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Intrinsic timescales characterize dynamics of endogenous fluctuations in neural activity. Variation of intrinsic timescales across the neocortex reflects functional specialization of cortical areas, but less is known about how intrinsic timescales change during cognitive tasks. We measured intrinsic timescales of local spiking activity within columns of area V4 in male monkeys performing spatial attention tasks. The ongoing spiking activity unfolded across at least two distinct timescales, fast and slow. The slow timescale increased when monkeys attended to the receptive fields location and correlated with reaction times. By evaluating predictions of several network models, we found that spatiotemporal correlations in V4 activity were best explained by the model in which multiple timescales arise from recurrent interactions shaped by spatially arranged connectivity, and attentional modulation of timescales results from an increase in the efficacy of recurrent interactions. Our results suggest that multiple timescales may arise from the spatial connectivity in the visual cortex and flexibly change with the cognitive state due to dynamic effective interactions between neurons.

The functional properties of neurons in the primary visual cortex (V1) are thought to be closely related to the structural properties of this network, but the specific relationships remain unclear. Previous theoretical studies have suggested that sparse coding, an energy-efficient coding method, might underlie the orientation selectivity of V1 neurons. We thus aimed to delineate how the neurons are wired to produce this feature. We constructed a model and endowed it with a simple Hebbian learning rule to encode images of natural scenes. The excitatory neurons fired sparsely in response to images and developed strong orientation selectivity. After learning, the connectivity between excitatory neuron pairs, inhibitory neuron pairs, and excitatory-inhibitory neuron pairs depended on firing pattern and receptive field similarity between the neurons. The receptive fields (RFs) of excitatory neurons and inhibitory neurons were well predicted by the RFs of presynaptic excitatory neurons and inhibitory neurons, respectively. The excitatory neurons formed a small-world network, in which certain local connection patterns were significantly overrepresented. Bidirectionally manipulating the firing rates of inhibitory neurons caused linear transformations of the firing rates of excitatory neurons, and vice versa. These wiring properties and modulatory effects were congruent with a wide variety of data measured in V1, suggesting that the sparse coding principle might underlie both the functional and wiring properties of V1 neurons.

Local circuit architecture facilitates the emergence of feature selectivity in the cerebral cortex1. In the hippocampus, it remains unknown whether local computations supported by specific connectivity motifs2 regulate the spatial receptive fields of pyramidal cells3. Here we developed an in vivo electroporation method for monosynaptic retrograde tracing4 and optogenetics manipulation at single-cell resolution to interrogate the dynamic interaction of place cells with their microcircuitry during navigation. We found a local circuit mechanism in CA1 whereby the spatial tuning of an individual place cell can propagate to a functionally recurrent subnetwork5 to which it belongs. The emergence of place fields in individual neurons led to the development of inverse selectivity in a subset of their presynaptic interneurons, and recruited functionally coupled place cells at that location. Thus, the spatial selectivity of single CA1 neurons is amplified through local circuit plasticity to enable effective multi-neuronal representations that can flexibly scale environmental features locally without degrading the feedforward input structure. Single-cell tracing and optogenetics manipulation in mice are used to show how spatial tuning of individual pyramidal cells in CA1 can propagate to and be amplified by their local subnetwork of neurons.

While cells within barrel cortex respond primarily to deflections of their principal whisker (PW), they also exhibit responses to non-principal, or adjacent, whiskers (AWs), albeit responses with diminished amplitudes and longer latencies. The origin of multiwhisker receptive fields of barrel cells remains a point of controversy within the experimental literature, with three contending possibilities: (i) barrel cells inherit their AW responses from the AW responses of thalamocortical (TC) cells within their aligned barreloid; (ii) the axons of TC cells within a barreloid ramify to innervate multiple barrels, rather than only terminating within their aligned barrel; (iii) lateral intracortical transmission between barrels conveys AW responsivity to barrel cells. In this work, we develop a detailed, biologically plausible model of multiple barrels in order to examine possibility (iii); in order to isolate the dynamics that possibility (iii) entails, we incorporate lateral connections between barrels while assuming that TC cells respond only to their PW and that TC cell axons are confined to their home barrel. We show that our model is capable of capturing a broad swath of experimental observations on multiwhisker receptive field dynamics within barrels, and we compare and contrast the dynamics of this model with model dynamics from prior work in which employ a similar general modeling strategy to examine possibility (i).

Neurons in the developing visual cortex undergo progressive functional maturation as indicated by the refinement of their visual feature selectivity. However, changes of the synaptic architecture underlying the maturation of spatial visual receptive fields (RFs) per se remain largely unclear. Here, loose-patch as well as single-unit recordings in layer 4 of mouse primary visual cortex (V1) of both sexes revealed that RF development in a post-eye-opening period is marked by an increased proportion of cortical neurons with spatially defined RFs, together with the increased signal-to-noise ratio (SNR) of spiking responses. By exploring excitatory and inhibitory synaptic RFs with whole-cell voltage clamp recordings, we observed a balanced enhancement of both synaptic excitation and inhibition, and that while the excitatory subfield size remains relatively constant during development, the inhibitory subfield is broadened. This balanced developmental strengthening of excitatory and inhibitory synaptic inputs results in enhanced visual responses and together with a reduction of spontaneous firing rate contributes to the maturation of visual cortical RFs. Visual deprivation by dark rearing impedes the normal strengthening of excitatory inputs but leaves the apparently normal enhancement of inhibition while preventing the broadening of the inhibitory subfield, leading to weakened RF responses and a reduced fraction of neurons exhibiting a clear RF, as compared to normally reared animals. Our data demonstrate that an experience-dependent and coordinated maturation of excitatory and inhibitory circuits underlie the functional development of visual cortical RFs. Significance Statement The organization of synaptic receptive fields (RFs) is a fundamental determinant of feature selectivity functions in the cortex. However, how changes of excitatory and inhibitory synaptic inputs lead to the functional maturation of visual RFs during cortical development remains not well-understood. In layer 4 of mouse primary visual cortex (V1), we show that a coordinated, balanced enhancement of synaptic excitation and inhibition contributes to the developmental maturation of spatially defined visual RFs. Visual deprivation by dark rearing partially interferes this process, resulting in a relatively more dominant inhibitory tone and a reduced fraction of neurons exhibiting clear RFs at the spike level. These data provide an unprecedented understanding of the functional development of visual cortical RFs at the synaptic level.

We conduct a comparative evaluation of the visual systems from the retina to the muscles of the mouse and the macaque monkey noting the differences and similarities between these two species. The topics covered include (1) visual-field overlap, (2) visual spatial resolution, (3) V1 cortical point-image [i.e., V1 tissue dedicated to analyzing a unit receptive field], (4) object versus motion encoding, (5) oculomotor range, (6) eye, head, and body movement coordination, and (7) neocortical and cerebellar function. We also discuss blindsight in rodents and primates which provides insights on how the neocortex mediates conscious vision in these species. This review is timely because the field of visuomotor neurophysiology is expanding beyond the macaque monkey to include the mouse; there is therefore a need for a comparative analysis between these two species on how the brain generates visuomotor responses.

Neurons in the primary visual cortex (V1) are often classified as simple or complex cells, but it is debated whether they are discrete hierarchical classes of neurons or if they represent a continuum of variation within a single class of cells. Herein, we show that simple and complex cells may arise commonly from the feedforward projections from the retina. From analysis of the cortical receptive fields in cats, we show evidence that simple and complex cells originate from the periodic variation of ON–OFF segregation in the feedforward projection of retinal mosaics, by which they organize into periodic clusters in V1. From data in cats, we observed that clusters of simple and complex receptive fields correlate topographically with orientation maps, which supports our model prediction. Our results suggest that simple and complex cells are not two distinct neural populations but arise from common retinal afferents, simultaneous with orientation tuning.

