Excitotoxic lesions of the superior colliculus preferentially impact multisensory neurons and multisensory integration

The superior colliculus (SC) plays an important role in integrating visual, auditory and somatosensory information, and in guiding the orientation of the eyes, ears and head. Previously we have shown that cats with unilateral SC lesions showed a preferential loss of multisensory orientation behaviors for stimuli contralateral to the lesion. Surprisingly, this behavioral loss was seen even under circumstances where the SC lesion was far from complete. To assess the physiological changes induced by these lesions, we employed single unit electrophysiological methods to record from individual neurons in both the intact and damaged SC following behavioral testing in two animals. In the damaged SC of these animals, multisensory neurons were preferentially reduced in incidence, comprising less than 25% of the sensory-responsive population (as compared with 49% on the control side). In those multisensory neurons that remained following the lesion, receptive fields were nearly twofold larger, and less than 25% showed normal patterns of multisensory integration, with those that did being found in areas outside of the lesion. These results strongly suggest that the multisensory behavioral deficits seen following SC lesions are the combined result of a loss of multisensory neurons and a loss of multisensory integration in those neurons that remain.     

Neonatal cortical ablation disrupts multisensory development in superior colliculus

The ability of cat superior colliculus (SC) neurons to synthesize information from different senses depends on influences from two areas of the cortex: the anterior ectosylvian sulcus (AES) and the rostral lateral suprasylvian sulcus (rLS). Reversibly deactivating the inputs to the SC from either of these areas in normal adults severely compromises this ability and the SC-mediated behaviors that depend on it. In this study, we found that removal of these areas in neonatal animals precluded the normal development of multisensory SC processes. At maturity there was a substantial decrease in the incidence of multisensory neurons, and those multisensory neurons that did develop were highly abnormal. Their cross-modal receptive field register was severely compromised, as was their ability to integrate cross-modal stimuli. Apparently, despite the impressive plasticity of the neonatal brain, it cannot compensate for the early loss of these cortices. Surprisingly, however, neonatal removal of either AES or rLS had comparatively minor consequences on these properties. At maturity multisensory SC neurons were quite common: they developed the characteristic spatial register among their unisensory receptive fields and exhibited normal adult-like multisensory integration. These observations suggest that during early ontogeny, when the multisensory properties of SC neurons are being crafted, AES and rLS may have the ability to compensate for the loss of one another's cortico-collicular influences so that normal multisensory processes can develop in the SC.     

The frontal eye fields target multisensory neurons in cat superior colliculus

While sensory corticotectal connections have received considerable attention, relatively little is known about the nature of superior colliculus neurons that receive input from the cortical frontal eye fields. The present experiments used microstimulation of indwelling electrodes in the frontal eye fields and single-unit recording in the superior colliculus to demonstrate that frontal afferents preferentially terminate on multisensory neurons in the colliculus. Furthermore, the medial and lateral subdivisions of the cat frontal eye fields access physiologically distinct populations of multisensory collicular neurons. Specifically, the medial subdivision preferentially activates neurons with visual and auditory sensory responses located medial within the colliculus, while the lateral subdivision preferentially activates collicular neurons with visual and somatosensory responses found more laterally. These data support reports distinguishing the medial and lateral subdivisions of the frontal eye fields in the cat and suggest that signals from each may route separately through the colliculus to induce or coordinate different components of gaze control. Received: 17 November 1998 / Accepted: 04 May 1999     

Cortex controls multisensory depression in superior colliculus

Multisensory depression is a fundamental index of multisensory integration in superior colliculus (SC) neurons. It is initiated when one sensory stimulus (auditory) located outside its modality-specific receptive field degrades or eliminates the neuron's responses to another sensory stimulus (visual) presented within its modality-specific receptive field. The present experiments demonstrate that the capacity of SC neurons to engage in multisensory depression is strongly dependent on influences from two cortical areas (the anterior ectosylvian and rostral lateral suprasylvian sulci). When these cortices are deactivated, the ability of SC neurons to synthesize visual-auditory inputs in this way is compromised; multisensory responses are disinhibited, becoming more vigorous and in some cases indistinguishable from responses to the visual stimulus alone. Although obtaining a more robust multisensory SC response when cortex is nonfunctional than when it is functional may seem paradoxical, these data may help explain previous observations that the loss of these cortical influences permits visual orientation behavior in the presence of a normally disruptive auditory stimulus.     

Distribution across cortical areas of neurons projecting to the superior colliculus in new world monkeys

Surprisingly little is known about the proportions of projections of different areas and regions of neocortex to the superior colliculus in primates. To obtain an overview of such projection patterns, we placed a total of 10 injections of retrograde tracers in the superior colliculus of three New World monkeys (Callithrix, Callicebus, and Aotus). Because cortex was flattened and cut parallel to the surface, labeled corticotectal neurons could be accurately located relative to architectonic boundaries and surface features. While there was variability across cases and injection sites, the summed results clearly support several conclusions. One, three well-defined visual areas, V1 (18%), V2 (14%), and MT (11%), contributed nearly half of the total of labeled cells. Two, several other visual areas (V3, DL, DM, and FST) that are early in the processing hierarchy provided another fifth of the total. Three, inferior temporal visual areas of the ventral stream provided only minor projections. Four, visuomotor fields (FEF, FV, cortex in the region of SEF, and posterior parietal cortex) contained less than 10% of the labeled neurons. Five, few labeled neurons were in auditory or somatosensory areas. The results indicate that cortical inputs to the superior colliculus originate predominantly from early visual areas rather than from multimodal or visuomotor areas.     

