Search

The brain's visual cortex processes information concerning form, pattern, and motion within functional maps that reflect the layout of neuronal circuits. We analyzed functional maps of orientation preference in the ferret, tree shrew, and galago--three species separated since the basal radiation of placental mammals more than 65 million years ago--and found a common organizing principle. A symmetry-based class of models for the self-organization of cortical networks predicts all essential features of the layout of these neuronal circuits, but only if suppressive long-range interactions dominate development. We show mathematically that orientation-selective long-range connectivity can mediate the required interactions. Our results suggest that serf-organization has canalized the evolution of the neuronal circuitry underlying orientation preference maps into a single common design. 10.1126/science.1194869

Experience-dependent cortical plasticity has been studied by using loss-of-function methods. Here, we take the complementary approach of using a genetic gain-of-function that enhances plasticity. We show that a constitutively active form of H-ras ([H-ras.sup.G12V]), expressed presynaptically at excitatory synapses in mice, accelerates and enhances multiple, mechanistically distinct forms of plasticity in the developing visual cortex. In vivo, [H-ras.sup.G12V] not only increased the rate of ocular dominance change in response to monocular deprivation (MD), but also accelerated recovery from deprivation by reverse occlusion. In vitro, [H-ras.sup.G12v] expression decreased baseline presynaptic release probability and enhanced presynaptically expressed longterm potentiation (LTP). [H-ras.sup.G12v] expression also accelerated the increase following M D in the frequency of miniature excitatory potentials, mirroring accelerated plasticity in vivo. These findings demonstrate accelerated neocortical plasticity, which offers an avenue toward future therapies for many neurological and neuropsychiatric disorders. gain of function | monocular deprivation | mouse | ocular dominance | presynaptic long-term potentiation doi/ 10.1073/pnas.1013866107

Immune molecules have been discovered recently to play critical roles in the development, function, and plasticity of the cerebral cortex. MHC class I (MHCI) molecules are expressed in the central nervous system and regulate activity-dependent refinement of visual projections during late postnatal development. They have also been implicated in neurodevelopmental diseases such as schizophrenia and autism. Despite the excitement generated by these unique roles for immune proteins in the brain, little is known about how these molecules regulate cortical connections. The first step toward elucidating the mechanism is to identify the spatial and temporal distribution of MHCI proteins throughout development. Using a pan-specific antibody that recognizes many MHCI variants for biochemistry and immunohistochemistry, we found that MHCI proteins are expressed in the rat visual cortex at all ages examined--during the peak of synaptogenesis, the critical period of synaptic refinement, and adulthood. Their abundance in the cortex peaked during early postnatal development, declining during periods of plasticity and adulthood. In contrast to current assumptions, pre- and postembedding immunogold electron microscopy (EM) revealed that MHCI proteins were present both pre--and postsynaptically at all ages examined. They were often found in the postsynaptic density and were closely associated with synaptic vesicles in the presynaptic terminal. These results suggest a previously undescribed model in which MHCI molecules function on both sides of the synapse to regulate connectivity in the mammalian visual cortex before, during, and after the establishment of connections. neuroimmunology | HLA | MHCI | synapse elimination I synapse formation doi/ 10.1073/pnas.1006087107

Despite the importance of vision for spatial navigation, blind subjects retain the ability to represent spatial information and to move independently in space to localize and reach targets. However, the neural correlates of navigation in subjects lacking vision remain elusive. We therefore used functional MRI (fMRI) to explore the cortical network underlying successful navigation in blind subjects. We first trained congenitally blind and blindfolded sighted control subjects to perform a virtual navigation task with the tongue display unit (TDU), a tactile-to-vision sensory substitution device that translates a visual image into electrotactile stimulation applied to the tongue. After training, participants repeated the navigation task during fMRI. Although both groups successfully learned to use the TDU in the virtual navigation task, the brain activation patterns showed substantial differences. Blind but not blindfolded sighted control subjects activated the parahippocampus and visual cortex during navigation, areas that are recruited during topographical learning and spatial representation in sighted subjects. When the navigation task was performed under full vision in a second group of sighted participants, the activation pattern strongly resembled the one obtained in the blind when using the TDU. This suggests that in the absence of vision, cross-modal plasticity permits the recruitment of the same cortical network used for spatial navigation tasks in sighted subjects. cross-modal plasticity | parahippocampus | sensory substitution spatial navigation | visual cortex doi/10.1073/pnas.1006199107

