The role of feedback projections in feature tuning and neuronal excitability in the early primate visual system.

A general assumption in visual neuroscience is that basic receptive field properties such as orientation and direction selectivity are constructed within intrinsic neuronal circuits and feedforward projections. In addition, it is assumed that general neuronal excitability and responsiveness in early visual areas is to a great extent independent of feedback input originating in areas higher in the stream. Here, we review the contribution of feedback projections from MT, V4 and pulvinar to the receptive field properties of V2 neurons in the anesthetized and paralyzed monkey. Importantly, our results contradict both of these assumptions. We separately inactivated each of these three brain regions using GABA pressure injections, while simultaneously recording V2 single unit activity before and hours after inactivation. Recordings and GABA injections were carried out in topographically corresponding regions of the visual field. We outline the changes in V2 activity, responsiveness and receptive field properties for early, mid and late post-injection phases. Immediately after injection, V2 activity is globally suppressed. Subsequently, there is an increase in stimulus-driven relative to spontaneous neuronal activity, which improves the signal-to-noise coding for the oriented moving bars. Notably, V2 tuning properties change substantially relative to its pre-injection selectivity profile. The resulting increase or decrease in selectivity could not be readily predicted based on the selectivity profile of the inactivated site. Finally, V2 activity rebounds before returning to it pre-injection profile Our results show that feedback projections profoundly impact neuronal circuits in early visual areas, and may have been heretofore largely underestimated in their physiological role.

GABA-induced inactivation of Cebus apella V2 neurons: effects on orientation tuning and direction selectivity.

We investigated the GABA-induced inactivation of V2 neurons and terminals on the receptive field properties of this area in an anesthetized and paralyzed Cebus apella monkey. Extracellular single-unit activity was recorded using tungsten microelectrodes in a monkey before and after pressure-injection of a 0.25 or 0.5 M GABA solution. The visual stimulus consisted of a bar moving in 8 possible directions. In total, 24 V2 neurons were studied before and after blocker injections in 4 experimental sessions following GABA injection into area V2. A group of 10 neurons were studied over a short period. An additional 6 neurons were investigated over a long period after the GABA injection. A third group of 8 neurons were studied over a very long period. Overall, these 24 neurons displayed an early (1-20 min) significant general decrease in excitability with concomitant changes in orientation or direction selectivity. GABA inactivation in area V2 produced robust inhibition in 80% and a significant change in directional selectivity in 60% of the neurons examined. These GABA projections are capable of modulating not only levels of spontaneous and driven activity of V2 neurons but also receptive field properties such as direction selectivity.

GABA-induced inactivation of Cebus apella V2 neurons: effects on orientation tuning and direction selectivity

We investigated the GABA-induced inactivation of V2 neurons and terminals on the receptive field properties of this area in an anesthetized and paralyzed Cebus apella monkey. Extracellular single-unit activity was recorded using tungsten microelectrodes in a monkey before and after pressure-injection of a 0.25 or 0.5 M GABA solution. The visual stimulus consisted of a bar moving in 8 possible directions. In total, 24 V2 neurons were studied before and after blocker injections in 4 experimental sessions following GABA injection into area V2. A group of 10 neurons were studied over a short period. An additional 6 neurons were investigated over a long period after the GABA injection. A third group of 8 neurons were studied over a very long period. Overall, these 24 neurons displayed an early (1-20 min) significant general decrease in excitability with concomitant changes in orientation or direction selectivity. GABA inactivation in area V2 produced robust inhibition in 80% and a significant change in directional selectivity in 60% of the neurons examined. These GABA projections are capable of modulating not only levels of spontaneous and driven activity of V2 neurons but also receptive field properties such as direction selectivity.

Changes of ongoing activity in Cebus monkey perirhinal cortex correlate with behavioral performance.