We tested how a stimulus gestalt, defined by the neuronal interaction between local and global features of a stimulus, is represented within human primary visual cortex (V1). We used high-resolution fMRI, which serves as a surrogate of neuronal activation, to measure co-fluctuations within subregions of V1 as (male and female) subjects were presented with peripheral stimuli, each with different global configurations. We found stronger cross-hemisphere correlations when fine-scale V1 cortical subregions represented parts of the same object compared with different objects. This result was consistent with the vertical bias in global processing and, critically, was independent of the task and local discontinuities within objects. Thus, despite the relatively small receptive fields of neurons within V1, global stimulus configuration affects neuronal processing via correlated fluctuations between regions that represent different sectors of the visual field.SIGNIFICANCE STATEMENTWe provide the first evidence for the impact of global stimulus configuration on cross-hemispheric fMRI fluctuations, measured in human primary visual cortex. Our results are consistent with changes in the level of γ-band synchrony, which has been shown to be affected by global stimulus configuration, being reflected in the level fMRI co-fluctuations. These data help narrow the gap between knowledge of global stimulus configuration encoding at the single-neuron level versus at the behavioral level.

Diplopia (double vision) in strabismus is prevented by suppression of the image emanating from one eye. In a recent study conducted in two macaques raised with exotropia (an outward ocular deviation) but having normal acuity in each eye, simultaneous display of stimuli to each eye did not induce suppression in V1 neurons. Puzzled by this negative result, we have modified our protocol to display stimuli in a staggered sequence, rather than simultaneously. Additional recordings were made in the same two macaques, following two paradigms. In trial type 1, the receptive field in one eye was stimulated with a sine-wave grating while the other eye was occluded. After 5 s, the occluder was removed and the neuron was stimulated for another 5 s. The effect of uncovering the eye, which potentially exposed the animal to diplopia, was quantified by the peripheral retinal interaction index (PRII). In trial type 2, the receptive field in the fixating eye was stimulated with a grating during binocular viewing. After 5 s, a second grating appeared in the receptive field of the nonfixating eye. The impact of the second grating, which had the potential to generate visual confusion, was quantified by the receptive field interaction index (RFII). For 82 units, the mean PRII was 0.48 ± 0.05 (0.50 = no suppression) and the mean RFII was 0.46 ± 0.08 (0.50 = no suppression). These values suggest mild suppression, but the modest decline in spike rate registered during the second epoch of visual stimulation might have been due to neuronal adaptation, rather than interocular suppression. In a few instances neurons showed unequivocal suppression, but overall, these recordings did not support the contention that staggered stimulus presentation is more effective than simultaneous stimulus presentation at evoking interocular suppression in V1 neurons. NEW & NOTEWORTHY In strabismus, double vision is prevented by interocular suppression. It has been reported that inhibition of neuronal firing in the primary visual cortex occurs only when stimuli are presented sequentially, rather than simultaneously. However, these recordings in alert macaques raised with exotropia showed, with rare exceptions, little evidence to support the concept that staggered stimulus presentation is more effective at inducing interocular suppression of V1 neurons.

Neural response properties that typify primary sensory afferents are critical to fully appreciate because they establish and, ultimately represent, the fundamental coding design used for higher-level processing. Studies illuminating the center-surround receptive fields of retinal ganglion cells, for example, were ground-breaking because they determined the foundation of visual form detection. For the auditory system, a basic organizing principle of the spiral ganglion afferents is their extensive electrophysiological heterogeneity establishing diverse intrinsic firing properties in neurons throughout the spiral ganglion. Moreover, these neurons display an impressively large array of neurotransmitter receptor types that are responsive to efferent feedback. Thus, electrophysiological diversity and its neuromodulation are a fundamental encoding mechanism contributed by the primary afferents in the auditory system. To place these features into context, we evaluated the effects of hyperpolarization and cAMP on threshold level as indicators of overall afferent responsiveness in CBA/CaJ mice of either sex. Hyperpolarization modified threshold gradients such that distinct voltage protocols could shift the relationship between sensitivity and stimulus input to reshape resolution. This resulted in an “accordion effect” that appeared to stretch, compress, or maintain responsivity across the gradient of afferent thresholds. cAMP targeted threshold and kinetic shifts to rapidly adapting neurons, thus revealing multiple cochleotopic properties that could potentially be independently regulated. These examples of dynamic heterogeneity in primary auditory afferents not only have the capacity to shift the range, sensitivity, and resolution, but to do so in a coordinated manner that appears to orchestrate changes with a seemingly unlimited repertoire.SIGNIFICANCE STATEMENTHow do we discriminate the more nuanced qualities of the sound around us? Beyond the basics of pitch and loudness, aspects, such as pattern, distance, velocity, and location, are all attributes that must be used to encode acoustic sensations effectively. While higher-level processing is required for perception, it would not be unexpected if the primary auditory afferents optimized receptor input to expedite neural encoding. The findings reported herein are consistent with this design. Neuromodulation compressed, expanded, shifted, or realigned intrinsic electrophysiological heterogeneity to alter neuronal responses selectively and dynamically. This suggests that diverse spiral ganglion phenotypes provide a rich substrate to support an almost limitless array of coding strategies within the first neural element of the auditory pathway.

When presented with locally paired dots moving in opposite directions, motion selective neurons in the middle temporal cortex (MT) reduce firing while neurons in V1 are unaffected. This physiological effect is known as motion opponency. The current study used psychophysics to investigate the neural circuit underlying motion opponency. We asked whether opposing motion signals could arrive from different eyes into the receptive field of a binocular neuron while still maintaining motion opponency. We took advantage of prior findings that orientation discrimination of the motion axis (along which paired dots oscillate) is harder when dots move counter-phase than in-phase, an effect associated with motion opponency. We found that such an effect disappeared when paired dots originated from different eyes. This suggests that motion opponency, at some point, involves strictly monocular processing. This does not mean that motion opponency is entirely monocular. Further, we found that the effect of a Glass pattern disappeared under similar viewing conditions, suggesting that Glass pattern perception also involves some strictly monocular processing.

Cone photoreceptors are the first neurons along the visual pathway that exhibit center-surround antagonistic receptive fields, the basic building blocks for spatial information processing in the visual system. The surround responses in cones are mediated by the horizontal cells (HCs) via multiple feedback synaptic mechanisms. It has been controversial on which mechanisms are responsible for the surround-elicited depolarizing responses in cones (ΔVCone(s)), and whether the surround responses of various types of cones are mediated by the same HC feedback mechanisms. In this report, we studied ΔVCone(s)) of four types of cones in the salamander retina, and found that they are mediated by feedback synapses from A-type, B-type or A- and B-type HCs. ΔVCone(s) are observable in the presence of concomitant center light spots, and surround + center light stimuli of various intensity, size and wavelength differentially activate the feedback synapses from A- and B-type HCs to cones. We found that ΔVCone(s) of the L-cones are mediated by both A- and B-type HCs, those of the P- and S-cones by B-type HCs, and those of the A-cones by the A-type HCs. Moreover, our results suggest that B-type HCs mediate ΔVCone(s) through both GABAergic and GluT-ClC feedback synaptic mechanisms, and A-type HCs mediate ΔVCone(s) via the GluT-ClC feedback mechanism. Feedback synaptic mechanisms that increase calcium influx in cone synaptic terminals play important roles in mediating the antagonistic surround responses in the postsynaptic bipolar cells, but they may not generate enough current to depolarize the cones and significantly contribute to ΔVCone(s).

