Arrangement of orientation pinwheel centers around area 17/18 transition zone in cat visual cortex

In the primary visual cortex of higher mammals, orientation preferences are represented continuously except for singular points, so-called pinwheel centers. In spite of the uniqueness of orientation pinwheel centers, very little is known about the pattern of their arrangement. In this study we examined the arrangement of orientation pinwheel centers in the cat visual cortex by optical imaging of intrinsic signals. Our results demonstrate that orientation pinwheel centers are arranged in a unique geometric pattern around the area 17/18 transition zone: pinwheel centers of the same type are arranged in rows parallel to the transition zone, and rows of clockwise and counterclockwise pinwheel centers are arranged alternately. We suggest that the areal border imposes a strong restriction on the pattern formation of orientation preference maps in the visual cortex.     

Intracortical excitation of spiny neurons in layer 4 of cat striate cortex in vitro

Recordings were made from pairs of neurons in cat striate visual cortex in vitro to study the AMPA-channel-mediated components of intracortical excitatory synaptic connections between layer 4 spiny neurons and between layer 6 and layer 4 spiny neurons. Forty-six of the 72 cells recorded were identified morphologically. They consisted of spiny stellate and pyramidal cells in layer 4, and pyramidal cells in layer 6. Connections between layer 4 excitatory cells involve excitatory postsynaptic potentials (EPSPs) averaging 949 microV, with an average coefficient of variation of 0.21 (n = 30). The synapses operate at very high release probabilities (0.69-0.98). With repetitive stimulation these EPSPs show varying degrees of depression, largely mediated by presynaptic changes in release probability. Four pairs of layer 4 cells were reciprocally connected. The connections from layer 6 to layer 4 involve smaller, more variable EPSPs, with an average amplitude of 214 microV, and average coefficient of variation 0.72 (n = 7). These synapses operate at moderately high release probabilities (0.37-0.56). They show facilitation with repetitive stimulation, mediated largely by presynaptic changes in release probability. One excitatory connection from a layer 4 neuron to a layer 6 pyramidal cell was also detected. Thus, layer 4 spiny neurons receive effective excitation from two intracortical sources that have different synaptic dynamics and are likely to contribute significantly to the temporal properties of these cells in vivo.     

The connections of layer 4 subdivisions in the primary visual cortex (V1) of the owl monkey

The primary visual cortex (V1) of primates receives signals from parallel lateral geniculate nucleus (LGN) channels. These signals are utilized by the laminar and compartmental [i.e. cytochrome oxidase (CO) blob and interblob] circuitry of V1 to synthesize new output pathways appropriate for the next steps of analysis. Within this framework, this study had two objectives: (i) to analyze the con- nections between primary input and output layers and compartments of V1; and (ii) to determine differences in connection patterns that might be related to species differences in physiological properties in an effort to link specific pathways to visual functions. In this study we examined the intrinsic interlaminar connections of V1 in the owl monkey, a nocturnal New World monkey, with a special emphasis on the projections from layer 4 to layer 3. Interlaminar connections were labeled via small iontophoretic or pressure injections of tracers [horseradish peroxidase, biocytin, biotinylated dextrine amine (BDA) or cholera toxin subunit B conjugated to colloidal gold particles]. Our most significant finding was that layer 4 (4C of Brodmann) can be divided into three tiers based upon projections to the superficial layers. Specifically, we find that 4alpha (4Calpha), 4beta (4Cbeta) and 4ctr send primary projections to layers 3C (4B), 3Bbeta (4A) and 3Balpha (3B), respectively. Examination of laminar structure with Nissl staining supports a tripartite organization of layer 4. The cortical output layer above layer 3Balpha (3B) (e.g. layer 3A) does not appear to receive any direct connections from layer 4 but receives heavy input from layers 3Balpha (3B) and 3C (4B). Some connectional differences also were observed between the subdivisions of layer 3 and the infragranular layers. No consistent differences in connections were observed that distinguished CO blobs from interblobs or that could be correlated with differences in visual lifestyle (nocturnal versus diurnal) when compared with connectional data in other primates. Re-examination of data from previous studies in squirrel and macaque monkeys suggests that the tripartite organization of layer 4 and the unique projection pattern of layer 4ctr are not restricted to owl monkeys, but are common to a number of primate species.     

