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].
Specifically, for the case of a weak stimulus, a characteristic bimodal distribution is obtained for the activation of a downstream signaling molecule indicating large cell-to-cell fluctuations.
Hence, for the case of a weak stimulus, we need a minimum of two separate rate constants to generate slow activation with large cell-to-cell variability.
For visuo-auditory association experiments, the weak stimulus was changed to a visual light stimulus.
This weak stimulus was paired with a frequency that evoked the best neuronal response (fB, strong stimulus) for 36 trials (P36).
After the pairings of weak and strong stimuli, neuronal responses to the weak stimulus were examined at different time delays.
After local infusion of CCK, the weak stimulus f1 was paired with a strong stimulus at the best frequency (fB= 14 kHz, f1+fB) for 10 trials (P10; note that f1 and fB were presented in a sequential manner).
ATP injection barely induced cytotoxic iNOS expression (Figure 6), possibly because ATP is a weak inflammatory stimulus for induction of iNOS expression (Figure S4).
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).