The purpose of this study was to investigate activation-induced hypermetabolism and hyperemia by using a multifrequency (4, 8, and 16 Hz) reversing-checkerboard visual stimulation paradigm. Specifically, we sought to (i) quantify the relative contributions of the oxidative and nonoxidative metabolic pathways in meeting the increased energy demands [i.e., ATP production ([J.sub.ATP])] of task-induced neuronal activation and (ii) determine whether task-induced cerebral blood flow (CBF) augmentation was driven by oxidative or nonoxidative metabolic pathways. Focal increases in CBF, cerebral metabolic rate of oxygen (CMR[O.sub.2]; i.e., index of aerobic metabolism), and lactate production ([J.sub.Lac]; i.e., index of anaerobic metabolism) were measured by using physiologically quantitative MRI and spectroscopy methods. Task-induced increases in [J.sub.ATP] were small (12.2-16.7%) at all stimulation frequencies and were generated by aerobic metabolism (approximately 98%), with %[DELTA][J.sub.ATP] being linearly correlated with the percentage change in CMR[O.sub.2] (r = 1.00, P < 0.001). In contrast, task-induced increases in CBF were large (51.7-65.1%) and negatively correlated with the percentage change in CMR[O.sub.2] (r = -0.64, P= 0.024), but positively correlated with %[DELTA][J.sub.Lac] (r = 0.91, P < 0.001). These results indicate that (i) the energy demand of task-induced brain activation is small (approximately 15%) relative to the hyperemic response (approximately 60%), (ii) this energy demand is met through oxidative metabolism, and (iii) the CBF response is mediated by factors other than oxygen demand. cerebral metabolic rate of oxygen | lactate production doi/ 10.1073/pnas.0909711107

Thalamic inputs strongly drive neurons in the primary visual cortex, even though these neurons constitute only ~5% of the synapses on layer 4 spiny stellate simple ceils. We modeled the feedforward excitatory and inhibitory inputs to these cells based on in vivo recordings in cats, and we found that the reliability of spike transmission increased steeply between 20 and 40 synchronous thalamic inputs in a time window of 5 milliseconds, when the reliability per spike was most energetically efficient. The optimal range of synchronous inputs was influenced by the balance of background excitation and inhibition in the cortex, which could gate the flow of information into the cortex. Ensuring reliable transmission by spike synchrony in small populations of neurons may be a general principle of cortical function. 10.1126/science.1183108

We describe a miniaturized head-mounted multiphoton microscope and its use for recording [Ca.sup.2+] transients from the somata of layer 2/3 neurons in the visual cortex of awake, freely moving rats. Images contained up to 20 neurons and were stable enough to record continuously for >5 min per trial and 20 trials per imaging session, even as the animal was running at velocities of up to 0.6 m/s. Neuronal [Ca.sup.2+] transients were readily detected, and responses to various static visual stimuli were observed during free movement on a running track. Neuronal activity was sparse and increased when the animal swept its gaze across a visual stimulus. Neurons showing preferential activation by specific stimuli were observed in freely moving animals. These results demonstrate that the multiphoton fiberscope is suitable for functional imaging in awake and freely moving animals. calcium imaging | head-mounted microscope | neuronal activity | two-photon | visual cortex www.pnas.org/cgi/doi/10.1073/pnas.0903680106

The mechanisms of attention prioritize sensory input for efficient perceptual processing. Influential theories suggest that attentional biases are mediated via preparatory activation of task-relevant perceptual representations in visual cortex, but the neural evidence for a preparatory coding model of attention remains incomplete. In this experiment, we tested core assumptions underlying a preparatory coding model for attentional bias. Exploiting multivoxel pattern analysis of functional neuroimaging data obtained during a non-spatial attention task, we examined the locus, time-course, and functional significance of shape-specific preparatory attention in the human brain. Following an attentional cue, yet before the onset of a visual target, we observed selective activation of target-specific neural subpopulations within shape-processing visual cortex (lateral occipital complex). Target-specific modulation of baseline activity was sustained throughout the duration of the attention trial and the degree of target specificity that characterized preparatory activation patterns correlated with perceptual performance. We conclude that top-down attention selectively activates target-specific neural codes, providing a competitive bias favoring task-relevant representations over competing representations distributed within the same subregion of visual cortex. top-down bias | visual attention www.pnas.org/cgi/doi.10.1073/pnas.0905306106