Functional diversity of layer IV spiny neurons in rat somatosensory cortex: quantitative morphology of electrophysiologically characterized and biocytin labeled cells

Previous analyses of the spiny layer IV neurons have almost exclusively focused on spiny stellate cells. Here we provide detailed morphological data characterizing three subpopulations of spiny neurons in slices of adolescent rats: (i) spiny stellate cells (58%), (ii) star pyramidal cells (25%) and (iii) pyramidal cells (17%), which can be distinguished objectively by the preferential orientation of their dendritic stems. Spiny stellate cells lacked an apical dendrite and frequently confined their dendritic and axonal arbors to the respective column. Star pyramidal and pyramidal cells possessed an apical dendrite, which reached the supragranular layers. Their axonal arbors were similar, showing both a columnar component and transcolumnar branches with direct transbarrel projections. However, a small fraction of star pyramidal cells possessed few or even no transcolumnar branches. Electrophysiologically, all three types of neurons were either regular-spiking or intrinsically burst-spiking without a significant relation to the morphological subtypes. The basic synaptic properties of thalamic inputs were also independent of the type of target layer IV spiny neuron. All remained subthreshold and showed paired-pulse depression. In conclusion, the columnar axonal arborization of spiny stellate cells is supplemented by a significant oblique to horizontal projection pattern in pyramidal-like neurons. This offers a structural basis for either segregation or early context-dependent integration of tactile information, in a cell-type specific manner.     

Laminar patterns of local excitatory input to layer 5 neurons in macaque primary visual cortex

Layer 5 neurons in primary visual cortex make putative reciprocal feedback connections to the superficial layers. To test this hypothesis, we employed scanning laser photostimulation combined with intracellular dye injection to examine local functional excitatory inputs to and axonal projections from individual layer 5 neurons in brain slices from monkey V1. In contrast with previous studies of other V1 neurons, layer 5 neurons received significant input from nearly all of the cortical layers, suggesting individual layer 5 cells integrate information from a broad range of input sources. Nevertheless relative strengths of laminar inputs varied across neurons. Cluster analysis of relative strength of laminar inputs to individual layer 5 neurons revealed four discrete clusters representing recurring input patterns; each cluster included both excitatory and inhibitory neurons. Twenty-five of 40 layer 5 neurons fell into two clusters, both characterized by very strong input from superficial layers. These input patterns are consistent with layer 5 neurons providing feedback to superficial layers. The remaining 15 neurons received stronger input from deep layers. Differences in input from layer 4Calpha versus 4Cbeta also suggest specific associations of the magnocellular and parvocellular visual pathways, with populations receiving stronger input from deep versus superficial cortical layers.     

The spatial pattern of response magnitude and selectivity for orientation and direction in cat visual cortex

Optical imaging studies of orientation and direction preference in visual cortex have typically used vector averaging to obtain angle and magnitude maps. This method has shown half-rotation orientation singularities (pinwheels) located within regions of low orientation vector magnitude. Direction preference is generally orthogonal to orientation preference, but often deviates from this, particularly in regions of low direction vector magnitude. Linear regions of rapid change in direction preference terminate in or near orientation singularities. The vector-averaging method is problematic however because it does not clearly disambiguate spatial variation in orientation tuning width from variation in height. It may also wrongly estimate preferred direction in regions where preference is weak. In this paper we analyze optical maps of cat visual cortex by fitting model tuning functions to the responses. This new method reveals features not previously evident. Orientation tuning height and width vary independently across the map: tuning height is always low near singularities, however regions of broad and narrow orientation tuning width can be found in regions of low tuning height, often alternating in a spoke-like fashion around singularities. Orientation and direction preference angles are always closely orthogonal. Reversals in direction preference form lines that originate precisely in orientation singularities.     

The effects of aging on layer 1 of primary visual cortex in the rhesus monkey

The effect of age on layer 1 in primary visual cortex was determined in 19 rhesus monkeys of various ages. Twelve of the monkeys had been behaviorally tested. With age layer 1 becomes thinner and the glial limiting membrane becomes thicker. In the neuropil of layer 1 many of the dendrites in old monkeys appear to be degenerating and, as a consequence, electron micrographs from old monkeys display fewer dendritic and spine profiles per unit area than in young monkeys. As determined using both the disector and size-frequency methods, there is also a concomitant decrease in the numerical density of synapses with age. Although there is a significant correlation between the thinning of layer 1 in area 17 and age, there is no significant correlation between either the thinning of layer 1 or its loss of synapses and any of the behavioral measures of memory function obtained from the 12 behaviorally tested monkeys. Similar morphological changes with age occur in layer 1 of prefrontal cortex of these same monkeys, but in area 46 both the thinning of layer 1 and the loss of synapses show a significant correlation with behavioral measures of memory function. These differences between layer 1 in these two cortical areas presumably relate to the fact that prefrontal cortex has a greater role in subserving cognition than does primary visual cortex.     

