Corticothalamic feedback and sensory processing

Although nearly half of the synaptic input to neurons in the dorsal thalamus comes from the cerebral cortex, the role of corticothalamic projections in sensory processing remains elusive. Although sensory afferents certainly establish the basic receptive field properties of thalamic neurons, increasing evidence indicates that feedback from the cortex plays a crucial role in shaping thalamic responses. Here, we review recent work on the corticothalamic pathways associated with the visual, auditory, and somatosensory systems. Collectively, these studies demonstrate that sensory responses of thalamic neurons result from dynamic interactions between feedforward and feedback pathways.     

Corticothalamic interactions in the transfer of visual information

Thalamic function does not stand apart, as a discrete processing step, from the cortical circuitry. The thalamus receives extensive feedback from the cortex and this influences the firing pattern, synchronization and sensory response mode of relay cells. A crucial question concerns the extent to which the feedback simply controls the state and transmission mode of relay cells and the extent to which the feedback participates in the specific processing of sensory information. Using examples from experiments examining the influence of feedback from the visual cortex to the lateral geniculate nucleus (LGN), we argue that thalamic mechanisms are selectively focused by visually driven feedback to optimize the thalamic contribution to segmentation and global integration. This involves effects on both the temporal and spatial parameters characterizing the responses of LGN cells and includes, for example, motion-driven feedback effects from MT (middle temporal visual area) relayed via layer 6 of V1 (primary visual cortex).     

Learning to link visual contours

In complex visual scenes, linking related contour elements is important for object recognition. This process, thought to be stimulus driven and hard wired, has substrates in primary visual cortex (V1). Here, however, we find contour integration in V1 to depend strongly on perceptual learning and top-down influences that are specific to contour detection. In naive monkeys, the information about contours embedded in complex backgrounds is absent in V1 neuronal responses and is independent of the locus of spatial attention. Training animals to find embedded contours induces strong contour-related responses specific to the trained retinotopic region. These responses are most robust when animals perform the contour detection task but disappear under anesthesia. Our findings suggest that top-down influences dynamically adapt neural circuits according to specific perceptual tasks. This may serve as a general neuronal mechanism of perceptual learning and reflect top-down mediated changes in cortical states.     

Reciprocal inhibition and slow calcium decay in perigeniculate interneurons explain changes of spontaneous firing of thalamic cells caused by cortical inactivation

The role of cortical feedback in the thalamocortical processing loop has been extensively investigated over the last decades. With an exception of several cases, these searches focused on the cortical feedback exerted onto thalamo-cortical relay (TC) cells of the dorsal lateral geniculate nucleus (LGN). In a previous, physiological study, we showed in the cat visual system that cessation of cortical input, despite decrease of spontaneous activity of TC cells, increased spontaneous firing of their recurrent inhibitory interneurons located in the perigeniculate nucleus (PGN). To identify mechanisms underlying such functional changes we conducted a modeling study in NEURON on several networks of point neurons with varied model parameters, such as membrane properties, synaptic weights and axonal delays. We considered six network topologies of the retino-geniculo-cortical system. All models were robust against changes of axonal delays except for the delay between the LGN feed-forward interneuron and the TC cell. The best representation of physiological results was obtained with models containing reciprocally connected PGN cells driven by the cortex and with relatively slow decay of intracellular calcium. This strongly indicates that the thalamic reticular nucleus plays an essential role in the cortical influence over thalamo-cortical relay cells while the thalamic feed-forward interneurons are not essential in this process. Further, we suggest that the dependence of the activity of PGN cells on the rate of calcium removal can be one of the key factors determining individual cell response to elimination of cortical input.     

Development of spatial coarse-to-fine processing in the visual pathway

The sequential analysis of information in a coarse-to-fine manner is a fundamental mode of processing in the visual pathway. Spatial frequency (SF) tuning, arguably the most fundamental feature of spatial vision, provides particular intuition within the coarse-to-fine framework: low spatial frequencies convey global information about an image (e.g., general orientation), while high spatial frequencies carry more detailed information (e.g., edges). In this paper, we study the development of cortical spatial frequency tuning. As feedforward input from the lateral geniculate nucleus (LGN) has been shown to have significant influence on cortical coarse-to-fine processing, we present a firing-rate based thalamocortical model which includes both feedforward and feedback components. We analyze the relationship between various model parameters (including cortical feedback strength) and responses. We confirm the importance of the antagonistic relationship between the center and surround responses in thalamic relay cell receptive fields (RFs), and further characterize how specific structural LGN RF parameters affect cortical coarse-to-fine processing. Our results also indicate that the effect of cortical feedback on spatial frequency tuning is age-dependent: in particular, cortical feedback more strongly affects coarse-to-fine processing in kittens than in adults. We use our results to propose an experimentally testable hypothesis for the function of the extensive feedback in the corticothalamic circuit.     

