Mechanisms underlying direction selectivity of neurons in the primary visual cortex of the macaque

1. We studied the effects of blocking intracortical inhibition by microiontophoretic administration of bicuculline methiodide (BMI), a selective antagonist for gamma-aminobutyric acid-A receptors, on direction sensitivity of 103 neurons in the primary visual cortex (VI) of anesthetized and paralyzed monkeys. 2. The direction selectivity index (DSI) of each cell was calculated for the control response and response during the BMI administration at the optimal stimulus orientation to assess the directionality of an individual cell. 3. The averaged direction tuning of visual responses of cells was sharp in layers IVa and IVb, moderate in both interblob and blob regions of layer II/III and layers V and VI, and poor in layers IVc alpha and IVc beta. 4. Iontophoretic administration of BMI uncovered or facilitated responses to stimuli moving in the nonpreferred direction, and reduced DSIs of cells to a varying extent in all the layers except layer VI. Responses to stimuli moving in the preferred direction were also facilitated so that a slight bias of response toward the originally preferred direction remained during BMI administration in most cells. 5. Most of the cells in layers II/III (both blobs and interblobs) and IVb that receive inputs from layers IVc alpha and IVc beta showed a clear reduction of direction selectivity during BMI administration. This result suggests that intracortical inhibition plays an important role in the elaboration of direction selectivity at the second stage of information processing in VI. 6. The direction selectivity of cells in layer VI was most resistant to the effects of BMI, suggesting that it is dependent on excitatory inputs that are already direction selective, even though the sample size of this layer was small. 7. In direction-selective cells outside layer VI, responses to a stimulus moving in the preferred direction were enhanced in a way that was linearly related with those in the nonpreferred direction as the BMI dose was increased. This suggests that various amounts of inhibition interact linearly with directionally biased excitatory inputs to raise the firing threshold to various levels so as to produce various degrees of directionality. 8. These results suggest that, in most of the directionally sensitive cells except for those in layer VI, there are excitatory inputs which are bidirectional but slightly biased to one direction, and that the intracortical inhibition raises a threshold level of responses to excitatory inputs so that the response become direction selective.     

Temporal dynamics of chromatic tuning in macaque primary visual cortex

The ability to distinguish colour from intensity variations is a difficult computational problem for the visual system because each of the three cone photoreceptor types absorb all wavelengths of light, although their peak sensitivities are at relatively short (S cones), medium (M cones), or long (L cones) wavelengths. The first stage in colour processing is the comparison of the outputs of different cone types by spectrally opponent neurons in the retina and upstream in the lateral geniculate nucleus. Some neurons receive opponent inputs from L and M cones, whereas others receive input from S cones opposed by combined signals from L and M cones. Here we report how the outputs of the L/M- and S-opponent geniculate cell types are combined in time at the next stage of colour processing, in the macaque primary visual cortex (V1). Some V1 neurons respond to a single chromatic region, with either a short (68-95 ms) or a longer (96-135 ms) latency, whereas others respond to two chromatic regions with a difference in latency of 20-30 ms. Across all types, short latency responses are mostly evoked by L/M-opponent inputs whereas longer latency responses are evoked mostly by S-opponent inputs. Furthermore, neurons with late S-cone inputs exhibit dynamic changes in the sharpness of their chromatic tuning over time. We propose that the sparse, S-opponent signal in the lateral geniculate nucleus is amplified in area V1, possibly through recurrent excitatory networks. This results in a delayed, sluggish cortical S-cone signal which is then integrated with L/M-opponent signals to rotate the lateral geniculate nucleus chromatic axes.     

Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys

The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.     

Object-based attention in the primary visual cortex of the macaque monkey

Typical natural visual scenes contain many objects, which need to be segregated from each other and from the background. Present theories subdivide the processes responsible for this segregation into a pre-attentive and attentive system. The pre-attentive system segregates image regions that 'pop out' rapidly and in parallel across the visual field. In the primary visual cortex, responses to pre-attentively selected image regions are enhanced. When objects do not segregate automatically from the rest of the image, the time-consuming attentive system is recruited. Here we investigate whether attentive selection is also associated with a modulation of firing rates in area V1 of the brain in monkeys trained to perform a curve-tracing task. Neuronal responses to the various segments of a target curve were simultaneously enhanced relative to responses evoked by a distractor curve, even if the two curves crossed each other. This indicates that object-based attention is associated with a response enhancement at the earliest level of the visual cortical processing hierarchy.     