Descending projections from extrastriate visual cortex modulate responses of cells in primary auditory cortex

Primary sensory cortical responses are modulated by the presence or expectation of related sensory information in other modalities, but the sources of multimodal information and the cellular locus of this integration are unclear. We investigated the modulation of neural responses in the murine primary auditory cortical area Au1 by extrastriate visual cortex (V2). Projections from V2 to Au1 terminated in a classical descending/modulatory pattern, with highest density in layers 1, 2, 5, and 6. In brain slices, whole-cell recordings revealed long latency responses to stimulation in V2L that could modulate responses to subsequent white matter (WM) stimuli at latencies of 5-20 ms. Calcium responses imaged in Au1 cell populations showed that preceding WM with V2L stimulation modulated WM responses, with both summation and suppression observed. Modulation of WM responses was most evident for near-threshold WM stimuli. These data indicate that corticocortical projections from V2 contribute to multimodal integration in primary auditory cortex.     

The existence of a layer IV in the rat motor cortex

We have reconstructed the laminar pattern of rat primary motor cortex (Fr1) using a computerized analysis system based on the so-called 'optical dissector'. Data were visualized on a graphics terminal. In contrast to current views, which state that there is no prominent layer IV in the motor cortex of the rat, our method of analysis revealed a genuine layer IV consisting of densely packed small neurons.      

An intracellular study of the contrast-dependence of neuronal activity in cat visual cortex

Extracellular recordings indicate that mechanisms that control contrast gain of neuronal discharge are found in the retina, thalamus and cortex. In addition, the cortex is able to adapt its contrast response function to match the average local contrast. Here we examine the neuronal mechanism of contrast adaptation by direct intracellular recordings in vivo. Both simple (n = 3) and complex cells (n = 4) show contrast adaptation during intracellular recording. For simple cells, that the amplitude of fluctuations in membrane potential induced by a drifting grating stimulus follows a contrast response relation similar to lateral geniculate relay cells, and does not reflect the high gain and adaptive properties seen in the action potential discharge of the neurons. We found no evidence of significant shunting inhibition that could explain these results. In complex cells there was no change in the mean membrane potential for different contrast stimuli or different states of adaptation, despite marked changes in discharge rate. We use a simplified electronic model to discuss the central features of our results and to explain the disparity between the contrast response functions of the membrane potential and action potential discharge in simple cells.      

Localization of activity-dependent changes in blood volume to submillimeter-scale functional domains in cat visual cortex

We have examined whether blood volume changes induced by neural activation are controlled precisely enough for us to visualize the submillimeter-scale functional structure in anesthetized and awake cat visual cortex. To activate the submillimeter-scale functional structures such as iso-orientation domains in the cortex, visual stimuli (gratings) were presented to the cats. Two methods were used to examine the spatial precision of blood volume changes including changes in total hemoglobin content and changes in plasma volume: (i) intrinsic signal imaging at the wavelength of hemoglobin's isosbestic point (569 nm) and (ii) imaging of absorption changes of an intravenously injected dye. Both measurements showed that the visual stimuli elicited stimulus-nonspecific and stimulus-specific blood volume changes in the cortex. The former was not spatially localized, while the latter was confined to iso-orientation domains. From the measurement of spatial separation of the iso-orientation domains, we estimated the spatial resolution of stimulus-specific blood volume changes to be as high as 0.6 mm. The changes in stimulus-nonspecific and -specific blood volume were not linearly correlated. These results suggest the existence of fine blood volume control mechanisms in the capillary bed in addition to global control mechanisms in arteries.     

Estimates of the net excitatory currents evoked by visual stimulation of identified neurons in cat visual cortex

The action potential discharge response of single neurons to both visual stimulation and injections of current were obtained during intracellular recordings in cat visual cortex in order to estimate the net excitatory current arriving at the soma during visual stimulation. Of 45 neurons recorded intracellularly, 19 pyramidal neurons and one basket cell were labelled with horseradish peroxidase. The discharge of all neurons adapted to constant current. For 40 neurons, a single exponential provided a good fit to the adapting discharge (r2 = 0.73 +/- 0.03) for all current intensities. Superficial layer neurons were significantly faster adapting [P < 0.001, mean (+/- SEM) time constant of adaptation = 11.5 +/- 1.3 ms; n = 20] than deep layer neurons (mean time constant of adaptation = 51.4 +/- 6.4 ms; n = 10). The percentage adaptation of the spike frequency, %(peak - adapted rate)/peak, was determined from the fitted exponential. Superficial layer neurons adapted significantly more strongly (P < 0.01, mean = 67 +/- 3%) than deep layer neurons (mean = 51 +/- 5%). The mean firing frequency in response to a current step of 320 ms duration had a linear relationship to the amplitude of the injected current (slope 66 spikes/s/nA; origin zero, mean r2 = 0.94; n = 33). This relationship provided a means of estimating the net peak excitatory current generated by visual stimuli. The estimated mean peak somatic current during the passage of a bar across the receptive field was 1.1 nA and the average current for the duration of the visually evoked discharge was 0.64 nA (n = 17). The transfer response of real and model neurons was obtained by differentiating the discharge response to a step input current and was then used to predict the output of the neuron following an arbitrary input. When these transfer responses were convolved with known input signals in model neurons, the predicted output was close to the simulated response of the model neuron to the same input waveforms. The transfer response was calculated for eight real neurons. Estimates of the net excitatory current arriving at the soma during visual stimulation was obtained by deconvolution. The mean peak somatic current for these neurons was 0.62 nA.      