Sensory receptive fields are large enough that they can contain more than one perceptible stimulus. How, then, can the brain encode information abouteachof the stimuli that may be present at a given moment? We recently showed that when more than one stimulus is present, single neurons can fluctuate between coding one vs. the other(s) across some time period, suggesting a form of neural multiplexing of different stimuli (Caruso et al., 2018). Here we investigate (a) whether such coding fluctuations occur in early visual cortical areas; (b) how coding fluctuations are coordinated across the neural population; and (c) how coordinated coding fluctuations depend on the parsing of stimuli into separate vs. fused objects. We found coding fluctuations do occur in macaque V1 but only when the two stimuli form separate objects. Such separate objects evoked a novel pattern of V1 spike count (“noise”) correlations involving distinct distributions of positive and negative values. This bimodal correlation pattern was most pronounced among pairs of neurons showing the strongest evidence for coding fluctuations or multiplexing. Whether a given pair of neurons exhibited positive or negative correlations depended on whether the two neurons both responded better to the same object or had different object preferences. Distinct distributions of spike count correlations based on stimulus preferences were also seen in V4 for separate objects but not when two stimuli fused to form one object. These findings suggest multiple objects evoke different response dynamics than those evoked by single stimuli, lending support to the multiplexing hypothesis and suggesting a means by which information about multiple objects can be preserved despite the apparent coarseness of sensory coding.Significance StatementHow the brain separates information about multiple objects despite overlap in the neurons responsive to each item is not well understood. Here we show that some neurons in V1 exhibit coding fluctuations in response to two objects, and that these coding fluctuations are coordinated at the population level in ways that are not observed for single objects. Broadly similar results were obtained in V4. These response dynamics lend support to the hypothesis that information about individual objects may be multiplexed across the neural population, preserving information about each item despite the coarseness of sensory coding.

Reactivation of earlier perceptual activity is thought to underlie long-term memory recall. Despite evidence for this view, it is unclear whether mnemonic activity exhibits the same tuning properties as feedforward perceptual activity. Here, we leverage population receptive field models to parameterize fMRI activity in human visual cortex during spatial memory retrieval. Though retinotopic organization is present during both perception and memory, large systematic differences in tuning are also evident. Whereas there is a three-fold decline in spatial precision from early to late visual areas during perception, this pattern is not observed during memory retrieval. This difference cannot be explained by reduced signal-to-noise or poor performance on memory trials. Instead, by simulating top-down activity in a network model of cortex, we demonstrate that this property is well explained by the hierarchical structure of the visual system. Together, modeling and empirical results suggest that computational constraints imposed by visual system architecture limit the fidelity of memory reactivation in sensory cortex.

Key points M1 intrinsically photosensitive retinal ganglion cells (ipRGCs) are known to encode absolute light intensity (irradiance) for non-image-forming visual functions (subconscious vision), such as circadian photoentrainment and the pupillary light reflex. It remains unclear how M1 cells respond to relative light intensity (contrast) and patterned visual signals. The present study identified a special form of contrast sensitivity (suppressed-by-contrast) in M1 cells, suggesting a role of patterned visual signals in regulating non-image-forming vision and a potential role of M1 ipRGCs in encoding image-forming visual cues. The study also uncovered a synaptic mechanism and a retinal circuit mediated by vesicular glutamate transporter 3 (vGluT3) amacrine cells that underlie the suppressed-by-contrast response of M1 cells. M1 ipRGC subtypes (M1a and M1b) were revealed that are distinguishable based on synaptic connectivity with vGluT3 amacrine cells, receptive field properties, intrinsic photo sensitivity and membrane excitability, and morphological features, suggesting a division of visual tasks among discrete M1 subpopulations. Abstract The M1 type ipRGC (intrinsically photosensitive retinal ganglion cell) is known to encode ambient light signals for non-image-forming visual functions such as circadian photo-entrainment and the pupillary light reflex. Here, we report that a subpopulation of M1 cells (M1a) in the mouse retina possess the suppressed-by-contrast (sbc) trigger feature that is a receptive field property previously found only in ganglion cells mediating image-forming vision. Using optogenetics and the dual patch clamp technique, we found that vesicular glutamate transporter 3 (vGluT3) (vGluT3) amacrine cells make glycinergic, but not glutamatergic, synapses specifically onto M1a cells. The spatiotemporal and pharmacological properties of visually evoked responses of M1a cells closely matched the receptive field characteristics of vGluT3 cells, suggesting a major role of the vGluT3 amacrine cell input in shaping the sbc trigger feature of M1a cells. We found that the other subpopulation of M1 cells (M1b), which did not receive a direct vGluT3 cell input, lacked the sbc trigger feature, being distinctively different from M1a cells in intrinsic photo responses, membrane excitability, receptive-field characteristics and morphological features. Together, the results reveal a retinal circuit that uses the sbc trigger feature to regulate irradiance coding and potentially send image-forming cues to non-image-forming visual centres in the brain.

Negative afterimages are perceptual phenomena that occur after physical stimuli disappear from sight. Their origin is linked to transient post-stimulus responses of visual neurons. The receptive fields (RFs) of these subcortical ON- and OFF-center neurons exhibit antagonistic interactions between central and surrounding visual space, resulting in selectivity for stimulus polarity and size. These two features are closely intertwined, yet their relationship to negative afterimage perception remains unknown. Here we tested whether size differentially affects the perception of bright and dark negative afterimages in humans of both sexes, and how this correlates with neural mechanisms in subcortical ON and OFF cells. Psychophysically, we found a size-dependent asymmetry whereby dark disks produce stronger and longer-lasting negative afterimages than bright disks of equal contrast at sizes >0.8°. Neurophysiological recordings from retinal and relay cells in female cat dorsal lateral geniculate nucleus showed that subcortical ON cells exhibited stronger sustained post-stimulus responses to dark disks, than OFF cells to bright disks, at sizes >1°. These sizes agree with the emergence of center-surround antagonism, revealing stronger suppression to opposite-polarity stimuli for OFF versus ON cells, particularly in dorsal lateral geniculate nucleus. Using a network-based retino-geniculate model, we confirmed stronger antagonism and temporal transience for OFF-cell post-stimulus rebound responses. A V1 population model demonstrated that both strength and duration asymmetries can be propagated to downstream cortical areas. Our results demonstrate how size-dependent antagonism impacts both the neuronal post-stimulus response and the resulting afterimage percepts, thereby supporting the idea of perceptual RFs reflecting the underlying neuronal RF organization of single cells. SIGNIFICANCE STATEMENT Visual illusions occur when sensory inputs and perceptual outcomes do not match, and provide a valuable tool to understand transformations from neural to perceptual responses. A classic example are negative afterimages that remain visible after a stimulus is removed from view. Such perceptions are linked to responses in early visual neurons, yet the details remain poorly understood. Combining human psychophysics, neurophysiological recordings in cats and retino-thalamo-cortical computational modeling, our study reveals how stimulus size and the receptive-field structure of subcortical ON and OFF cells contributes to the parallel asymmetries between neural and perceptual responses to bright versus dark afterimages. Thus, this work provides a deeper link from the underlying neural mechanisms to the resultant perceptual outcomes.