Responsiveness of neurons in the posterior inferotemporal cortex to visual patterns in the macaque monkey

Using anesthetized and immobilized monkeys, responses of neurons in the posterior inferotemporal cortex to visual patterns were examined. Response properties were compared between the sulcus and the gyrus, extending between the anterior tip of the posterior middle temporal sulcus and the inferior occipital sulcus. Of 682 neurons tested, 37% in the sulcus (134/365) and 36% in the gyrus (113/317) responded to one or more patterns. The preference of neurons for patterns varied from neuron to neuron; some neurons responded selectively to one particular pattern, whereas others responded to two or more patterns. To evaluate response properties of neurons, two indices were calculated (the pattern preference index and the pattern selectivity index). The distributions of these indices in the sulcus did not differ significantly from those of the gyrus. Furthermore, the relationship between the pattern preference index and the pattern selectivity index for each neuron was almost the same in these two portions; most neurons responding to a small number of patterns showed inhibitory or weak responses to the worst pattern. In both portions, most neurons had receptive fields with small eccentricities and receptive field sizes were almost the same. These results suggest that the cortex in the sulcus in the posterior inferotemporal cortex is involved in the detection of features of visual patterns, similarly to the cortex in the gyrus.     

Linearity and normalization in simple cells of the macaque primary visual cortex

Simple cells in the primary visual cortex often appear to compute a weighted sum of the light intensity distribution of the visual stimuli that fall on their receptive fields. A linear model of these cells has the advantage of simplicity and captures a number of basic aspects of cell function. It, however, fails to account for important response nonlinearities, such as the decrease in response gain and latency observed at high contrasts and the effects of masking by stimuli that fail to elicit responses when presented alone. To account for these nonlinearities we have proposed a normalization model, which extends the linear model to include mutual shunting inhibition among a large number of cortical cells. Shunting inhibition is divisive, and its effect in the model is to normalize the linear responses by a measure of stimulus energy. To test this model we performed extracellular recordings of simple cells in the primary visual cortex of anesthetized macaques. We presented large stimulus sets consisting of (1) drifting gratings of various orientations and spatiotemporal frequencies; (2) plaids composed of two drifting gratings; and (3) gratings masked by full-screen spatiotemporal white noise. We derived expressions for the model predictions and fitted them to the physiological data. Our results support the normalization model, which accounts for both the linear and the nonlinear properties of the cells. An alternative model, in which the linear responses are subject to a compressive nonlinearity, did not perform nearly as well.     

Reaction of visual cortex neurons to cross-like figures during local inhibition blockade

Incidental finding of a primary malignant lymphoma of the ovary in a 20-year-old patient is presented. Two and a half years following ablative surgery and adjuvant chemotherapy, the patient is alive and disease free. Ovarian lymphoma is a disease of reportedly poor prognosis. However, many previously reported cases of ovarian lymphoma actually represented ovarian involvement by a more diffuse lymphomatous process. If stringent criteria are used for case selection, true primary ovarian lymphoma usually carries a favorable prognosis.     

Gating of neuronal responses in macaque primary visual cortex by an attentional spotlight

Neuronal responses were recorded from the striate cortex of monkeys trained to perform visual discrimination at locations in the visual field to which their attention was drawn. A subset of neurons showed vigorous responses to visual stimuli for trials in which the monkey was directing its attention to the respective receptive field location. In trials where attention is directed elsewhere, responses to the same stimuli were significantly reduced. In some cells the early response component was not modulated by attention, but later components were affected by the locus of attention. The results suggest the operation of a feedback in the paradigm that spotlights a topographically restricted area of V1 for further processing at higher levels.     

A local circuit approach to understanding integration of long-range inputs in primary visual cortex

Integration of inputs by cortical neurons provides the basis for the complex information processing performed in the cerebral cortex. Here, we have examined how primary visual cortical neurons integrate classical and nonclassical receptive field inputs. The effect of nonclassical receptive field stimuli and, correspondingly, of long-range intracortical inputs is known to be context-dependent: the same long-range stimulus can either facilitate or suppress responses, depending on the level of local activation. By constructing a large-scale model of primary visual cortex, we demonstrate that this effect can be understood in terms of the local cortical circuitry. Each receptive field position contributes both excitatory and inhibitory inputs; however, the inhibitory inputs have greater influence when overall receptive field drive is greater. This mechanism also explains contrast-dependent modulations within the classical receptive field, which similarly switch between excitatory and inhibitory. In order to simplify analysis and to explain the fundamental mechanisms of the model, self-contained modules that capture nonlinear local circuit interactions are constructed. This work supports the notion that receptive field integration is the result of local processing within small groups of neurons rather than in single neurons.     