Dynamics of directional selectivity in area 18 and PMLS of the cat

Visual latencies and temporal dynamics of area 18 and PMLS direction-selective complex cells were defined with a reverse correlation method. The method allowed us to analyze the time course of responses to motion steps, without confounding temporal integration effects. Several measures of response latency and direction tuning dynamics were quantified: optimal latency (OL), latency of first and last significant responses (FSR, LSR), the increase and decrease of direction sensitivity in time, and the change of direction tuning in time. FSR, OL and LSR values for PMLS and area 18 largely overlapped. The small differences in mean latencies (3-4 ms for FSR and OL and 11.9 ms for the LSR) were not statistically significant. All cells in area 18 and the vast majority of cells in PMLS showed no systematic changes in preferred direction (monophasic neurons). In PMLS 5 out of 41 cells showed a reversal of preferred direction after approximately 56 ms relative to their OL (biphasic neurons). Monophasic cells showed no systematic changes in direction tuning width during the interval from FSR to LSR. In both areas, development of direction sensitivity was significantly faster than return to the non-direction sensitive state, but no significant difference was found between the two areas. We conclude that, for the monophasic type of direction-selective complex cells, the dynamics of primary motion processing are highly comparable for area 18 and PMLS. This suggests that motion information is predominantly processed in parallel, presumably based on input from the fast conducting thalamocortical Y-pathway.     

High response reliability of neurons in primary visual cortex (V1) of alert, trained monkeys

The reliability of neuronal responses determines the resources needed to represent the external world and constrains the nature of the neural code. Studies of anesthetized animals have indicated that neuronal responses become progressively more variable as information travels from the retina to the cortex. These results have been interpreted to indicate that perception must be based on pooling across relatively large numbers of cells. However, we find that in alert monkeys, responses in primary visual cortex (V1) are as reliable as the inputs from the retina and the thalamus. Moreover, when the effects of fixational eye movements were minimized, response variability (variance/mean - Fano factor, FF) in all V1 layers was low. When presenting optimal stimuli, the median FF was 0.3. High variability, FF approximately 1, was found only near threshold. Our results suggest that in natural vision, suprathreshold perception can be based on small numbers of optimally stimulated cells.     

Relationships of local inhibitory and excitatory circuits to orientation preference maps in ferret visual cortex.

The contribution and precise role of intracortical circuits in generating orientation tuned responses in visual cortical neurons is still controversial. To address this question, the relationship between excitatory and inhibitory synaptic connections and orientation maps in ferret striate cortex was investigated by combining in vivo optical imaging and in vitro scanning laser photostimulation. Excitatory and inhibitory inputs to pyramidal cells originated preferentially from regions with similar orientation preference. Prominent cross-orientation inhibition was not observed, arguing against cross-orientation models of orientation selectivity. The tuning of inhibitory inputs was significantly broader in both layer 2/3 and layer 5/6 pyramidal neurons compared to the tuning of excitatory inputs. Local excitatory inputs were more prominent in the 0-20 degrees tuning difference range between pre- and postsynaptic cells than inhibitory inputs, whereas inhibition dominated in the 20-40 degrees tuning difference range. These differences in tuning of excitatory and inhibitory inputs onto individual cells are consistent with the predictions of recurrent models of orientation selectivity.     