Gain-control mechanisms adjust neuronal responses to accommodate the wide range of stimulus conditions in the natural environment. Contrast gain control and extraclassical surround suppression are two manifestations of gain control that govern the responses of neurons in the early visual system. Understanding how these two forms of gain control interact has important implications for the detection and discrimination of stimuli across a range of contrast conditions. Here, we report that stimulus contrast affects spatial integration in the lateral geniculate nucleus of alert macaque monkeys (male and female), whereby neurons exhibit a reduction in the strength of extraclassical surround suppression and an expansion in the preferred stimulus size with low-contrast stimuli compared with high-contrast stimuli. Effects were greater for magnocellular neurons than for parvocellular neurons, indicating stream-specific interactions between stimulus contrast and stimulus size. Within the magnocellular pathway, contrast-dependent effects were comparable for ON-center and OFF-center neurons, despite ON neurons having larger receptive fields, less pronounced surround suppression, and more pronounced contrast gain control than OFF neurons. Together, these findings suggest that the parallel streams delivering visual information from retina to primary visual cortex, serve not only to broaden the range of signals delivered to cortex, but also to provide a substrate for differential interactions between stimulus contrast and stimulus size that may serve to improve stimulus detection and stimulus discrimination under pathway-specific lower and higher contrast conditions, respectively. SIGNIFICANCE STATEMENT Stimulus contrast is a salient feature of visual scenes. Here we examine the influence of stimulus contrast on spatial integration in the lateral geniculate nucleus (LGN). Our results demonstrate that increases in contrast generally increase extraclassical suppression and decrease the size of optimal stimuli, indicating a reduction in the extent of visual space from which LGN neurons integrate signals. Differences between magnocellular and parvocellular neurons are noteworthy and further demonstrate that the feedforward parallel pathways to cortex increase the range of information conveyed for downstream cortical processing, a range broadened by diversity in the ON and OFF pathways. These results have important implications for more complex visual processing that underly the detection and discrimination of stimuli under varying natural conditions.

Several neuroimaging studies have shown the somatotopy of body part representations in primary somatosensory cortex (S1), but the functional hierarchy of distinct subregions in human S1 has not been adequately addressed. The current study investigates the functional hierarchy of cyto-architectonically distinct regions, Brodmann areas BA3, BA1, and BA2, in human S1. During functional MRI experiments, we presented participants with vibrotactile stimulation of the fingertips at three different vibration frequencies. Using population Receptive Field (pRF) modeling of the fMRI BOLD activity, we identified the hand region in S1 and the somatotopy of the fingertips. For each voxel, the pRF center indicates the finger that most effectively drives the BOLD signal, and the pRF size measures the spatial somatic pooling of fingertips. We find a systematic relationship of pRF sizes from lower-order areas to higher-order areas. Specifically, we found that pRF sizes are smallest in BA3, increase slightly towards BA1, and are largest in BA2, paralleling the increase in visual receptive field size as one ascends the visual hierarchy. Additionally, we find that the time-to-peak of the hemodynamic response in BA3 is roughly 0.5 s earlier compared to BA1 and BA2, further supporting the notion of a functional hierarchy of subregions in S1. These results were obtained during stimulation of different mechanoreceptors, suggesting that different afferent fibers leading up to S1 feed into the same cortical hierarchy.

Experience-dependent plasticity within visual cortex is controlled by postnatal maturation of inhibitory circuits, which are both morphologically diverse and precisely connected. Gene-targeted disruption of the voltage-dependent potassium channel Kv3.1 broadens action potentials and reduces net inhibitory function of parvalbumin (PV)-positive GABA subtypes within the neocortex. In mice lacking Kv3.1, the rate of input loss from an eye deprived of vision was slowed two-fold, despite otherwise normal critical period timecourse and receptive field properties. Rapid ocular dominance plasticity was restored by local or systemic enhancement of GABAergic transmission with acute benzodiazepine infusion. Diazepam instead exacerbated a global suppression of slow-wave oscillations during sleep described previously in these mutant mice, which therefore did not account for the rescued plasticity. Rapid ocular dominance shifts closely reflected Kv3.1 gene dosage that prevented prolonged spike discharge of their target pyramidal cells in vivo or the spike amplitude decrement of fast-spiking cells during bouts of high-frequency firing in vitro. Late postnatal expression of this unique channel in fast-spiking interneurons thus subtly regulates the speed of critical period plasticity with implications for mental illnesses.

Key points Responses to natural scenes are the business of the retina. We find primate ganglion cell responses to such scenes consistent with those to simpler stimuli. A biophysical model confirmed this and predicted ganglion cell responses with close-to-retinal reliability. Primate ganglion cell responses to natural scenes were driven by temporal variations in color and luminance over the receptive field center caused by eye movements, and little influenced by interaction of center and surround with structure in the scene. We discuss implications in the context of efficient coding of the visual environment. Much information in a higher spatiotemporal frequency band is concentrated in the magnocellular pathway. Abstract Responses of visual neurons to natural scenes provide a link between classical descriptions of receptive field structure and visual perception of the natural environment. A natural scene video with a movement pattern resembling that of primate eye movements was used to evoke responses from macaque ganglion cells. Cell responses were well described through known properties of cell receptive fields. Different analyses converge to show that responses primarily derive from the temporal pattern of stimulation derived from eye movements, rather than spatial receptive field structure beyond center size and position. This was confirmed using a model that predicted ganglion cell responses close to retinal reliability, with only a small contribution of the surround relative to the center. We also found that the spatiotemporal spectrum of the stimulus is modified in ganglion cell responses, and this can reduce redundancy in the retinal signal. This is more pronounced in the magnocellular pathway, which is much better suited to transmit the detailed structure of natural scenes than the parvocellular pathway. Whitening is less important for chromatic channels. Taken together, this shows how a complex interplay across space, time and spectral content sculpts ganglion cell responses. This article is protected by copyright. All rights reserved.

Over the past few years, the various areas that surround the primary visual cortex (V1) in the mouse have been associated with many functions, ranging from higher order visual processing to decision-making. Recently, some studies have shown that higher order visual areas influence the activity of the primary visual cortex, refining its processing capabilities. Here, we studied how in vivo optogenetic inactivation of two higher order visual areas with different functional properties affects responses evoked by moving bars in the primary visual cortex. In contrast with the prevailing view, our results demonstrate that distinct higher order visual areas similarly modulate early visual processing. In particular, these areas enhance stimulus responsiveness in the primary visual cortex, by more strongly amplifying weaker compared with stronger sensory-evoked responses (for instance specifically amplifying responses to stimuli not moving along the direction preferred by individual neurons) and by facilitating responses to stimuli entering the receptive field of single neurons. Such enhancement, however, comes at the expense of orientation and direction selectivity, which increased when the selected higher order visual areas were inactivated. Thus, feedback from higher order visual areas selectively amplifies weak sensory-evoked V1 responses, which may enable more robust processing of visual stimuli.

Significant surround modulation was reported in the cortical areas corresponding to the periphery of the visual field, whereas no clear surround modulation was reported in the center. To understand the neural bases underlying the differences of the functions between the cortical areas corresponding to the center and periphery of the visual field, responses of the cells in the cat early visual cortex with their receptive fields in the center and periphery of the visual field were recorded by using multichannel electrodes, and cross-correlations of the spikes in the responses to the full-field stimuli, and the center-surround stimuli, which contained a grating in a central patch and a surround grating, were analyzed. Percentages of the cell pairs showing significant cross-correlation were larger in the cortical areas corresponding to the periphery than the center. In the center of the visual field, the percentages of the cell pairs showing significant cross-correlation significantly decreased as the separation of the recording points increased, and the time lags of the peaks of the cross-correlogram distributed around zero. In the periphery of the visual field, the time lags of the peaks of the cross-correlogram distributed more widely and increased as the separation of the recording points increased. In the responses to the center-surround stimuli in the preferred orientation of each cell, percentages of the cell pairs showing significant cross-correlation were larger in the periphery than the center. These results suggest that more lateral interactions occur in the cortical areas corresponding to the periphery than the center of the visual field.

Somatotopy is an important guiding principle for sensory fiber organization in the primary somatosensory cortex (S1), which reflects tactile information processing and is associated with disease-related reorganization. However, it is difficult to measure the neuronal encoding scheme in S1 in vivo in normal participants. Here, we investigated the somatotopic map of the undominant hand using a Bayesian population receptive field (pRF) model. The model was established in hand space with between- and within-digit dimensions. In the between-digit dimension, orderly representation was found, which had low variability across participants. The pRF shape tended to be elliptical for digits with high spatial acuity, for which the long axis was along the within-digit dimension. In addition, the pRF width showed different change trends in the 2 dimensions across digits. These results provide new insights into the neural mechanisms in S1, allowing for in-depth investigation of somatosensory information processing and disease-related reorganization.

