Multiple adaptable mechanisms early in the primate visual pathway.

We describe experiments that isolate and characterize multiple adaptable mechanisms that influence responses of orientation-selective neurons in primary visual cortex (V1) of anesthetized macaque (Macaca fascicularis). The results suggest that three adaptable stages of machinery shape neural responses in V1: a broadly tuned early stage and a spatio-temporally tuned later stage, both of which provide excitatory input, and a normalization pool that is also broadly tuned. The early stage and the normalization pool are revealed by adapting gratings that themselves fail to evoke a response from the neuron: either low temporal frequency gratings at the null orientation or gratings of any orientation drifting at high temporal frequencies. When effective, adapting stimuli that altered the sensitivity of these two mechanisms caused reductions of contrast gain and often brought about a paradoxical increase in response gain due to a relatively greater desensitization of the normalization pool. The tuned mechanism is desensitized only by stimuli well matched to a neuron's receptive field. We could thus infer desensitization of the tuned mechanism by comparing effects obtained with adapting gratings of preferred and null orientation modulated at low temporal frequencies.

Nonlinear signal summation in magnocellular neurons of the macaque lateral geniculate nucleus.

Magnocellular (M-), but not parvocellular (P-), neurons of the macaque lateral geniculate nucleus (LGN) differ distinctively in their responses to counterphase-modulated and drifting gratings. Relative to stimulation with drifting gratings, counterphase modulation reduces the responses of M- cells in a band around 25 Hz, producing a "notch" in the temporal modulation transfer function (tMTF). The notch is prominent in nearly every M- cell with little variation in the temporal frequency at which it is deepest. The machinery responsible for the notch lies mostly outside the classical linear center. Directly driving the notching mechanism with annular gratings evokes no linear response but elicits a second harmonic (F2) modulation of the discharge accompanied by a drop in the mean discharge (F0). Analysis of the S- potential, which reveals inputs from ganglion cells, shows that 1) tMTFs of the afferent retinal ganglion cells are not notched and 2) during stimulation with annular gratings, the second harmonic component is present, but the drop in the F0 is largely absent from the responses of parasol ganglion cells. These results suggest that the notch is caused by the combined action of the linear response and the second harmonic response, both inherited from retina, and a suppression that originates after the retina. Our results reveal a distinctive signal transformation in the LGN and they show that nearly every M- cell exhibits a spatial nonlinearity like that observed in Y cells of the cat.

A new code for contrast in the primate visual pathway.

We characterize a hitherto undocumented type of neuron present in the regions bordering the principal layers of the macaque lateral geniculate nucleus. Neurons of this type were distinguished by a high and unusually regular maintained discharge that was suppressed by spatiotemporal modulation of luminance or chromaticity within the receptive field. The response to any effective stimulus was a reduction in discharge, reminiscent of the "suppressed-by-contrast" cells of the cat retina. To a counterphase-modulated grating, the response was a phase-insensitive suppression modulated at twice the stimulus frequency, implying a receptive field comprised of multiple mechanisms that generate rectifying responses. This distinctive nonlinearity makes the neurons well suited to computing a measure of contrast energy; such a signal might be important in regulating sensitivity early in visual cortex.

Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling.

Airway epithelial cells have a major role in initiating inflammation in response to bacterial pathogens. Through the immediate induction of CXCL8 and cytokine expression, polymorphonuclear cells are mobilized and activated to eradicate the infecting organisms. However, the influx of polymorphonuclear cells and the effects of their toxic exoproducts impede respiratory function. We postulated that respiratory epithelial cells must also participate in the regulation of their own proinflammatory signaling. Both Staphylococcus aureus and Pseudomonas aeruginosa were found to potently activate IL-6 expression immediately upon contact with epithelial cells, and by 1 h induced TNF-alpha converting enzyme (TACE) transcription. By 4 h of bacterial exposure, TACE colocalized with IL-6Ralpha on the apical surface of airway cells, and by 24 h, soluble IL-6Ralpha accumulated in the cell culture supernatant. Epithelial IL-6 and soluble IL-6Ralpha were shown to participate in trans-signaling, interacting with membrane-associated gp130 to activate CCL-2 expression and inhibit additional CXCL8 production. Thus, bacteria are physiological activators of TACE expression, which provides a mechanism to regulate inflammatory signaling that is initiated by airway epithelial cells.