Organization of horizontal axons in the inferior temporal cortex and primary visual cortex of the macaque monkey

We investigated the organization of horizontal connections at two distinct hierarchical levels in the ventral visual cortical pathway of the monkey, the inferior temporal (TE) and primary visual (V1) cortices. After injections of anterograde tracers into layers 2 and 3, clusters of terminals ('patches') of labeled horizontal collaterals in TE appeared at various distances up to 8 mm from the injection site, while in V1 clear patches were distributed only within 2 mm. The size and spacing of these patches in TE were larger and more irregular than those observed in V1. The labeling intensity of patches in V1 declined sharply with distance from the injection site. This tendency was less obvious in TE; a number of densely labeled patches existed at distant sites beyond weakly labeled patches. While injections into both areas resulted in an elongated pattern of patches, the anisotropy was greater in TE than in V1 for injections of a similar size. Dual tracer injections and larger-sized injections further revealed that the adjacent sites in TE had spatially distinct horizontal projections, compared to those in V1. These area-specific characteristics of the horizontal connections may contribute to the differences in visual information processing of TE and V1.     

Increased receptive field size in the surround of chronic lesions in the adult cat visual cortex

Visual cortical lesions destroy the target cells for geniculocortical fibers from a certain retinotopic region. This leads to a cortical scotoma. We have investigated the receptive fields of cells in the visual cortex before, 2 days and 2 months after focal ibotenic acid lesions in the adult cat visual cortex and have found signs of receptive field plasticity in the surroundings of the chronic but not the acute and subacute excitotoxic lesions. In the subacute state (first two days post lesion) receptive field sizes of cells at the border of the lesion were reduced in size or remained unchanged. Remapping of cortical receptive fields 2 months later revealed a number of cells with multifold enlarged receptive fields at the border of the lesion. The cells with enlarged receptive fields displayed orientation and direction selectivity like normal cells. The size increase appeared not specifically directed towards the scotoma; however, the enlarged receptive fields can reduce the extent of a cortical scotoma, since previously unresponsive regions of the visual field activate cortical cells at the border of the lesion. This late receptive field plasticity could serve as a mechanism for the filling-in of cortical scotomata observed in patients with visual cortex lesions.     

Human-specific organization of primary visual cortex: alternating compartments of dense Cat-301 and calbindin immunoreactivity in layer 4A

There is evidence that the cortical anatomy of the magnocellular (M) visual pathway, which carries information about motion and luminance contrast, was modified in human evolution. Recent results indicate that layer 4A of humans contains a meshwork of tissue bands that stain densely for nonphosphorylated neurofilament (NPNF), a protein that is preferentially expressed in elements of the M pathway, whereas apes and monkeys lack a comparable pattern. Here we examined the distribution of staining for Cat-301 -- a monoclonal antibody well established to stain M-related structures preferentially -- in area V1 of humans, apes (chimpanzees, orangutan), Old World monkeys (macaques) and New World monkeys (spider monkeys, squirrel monkeys). Single-staining experiments, using a peroxidase-tetramethylbenzidine (TMB) reaction, revealed alternating zones of dark and light staining for Cat-301 in layer 4A of humans, similar to those observed with NPNF. Double-staining studies in humans revealed that Cat-301-immunoreactive somas and neuropil were localized within the same tissue bands that stained strongly for NPNF and, furthermore, that these bands alternated with irregularly shaped territories that stained very strongly for calbindin. Nonhuman primates, by contrast to humans, displayed weak Cat-301 and calbindin staining in layer 4A. The co-localization of Cat-301 and NPNF in human layer 4A, and the weak staining for these molecules in layer 4A of other primates, suggests that the cortical representation of the M channel was modified in recent human evolution. The calbindin-rich compartments in human layer 4A cannot be related to a particular geniculostriate pathway on neurochemical grounds; they may constitute an interneuronal population that increased in human evolution.     

The projection from V1 to extrastriate area 21a: a second patchy efferent pathway colocalizes with the CO blob columns in cat visual cortex

The different patchy organizations of neurons projecting from primary visual cortex (area 17) to the various extrastriate areas may contribute to functional differences in the output to each of these areas. The pattern of neurons projecting to extrastriate area 21a was examined using large injections of retrograde tracers and compared to the pattern shown by neurons projecting to the lateral suprasylvian area (LS). Patches of neurons projecting to 21a showed a bimodal laminar distribution, with numerous labeled cells in the upper and lower third of layer 3 bracketing a sparsely labeled central third; LS-projecting neurons were confined to the lower and middle thirds of layer 3. The 21a projecting cells were relatively tighter in their clustering pattern than the LS projecting cells, i. e. the difference in labeling density between patch and interpatch zones was greater for 21a-projecting cells than for LS-projecting cells. As previously shown for the LS-projecting cells, patches of 21a-projecting cells colocalized with CO blob columns in area 17. Combined with our earlier results, this study shows that the CO blob compartments in area 17 give rise to at least two distinct efferent pathways, one projecting to LS and the other to 21a, and furthermore suggest that each pathway may carry unique information to its extrastriate target.