A Cebus apella monkey weighing 4 kg was trained in a saccadic eye movement task and while the animal performed the task we recorded the extracellular activity of perirhinal cortical neurons. Although the task was very simple and maintained at a constant level of difficulty, we observed considerable changes in the performance of the monkey within each experimental session. The behavioral states responsible for such variation may be related to arousal, motivation or attention of the animal while engaged in the task. In approximately 20% (16/82) of the units recorded, long-term direct or inverse correlations could be demonstrated between the monkey's behavioral state and the cells' ongoing activity (independent of the visual stimulation or of the specific behavior along a trial). The perirhinal cortex and other medial temporal structures have long been associated with normal memory function. The data presented here were interpreted in terms of recent reports focusing on the subcortical afferents to temporal lobe structures and their possible role in controlling arousal, motivation, or attention.

Changes of ongoing activity in Cebus monkey perirhinal cortex correlate with behavioral performance

A Cebus apella monkey weighing 4 kg was trained in a saccadic eye movement task and while the animal performed the task we recorded the extracellular activity of perirhinal cortical neurons. Although the task was very simple and maintained at a constant level of difficulty, we observed considerable changes in the performance of the monkey within each experimental session. The behavioral states responsible for such variation may be related to arousal, motivation or attention of the animal while engaged in the task. In approximately 20 percent (16/82) of the units recorded, long-term direct or inverse correlations could be demonstrated between the monkey's behavioral state and the cells' ongoing activity (independent of the visual stimulation or of the specific behavior along a trial). The perirhinal cortex and other medial temporal structures have long been associated with normal memory function. The data presented here were interpreted in terms of recent reports focusing on the subcortical afferents to temporal lobe structures and their possible role in controlling arousal, motivation, or attention.

Effects of inactivation of the lateral pulvinar on response properties of second visual area cells in Cebus monkeys.

1. In the present study, we investigated the influence of the pulvinar nucleus upon response properties of single cells in the second visual area (V2) of Cebus monkeys. The method used consisted of the inactivation of a portion of the lateral pulvinar by GABA injections while studying the response properties of cells in V2 at the same visuotopic location as that of the inactivation. 2. After GABA injection in the pulvinar, most cells in V2 (67%) showed changes in spontaneous and/or stimulus-driven activities. Contrary to the effect found with inactivation of the striate cortex, which promotes a reduction in the response of V2 neurons, we found that the main effect of pulvinar inactivation was an increment in stimulus-driven responses of V2 cells (39% of units studied). A reduction of responses was observed in 27% of units. 3. A change in orientation and/or direction selectivity was found in 91% of cells after inactivation of the pulvinar. Most commonly, the orientation selectivity of a neuron was decreased during pulvinar inactivation. 4. The inactivation results indicate that the pulvinar projections have a modulatory effect on the activity of V2 cells.

Contributions of stimulus valence and arousal to visual activation during emotional perception.

Neuroimaging experiments have revealed that the visual cortex is involved in the processing of affective stimuli: seeing emotional pictures leads to greater activation than seeing neutral ones. It is unclear, however, whether such differential activation is due to stimulus valence or whether the results are confounded by arousal level. In order to investigate the contributions of valence and arousal to visual activation, we created a new category of "interesting" stimuli designed to have high arousal, but neutral valence, and employed standard neutral, unpleasant, and pleasant picture categories. Arousal ratings for pleasant and neutral pictures were equivalent, as were valence ratings for interesting and neutral pictures. Differential activation for conditions matched for arousal (pleasant vs neutral) as well as matched for valence (interesting vs neutral) indicated that both stimulus valence and arousal contributed to visual activation.