Sound-driven synaptic inhibition in primary visual cortex

Multimodal objects and events activate many sensory cortical areas simultaneously. This is possibly reflected in reciprocal modulations of neuronal activity, even at the level of primary cortical areas. However, the synaptic character of these interareal interactions, and their impact on synaptic and behavioral sensory responses are unclear. Here, we found that activation of auditory cortex by a noise burst drove local GABAergic inhibition on supragranular pyramids of the mouse primary visual cortex, via cortico-cortical connections. This inhibition was generated by sound-driven excitation of a limited number of cells in infragranular visual cortical neurons. Consequently, visually driven synaptic and spike responses were reduced upon bimodal stimulation. Also, acoustic stimulation suppressed conditioned behavioral responses to a dim flash, an effect that was prevented by acute blockade of GABAergic transmission in visual cortex. Thus, auditory cortex activation by salient stimuli degrades potentially distracting sensory processing in visual cortex by recruiting local, translaminar, inhibitory circuits.     

Intracellular and computational evidence for a dominant role of internal network activity in cortical computations

The mammalian cerebral cortex is characterized by intense spontaneous activity, depending on brain region, age, and behavioral state. Classically, the cortex is considered as being driven by the senses, a paradigm which corresponds well to experiments in quiescent or deeply anesthetized states. In awake animals, however, the spontaneous activity cannot be considered as 'background noise', but is of comparable-or even higher-amplitude than evoked sensory responses. Recent evidence suggests that this internal activity is not only dominant, but also it shares many properties with the responses to natural sensory inputs, suggesting that the spontaneous activity is not independent of the sensory input. Such evidence is reviewed here, with an emphasis on intracellular and computational aspects. Statistical measures, such as the spike-triggered average of synaptic conductances, show that the impact of internal network state on spiking activity is major in awake animals. Thus, cortical activity cannot be considered as being driven by the senses, but sensory inputs rather seem to modulate and modify the internal dynamics of cerebral cortex. This view offers an attractive interpretation not only of dreaming activity (absence of sensory input), but also of several mental disorders.     

Experience-driven axon retraction without binocular imbalance in developing visual cortex

Refinement of the neural circuit during brain maturation is regulated by experience-driven neural activity. In the mammalian visual cortex, monocular visual deprivation (MD) in the early postnatal life causes a significant loss of cortical responses to a deprived eye and the retraction of input axons serving the deprived eye. A competitive interaction between inputs serving both eyes has been supposed to underlie the effects of MD because the loss of cortical response is much weaker when both eyes are deprived of vision. Also, the input axons do not retract after binocular deprivation. Here, we report that uncorrelated activity between presynaptic and postsynaptic neurons can solely lead to the retraction of geniculocortical axons in the absence of activity imbalance between two inputs. We analyzed the morphology of geniculocortical axons in a pharmacologically inhibited visual cortex of animals with normal vision and of binocularly deprived animals. In the normal vision animals, the axonal arbors in the inhibited cortex showed robust retraction. On the other hand, the arbors in binocularly deprived animals remained mostly intact. These results suggest that a homosynaptic associative mechanism, rather than a heterosynaptic competition between inputs, may play an important role in experience-driven axon retraction.     

