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In the visual system, the response to a stimulus in a neuron’s receptive field can be modulated by stimulus context, and the strength of these contextual influences vary with stimulus intensity. Recent work has shown how a theoretical model, the stabilized supralinear network (SSN), can account for such modulatory influences, using a small set of computational mechanisms. While the predictions of the SSN have been confirmed in primary visual cortex (V1), its computational principles apply with equal validity to any cortical structure. We have therefore tested the generality of the SSN by examining modulatory influences in the middle temporal area (MT) of the macaque visual cortex, using electrophysiological recordings and pharmacological manipulations. We developed a novel stimulus that can be adjusted parametrically to be larger or smaller in the space of all possible motion directions. We found, as predicted by the SSN, that MT neurons integrate across motion directions for low-contrast stimuli, but that they exhibit suppression by the same stimuli when they are high in contrast. These results are analogous to those found in visual cortex when stimulus size is varied in the space domain. We further tested the mechanisms of inhibition using pharmacologically manipulations of inhibitory efficacy. As predicted by the SSN, local manipulation of inhibitory strength altered firing rates, but did not change the strength of surround suppression. These results are consistent with the idea that the SSN can account for modulatory influences along different stimulus dimensions and in different cortical areas.Significance StatementVisual neurons are selective for specific stimulus features in a region of visual space known as the receptive field, but can be modulated by stimuli outside of the receptive field. The SSN model has been proposed to account for these and other modulatory influences, and tested in V1. As this model is not specific to any particular stimulus feature or brain region, we wondered whether similar modulatory influences might be observed for other stimulus dimensions and other regions. We tested for specific patterns of modulatory influences in the domain of motion direction, using electrophysiological recordings from MT. Our data confirm the predictions of the SSN in MT, suggesting that the SSN computations might be a generic feature of sensory cortex.

Early in development, the cat primary visual cortex (V1) is dominated by inputs driven by the contralateral eye. The pattern then reorganizes into ocular dominance columns that are roughly equally distributed between inputs serving the two eyes. This reorganization does not occur if the eyes are kept closed. The mechanism of this equalization is unknown. It has been argued that it is unlikely to involve Hebbian activity-dependent learning rules, on the assumption that these would favor an initially dominant eye. The reorganization occurs at the onset of the critical period (CP) for monocular deprivation (MD), the period when MD can cause a shift of cortical innervation in favor of the nondeprived eye. In mice, the CP is opened by the maturation of cortical inhibition, which does not occur if the eyes are kept closed. Here we show how these observations can be united: under Hebbian rules of activity-dependent synaptic modification, strengthening of intracortical inhibition can lead to equalization of the two eyes' inputs. Furthermore, when the effects of homeostatic synaptic plasticity or certain other mechanisms are incorporated, activity-dependent learning can also explain how MD causes a shift toward the open eye during the CP despite the drive by inhibition toward equalization of the two eyes' inputs. Thus, assuming similar mechanisms underlie the onset of the CP in cats as in mice, this and activity-dependent learning rules can explain the interocular equalization observed in cat V1 and its failure to occur without visual experience.

Previously, we proposed a model of the circuitry underlying simple-cell responses in cat primary visual cortex (V1) layer 4. We argued that the ordered arrangement of lateral geniculate nucleus inputs to a simple cell must be supplemented by a component of feedforward inhibition that is untuned for orientation and responds to high temporal frequencies to explain the sharp contrast-invariant orientation tuning and low-pass temporal frequency tuning of simple cells. The temporal tuning also requires a significant NMDA component in geniculocortical synapses. Recent experiments have revealed cat V1 layer 4 inhibitory neurons with two distinct types of receptive fields (RFs): complex RFs with mixed ON/OFF responses lacking in orientation tuning, and simple RFs with normal, sharp-orientation tuning (although, some respond to all orientations). We show that complex inhibitory neurons can provide the inhibition needed to explain simple-cell response properties. Given this complex cell inhibition, antiphase or “push-pull” inhibition from tuned simple inhibitory neurons acts to sharpen spatial frequency tuning, lower responses to low temporal frequency stimuli, and increase the stability of cortical activity.

Neurons in the primary visual cortex of higher mammals respond selectively to light/dark borders of a particular orientation. The receptive fields of simple cells, a type of orientation-selective cell, consist of adjacent, oriented regions alternately receiving ON-center and OFF-center excitatory input. I show that this segregation of inputs within receptive fields can occur through an activity-dependent competition between ON-center and OFF-center inputs, just as segregation of inputs between different postsynaptic cells into ocular dominance columns appears to occur through activity-dependent competition between left-eye and right-eye inputs. These different outcomes are proposed to result, not from different mechanisms, but from different spatial structures of the correlations in neural activity among the competing inputs in each case. Simple cells result if ON-center inputs are best correlated with other ON-center inputs, and OFF with OFF, at small retinotopic separations, but ON-center inputs are best correlated with OFF-center inputs at larger separations. This hypothesis leads robustly to development of simple cell receptive fields selective for orientation and spatial frequency, and to the continuous and periodic arrangement of preferred orientation across the cortex. Input correlations determine the mean preferred spatial frequency and degree of orientation selectivity. Estimates of these correlations based on measurements in adult cat retina (Mastronarde, 1983a,b) produce quantitative predictions for the mean preferred spatial frequencies of cat simple cells across eccentricities that agree with experiments (Movshon et al., 1978b). Intracortical interactions are the primary determinant of cortical organization. Simple cell spatial phases can play a key role in this organization, so arrangements of spatial phases and preferred orientations may need to be studied together to understand either alone. Possible origins for other cortical features including spatial frequency clusters, afferent ON/OFF segregation, blobs, pinwheels, and opponent inhibition within simple cell receptive fields are suggested. A number of strong experimental tests of the hypothesis are proposed.

Cholinergic synaptic vesicles purified from the electric organ of the marine ray, Discopyge ommata, contain 2 different size classes of GTP- binding proteins: one or more with an apparent molecular weight (MW) between 37 and 41 kDa, and 3 major and at least 2 minor proteins with MW between 20 and 29 kDa. These GTP-binding proteins were detectable using the alpha 32P-GTP overlay technique and covalent modification with bacterial toxins. The higher MW GTP-binding proteins are ADP- ribosylated by pertussis toxin and 2 of the lower MW GTP-binding proteins are sensitive to botulinum toxin.