Alessandra Angelucci

Reaching beyond the classical receptive field of V1 neurons: horizontal or feedback axons?

It is commonly assumed that the orientation-selective surround field of neurons in primary visual cortex (V1) is due to interactions provided solely by intrinsic long-range horizontal connections. We review evidence for and against this proposition and conclude that horizontal connections are too slow and cover too little visual field to subserve all the functions of suppressive surrounds of V1 neurons in the macaque monkey. We show that the extent of visual space covered by horizontal connections corresponds to the region of low contrast summation of the receptive field center mechanism. This region encompasses the classically defined receptive field center and the proximal surround. Beyond this region, feedback connections are the most likely substrate for surround suppression. We present evidence that inactivation of higher order areas leads to a major decrease in the strength of the suppressive surround of neurons in lower order areas, supporting the hypothesis that feedback connections play a major role in center-surround interactions.

The Role of Feedback in Shaping the Extra-Classical Receptive Field of Cortical Neurons: A Recurrent Network Model

The responses of neurons in sensory cortices are affected by the spatial context within which stimuli are embedded. In the primary visual cortex (V1), orientation-selective responses to stimuli in the receptive field (RF) center are suppressed by similarly oriented stimuli in the RF surround. Surround suppression, a likely neural correlate of perceptual figure–ground segregation, is traditionally thought to be generated within V1 by long-range horizontal connections. Recently however, it has been shown that these connections are too short and too slow to mediate fast suppression from distant regions of the RF surround. We use an anatomically and physiologically constrained recurrent network model of macaque V1 to show how interareal feedback connections, which are faster and longer-range than horizontal connections, can generate “far” surround suppression. We provide a novel solution to the puzzle of how surround suppression can arise from excitatory feedback axons contacting predominantly excitatory neurons in V1. The basic mechanism involves divergent feedback connections from the far surround targeting pyramidal neurons sending monosynaptic horizontal connections to excitatory and inhibitory neurons in the RF center. One of several predictions of our model is that the “suppressive far surround” is not always suppressive, but can facilitate the response of the RF center, depending on the amount of excitatory drive to the local inhibitors. Our model provides a general mechanism of how top-down feedback signals directly contribute to generating cortical neuron responses to simple sensory stimuli.

Comparison of spatial summation properties of neurons in macaque V1 and V2.

In visual cortex, responses to stimulation of the receptive field (RF) are modulated by simultaneous stimulation of the RF surround. The mechanisms for surround modulation remain unidentified. We previously proposed that in the primary visual cortex (V1), near surround modulation is mediated by geniculocortical and horizontal connections and far surround modulation by interareal feedback connections. To understand spatial integration in the secondary visual cortex (V2) and its underlying circuitry, we have characterized spatial summation in different V2 layers and stripe compartments and compared it to that in V1. We used grating stimuli in circular and annular apertures of different sizes to estimate the extent and sensitivity of RF and surround components in V1 and V2. V2 RFs and surrounds were twice as large as those in V1. As in V1, V2 RFs doubled in size when measured at low contrast. In both V1 and V2, surrounds were about fivefold the size of the RF and the far surround could exceed 12.5° in radius, averaging 5.5° in V1 and 9.2° in V2. The strength of surround suppression was similar in both areas. Thus although differing in spatial scale, the interactions among RF components are similar in V1 and V2, suggesting similar underlying mechanisms. As in V1, the extent of V2 horizontal connections matches that of the RF center, but is much smaller than the largest far surrounds, which likely derive from interareal feedback. In V2, we found no laminar or stripe differences in size and magnitude of surround suppression, suggesting conservation across stripes of the basic circuit for surround modulation.

Contribution of feedforward thalamic afferents and corticogeniculate feedback to the spatial summation area of macaque V1 and LGN.