A quintessential feature of the neocortex is its laminar organization, and characterizing the activity patterns in different layers is an important step in understanding cortical processing. Using in vivo whole-cell recordings in rat visual cortex, we show that the temporal patterns of ongoing synaptic inputs to pyramidal neurons exhibit clear laminar specificity. Although low-frequency (~2 Hz) activity is widely observed in layer 2/3 (L2/3), a narrow-band fast oscillation (10-15 Hz) is prominent in layer 5 (L5). This fast oscillation is carried exclusively by excitatory inputs. Moreover, the frequency of ongoing activity is strongly correlated with the spatiotemporal window of visual integration: Neurons with fast-oscillating spontaneous inputs exhibit transient visual responses and small receptive fields (RFs), whereas those with slow inputs show prolonged responses and large RFs. These findings suggest that the neural representation of visual information within each layer is strongly influenced by the temporal dynamics of the local network manifest in spontaneous activity. lamina | ongoing activity | patch clamp | pyramidal cell | vision doi/ 10.1073/pnas.0903962106

Electrical recordings in humans and monkeys show attentional enhancement of evoked responses and gamma synchrony in ventral stream cortical areas. Does this synchrony result from intrinsic activity in visual cortex or from inputs from other structures? Using paired recordings in the frontal eye field (FEF) and area V4, we found that attention to a stimulus in their joint receptive field leads to enhanced oscillatory coupling between the two areas, particularly at gamma frequencies. This coupling appeared to be initiated by FEF and was time-shifted by about 8 to 13 milliseconds across a range of frequencies. Considering the expected conduction and synaptic delays between the areas, this time-shifted coupling at gamma frequencies may optimize the postsynaptic impact of spikes from one area upon the other, improving cross-area communication with attention.

Both single and repeated visual stimuli produce waves of activity in the visual cortex of freshwater turtles. Large-scale, biophysically realistic models of the visual cortex capture the basic features of the waves produced by single stimuli. However, these models do not respond to repetitive stimuli due to the presence of a long-lasting hyperpolarization that follows the initial wave. This paper modifies the large-scale model so that it responds to repetitive stimuli by incorporating Hebbian and anti-Hebbian learning rules in synapses in the model. The resulting adaptive model responds to repetitive stimuli with repetitive waves. However, repeated presentation of a stimulus to a restricted region of visual space produces a habituation in the model in the same way it does in the real cortex. Index Terms--Hebbian learning, large-scale cortex model, synaptic adaptation, turtle visual cortex.

In this paper, a new model seeking to emulate the way the visual cortex processes information and interacts with subcortical areas to produce higher level brain functions is described. We developed a macroscopic approach that incorporates salient attributes of the cortex based on combining tools of nonlinear dynamics, information theory, and the known organizational and anatomical features of cortex. Justifications for this approach and demonstration of its effectiveness are presented. We also demonstrate certain capabilities of this model in producing efficient sparse representations and providing the cortical computational maps. Index Terms--Chaos, cortex, cortical maps, information processing, self-organization.

We studied Whether detectable percepts could be produced by electrical stimulation of intracranial electrodes placed over human visual areas identified with fMRI. Identification of areas was confirmed by recording Iocal-field potentials from the electrode, such as face-selective electrical responses from electrodes over the fusiform face area (FFA). The probability of detecting electrical stimulation of a visual area varied with the position of the area in the visual cortical hierarchy. Stimulation of early visual areas including V1, V2, and V3 was almost always detected, whereas stimulation of late visual areas such as FFA was rarely detected. When percepts were elicited from late areas, subjects reported that they were simple shapes and colors, similar to the descriptions of percepts from early areas. There were no reports of elaborate percepts, such as faces, even in areas like FFA, where neurons have complex response properties. For sites eliciting percepts, the detection threshold was determined by varying the stimulation current as subjects performed a forced-choice detection task. Current thresholds were similar for late and early areas. The similarity between both percept quality and threshold across early and late areas suggests the presence of functional microcircuits that link electrical stimulation with perception. fMRI | human visual cortex | visual perception

