CR stimulation are delivered one after another, and the first stage comes at a particularly weak stimulation intensity.
This stimulation approach might be clinically beneficial in patients suffering from brain diseases characterized by abnormal neuronal synchrony where a first treatment stage should be performed at particularly weak stimulation intensities in order to avoid side effects.
Our computational results might open up novel opportunities to effectively induce sustained desynchronization at particularly weak stimulation intensities, thereby avoiding side effects, e.g., in the case of deep brain stimulation.
Such relatively weak stimulation of the MLR produced locomotor movements after a relatively long delay, which featured neuronal interactions in the hindbrain.
In the regime of linear responses, i.e., for weak stimulation, we used an alternative method of sensitivity estimation [28]: the external force was zero mean broadband Gaussian noise with the standard deviation σ s, band-limited to the cutoff frequency of fc = 200 Hz, Fext(t) = s(t).
But upon simultaneous weak stimulation, both synapses undergo LTP in a cooperative fashion.
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