The brain decade in debate: VI. Sensory and motor maps: dynamics and plasticity

This article is an edited transcription of a virtual symposium promoted by the Brazilian Society of Neuroscience and Behavior (SBNeC). Although the dynamics of sensory and motor representations have been one of the most studied features of the central nervous system, the actual mechanisms of brain plasticity that underlie the dynamic nature of sensory and motor maps are not entirely unraveled. Our discussion began with the notion that the processing of sensory information depends on many different cortical areas. Some of them are arranged topographically and others have non-topographic (analytical) properties. Besides a sensory component, every cortical area has an efferent output that can be mapped and can influence motor behavior. Although new behaviors might be related to modifications of the sensory or motor representations in a given cortical area, they can also be the result of the acquired ability to make new associations between specific sensory cues and certain movements, a type of learning known as conditioning motor learning. Many types of learning are directly related to the emotional or cognitive context in which a new behavior is acquired. This has been demonstrated by paradigms in which the receptive field properties of cortical neurons are modified when an animal is engaged in a given discrimination task or when a triggering feature is paired with an aversive stimulus. The role of the cholinergic input from the nucleus basalis to the neocortex was also highlighted as one important component of the circuits responsible for the context-dependent changes that can be induced in cortical maps

The brain decade in debate: VI. Sensory and motor maps: dynamics and plasticity.

This article is an edited transcription of a virtual symposium promoted by the Brazilian Society of Neuroscience and Behavior (SBNeC). Although the dynamics of sensory and motor representations have been one of the most studied features of the central nervous system, the actual mechanisms of brain plasticity that underlie the dynamic nature of sensory and motor maps are not entirely unraveled. Our discussion began with the notion that the processing of sensory information depends on many different cortical areas. Some of them are arranged topographically and others have non-topographic (analytical) properties. Besides a sensory component, every cortical area has an efferent output that can be mapped and can influence motor behavior. Although new behaviors might be related to modifications of the sensory or motor representations in a given cortical area, they can also be the result of the acquired ability to make new associations between specific sensory cues and certain movements, a type of learning known as conditioning motor learning. Many types of learning are directly related to the emotional or cognitive context in which a new behavior is acquired. This has been demonstrated by paradigms in which the receptive field properties of cortical neurons are modified when an animal is engaged in a given discrimination task or when a triggering feature is paired with an aversive stimulus. The role of the cholinergic input from the nucleus basalis to the neocortex was also highlighted as one important component of the circuits responsible for the context-dependent changes that can be induced in cortical maps.

Distribution of calbindin, parvalbumin and calretinin in the lateral geniculate nucleus and superior colliculus in Cebus apella monkeys.

We studied the distribution of the calcium-binding proteins calbindin, parvalbumin and calretinin, in the superior colliculus and in the lateral geniculate nucleus of Cebus apella, a diurnal New World monkey. In the superior colliculus, these calcium-binding proteins show different distribution patterns throughout the layers. After reaction for calretinin one observes a heavy staining of the neuropil with few labeled cells in superficial layers, a greater number of large and medium-sized cells in the stratum griseum intermediale, and small neurons in deep layers. The reaction for calbindin revealed a strong staining of neuropil with a large number of small and well stained cells, mainly in the upper half of the stratum griseum superficiale. Intermediate layers were more weakly stained and depicted few neurons. There were few immunopositive cells and little neuropil staining in deep layers. The reaction for parvalbumin showed small and medium-sized neurons in the superficial layers, a predominance of large stellate cells in the stratum griseum intermediale, and medium-sized cells in the deep layers. In the lateral geniculate nucleus of Cebus, parvalbumin is found in the cells of both the P and M pathways, whereas calbindin is mainly found in the interlaminar and S layers, which are part of the third visual pathway. Calretinin was only found in cells located in layer S. This pattern is similar to that observed in Macaca, showing that these calcium-binding proteins reveal different components of the parallel visual pathways both in New and Old World monkeys.

Connectional and neurochemical subdivisions of the pulvinar in Cebus monkeys.