Simultaneous presentation of multiple stimuli can reduce the firing rates of neurons in extrastriate visual cortex below the rate elicited by a single preferred stimulus. We describe computational results suggesting how this remarkable effect may arise from strong excitatory drive to a substantial local population of fast-spiking inhibitory interneurons, which can lead to a loss of coherence in that population and thereby raise the effectiveness of inhibition. We propose that in attentional states fast-spiking interneurons may be subject to a bath of inhibition resulting from cholinergic activation of a second class of inhibitory interneurons, restoring conditions needed for gamma rhythmicity. Oscillations and coherence are emergent features, not assumptions, in our model. The gamma oscillations in turn support stimulus competition. The mechanism is a form of 'oscillatory selection,' in which neural interactions change phase relationships that regulate firing rates, and attention shapes those neural interactions. cholinergic modulation | selective attention | gamma rhythm

A ubiquitous feature of neuronal responses within a cortical area is their high degree of inhomogeneity. Even cells within the same functional column are known to have highly heterogeneous response properties when the same stimulus is presented. Whether the wide diversity of neuronal responses is an epiphenomenon or plays a role for cortical function is unknown. Here, we examined the relationship between the heterogeneity of neuronal responses and population coding. Contrary to our expectation, we found that the high variability of intrinsic response properties of individual cells changes the structure of neuronal correlations to improve the information encoded in the population activity. Thus, the heterogeneity of neuronal responses is in fact beneficial for sensory coding when stimuli ate decoded from the population response. computational modeling | information coding | sensory cortex | visual cortex | neuronal populations

fMRI is a tool to study brain function noninvasively that can reliably identify sites of neural involvement for a given task. However, to what extent can fMRI signals be related to measures obtained in electrophysiology? Can the blood-oxygen-level-dependent signal be interpreted as spatially pooled spiking activity? Here we combine knowledge from neurovascular coupling, functional imaging and neurophysiology to discuss whether fMRI has succeeded in demonstrating one of the most established functional properties in the visual brain, namely directional selectivity in the motion-processing region V5/ MT+. We also discuss differences of fMRI and electrophysiology in their sensitivity to distinct physiological processes. We conclude that fMRI constitutes a complement, not a poor-resolution substitute, to invasive techniques, and that it deserves interpretations that acknowledge its stand as a separate signal.

Animals process information about many stimulus features simultaneously, swiftly (in a few 100 ms), and robustly (even when individual neurons do not themselves respond reliably). When the brain carries, codes, and certainly when it decodes information, it must do so through some coarse-grained projection mechanism. How can a projection retain information about network dynamics that covers multiple features, swiftly and robustly? Here, by a coarse-grained projection to event trees and to the event chains that comprise these trees, we propose a method of characterizing dynamic information of neuronal networks by using a statistical collection of spatial-temporal sequences of relevant physiological observables (such as sequences of spiking multiple neurons). We demonstrate, through idealized point neuron simulations in small networks, that this event tree analysis can reveal, with high reliability, information about multiple stimulus features within short realistic observation times. Then, with a large-scale realistic computational model of V1, we show that coarse-grained event trees contain sufficient information, again over short observation times, for fine discrimination of orientation, with results consistent with recent experimental observation. information transmission | neuronal coding | orientation selectivity primary visual cortex

Neurons in the developing CNS tend to send out long axon collaterals to multiple target areas. For these neurons to attain specific connections, some of their axon collaterals are subsequently pruned--a process called stereotyped axon pruning. One of the most striking examples of stereotyped pruning in the CNS is the pruning of corticospinal tract (CST) axons. The long CST collaterals from layer V neurons of the visual and motor cortices are differentially pruned during development. Here we demonstrate that select plexins and neuropilins, which serve as coreceptors for semaphorins, are expressed in visual cortical neurons at the time when CST axon collaterals are stereotypically pruned. By analyzing mutant mice, we find that the pruning of visual, but not motor, CST axon collaterals depends on plexin-A3, plexin-A4, and neuropilin-2. Expression pattern study suggests that Sema3F is a candidate local cue for the pruning of visual CST axons. Using electron microscopic analysis, we also show that visual CST axon collaterals form synaptic contacts in the spinal cord before pruning and that the unpruned collaterals in adult mutant mice are unmyelinated and maintain their synaptic contacts. Our results indicate that the stereotyped pruning of the visual and motor CST axon collaterals is differentially regulated and that this specificity arises from the differential expression of plexin receptors in the cortex. axon pruning | corticospinal tract | plexin