Morphological variation of layer III pyramidal neurones in the occipitotemporal pathway of the macaque monkey visual cortex

We compared the morphological characteristics of layer III pyramidal neurones in different visual areas of the occipitotemporal cortical 'stream', which processes information related to object recognition in the visual field (including shape, colour and texture). Pyramidal cells were intracellularly injected with Lucifer Yellow in cortical slices cut tangential to the cortical layers, allowing quantitative comparisons of dendritic field morphology, spine density and cell body size between the blobs and interblobs of the primary visual area (V1), the interstripe compartments of the second visual area (V2), the fourth visual area (V4) and cytoarchitectonic area TEO. We found that the tangential dimension of basal dendritic fields of layer III pyramidal neurones increases from caudal to rostral visual areas in the occipitotemporal pathway, such that TEO cells have, on average, dendritic fields spanning an area 5-6 times larger than V1 cells. In addition, the data indicate that V1 cells located within blobs have significantly larger dendritic fields than those of interblob cells. Sholl analysis of dendritic fields demonstrated that pyramidal cells in V4 and TEO are more complex (i.e. exhibit a larger number of branches at comparable distances from the cell body) than cells in V1 or V2. Moreover, this analysis demonstrated that the dendrites of many cells in V1 cluster along specific axes, while this tendency is less marked in extrastriate areas. Most notably, there is a relatively large proportion of neurones with 'morphologically orientation-biased' dendritic fields (i.e. branches tend to cluster along two diametrically opposed directions from the cell body) in the interblobs in V1, as compared with the blobs in V1 and extrastriate areas. Finally, counts of dendritic spines along the length of basal dendrites revealed similar peak spine densities in the blobs and the interblobs of V1 and in the V2 interstripes, but markedly higher spine densities in V4 and TEO. Estimates of the number of dendritic spines on the basal dendritic fields of layer III pyramidal cells indicate that cells in V2 have on average twice as many spines as V1 cells, that V4 cells have 3.8 times as many spines as V1 cells, and that TEO cells have 7.5 times as many spines as V1 cells. These findings suggest the possibility that the complex response properties of neurones in rostral stations in the occipitotemporal pathway may, in part, be attributed to their larger and more complex basal dendritic fields, and to the increase in both number and density of spines on their basal dendrites.     

Relationships between local synaptic connections and orientation domains in primary visual cortex

Combined optical imaging of ferret primary visual cortex in vivo and scanning laser photostimulation in brain slices were used to determine the spatial relationships between synaptic inputs onto individual neurons and the pattern of orientation columns. In the upper cortical layers, both excitatory and inhibitory inputs originated primarily from regions with orientation tuning similar to that of the recorded neurons; the shapes of the input tuning curves were indistinguishable. The orientation distributions of both types of inputs centered around the orientation of the recorded neurons, and no evidence for preferential cross-orientation inputs, either excitatory or inhibitory, was observed. These patterns of synaptic connectivity are most consistent with feedforward models for generation of orientation selectivity and are inconsistent with the patterns required by models based on cross-orientation inhibition.     

Magnocellular and parvocellular contributions to the responses of neurons in macaque striate cortex

Anatomical and physiological studies of the primate visual system have suggested that the signals relayed by the magnocellular and parvocellular subdivisions of the LGN remain segregated in visual cortex. It has been suggested that this segregation may account for the known differences in visual function between the parietal and temporal cortical processing streams in extrastriate visual cortex. To test directly the hypothesis that the temporal stream of processing receives predominantly parvocellular signals, we recorded visual responses from the superficial layers of V1 (striate cortex), which give rise to the temporal stream, while selectively inactivating either the magnocellular or parvocellular subdivisions of the LGN. Inactivation of the parvocellular subdivision reduced neuronal responses in the superficial layers of V1, but the effects of magnocellular blocks were generally as pronounced or slightly stronger. Individual neurons were found to receive contributions from both pathways. We furthermore found no evidence that magnocellular contributions were restricted to either the cytochrome oxidase blobs or interblobs in V1. Instead, magnocellular signals made substantial contributions to responses throughout the superficial layers. Thus, the regions within V1 that constitute the early stages of the temporal processing stream do not appear to contain isolated parvocellular signals. These results argue against a direct mapping of the subcortical magnocellular and parvocellular pathways onto the parietal and temporal streams of processing in cortex.     