Based on cytoarchitectonic criteria, the primate pulvinar nucleus has been subdivided into medial (PM), lateral (PL), and inferior (PI) regions. However, these subdivisions show no correlation with those established by electrophysiological, immunocytochemical, or neuroanatomical tracer studies. In this work, we studied the connections of the pulvinar nucleus of Cebus monkey with visual areas V1, V2, V4, MT, and PO by means of retrograde fluorescent tracers injected into these areas. Based on the projection zones to cortical visual areas, the visual portion of the pulvinar of Cebus monkey was subdivided into three subregions: P1, P2, and P3, similar to those described in the macaque (Ungerleider et al., 1984). In Cebus, P1 includes the centrolateral portion of traditionally defined PI and adjacent portion of PL. P2 is located in the dorsal portion of PL and P3 includes the medial portion of PI and extends dorsally into adjacent PL and PM. In addition, we studied the histology of the pulvinar using multiple criteria, such as cytoarchitecture and myeloarchitecture; histochemistry for cytochrome oxidase, NADPH-diaphorase, and acetylcholinesterase; and immunocytochemistry for two calcium-binding proteins, calbindin and parvalbumin, and for a neurofilament recognized by the SMI-32 antibody. Some of these stains, mainly calbindin, showed additional subdivisions of the Cebus pulvinar, beyond the traditional PI, PL, and PM. Based on this immunohistochemical staining, the border of PI is moved dorsally above the brachium of the superior colliculus and PI can be subdivided in five regions (PI(P), PI(M), PI(C), PI(L), and PI(LS)). Regions P1, P2, and P3 defined based on efferent connections with cortical visual areas are not architectonically/neurochemically homogeneous. Rather they appear to consist of further chemoarchitectonic subdivisions. These distinct histochemical regions might be related to different functional modules of visual processing within one connectional area.

"Third tier" ventral extrastriate cortex in the New World monkey, Cebus apella.

The ventral extrastriate cortex adjacent to the second visual area was studied in the New World monkey Cebus apella, using anaesthetised preparations. The visuotopic organisation and myeloarchitecture of this region demonstrate the existence of a distinct strip of cortex, 3-4 mm wide, with an ordered representation of the contralateral upper visual quadrant, up to 60 degrees eccentricity. This upper-quadrant representation is probably homologous to the ventral subdivision of the third visual complex (V3v) of Old World monkeys, also known as the ventral posterior area. The representation of the horizontal meridian in V3v forms its posterior and medial border with V2, while the upper vertical meridian is represented anterior and laterally, forming a congruent border with the fourth visual area (V4). Central visual fields are represented in posterior and lateral portions of V3v, in the inferior occipital sulcus, while the periphery of the visual field is represented anteriorly, on the tentorial surface. Cortex anterior to V3v, at the ventral occipitotemporal transition, had neurones that had poor visual responses. No representation of the lower quadrant was found adjacent to V3v in ventral cortex. However, we observed cells with perifoveal receptive fields centred in the lower quadrant immediately dorsal to V3v, around the junction of the inferior occipital and lunate sulci. These observations argue against the idea that V3v is an area restricted to the ventral cortex in New World monkeys and support the conclusions of previous anatomical studies in Cebus that showed a continuity of myeloarchitecture and connectional patterns between ventral and lateral extrastriate cortices. Together, these data suggest that V3v may be part of a larger area that extends into dorsolateral extrastriate cortex, overlapping to some extent with the caudal subdivision of the dorsolateral area described in other New World monkeys.

Visual cortical projections and chemoarchitecture of macaque monkey pulvinar.

We investigated the patterns of projections from the pulvinar to visual areas V1, V2, V4, and MT, and their relationships to pulvinar subdivisions based on patterns of calbindin (CB) immunostaining and estimates of visual field maps (P(1), P(2) and P(3)). Multiple retrograde tracers were placed into V1, V2, V4, and/or MT in 11 adult macaque monkeys. The inferior pulvinar (PI) was subdivided into medial (PI(M)), posterior (PI(P)), central medial (PI(CM)), and central lateral (PI(CL)) regions, confirming earlier CB studies. The P(1) map includes PI(CL) and the ventromedial portion of the lateral pulvinar (PL), P(2) is found in ventrolateral PL, and P(3) includes PI(P), PI(M), and PI(CM). Projections to areas V1 and V2 were found to be overlapping in P(1) and P(2), but those from P(2) to V2 were denser than those to V1. V2 also received light projections from PI(CM) and, less reliably, from PI(M). Neurons projecting to V4 and MT were more abundant than those projecting to V1 and V2. Those projecting to V4 were observed in P(1), densely in P(2), and also in PI(CM) and PI(P) of P(3). Those projecting to MT were found in P(1)- P(3), with the heaviest projection from P(3). Projections from P(3) to MT and V4 were mainly interdigitated, with the densest to MT arising from PI(M) and the densest to V4 arising from PI(P) and PI(CM). Because the calbindin-rich and -poor regions of P(3) corresponded to differential patterns of cortical connectivity, the results suggest that CB may further delineate functional subdivisions in the pulvinar.