Neurons in the primary visual cortex (V1) respond best to oriented gratings of optimal size within their receptive field (RF) and are suppressed by larger gratings involving the nonclassical RF surround. A V1 neurons optimal stimulus size is larger at lower stimulus contrast. A central question in visual neuroscience is what circuits generate the size tuning of V1 cells. We recently demonstrated that V1 horizontal connections integrate signals within a region of the RF center corresponding to the V1 neurons optimal stimulus size at low contrast; extrastriate feedback connections to V1, instead, are longer range and can integrate signals from the most distant regions of the V1 cells RF surround. Here, we have determined the contribution of geniculocortical feedforward and corticogeniculate feedback connections to the size‐tuning of macaque V1 and lateral geniculate (LGN) neurons, respectively. Specifically, we have quantitatively compared the visuotopic extent of geniculate feedforward afferents to V1 with the size of the RF center and surround of neurons in the V1 input layers and the visuotopic extent of V1 feedback connections to the LGN with the RF size of cells in V1 layer 6, where these connections originate. We find geniculate feedforward connections to provide visuotopic information to V1 that is spatially coextensive with the V1 neurons optimal stimulus size measured with high‐contrast gratings. V1 feedback connections restrict their influence to an LGN region visuotopically coextensive with the size of the minimum response field (or classical RF) of V1 layer 6 cells and commensurate with the LGN region from which they receive feedforward connections. J. Comp. Neurol. 498:330–351, 2006.

Strong Recurrent Networks Compute the Orientation Tuning of Surround Modulation in the Primate Primary Visual Cortex

In macaque primary visual cortex (V1), neuronal responses to stimuli inside the receptive field (RF) are modulated by stimuli in the RF surround. This modulation is orientation specific. Previous studies suggested that, for some cells, this specificity may not be fixed but changes with the stimulus orientation presented to the RF. We demonstrate, in recording studies, that this tuning behavior is instead highly prevalent in V1 and, in theoretical work, that it arises only if V1 operates in a regime of strong local recurrence. Strongest surround suppression occurs when the stimuli in the RF and the surround are iso-oriented, and strongest facilitation when the stimuli are cross-oriented. This is the case even when the RF is suboptimally activated by a stimulus of nonpreferred orientation but only if this stimulus can activate the cell when presented alone. This tuning behavior emerges from the interaction of lateral inhibition (via the surround pathways), which is tuned to the preferred orientation of the RF, with weakly tuned, but strong, local recurrent connections, causing maximal withdrawal of recurrent excitation at the feedforward input orientation. Thus, horizontal and feedback modulation of strong recurrent circuits allows the tuning of contextual effects to change with changing feedforward inputs.

Different Orientation Tuning of Near- and Far-Surround Suppression in Macaque Primary Visual Cortex Mirrors Their Tuning in Human Perception

In primary visual cortex (V1), neuronal responses to stimuli inside the receptive field (RF) are usually suppressed by stimuli in the RF surround. This suppression is orientation specific. Similarly, in human vision surround stimuli can suppress perceived contrast of a central stimulus in an orientation-dependent manner. The surround consists of two regions likely generated by different circuits: a near-surround generated predominantly by geniculocortical and intra-V1 horizontal connections, and a far-surround generated exclusively by interareal feedback. Using stimuli confined to the near- or far-surround of V1 neurons, and similar stimuli in human psychophysics, we find that near-surround suppression is more sharply orientation tuned than far-surround suppression in both macaque V1 and human perception. These results point to a similarity between surround suppression in macaque V1 and human vision, and suggest that feedback circuits are less orientation biased than horizontal circuits. We find the sharpest tuning of near-surround suppression in V1 layers (3, 4B, 4Cα) with patterned and orientation-specific horizontal connections. Sharpest tuning of far-surround suppression occurs in layer 4B, suggesting greater orientation specificity of feedback to this layer. Different orientation tuning of near- and far-surround suppression may reflect a statistical bias in natural images, whereby nearby edges have higher probability than distant edges of being co-oriented and belonging to the same contour. Surround suppression would, thus, increase the coding efficiency of frequently co-occurring contours and the saliency of less frequent ones. Such saliency increase can help detect small orientation differences in nearby edges (for contour completion), but large orientation differences in distant edges (for directing saccades/attention).

Four projection streams from primate V1 to the cytochrome oxidase stripes of V2

In the primate visual system, areas V1 and V2 distribute information they receive from the retina to all higher cortical areas, sorting this information into dorsal and ventral streams. Therefore, knowledge of the organization of projections between V1 and V2 is crucial to understand how the cortex processes visual information. In primates, parallel output pathways from V1 project to distinct V2 stripes. The traditional tripartite division of V1-to-V2 projections was recently replaced by a bipartite scheme, in which thin stripes receive V1 inputs from blob columns, and thick and pale stripes receive common input from interblob columns. Here, we demonstrate that thick and pale stripes, instead, receive spatially segregated V1 inputs and that the interblob is partitioned into two compartments: the middle of the interblob projecting to pale stripes and the blob/interblob border region projecting to thick stripes. Double-labeling experiments further demonstrate that V1 cells project to either thick or pale stripes, but rarely to both. We also find laminar specialization of V1 outputs, with layer 4B contributing projections mainly to thick stripes, and no projections to one set of pale stripes. These laminar differences suggest different contribution of magno, parvo, and konio inputs to each V1 output pathway. These results provide a new foundation for parallel processing models of the visual system by demonstrating four V1-to-V2 pathways: blob columns-to-thin stripes, blob/interblob border columns-to-thick stripes, interblob columns-to-palelateral stripes, layer 2/3–4A interblobs-to-palemedial stripes.