Fast-adapting type 1 (FA-1) and slowly-adapting type 1 (SA-1) first-order tactile neurons provide detailed spatiotemporal tactile information when we touch objects with fingertips. The distal axon of these neuron types branches in the skin and innervates many receptor organs associated with fingerprint ridges (Meissner corpuscles and Merkel cell neurite complexes, respectively), resulting in heterogeneous receptive fields whose sensitivity topography includes many highly sensitive zones or “subfields.” In experiments on humans of both sexes, using raised dots that tangentially scanned the receptive field we examined the spatial acuity of the subfields of FA-1 and SA-1 neurons and its constancy across scanning speed and direction. We report that the sensitivity of the subfield arrangement for both neuron types on average corresponds to a spatial period of ∼0.4 mm and provide evidence that a subfield's spatial selectivity arises because its associated receptor organ measures mechanical events limited to a single papillary ridge. Accordingly, the sensitivity topography of a neuron's receptive fields is quite stable over repeated mappings and over scanning speeds representative of real-world hand use. The sensitivity topography is substantially conserved also for different scanning directions, but the subfields can be relatively displaced by direction-dependent shear deformations of the skin surface.SIGNIFICANCE STATEMENTThe branching of the distal axon of human first-order tactile neurons with receptor organs associated with fingerprint ridges (Meissner and Merkel end-organs) results in cutaneous receptive fields composed of several distinct subfields spread across multiple ridges. We show that the subfields' spatial selectivity typically corresponds to the dimension of the ridges (∼0.4 mm) and a neuron's subfield layout is well preserved across tangential movement speeds and directions representative of natural use of the fingertips. We submit that the receptor organs underlying subfields essentially measure mechanical events at individual ridges. That neurons receive convergent input from multiple subfields does not preclude the possibility that spatial details can be resolved on the scale of single fingerprint ridges by a population code.

Choosing an action in response to visual cues relies on cognitive processes, such as perception, evaluation, and prediction, which can modulate visual representations even at early processing stages. In the mouse, it is challenging to isolate cognitive modulations of sensory signals because concurrent overt behavior patterns, such as locomotion, can also have brainwide influences. To address this challenge, we designed a task, in which head-fixed mice had to evaluate one of two visual cues. While their global shape signaled the opportunity to earn reward, the cues provided equivalent local stimulation to receptive fields of neurons in primary visual (V1) and anterior cingulate cortex (ACC). We found that mice evaluated these cues within few hundred milliseconds. During this period, ∼30% of V1 neurons became cue-selective, with preferences for either cue being balanced across the recorded population. This selectivity emerged in response to the behavioral demands because the same neurons could not discriminate the cues in sensory control measurements. In ACC, cue evaluation affected a similar fraction of neurons; emerging selectivity, however, was stronger than in V1, and preferences in the recorded population were biased toward the cue promising reward. Such a biased selectivity regime might allow the mouse to infer the promise of reward simply by the overall level of activity. Together, these experiments isolate the impact of task demands on neural responses in mouse cerebral cortex, and document distinct neural signatures of cue evaluation in V1 and ACC.SIGNIFICANCE STATEMENTPerforming a cognitive task, such as evaluating visual cues, not only recruits frontal and parietal brain regions, but also modulates sensory processing stages. We trained mice to evaluate two visual cues, and show that, during this task, ∼30% of neurons recorded in V1 became selective for either cue, although they provided equivalent visual stimulation. We also show that, during cue evaluation, mice frequently move their eyes, even under head fixation, and that ignoring systematic differences in eye position can substantially obscure the modulations seen in V1 neurons. Finally, we document that modulations are stronger in ACC, and biased toward the reward-predicting cue, suggesting a transition in the neural representation of task-relevant information across processing stages in mouse cerebral cortex.

How neurons encode natural stimuli is a fundamental question for sensory neuroscience. In the early visual system, standard encoding models assume that neurons linearly filter incoming stimuli through their receptive fields, but artificial stimuli, such as contrast-reversing gratings, often reveal nonlinear spatial processing. We investigated to what extent such nonlinear processing is relevant for the encoding of natural images in retinal ganglion cells in mice of either sex., How neurons encode natural stimuli is a fundamental question for sensory neuroscience. In the early visual system, standard encoding models assume that neurons linearly filter incoming stimuli through their receptive fields, but artificial stimuli, such as contrast-reversing gratings, often reveal nonlinear spatial processing. We investigated to what extent such nonlinear processing is relevant for the encoding of natural images in retinal ganglion cells in mice of either sex. We found that standard linear receptive field models yielded good predictions of responses to flashed natural images for a subset of cells but failed to capture the spiking activity for many others. Cells with poor model performance displayed pronounced sensitivity to fine spatial contrast and local signal rectification as the dominant nonlinearity. By contrast, sensitivity to high-frequency contrast-reversing gratings, a classical test for nonlinear spatial integration, was not a good predictor of model performance and thus did not capture the variability of nonlinear spatial integration under natural images. In addition, we also observed a class of nonlinear ganglion cells with inverse tuning for spatial contrast, responding more strongly to spatially homogeneous than to spatially structured stimuli. These findings highlight the diversity of receptive field nonlinearities as a crucial component for understanding early sensory encoding in the context of natural stimuli. SIGNIFICANCE STATEMENT Experiments with artificial visual stimuli have revealed that many types of retinal ganglion cells pool spatial input signals nonlinearly. However, it is still unclear how relevant this nonlinear spatial integration is when the input signals are natural images. Here we analyze retinal responses to natural scenes in large populations of mouse ganglion cells. We show that nonlinear spatial integration strongly influences responses to natural images for some ganglion cells, but not for others. Cells with nonlinear spatial integration were sensitive to spatial structure inside their receptive fields, and a small group of cells displayed a surprising sensitivity to spatially homogeneous stimuli. Traditional analyses with contrast-reversing gratings did not predict this variability of nonlinear spatial integration under natural images.

Human functional magnetic resonance imaging (fMRI) and behavioral studies have established the roles of cortical areas along the Sylvian fissure in sensing subjective pain. Yet, little is known about how sensory aspects of painful information are represented and processed by neurons in these regions and how their electrophysiological activities are related to fMRI signals. The current study aims to partially address this critical knowledge gap by performing fMRI-guided microelectrode mapping and recording studies in the homologous region of the parietal operculum in squirrel monkeys under light anesthesia. In each animal studied (n = 8), we detected mesoscale mini-networks for heat nociception in cortical regions around the lateral sulcus. Within the network, we discovered a ∼1.5 × 1.5-mm2-sized cortical patch that solely contained heat nociceptive neurons that aligned with the heat fMRI activation locus. These neurons responded slowly to thermal (heat and cold) nociceptive stimuli exclusively, continued firing for several seconds after the succession of stimulation, and exhibited multidigit receptive fields and high spontaneous firing rates. Similar to the fMRI responses, increasing temperatures in the nociceptive range led to a nonlinear increase in firing rates. The finding of a clustering of heat nociceptive neurons provides novel insights into the unique functional organization of thermal nociception in the S2 subregion of the primate brain. With fMRI, it supports the existence of a modality-preferred heat nociceptive patch that is spatially separated and intermingled with touch patches containing neurons with comparable receptive fields and the presence of functionally distinct mini-networks in primate opercular cortex.