Filling-in topographically organized distributed networks

We propose a framework for understanding visual perception based on a topographically organized, functionally distributed network. In this proposal the extraction of shape boundaries starts at retinal ganglion cells with concentric receptive fields. This information, relayed through the lateral geniculate necleus, creates a neural representation of negative and positive boundaries in a set of topographically connected and organized visual areas. After boundary extraction, several processes involving contrast, brightness, texture and motion extraction take place in subsequent visual areas in different cortical modules. Following these steps of processing, filling-in processes at different levels, within each area, and in separate channels, propagate locally to transform boundary representations onto surfaces representations. These partial representations of the image propagate back and forth in the network, yielding a neural representation of the original image. We propose that completion takes places in a wide cortical circuit that heavily relies on V1, where long-range information helps determine contour responses at specific topographically organized locations. Neural representations of illusory contours would emerge in circuits involving primarily area V2. The neural representation of filling-in of a peripheral stimulus in a dynamic surround (such as in texture filling-in) would depend on circuits involving primarily cells in areas V2 and V3, and would include competitive mechanisms required for figure to ground segregation. Finally, we suggest that multiple representations of the stimulus engage competitive mechanisms that select the "most likely hypothesis". Such choice behavior would rely on winner-take-all mechanisms capable of constructing a single neural representation of perceived objects.

Filling-in in topographically organized distributed networks.

We propose a framework for understanding visual perception based on a topographically organized, functionally distributed network. In this proposal the extraction of shape boundaries starts at retinal ganglion cells with concentric receptive fields. This information, relayed through the lateral geniculate nucleus, creates a neural representation of negative and positive boundaries in a set of topographically connected and organized visual areas. After boundary extraction, several processes involving contrast, brightness, texture and motion extraction take place in subsequent visual areas in different cortical modules. Following these steps of processing, filling-in processes at different levels, within each area, and in separate channels, propagate locally to transform boundary representations onto surfaces representations. These partial representations of the image propagate back and forth in the network, yielding a neural representation of the original image. We propose that completion takes places in a wide cortical circuit that heavily relies on V1, where long-range information helps determine contour responses at specific topographically organized locations. Neural representations of illusory contours would emerge in circuits involving primarily area V2. The neural representation of filling-in of a peripheral stimulus in a dynamic surround (such as in texture filling-in) would depend on circuits involving primarily cells in areas V2 and V3, and would include competitive mechanisms required for figure to ground segregation. Finally, we suggest that multiple representations of the stimulus engage competitive mechanisms that select the "most likely hypothesis". Such choice behavior would rely on winner-take-all mechanisms capable of constructing a single neural representation of perceived objects.

Area V4 in Cebus monkey: extent and visuotopic organization.

We used electrophysiological mapping and myeloarchitectural criteria in order to define the location, extent and visual topography of the fourth visual area (V4) in anesthetized and paralyzed Cebus monkey. Based on these criteria, the borders of V4 with surrounding areas were defined both on the dorsal and ventral cortical surfaces. In addition, to better visualize the visuotopic organization and to evaluate its regularity, we constructed bidimensional maps and projected the recording sites onto them. Area V4 has an almost complete representation of the binocular visual field with the lower visual field represented dorsally (V4d) and the upper field ventrally (V4v). We found this representation to be more extensive than those previously described. The representation of the central portion of the visual field is largely expanded in comparison with that of the periphery. This emphasis in central vision could be related with the involvement of V4 in the ventral stream of visual information processing. Receptive field size increases with increasing eccentricity, while cortical magnification factor decreases. The cortical magnification factor measured along isopolar lines is, on average, 1.5-2.0 times greater than that measured along the isoeccentric lines, suggesting the existence of a small anisotropy in central and peripheral V4.