Optogenetic Stimulation of the Corticothalamic Pathway Affects Relay Cells and GABAergic Neurons Differently in the Mouse Visual Thalamus

The dorsal lateral geniculate nucleus (dLGN) serves as the primary conduit of retinal information to visual cortex. In addition to retinal input, dLGN receives a large feedback projection from layer VI of visual cortex. Such input modulates thalamic signal transmission in different ways that range from gain control to synchronizing network activity in a stimulus-specific manner. However, the mechanisms underlying such modulation have been difficult to study, in part because of the complex circuitry and diverse cell types this pathway innervates. To address this and overcome some of the technical limitations inherent in studying the corticothalamic (CT) pathway, we adopted a slice preparation in which we were able to stimulate CT terminal arbors in the visual thalamus of the mouse with blue light by using an adeno-associated virus to express the light-gated ion channel, ChIEF, in layer VI neurons. To examine the postsynaptic responses evoked by repetitive CT stimulation, we recorded from identified relay cells in dLGN, as well as GFP expressing GABAergic neurons in the thalamic reticular nucleus (TRN) and intrinsic interneurons of dLGN. Relay neurons exhibited large glutamatergic responses that continued to increase in amplitude with each successive stimulus pulse. While excitatory responses were apparent at postnatal day 10, the strong facilitation noted in adult was not observed until postnatal day 21. GABAergic neurons in TRN exhibited large initial excitatory responses that quickly plateaued during repetitive stimulation, indicating that the degree of facilitation was much larger for relay cells than for TRN neurons. The responses of intrinsic interneurons were smaller and took the form of a slow depolarization. These differences in the pattern of excitation for different thalamic cell types should help provide a framework for understanding how CT feedback alters the activity of visual thalamic circuitry during sensory processing as well as different behavioral or pathophysiological states.     

纹外皮层PMLS区反馈投射对初级视皮层神经元反应特性的影响

神经系统中存在大量下行投射,与上行输入一起形成复杂的前馈与反馈回路,调控神经信号的传导和处理,但目前对皮层内反馈投射的功能作用认识还比较薄弱.通过微量注射抑制性神经递质γ-氨基丁酸(γ-aminobutyric acid,GABA),使猫纹外皮层后内侧外上雪氏区(area posteromedial lateral suprasylvian,PMLS)局部可逆性失活,使用胞外记录方法,研究初级视皮层17区神经元反应特性的变化.实验结果显示,PMLS区失活后,17区细胞对运动刺激的反应总体减弱,反应的相对稳定性基本不变,最高发放率/自发之比有所下降.与此同时,细胞的方向选择性指数减小,朝向选择性无显著变化.除少数"双向"反应细胞外,绝大部分细胞的最优方向基本不变.进一步分析发现,细胞对各个方向刺激的反应普遍下降,最优方向上的下降程度最大,是导致方向选择性减弱的主要原因.这些结果表明,PMLS区反馈投射可增强初级视皮层的方向选择性,而对朝向选择性影响有限.这一作用特点体现了PMLS区在皮层中偏重处理运动视觉信息的功能.     

Mouse visual cortex

Neurons in mouse visual cortex have diverse receptive field properties and they respond selectively to specific features of visual stimuli. Owing to the lateral position of the eyes, only about a third of the visual cortex receives input from both eyes, but many cells in this region are binocular. Similar to higher mammals, closing one eye during a critical period shifts the responses of cells, such that they are better driven by the non-deprived eye. In this review I illustrate how the combination of transgenic mouse technology with single cell recording and modern imaging techniques might lead to a further understanding of the mechanisms that underlie the development, plasticity, and function of the mammalian visual cortex.     

Parvalbumin-expressing interneurons linearly transform cortical responses to visual stimuli

The response of cortical neurons to a sensory stimulus is shaped by the network in which they are embedded. Here we establish a role of parvalbumin (PV)-expressing cells, a large class of inhibitory neurons that target the soma and perisomatic compartments of pyramidal cells, in controlling cortical responses. By bidirectionally manipulating PV cell activity in visual cortex we show that these neurons strongly modulate layer 2/3 pyramidal cell spiking responses to visual stimuli while only modestly affecting their tuning properties. PV cells' impact on pyramidal cells is captured by a linear transformation, both additive and multiplicative, with a threshold. These results indicate that PV cells are ideally suited to modulate cortical gain and establish a causal relationship between a select neuron type and specific computations performed by the cortex during sensory processing.     

Processing in layer 4 of the neocortical circuit: new insights from visual and somatosensory cortex

Recent experimental and theoretical results in cat primary visual cortex and in the whisker-barrel fields of rodent primary somatosensory cortex suggest common organizing principles for layer 4, the primary recipient of sensory input from the thalamus. Response tuning of layer 4 cells is largely determined by a local interplay of feed-forward excitation (directly from the thalamus) and inhibition (from layer 4 inhibitory interneurons driven by the thalamus). Feed-forward inhibition dominates excitation, inherits its tuning from the thalamic input, and sharpens the tuning of excitatory cells. Recurrent excitation enhances responses to effective stimuli.     