Modulation of intrinsic circuits by serotonin 5-HT3 receptors in developing ferret visual cortex

Serotonergic projections are widespread in the developing neocortex, but their functions are obscure. The effects of 5-HT3 receptor agonists on cortical circuit response properties were studied in slices of ferret primary visual cortex using high-speed optical imaging of voltage-sensitive dye signals and whole-cell patch-clamp recording. Activation of the 5-HT3 receptor decreased the amplitude and lateral extent of excitation throughout postnatal development. This effect peaks after eye opening, which indicates a function for serotonergic modulation of circuit responses during the period of refinement of cortical connections. Whole-cell patch-clamp recordings from single neurons revealed that synaptic responses evoked by white matter stimulation were reduced by 5-HT3 receptor agonists, whereas the frequency of spontaneous GABAergic synaptic currents was enhanced dramatically. This indicates that the modulation of spontaneous synaptic activity by fast-acting serotonin receptors is reflected in an inhibition of the circuit response, in line with the notion of background synaptic activity altering the spatiotemporal integration properties of cortical cells by changing their membrane potential and their electrotonic structure. These mechanisms may regulate the response properties of intrinsic circuits in both the adult and developing neocortex.     

Integration of local inputs in visual cortex

In mammalian visual cortex, local connections are ubiquitous, extensively linking adjacent neurons of all types. In this study, optical maps of intrinsic signals and responses from single neurons were obtained from the same region of cat visual cortex while the effectiveness of the local cortical circuitry was altered by focally disinhibiting neurons within a column of known orientation preference. Maps of intrinsic signals indicated that local connections provide strong and functional subthreshold inputs to neighboring columns of other orientation preferences, altering the observed orientation preference to that of the disinhibited column. However, measuring the suprathreshold response using single-cell recordings revealed only mild changes of preferred orientation over the affected region. Because strongly tuned subthreshold inputs from cortex only marginally affect the tuning of a cortical cell's output, it is concluded that local cortical inputs are integrated weakly compared to geniculate inputs. Such circuitry potentially allows for the normalization of responses across a wide range of input activity through local averaging.     

The orientation and direction selectivity of cells in macaque visual cortex

Quantitative data are presented on the orientation and direction specificity of the responses of cells in macaque monkey striate cortex. There is a bimodal distribution of direction-specific and nondirection-specific cells, with similar orientation tuning in each class. Cells range in orientation bandwidth at half amplitude from 6 degrees to 360 degrees (i.e. no orientation tuning), with a median near 40 degrees. Foveal-parafoveal and simple-complex subsamples show similar ranges of orientation bandwidths as well as similar medians (the bandwidths being somewhat broader than those found in cat cortex). The foveal subsample and a high-spatial-frequency subsample have more horizontal and vertical optimal orientations than oblique ones. Most cells show inhibition to some orientations, as well as excitation to others. Minimum-response orientations are generally less than 90 degrees from the optimal orientation--indicating maximum inhibition adjacent to the excitatory orientations. Three simple receptive field models are shown to differ in their abilities to account for these results.     

Satiety-responsive neurons in the medial orbitofrontal cortex of the macaque.

Feeding-related gustatory, olfactory, and visual activation of the orbitofrontal cortex (OFC) decreases following satiety. Previous neurophysiological studies have concentrated on the caudolateral OFC (clOFC). We describe satiety-induced modulation of 23 gustatory, 5 water, and 15 control neurons in the medial OFC (mOFC), where gustatory neurons represent a much larger percentage of the population. For 15 of the 23 gustatory neurons (65%), every significant taste response evoked during pre-satiety testing decreased following satiety (X=70%). Responses evoked by the ineffective taste stimuli during pre-satiety testing were unchanged following satiety. The graded response decrements of the mOFC gustatory neurons stand in marked contrast to the clOFC responses, which are almost completely suppressed by satiety. Two other novel findings are reported here. First, all significant pre-satiety taste responses of four gustatory neurons increased following satiety (X=51%). Second, post-satiety emergent taste responses were observed in 7 of 15 neurons (47%) classified as non-responsive during pre-satiety testing. The presence of increased responsiveness and emergent gustatory neurons in the mOFC suggests that meal termination may require active processes as well as the passive loss of hedonic value. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A quantitative description of short-term plasticity at excitatory synapses in layer 2/3 of rat primary visual cortex