Receptive fields of primary auditory cortex (A1) neurons show excitatory neuronal frequency preference and diverse inhibitory sidebands. While the frequency preferences of excitatory neurons in local A1 areas can be heterogeneous, those of inhibitory neurons are more homogeneous. To date, the diversity and the origin of inhibitory sidebands in local neuronal populations and the relation between local cellular frequency preference and inhibitory sidebands are unknown. To reveal both excitatory and inhibitory subfields, we presented two-tone and pure tone stimuli while imaging excitatory neurons (Thy1) and two types of inhibitory neurons (parvalbumin and somatostatin) in L2/3 of mice A1. We classified neurons into six classes based on frequency response area (FRA) shapes and sideband inhibition depended both on FRA shapes and cell types. Sideband inhibition showed higher local heterogeneity than frequency tuning, suggesting that sideband inhibition originates from diverse sources of local and distant neurons. Two-tone interactions depended on neuron subclasses with excitatory neurons showing the most nonlinearity. Onset and offset neurons showed dissimilar spectral integration, suggesting differing circuits processing sound onset and offset. These results suggest that excitatory neurons integrate complex and nonuniform inhibitory input. Thalamocortical terminals also exhibited sideband inhibition, but with different properties from those of cortical neurons. Thus, some components of sideband inhibition are inherited from thalamocortical inputs and are further modified by converging intracortical circuits. The combined heterogeneity of frequency tuning and diverse sideband inhibition facilitates complex spectral shape encoding and allows for rapid and extensive plasticity.SIGNIFICANCE STATEMENTSensory systems recognize and differentiate between different stimuli through selectivity for different features. Sideband inhibition serves as an important mechanism to sharpen stimulus selectivity, but its cortical mechanisms are not entirely resolved. We imaged pyramidal neurons and two common classes of interneurons suggested to mediate sideband inhibition (parvalbumin and somatostatin positive) in the auditory cortex and inferred their inhibitory sidebands. We observed a higher degree of variability in the inhibitory sideband than in the local frequency tuning, which cannot be predicted from the relative high homogeneity of responses by inhibitory interneurons. This suggests that cortical sideband inhibition is nonuniform and likely results from a complex interplay between existing functional inhibition in the feedforward input and cortical refinement.

The fundamental receptive field (RF) architecture in human visual cortex becomes adult-like by age 5. However, visuo-spatial functions continue to develop until teenage years. This suggests that, despite the early maturation of the RF structure, functional interactions within and across RFs may mature slowly. Here, we used fMRI to investigate functional interactions among multiple stimuli in the visual cortex of school children (ages 8 to 12) in the context of biased competition theory. In the adult visual system, multiple objects presented in the same visual field compete for neural representation. These competitive interactions occur at the level of the RF and are therefore closely linked to the RF architecture. Like in adults, we found suppression of evoked responses in children’s visual cortex when multiple stimuli were presented simultaneously. Such suppression effects were modulated by the spatial distance between the stimuli as a function of RF size across the visual system. Our findings suggest that basic competitive interactions in the visual cortex of children above age 8 operate in an adult-like manner, with subtle differences in early visual areas and area MT. Our study establishes a paradigm and provides baseline data to investigate the neural basis of visuo-spatial processing in typical and atypical development.

The visual evoked potential (VEP) has been shown to reflect the size of the neural population activated by a processing mechanism selective to the temporal - and spatial luminance contrast property of a stimulus. We set out to better understand how the factors determining the neural response associated with these mechanisms. To do so we recorded the VEP from 14 healthy volunteers viewing two series of pattern reversing stimuli with identical temporal-and spatial luminance contrast properties. In one series the size of the elements increased towards the edge of the image, in the other it decreased. In the former element size was congruent with receptive field size across eccentricity, in the later it was incongruent. P100 amplitude to the incongruent series exceeded that obtained to the congruent series. Using electric dipoles due the excitatory neural response we accounted for this using dipole cancellation of electric dipoles of opposite polarity originating in supra- and infragranular layers of V1. The phasic neural response in granular lamina of V1 exhibited magnocellular characteristics, the neural response outside of the granular lamina exhibited parvocellular characteristics and was modulated by re-entrant projections. Using electric current density, we identified areas of the dorsal followed by areas of the ventral stream as the source of the re-entrant signal modulating infragranular activity. Our work demonstrates that the VEP does not signal reflect the overall level of a neural response but is the result of an interaction between electric dipoles originating from neural responses in different lamina of V1.

In 1981, I published a paper in the first issue of theJournal of Neurosciencewith my postdoctoral mentor, Alan Pearlman. It reported a quantitative analysis of the receptive field properties of neurons inreelermouse visual cortex and the surprising conclusion that although the neuronal somas were strikingly malpositioned, their receptive fields were unchanged. This suggested that in mouse cortex at least, neuronal circuits have very robust systems in place to ensure the proper formation of connections. This had the unintended consequence of transforming me from an electrophysiologist into a cellular and molecular neuroscientist who studied cell adhesion molecules and the molecular mechanisms they use to regulate axon growth. It took me a surprisingly long time to appreciate that your science is driven by the people around you and by the technologies that are locally available. As a professional puzzler, I like all different kinds of puzzles, but the most fun puzzles involve playing with other puzzlers. This is my story of learning how to find like-minded puzzlers to solve riddles about axon growth and regeneration.

The physiological characteristics of the marmoset second visual area (V2) are poorly understood compared with those of the primary visual area (V1). In this study, we observed the physiological response characteristics of V2 neurons in four healthy adult marmosets using intracortical tungsten microelectrodes. We recorded 110 neurons in area V2, with receptive fields located between 8° and 15° eccentricity. Most (88.2%) of these neurons were orientation selective, with half-bandwidths typically ranging between 10° and 30°. A significant proportion of neurons (28.2%) with direction selectivity had a direction index greater than 0.5. The vast majority of V2 neurons had separable spatial frequency and temporal frequency curves and, according to this criterion, they were not speed selective. The basic functional response characteristics of neurons in area V2 resemble those found in area V1. Our findings show that area V2 together with V1 are important in primate visual processing, especially in locating objects in space and in detecting an object’s direction of motion. The methods used in this study were approved by the Monash University Animal Ethics Committee, Australia (MARP 2009-2011) in 2009.

OBJECTIVE Retinal prostheses must be able to activate cells in a selective way in order to restore high-fidelity vision. However, inadvertent activation of far-away retinal ganglion cells (RGCs) through electrical stimulation of axon bundles can produce irregular and poorly controlled percepts, limiting artificial vision. In this work, we aim to provide an algorithmic solution to the problem of detecting axon bundle activation with a bi-directional epiretinal prostheses. METHODS The algorithm utilizes electrical recordings to determine the stimulation current amplitudes above which axon bundle activation occurs. Bundle activation is defined as the axonal stimulation of RGCs with unknown soma and receptive field locations, typically beyond the electrode array. The method exploits spatiotemporal characteristics of electrically-evoked spikes to overcome the challenge of detecting small axonal spikes. RESULTS The algorithm was validated using large-scale, single-electrode and short pulse, ex vivo stimulation and recording experiments in macaque retina, by comparing algorithmically and manually identified bundle activation thresholds. For 88% of the electrodes analyzed, the threshold identified by the algorithm was within ±10% of the manually identified threshold, with a correlation coefficient of 0.95. CONCLUSION This works presents a simple, accurate and efficient algorithm to detect axon bundle activation in epiretinal prostheses. SIGNIFICANCE The algorithm could be used in a closed-loop manner by a future epiretinal prosthesis to reduce poorly controlled visual percepts associated with bundle activation. Activation of distant cells via axonal stimulation will likely occur in other types of retinal implants and cortical implants, and the method may therefore be broadly applicable.