Callosally projecting neurons in the macaque monkey V1/V2 border are enriched in nonphosphorylated neurofilament protein.

Previous immunohistochemical studies combined with retrograde tracing in macaque monkeys have demonstrated that corticocortical projections can be differentiated by their content of neurofilament protein. The present study analyzed the distribution of nonphosphorylated neurofilament protein in callosally projecting neurons located at the V1/V2 border. All of the retrogradely labeled neurons were located in layer III at the V1/V2 border and at an immediately adjacent zone of area V2. A quantitative analysis showed that the vast majority (almost 95%) of these interhemispheric projection neurons contain neurofilament protein immunoreactivity. This observation differs from data obtained in other sets of callosal connections, including homotypical interhemispheric projections in the prefrontal, temporal, and parietal association cortices, that were found to contain uniformly low proportions of neurofilament protein-immunoreactive neurons. Comparably, highly variable proportions of neurofilament protein-containing neurons have been reported in intrahemispheric corticocortical pathways, including feedforward and feedback visual connections. These results indicate that neurofilament protein is a prominent neurochemical feature that identifies a particular population of interhemispheric projection neurons at the V1/V2 border and suggest that this biochemical attribute may be critical for the function of this subset of callosal neurons.

Tangential distribution of cytochrome oxidase-rich blobs in the primary visual cortex of macaque monkeys.

We studied the tangential distribution of cytochrome c oxidase (CytOx)-rich blobs in four striate cortices of three normal monkeys (Macaca mulatta). The spatial density and cross-sectional area of blobs were analyzed in CytOx-reacted tangential sections of flat-mounted preparations of the striate cortex (V1). Well-delimited CytOx-rich blobs were found in the middle portion of cortical layer III of the V1. Throughout the binocular field representation, the spatial density of blobs was nearly constant with a mean value of four to five blobs per mm2. In the monocular portions of V1, however, blob spatial density diminished. In all cases, the mean cross-sectional area of blobs was constant in the V1. The small variation of CytOx blob topography with visual field eccentricity contrasts with the variation described in previously published material.

GABAergic retinocollicular projection in the New World monkey Cebus apella.

GABA immunoreactivity was examined in the retina of the New World monkey Cebus apella. Labeled cell bodies were identified as horizontal, bipolar, interplexiform, amacrine and a population of putative ganglion cells. To determine whether ganglion cells were immunoreactive to GABA, double-labeling experiments were performed using Fast Blue as retrograde neuronal tracer injected into the superior colliculus. Retinas containing FB-labeled ganglion cells were subsequently incubated with antiserum against GABA. Although retinocollicular ganglion cells were found in three different layers (ganglion cell layer, inner nuclear layer and inner plexiform layer), our experiments revealed GABA-positive ganglion cells only in the outer half of the ganglion cell layer.

Cortical projections of area V2 in the macaque.

To determine the locus, extent and topograhic organization of cortical projections of area V2, we injected tritiated amino acids under electrophysiological control into 15 V2 sites in 14 macaques. The injection sites included the foveal representation and representations ranging from central to far peripheral eccentricities in both the upper and lower visual fields. The results indicated that all V2 sites project topographically back to V1 and forward to V3, V4 and MT. There is also a topographically organized projection from V2 to V4t, but this projection is limited to the lower visual field representation. V2 thus appears to project to virtually all the visual cortex within the occipital lobe. In addition to these projections to occipital visual areas, V2 sites representing eccentricities of approximately 30 degrees and greater project to three visual areas in parietal cortex-the medial superior temporal (MST), parieto-occipital (PO) and ventral intraparietal (VIP) areas. This peripheral field representation of V2 also projects to area VTF, a visual area located in area TF on the posterior parahippocampal gyrus. Projections from the peripheral field representation of V2 of parietal areas could provide a direct route for rapid activation of circuits serving spatial vision and spatial attention.