Emergent dynamics in a model of visual cortex

This paper proposes that the network dynamics of the mammalian visual cortex are highly structured and strongly shaped by temporally localized barrages of excitatory and inhibitory firing we call ‘multiple-firing events’ (MFEs). Our proposal is based on careful study of a network of spiking neurons built to reflect the coarse physiology of a small patch of layer 2/3 of V1. When appropriately benchmarked this network is capable of reproducing the qualitative features of a range of phenomena observed in the real visual cortex, including spontaneous background patterns, orientation-specific responses, surround suppression and gamma-band oscillations. Detailed investigation into the relevant regimes reveals causal relationships among dynamical events driven by a strong competition between the excitatory and inhibitory populations. It suggests that along with firing rates, MFE characteristics can be a powerful signature of a regime. Testable predictions based on model observations and dynamical analysis are proposed.     

Predictability of visual perturbation during locomotion: implications for corrective efference copy signaling

In guiding adaptive behavior, efference copy signals or corollary discharge are traditionally considered to serve as predictors of self-generated sensory inputs and by interfering with their central processing are able to counter unwanted consequences of an animal??s own actions. Here, in a speculative reflection on this issue, we consider a different functional role for such intrinsic predictive signaling, namely in stabilizing gaze during locomotion where resultant changes in head orientation in space require online compensatory eye movements in order to prevent retinal image slip. The direct activation of extraocular motoneurons by locomotor-related efference copies offers a prospective substrate for assisting self-motion derived sensory feedback, rather than being subtracted from the sensory signal to eliminate unwanted reafferent information. However, implementing such a feed-forward mechanism would be critically dependent on an appropriate phase coupling between rhythmic propulsive movement and resultant head/visual image displacement. We used video analyzes of actual locomotor behavior and basic theoretical modeling to evaluate head motion during stable locomotion in animals as diverse as Xenopus laevis tadpoles, teleost fish and horses in order to assess the potential suitability of spinal efference copies to the stabilization of gaze during locomotion. In all three species, and therefore regardless of aquatic or terrestrial environment, the head displacements that accompanied locomotor action displayed a strong correlative spatio-temporal relationship in correspondence with a potential predictive value for compensatory eye adjustments. Although spinal central pattern generator-derived efference copies offer appropriately timed commands for extraocular motor control during self-generated motion, it is likely that precise image stabilization requires the additional contributions of sensory feedback signals. Nonetheless, the predictability of the visual consequences of stereotyped locomotion renders intrinsic efference copy signaling an appealing mechanism for offsetting these disturbances, thus questioning the exclusive role traditionally ascribed to sensory-motor transformations in stabilizing gaze during vertebrate locomotion.     

Effect of inhibitory feedback on correlated firing of spiking neural network

Understanding the properties and mechanisms that generate different forms of correlation is critical for determining their role in cortical processing. Researches on retina, visual cortex, sensory cortex, and computational model have suggested that fast correlation with high temporal precision appears consistent with common input, and correlation on a slow time scale likely involves feedback. Based on feedback spiking neural network model, we investigate the role of inhibitory feedback in shaping correlations on a time scale of 100 ms. Notably, the relationship between the correlation coefficient and inhibitory feedback strength is non-monotonic. Further, computational simulations show how firing rate and oscillatory activity form the basis of the mechanisms underlying this relationship. When the mean firing rate holds unvaried, the correlation coefficient increases monotonically with inhibitory feedback, but the correlation coefficient keeps decreasing when the network has no oscillatory activity. Our findings reveal that two opposing effects of the inhibitory feedback on the firing activity of the network contribute to the non-monotonic relationship between the correlation coefficient and the strength of the inhibitory feedback. The inhibitory feedback affects the correlated firing activity by modulating the intensity and regularity of the spike trains. Finally, the non-monotonic relationship is replicated with varying transmission delay and different spatial network structure, demonstrating the universality of the results.     