To obtain deeper insights into the tactile processing pathway from a population-level point of view, we have modeled three stages of the tactile pathway from the periphery to the cortex in response to indentation and scanned edge stimuli at different orientations. Three stages in the tactile pathway are, (1) the first-order neurons which innervate the cutaneous mechanoreceptors, (2) the cuneate nucleus in the midbrain and (3) the cortical neurons of the somatosensory area. In the proposed network, the first layer mimics the spiking patterns generated by the primary afferents. These afferents have complex skin receptive fields. In the second layer, the role of lateral inhibition on projection neurons in the cuneate nucleus is investigated. The third layer acts as a biomimetic decoder consisting of pyramidal and cortical interneurons that correspond to heterogeneous receptive fields with excitatory and inhibitory sub-regions on the skin. In this way, the activity of pyramidal neurons is tuned to the specific edge orientations. By modifying afferent receptive field size, it is observed that the larger receptive fields convey more information about edge orientation in the first spikes of cortical neurons when edge orientation stimuli move across the patch of skin. In addition, the proposed spiking neural model can detect edge orientation at any location on the simulated mechanoreceptor grid with high accuracy. The results of this research advance our knowledge about tactile information processing and can be employed in prosthetic and bio-robotic applications.

The decrease in response with stimulus repetition is a common property observed in many sensory brain areas. This repetition suppression (RS) is ubiquitous in neurons of macaque inferior temporal (IT) cortex, the end-stage of the ventral visual pathway. The neural mechanisms of RS in IT are still unclear, and one possibility is that it is inherited from areas upstream to IT that show also RS. Since neurons in IT have larger receptive fields compared with earlier visual areas, we examined the inheritance hypothesis by presenting adapter and test stimuli at widely different spatial locations along both vertical and horizontal meridians and across hemifields. RS was present for distances between adapter and test stimuli up to 22° and when the two stimuli were presented in different hemifields. Also, we examined the position tolerance of the stimulus selectivity of adaptation by comparing the responses to a test stimulus following the same (repetition trial) or a different (alternation trial) adapter at a position different from the test stimulus. Stimulus-selective adaptation was still present and consistently stronger in the later phase of the response for distances up to 18°. Finally, we observed stimulus-selective adaptation in repetition trials even without a measurable excitatory response to the adapter stimulus. To accommodate these and previous data, we propose that at least part of the stimulus-selective adaptation in IT is based on short-term plasticity mechanisms within IT and/or reflects top-down activity from areas downstream to IT.

Restoring vision by stimulating the brain Electrical stimulation of the visual cortex has long been proposed as an approach to restoring vision in blind people. Previous studies positioned electrodes on the surface of the brain and thus required delivery of relatively high currents. However, this approach limits the number of electrodes that can be safely stimulated simultaneously, and such surface electrodes activate several millimeters of cortex, which results in a low spatial resolution. Chen et al. demonstrated that the simultaneous stimulation of multiple intracortical electrodes in the monkey primary visual cortex gives rise to the perception of shape and successive stimulation to the perception of motion (see the Perspective by Beauchamp and Yoshor). This major improvement provides proof of concept for the use of electrical microstimulation to create a form of artificial vision in the blind. Science , this issue p. 1191 ; see also p. 1165

Neurons in the visual system can be spatially organized according to their response properties such as receptive field location and feature selectivity. For example, the visual cortex of many mammalian species contains orientation and direction columns where neurons with similar preferences are clustered. Here, we examine whether such a columnar structure exists in the mouse superior colliculus (SC), a prominent visual center for motion processing. By performing large-scale physiological recording and two-photon calcium imaging in adult male and female mice, we show that direction-selective neurons in the mouse SC are not organized into stereotypical columns as a function of their preferred directions, although clusters of similarly tuned neurons are seen in a minority of mice. Nearby neurons can prefer similar or opposite directions in a largely position-independent manner. This finding holds true regardless of animal state (anesthetized vs awake, running vs stationary), SC depth (most superficial lamina vs deeper in the SC), research technique (calcium imaging vs electrophysiology), and stimulus type (drifting gratings vs moving dots, full field vs small patch). Together, these results challenge recent reports of region-specific organizations in the mouse SC and reveal how motion direction is represented in this important visual center.

The activity of motor cortex is necessary for accurate stepping on a complex terrain. How this activity is generated remains unclear. The goal of this study was to clarify the contribution of signals from the ventrolateral thalamus (VL) to formation of locomotion-related activity of motor cortex during vision-independent and vision-dependent locomotion. In two cats, we recorded the activity of neurons in layer V of motor cortex as cats walked on a flat surface and a horizontal ladder. We reversibly inactivated ~10% of the VL unilaterally with the glutamatergic transmission antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and analyzed how this affected the activity of motor cortex neurons. We examined neuronal subpopulations with somatosensory receptive fields on different segments of the forelimb and pyramidal tract projecting neurons (PTNs). We found that the VL contribution to the locomotion-related activity of motor cortex is very powerful and has both excitatory and inhibitory components. The magnitudes of both the excitatory and inhibitory contributions fluctuate over the step cycle and depend on locomotion task. On a flat surface, the VL contributes more excitation to the shoulder- and elbow-related neurons than the wrist/paw-related cells. The VL excites the shoulder-related group the most during the transition from stance to swing phase, while most intensively exciting the elbow-related group during the transition from swing to stance. The VL contributes more excitation for the fast- than slow-conducting PTNs. Upon transition to vision-dependent locomotion on the ladder, the VL contribution increases more for the wrist/paw-related neurons and slow-conducting PTNs. NEW & NOTEWORTHY How the activity of motor cortex is generated and the roles that different inputs to motor cortex play in formation of response properties of motor cortex neurons during movements remain unclear. This is the first study to characterize the contribution of the input from the ventrolateral thalamus (VL), the main subcortical input to motor cortex, to the activity of motor cortex neurons during vision-independent and vision-dependent locomotion.

SummaryReceptive fields (RFs) are a foundational concept in sensory neuroscience. The RF of a sensory neuron is shaped by the properties of its synaptic inputs from connected neurons. In the early visual system, retinotopic maps define a strict relationship between the location of a cell’s dendrites and its RF location in visual space1–3. Retinal ganglion cells (RGCs), the output cells of the retina, form dendritic mosaics that tile retinal space and have corresponding RF mosaics that tile visual space1,2. The precise location of dendrites in some RGCs has been shown to predict their RF shape4. Previously described ON-OFF RGCs have aligned dendrites in ON and OFF synaptic layers, so the cells respond to increments and decrements of light at the same locations in visual space5–8. Here we report a systematic offset between the ON and OFF RFs of an RGC type. Surprisingly, this property does not come from offset ON and OFF dendrites but instead arises from electrical synapses with RGCs of a different type. This circuit represents a new channel for direct communication between ON and OFF RGCs. Using a multi-cell model, we find that offset ON-OFF RFs could improve the precision with which edge location is represented in an RGC population.

Newly synthesized proteins support the development of functional neural circuits and previous work has suggested that dysregulated translation mediates certain forms of autism spectrum disorder (ASD). Here, we investigated the role of Target of Rapamycin Complex 1 (TORC1) in synaptic and dendritic development in vivo in the retinotectal system of Xenopus laevis tadpoles. We found that TORC1 signaling regulates dendritic growth and branching and that acute over-activation of TORC1 by Rheb overexpression drove enhanced maturation of excitatory synapses by recruiting AMPA receptors. Interestingly, TORC1 over-activation did not affect inhibitory transmission, resulting in a significant imbalance in the excitatory-to-inhibitory ratio. Rheb overexpression also enlarged excitatory visual input fields in tectal neurons, consistent with dysregulation of retinotopic input refinement and integration of the cell into the circuit. In contrast to other reports that mainly found impairments in synaptic inhibition using broad systemic deletion or mutation of TORC1 regulatory proteins, our findings from acute, local manipulation of TORC1 reveal its critical role in selectively regulating the number and maturity of excitatory, but not inhibitory, synapses in the developing brain.

