Endotoxin (a TLR4 agonist), flagellin (a TLR5 agonist), and outer membrane protein A (a TLR2 agonist) alone are each weak stimuli for NK cells of healthy volunteers, whereas in the presence of accessory cytokines (for example, IL-2, IL-15, IL-12, or IL-18) large amounts of IFN-γ are produced [ 23, 27].
In contrast, while IL-10 alone was a relatively weak stimulus for pri-miR-455 transcription, a combination of both IL-10 and LPS resulted in a much greater stimulation of pri-miR-455 than either LPS or IL-10 alone at 1 h, although this synergistic effect of LPS and IL-10 was not seen at 6 h (Fig. 8A).
These behaviors include "normalization" or sublinear summation of responses to multiple stimuli that becomes linear for weak stimuli and becomes "winner-take-all" for stimuli of strongly unequal strength; and surround suppression that becomes surround facilitation for a weak center stimulus.
This result also is consistent with the model of SR and attention proposed by Ward and Kitajo [57], in which a weighting function changes with stimulus strength, allowing SR for weak stimuli but enforcing attenuation of noise by attention for strong stimuli.
Specifically, the logic of the linearity test, and the structure of the model, assume linearity of the cone signal, which is a reasonable approximation for weak stimuli (Schnapf et al., 1990), but fails for stronger stimuli (J Angueyra and F Rieke, personal communication).
The basic result for weak stimuli is that the cortical response is a propagating wave whose amplitude decays exponentially with distance.
Before we introduce in detail the two models sketched in Fig. 2, it is worth to note that, for weak stimuli and weak independent noise, these models possess the same signal output cross-spectrum, the same power spectrum, and the same time-dependent output firing rate.
Rather, SR operates for weak stimuli in noise whether or not attention is being paid to them.
However, it is not clear how inflammation might modulate macrophage responses to weak stimuli by changing the extent of receptor clustering necessary for downstream signaling.
For mechanical signals, noise serves to boost weak stimuli.