An essential step in understanding visual processing is to characterize the neuronal receptive fields (RFs) at each stage of the visual pathway. However, RF characterization beyond simple cells in the primary visual cortex (V1) remains a major challenge. Recent application of spike-triggered covariance (STC) analysis has greatly facilitated characterization of complex cell RFs in anesthetized animals. Here we apply STC to RF characterization in awake monkey V1. We found up to nine subunits for each cell, including one or two dominant excitatory subunits as described by the standard model, along with additional excitatory and suppressive subunits with weaker contributions. Compared with the dominant subunits, the nondominant excitatory subunits prefer similar orientations and spatial frequencies but have larger spatial envelopes. They contribute to response invariance to small changes in stimulus orientation, position, and spatial frequency. In contrast, the suppressive subunits are tuned to orientations 45[degrees]-90[degrees] different from the excitatory subunits, which may underlie cross-orientation suppression. Together, the excitatory and suppressive subunits form a compact description of RFs in awake monkey V1, allowing prediction of the responses to arbitrary visual stimuli.

Byline: E. D. Bark (1), Yu. A. Tokareva (1), I. A. Shevelev (1) Keywords: [alpha]-rhythm; dynamics; visual cortex; illusions; scanning; phase; photostimulation; equivalent current dipole (ECD); electroencephalogram (EEG) Abstract: The numbers of [alpha]-rhythm equivalent current dipoles (ECD) arising in the human brain before and during rhythmic photostimulation at the [alpha]-rhythm frequency was studied in six healthy adult subjects. Dipoles were calculated using a single-dipole model for the whole of the [alpha]-range and three subranges by solution of inverse equations in a three-layer model of the head obtained by simultaneous use of EEG data and MRI tomograms of the subjects' heads. The number of apparent ECD was significantly associated with rhythmic photostimulation and depended on the phase of the [alpha]-rhythm wave at which stimulation started and on the type of visual illusion (circle, spiral, grid) appearing during this time. The relationship between these data and the hypothetical wave process scanning the human visual cortex at the frequency of the [alpha]-rhythm is discussed. Author Affiliation: (1) Laboratory for Analyzer Physiology, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5a Butlerov Street, 117485, Moscow, Russia Article History: Registration Date: 12/10/2004

Cellular responses in the V2 secondary visual cortex to simple as well as complex visual stimuli have been welt studied. However, the role of area V2 in visual memory remains unexplored. We found that layer 6 neurons of V2 are crucial for the processing of object-recognition memory (ORM). Using the protein regulator of G protein signaling--14 (RGS-14) as a tool we found that the expression of this protein into layer 6 neurons of rat-brain area V2 promoted the conversion of a normal short-term ORM that normally lasts for 45 minutes into tong-term memory detectable even after many months. Furthermore, elimination of the same-layer neurons by means of injection of a selective cytotoxin resulted in the complete loss of normal as welt as protein-mediated enhanced ORM.

Nijhawan argues convincingly that predictive mechanisms are pervasive in the central nervous system (CNS). However, scientific understanding of visual prediction requires one to formulate empirically testable neurophysiological models. The author's suggestions in this direction are to be evaluated on the basis of more realistic experimental methodologies and more plausible assumptions on the hierarchical character of the human visual cortex.

The extent to which visual processing can proceed in the visual hierarchy without awareness determines the magnitude of perceptual delay. Increasing data demonstrate that primary visual cortex (V1) is involved in consciousness, constraining the magnitude of visual delay. This makes it possible that visual delay is actually within the optimal lengths to allow sufficient computation; thus it might be unnecessary to compensate for visual delay.