Albinism is a congenital disorder where misrouting of the optic nerves at the chiasm gives rise to abnormal visual field representations in occipital cortex. In typical human development, the left occipital cortex receives retinal input predominantly from the right visual field, and vice-versa. In albinism, there is a more complete decussation of optic nerve fibers at the chiasm, resulting in partial representation of the temporal hemiretina (ipsilateral visual field) in the contralateral hemisphere. In this study, we characterize the receptive field properties for these abnormal representations by conducting detailed fMRI population receptive field mapping in a rare subset of participants with albinism and no ocular nystagmus. We find a nasal bias for receptive field positions in the abnormal temporal hemiretina representation. In addition, by modelling responses to bilateral visual field stimulation in the overlap zone, we found evidence in favor of discrete unilateral receptive fields, suggesting a conservative pattern of spatial selectivity in the presence of abnormal retinal input.

The recall of learned temporal sequences by a visual cue is an important form of experience-based neural plasticity. Here we observed such reactivation in awake human visual cortex using intracranial recording. After repeated exposure to a moving dot, a flash of the dot was able to trigger neural reactivation in the downstream receptive field along the motion path. This effect was observed only when the cue appeared near the receptive field. The estimated traveling speed was faster compared to the activation induced by the real motion. We suggest a range-limited, time-compressed reactivation as a result of repeated visual exposure in awake human visual cortex.

Efficiently mapping sensory stimuli onto motor programs is crucial for rapidly choosing appropriate behavioral responses. While neuronal mechanisms underlying simple, one-to-one sensorimotor mapping have been extensively studied, how the brain achieves complex, many-to-one sensorimotor mapping remains unclear. Here, we recorded single neuron activity from the lateral intraparietal (LIP) cortex of monkeys trained to map multiple spatial positions of visual cue onto two opposite saccades. We found that LIP neurons’ activity was consistent with directly mapping multiple cue positions to the associated saccadic direction (SDir) regardless of whether the visual cue appeared in or outside neurons’ receptive fields. Unlike the explicit encoding of the visual categories, such cue–target mapping (CTM)–related activity covaried with the associated SDirs. Furthermore, the CTM was preferentially mediated by visual neurons identified by memory-guided saccade. These results indicate that LIP plays a crucial role in the early stage of many-to-one sensorimotor transformation.

By using the multi-electrode array (MEA) recording technique in conjunction with white-noise checkerboard stimuli and reverse correlation methods, we studied modulatory actions of glycinergic and GABAergic interneurons on spatiotemporal profiles of ganglion cells (GCs) in dark-adapted mouse retinas. We found that application of 2 µM strychnine decreased receptive field center radii of GCs by a mean value of 11%, and shifted the GC receptive field (RF) centers by a mean distance of 28.3 µm. On the other hand, 200 µM picrotoxin + 100 µM bicuculline + 50 µM TPMPA increased GC receptive field center radii by a mean value of 19%, and shifted the GC RF centers by a mean distance of 53.7 µm. Glycinergic neurons in the mouse retina are narrow-field amacrine cells that have been shown to mediate ON-OFF crossover inhibitory synapses within the RGs’ RF center, therefore they may increase the size and shift the location of GC RF center by synergistic addition to bipolar cell inputs to GCs. GABAergic neurons are wide-field amacrine cells and horizontal cells that are known to mediate antagonistic surround responses of GCs, and thus they decrease the GCs’ RF center size. Our results suggest that a major global function of glycinergic and GABAergic interneurons in the mammalian retina is to provide the flexibility for adjusting the size and location of GCs’ RF centers. The apparent shifts of GC RF centers suggest that the synergistic addition by GlyACs and the surround inhibition by GABAergic interneurons are not spatially symmetrical within GC RFs.

Amacrine cells are a diverse population of interneurons in the retina that play a critical role in extracting complex features of the visual world and shaping the receptive fields of retinal output neurons (ganglion cells). While much of the computational power of amacrine cells is believed to arise from the immense mutual interactions among amacrine cells themselves, the intricate circuitry and functions of amacrine–amacrine interactions are poorly understood in general. Here we report a specific interamacrine pathway from a small-field, glutamate–glycine dual-transmitter amacrine cell (vGluT3) to a wide-field polyaxonal amacrine cell (PAS4/5). Distal tips of vGluT3 cell dendrites made selective glycinergic (but not glutamatergic) synapses onto PAS4/5 dendrites to provide a center-inhibitory, surround-disinhibitory drive that helps PAS4/5 cells build a suppressed-by-contrast (sbc) receptive field, which is a unique and fundamental trigger feature previously found only in a small population of ganglion cells. The finding of this trigger feature in a circuit upstream to ganglion cells suggests that the sbc form of visual computation occurs more widely in the retina than previously believed and shapes visual processing in multiple downstream circuits in multiple ways. We also identified two different subpopulations of PAS4/5 cells based on their differential connectivity with vGluT3 cells and their distinct receptive-field and luminance-encoding characteristics. Moreover, our results revealed a form of crosstalk between small-field and large-field amacrine cell circuits, which provides a mechanism for feature-specific local (1 mm) retinal activity.

Neural computation relies on the integration of synaptic inputs across a neuron’s dendritic arbour. However, it is far from understood how different cell types tune this process to establish cell-type specific computations. Here, using two-photon imaging of dendritic Ca2+ signals, electrical recordings of somatic voltage and biophysical modelling, we demonstrate that four morphologically distinct types of mouse retinal ganglion cells with overlapping excitatory synaptic input (transient Off alpha, transient Off mini, sustained Off, and F-mini Off) exhibit type-specific dendritic integration profiles: in contrast to the other types, dendrites of transient Off alpha cells were spatially independent, with little receptive field overlap. The temporal correlation of dendritic signals varied also extensively, with the highest and lowest correlation in transient Off mini and transient Off alpha cells, respectively. We show that differences between cell types can likely be explained by differences in backpropagation efficiency, arising from the specific combinations of dendritic morphology and ion channel densities., Neurons compute by integrating synaptic inputs across their dendritic arbor. Here, the authors show that distinct cell-types of mouse retinal ganglion cells that receive similar excitatory inputs have different biophysical mechanisms of input integration to generate their unique response tuning.

The detection and segmentation of meaningful figures from their background is a core function of vision. While work in non-human primates has implicated early visual mechanisms in this figure-ground modulation, neuroimaging in humans has instead largely ascribed the processing of figures and objects to higher stages of the visual hierarchy. Here, we used high-field fMRI at 7Tesla to measure BOLD responses to task-irrelevant orientation-defined figures in human early visual cortex, and employed a novel population receptive field (pRF) mapping-based approach to resolve the spatial profiles of two constituent mechanisms of figure-ground modulation: a local boundary response, and a further enhancement spanning the full extent of the figure region that is driven by global differences in features. Reconstructing the distinct spatial profiles of these effects reveals that figure enhancement modulates responses in human early visual cortex in a manner consistent with a mechanism of automatic, contextually-driven feedback from higher visual areas.Significance StatementA core function of the visual system is to parse complex 2D input into meaningful figures. We do so constantly and seamlessly, both by processing information about visible edges and by analyzing large-scale differences between figures and background. While influential neurophysiology work has characterized an intriguing mechanism that enhances V1 responses to perceptual figures, we have a poor understanding of how the early visual system contributes to figure-ground processing in humans. Here, we use advanced computational analysis methods and high-field human fMRI data to resolve the distinct spatial profiles of local edge and global figure enhancement in the early visual system (V1 and LGN); the latter is distinct and consistent a mechanism of automatic, stimulus-driven feedback from higher-level visual areas.