Cortical synapses exhibit several forms of short-term plasticity, but the contribution of this plasticity to visual response dynamics is unknown. In part, this is because the simple patterns of stimulation used to probe plasticity in vitro do not correspond to patterns of activity that occur in vivo. We have developed a method of quantitatively characterizing short-term plasticity at cortical synapses that permits prediction of responses to arbitrary patterns of stimulation. Synaptic responses were recorded intracellularly as EPSCs and extracellularly as local field potentials in layer 2/3 of rat primary visual cortical slices during stimulation of layer 4 with trains of electrical stimuli containing random mixtures of frequencies. Responses exhibited complex dynamics that were well described by a simple three-component model consisting of facilitation and two forms of depression, a stronger form that decayed exponentially with a time constant of several hundred milliseconds and a weaker, but more persistent, form that decayed with a time constant of several seconds. Parameters obtained from fits to one train were used to predict accurately responses to other random and constant frequency trains. Control experiments revealed that depression was not caused by a decrease in the effectiveness of extracellular stimulation or by a buildup of inhibition. Pharmacological manipulations of transmitter release and postsynaptic sensitivity suggested that both forms of depression are mediated presynaptically. These results indicate that firing evoked by visual stimuli is likely to cause significant depression at cortical synapses. Hence synaptic depression may be an important determinant of the temporal features of visual cortical responses.     

Generation of high-frequency oscillations in local circuits of rat somatosensory cortex cultures

1. Rhythmic cortical activity was investigated with intracellular recordings in cortex-striatum-mesencephalon organotypic cultures grown for 42 +/- 3 (SE) days in vitro. 2. Electrical stimulation of supragranular layers induced a self-sustained high-frequency oscillation (HFO) in pyramidal neurons and interneurons. 3. The HFO started 197 +/- 39 ms after stimulation and had a mean duration of 1.0 +/- 0.2 s and an initial frequency of 38 +/- 2 Hz. A decrease in frequency at a rate of 11.5 +/- 2.7 Hz/s started on average 547 +/- 109 ms after the onset of the HFO. 4. During the HFO, local interneurons and pyramidal neurons synchronized their activities. The synaptic origin of the HFO was confirmed by its reversal potential at -57 +/- 4 mV. 5. These results suggest that a self-maintained HFO can be induced in local cortical circuits by excitation of supragranular layers. This HFO would facilitate synchronization between distant cortical and thalamic regions.     

Cortical hierarchy reflected in the organization of intrinsic connections in macaque monkey visual cortex

Neuronal response properties vary markedly at increasing levels of the cortical hierarchy. At present it is unclear how these variations are reflected in the organization of the intrinsic cortical circuitry. Here we analyze patterns of intrinsic horizontal connections at different hierarchical levels in the visual cortex of the macaque monkey. The connections were studied in tangential sections of flattened cortices, which were injected with the anterograde tracer biocytin. We directly compared the organization of connections in four cortical areas representing four different levels in the cortical hierarchy. The areas were visual areas 1, 2, 4 and Brodman's area 7a (V1, V2, V4 and 7a, respectively). In all areas studied, injections labeled numerous horizontally coursing axons that formed dense halos around the injection sites. Further away, the fibers tended to form separate clusters. Many fibers could be traced along the way from the injection sites to the target clusters. At progressively higher order areas, there was a striking increase in the spread of intrinsic connections: from a measured distance of 2.1 mm in area V1 to 9.0 mm in area 7a. Average interpatch distance also increased from 0.61 mm in area V1 to 1.56 mm in area 7a. In contrast, patch size changed far less at higher order areas, from an average width of 230 micron(s) in area V1 to 310 micron(s) in area 7a. Analysis of synaptic bouton distribution along axons revealed that average interbouton distance remained constant at 6.4 micron(s) (median) in and out of the clusters and in the different cortical areas. Larger injections resulted in a marked increase in the number of labeled patches but only a minor increase in the spread of connections or in patch size. Thus, in line with the more global computational roles proposed for the higher order visual areas, the spread of intrinsic connections is increased with the hierarchy level. On the other hand, the clustered organization of the connections is preserved at higher order areas. These clusters may reflect the existence of cortical modules having blob-like dimensions throughout macaque monkey visual cortex.     

Processing of contrast polarity of visual images in inferotemporal cortex of the macaque monkey

Cells in the anterior part of the inferotemporal cortex (anterior IT) respond to moderately complex stimulus features of object images. To study dependency of their responses on contrast polarity of stimulus images, we selected cells with optimal stimuli that were defined only by shape and not related to texture or color, and examined effects of reversing the contrast of the image or removing it except for edges between dark and bright parts of the image ("outlining"). The contrast reversal produced a reduction of the response to the optimal stimulus by > 50% in 60% of tested cells; the outlining, in 70%. When the two transformations were considered together, 94% of the cells showed a reduction by > 50%. Effects of the transformations on shape selectivity were also studied by comparing responses to several different shapes each of whose contours were expressed in different ways. Statistically significant changes in relative effectiveness of the different shapes as a function of contour expression were observed in more than half of the cells. These results suggest that responses of individual cells in anterior IT carry information about contrast polarity as well as about shape.