Effects of cholinergic enhancement on visual stimulation, spatial attention, and spatial working memory

We compared behavioral and neural effects of cholinergic enhancement between spatial attention, spatial working memory (WM), and visual control tasks, using fMRI and the anticholinesterase physostigmine. Physostigmine speeded responses nonselectively but increased accuracy selectively for attention. Physostigmine also decreased activations to visual stimulation across all tasks within primary visual cortex, increased extrastriate occipital cortex activation selectively during maintained attention and WM encoding, and decreased parietal activation selectively during maintained attention. Finally, lateralization of occipital activation as a function of the visual hemifield toward which attention or memory was directed was decreased under physostigmine. In the case of attention, this effect correlated strongly with a decrease in a behavioral measure of selective spatial processing. Our results suggest that, while cholinergic enhancement facilitates visual attention by increasing activity in extrastriate cortex generally, it accomplishes this in a manner that reduces expectation-driven selective biasing of extrastriate cortex.     

A sparse object coding scheme in area V4

Sparse coding has long been recognized as a primary goal of image transformation in the visual system. Sparse coding in early visual cortex is achieved by abstracting local oriented spatial frequencies and by excitatory/inhibitory surround modulation. Object responses are thought to be sparse at subsequent processing stages, but neural mechanisms for higher-level sparsification are not known. Here, convergent results from macaque area V4 neural recording and simulated V4 populations trained on natural object contours suggest that sparse coding is achieved in midlevel visual cortex by emphasizing representation of acute convex and concave curvature. We studied 165 V4 neurons with a random, adaptive stimulus strategy to minimize bias and explore an unlimited range of contour shapes. V4 responses were strongly weighted toward contours containing acute convex or concave curvature. In contrast, the tuning distribution in nonsparse simulated V4 populations was strongly weighted toward low curvature. But as sparseness constraints increased, the simulated tuning distribution shifted progressively toward more acute convex and concave curvature, matching the neural recording results. These findings indicate a sparse object coding scheme in midlevel visual cortex based on uncommon but diagnostic regions of acute contour curvature.     

Simulating Spinal Border Cells and Cerebellar Granule Cells under Locomotion – A Case Study of Spinocerebellar Information Processing

The spinocerebellar systems are essential for the brain in the performance of coordinated movements, but our knowledge about the spinocerebellar interactions is very limited. Recently, several crucial pieces of information have been acquired for the spinal border cell (SBC) component of the ventral spinocerebellar tract (VSCT), as well as the effects of SBC mossy fiber activation in granule cells of the cerebellar cortex. SBCs receive monosynaptic input from the reticulospinal tract (RST), which is an important driving system under locomotion, and disynaptic inhibition from Ib muscle afferents. The patterns of activity of RST neurons and Ib afferents under locomotion are known. The activity of VSCT neurons under fictive locomotion, i.e. without sensory feedback, is also known, but there is little information on how these neurons behave under actual locomotion and for cerebellar granule cells receiving SBC input this is completely unknown. But the available information makes it possible to simulate the interactions between the spinal and cerebellar neuronal circuitries with a relatively large set of biological constraints. Using a model of the various neuronal elements and the network they compose, we simulated the modulation of the SBCs and their target granule cells under locomotion and hence generated testable predictions of their general pattern of modulation under this condition. This particular system offers a unique opportunity to simulate these interactions with a limited number of assumptions, which helps making the model biologically plausible. Similar principles of information processing may be expected to apply to all spinocerebellar systems.     

Feedback contributions to visual awareness in human occipital cortex

It has traditionally been assumed that processing within the visual system proceeds in a bottom-up, feedforward manner from retina to higher cortical areas. In addition to feedforward processing, it is now clear that there are also important contributions to sensory encoding that rely upon top-down, feedback (reentrant) projections from higher visual areas to lower ones. By utilizing transcranial magnetic stimulation (TMS) in a metacontrast masking paradigm, we addressed whether feedback processes in early visual cortex play a role in visual awareness. We show that TMS of visual cortex, when timed to produce visual suppression of an annulus serving as a metacontrast mask, induces recovery of an otherwise imperceptible disk. In addition to producing disk recovery, TMS suppression of an annulus was greater when a disk preceded it than when an annulus was presented alone. This latter result suggests that there are effects of the disk on the perceptibility of the subsequent mask that are additive and are revealed with TMS of the visual cortex. These results demonstrate spatial and temporal interactions of conscious vision in visual cortex and suggest that a prior visual stimulus can influence subsequent perception at early stages of visual encoding via feedback projections.