Multiple components of surround modulation in primary visual cortex: Multiple neural circuits with multiple functions?

The responses of neurons in primary visual cortex (V1) to stimulation of their receptive field (RF) are modulated by stimuli in the RF surround. This modulation is suppressive when the stimuli in the RF and surround are of similar orientation, but less suppressive or facilitatory when they are cross-oriented. Similarly, in human vision surround stimuli selectively suppress the perceived contrast of a central stimulus. Although the properties of surround modulation have been thoroughly characterized in many species, cortical areas and sensory modalities, its role in perception remains unknown. Here we argue that surround modulation in V1 consists of multiple components having different spatio-temporal and tuning properties, generated by different neural circuits and serving different visual functions. One component arises from LGN afferents, is fast, untuned for orientation, and spatially restricted to the surround region nearest to the RF (the near-surround); its function is to normalize V1 cell responses to local contrast. Intra-V1 horizontal connections contribute a slower, narrowly orientation-tuned component to near-surround modulation, whose function is to increase the coding efficiency of natural images in manner that leads to the extraction of object boundaries. The third component is generated by topdown feedback connections to V1, is fast, broadly orientation-tuned, and extends into the far-surround; its function is to enhance the salience of behaviorally relevant visual features. Far- and near-surround modulation, thus, act as parallel mechanisms: the former quickly detects and guides saccades/attention to salient visual scene locations, the latter segments object boundaries in the scene.

Circuits and Mechanisms for Surround Modulation in Visual Cortex

Surround modulation (SM) is a fundamental property of sensory neurons in many species and sensory modalities. SM is the ability of stimuli in the surround of a neurons receptive field (RF) to modulate (typically suppress) the neurons response to stimuli simultaneously presented inside the RF, a property thought to underlie optimal coding of sensory information and important perceptual functions. Understanding the circuit and mechanisms for SM can reveal fundamental principles of computations in sensory cortices, from mouse to human. Current debate is centered over whether feedforward or intracortical circuits generate SM, and whether this results from increased inhibition or reduced excitation. Here we present a working hypothesis, based on theoretical and experimental evidence, that SM results from feedforward, horizontal, and feedback interactions with local recurrent connections, via synaptic mechanisms involving both increased inhibition and reduced recurrent excitation. In particular, strong and balanced recurrent excitatory and inhibitory circuits play a crucial role in the computation of SM.

Two projection streams from macaque V1 to the pale cytochrome oxidase stripes of V2

In the primate visual cortex, areas V1 and V2 distribute information they receive from the retina to virtually all extrastriate cortex, parsing this information into dorsal and ventral streams. Therefore, understanding the connectivity between V1 and V2 is crucial to understand visual cortical processing. Cytochrome oxidase staining in V2 reveals a repeating pattern of pale–thick–pale–thin stripes. V1 sends parallel output pathways to distinct V2 stripes. Previous models proposed either three or two parallel V1-to-V2 pathways in macaque, but both models viewed the two pale stripes within a single stripe cycle as a single compartment. However, recent studies have suggested that the two pale stripes may be functionally distinct, and in marmosets they also differ anatomically in the laminar origin of projections they receive from V1. Here we have asked whether the two pale stripes are also anatomically distinct in macaque. We made small retrograde tracer injections in different pale stripe types. We found that while both pale stripes receive a predominant V1 input from layers 2/3, only one set of pale stripes (pale lateral) receives significant projections from layer 4B, while the other set (pale medial) receives few or no layer 4B projections. Moreover, different tracer injections in nearby pale stripe types revealed that 97–99% of layer 2/3 cells only project to a single pale stripe type. These results demonstrate that in macaque, the two pale stripes are anatomically distinct compartments, and support the notion of two distinct projection streams from V1 to the two pale stripes of V2.