Superior colliculus neurons use distinct operational modes in the integration of multisensory stimuli

Many neurons in the superior colliculus (SC) integrate sensory information from multiple modalities, giving rise to significant response enhancements. Although enhanced multisensory responses have been shown to depend on the spatial and temporal relationships of the stimuli as well as on their relative effectiveness, these factors alone do not appear sufficient to account for the substantial heterogeneity in the magnitude of the multisensory products that have been observed. Toward this end, the present experiments have revealed that there are substantial differences in the operations used by different multisensory SC neurons to integrate their cross-modal inputs, suggesting that intrinsic differences in these neurons may also play an important deterministic role in multisensory integration. In addition, the integrative operation employed by a given neuron was found to be well correlated with the neuron's dynamic range. In total, four categories of SC neurons were identified based on how their multisensory responses changed relative to the predicted addition of the two unisensory inputs as stimulus effectiveness was altered. Despite the presence of these categories, a general rule was that the most robust multisensory enhancements were seen with combinations of the least effective unisensory stimuli. Together, these results provide a better quantitative picture of the integrative operations performed by multisensory SC neurons and suggest mechanistic differences in the way in which these neurons synthesize cross-modal information.     

Visual, auditory, and somatosensory convergence on cells in superior colliculus results in multisensory integration

Convergence of inputs from different sensory modalities onto individual neurons is a phenomenon that occurs widely throughout the brain at many phyletic levels and appears to represent a basic neural mechanism by which an organism integrates complex environmental stimuli. In the present study, neurons in the superior colliculus (SC) were used as a model to examine how single neurons deal with simultaneous cues from different sensory modalities (e.g., visual, auditory, somatosensory). The functional result of multisensory convergence on an individual cell was determined by comparing the responses evoked from it by a combined-modality (multimodal) stimulus with those elicited by each (unimodal) component of that stimulus presented alone. Superior colliculus cells exhibited profound changes in their activity when individual sensory stimuli were combined. These "multisensory interactions" were found to be widespread among deep laminae cells and fell into one of two functional categories: response enhancement, characterized by a significant increase in the number of discharges evoked; and response depression, characterized by a significant decrease in the discharges elicited. Multisensory response interactions most often reflected a multiplicative, rather than summative, change in activity. Their absolute magnitude varied from cell to cell and, when stimulus conditions were altered, within the same cell. However, the percentage change of enhanced interactions was generally inversely related to the vigor of the responses that could be evoked by presenting each unimodal stimulus alone and suggest that the potential for response amplification was greatest when responses evoked by individual stimuli were weakest. The majority of cells exhibiting multi-sensory characteristics were demonstrated to have descending efferent projections and thus had access to premotor and motor areas of the brain stem and spinal cord involved in SC-mediated attentive and orientation behaviors. These data show that multisensory convergence provides the descending efferent cells of the SC with a dynamic response character. The responses of these cells and the SC-mediated behaviors that they underlie need not be immutably tied to the presence of any single stimulus, but can vary in response to the particular complex of stimuli present in the environment at any given moment.     

The influence of visual and auditory receptive field organization on multisensory integration in the superior colliculus

The spatial register of the different receptive fields of multisensory neurons in the superior colliculus (SC) plays a significant role in determining the responses of these neurons to cross-modal stimulus combinations. Spatially coincident visual-auditory stimuli fall within these overlapping receptive fields and generally produce response enhancements that exceed the individual modality-specific responses and can exceed their sum. Yet, in this context, it has not been clear how "spatial coincidence" is operationally defined. Given the large size of SC receptive fields, visual and auditory stimuli could be within their respective receptive fields even when there are substantial spatial disparities between them. Indeed, previous observations have raised the possibility that there may be a second level of determinism in how SC neurons deal with the relative spatial locations of within-field cross-modal stimuli; specifically, that multisensory response enhancements become progressively weaker as the within-field visual and auditory stimuli become increasingly disparate. While the present experiments demonstrated that SC multisensory neurons have heterogeneous receptive fields, and that the greatest number of impulses evoked were by stimuli that fell within the area of cross-modal receptive field overlap, they also indicate that there is no systematic relationship between cross-modal stimulus disparity and the magnitude of multisensory response enhancement. Thus, two within-field cross-modal stimuli produced the same proportionate change (i.e., multisensory response enhancement) when they were widely disparate as they did when they overlapped one another in space. These observations indicate that cross-modal spatial coincidence can be defined operationally by the borders of an SC neuron's receptive fields regardless of the size of those receptive fields and/or the absolute spatial disparity between within-field cross-modal stimuli. Electronic Publication     

Sensori-motor integration in the primate superior colliculus

The sudden onset of a novel stimulus usually triggers orienting responses of the eyes, head and external ears (pinnae). These responses facilitate the reception of additional signals originating from the source of the stimulus and assist in the sensory guidance of appropriate limb and body movements. A midbrain structure, the superior colliculus, plays a critical role in triggering and organizing orienting movements and is a particularly interesting structure for studying the neural computations involved in the translation of sensory signals into motor commands. Auditory, somatosensory and visual signals converge in its deep layers, where neurons are found that generate motor commands for eye, head and pinna movements. This article focuses on the role of the superior colliculus in the control of saccadic (quick, high-velocity) eye movements with particular regard to three issues related to the functional properties of collicular neurons. First, how do neurons with large movement fields specify accurately the direction and amplitude of an eye movement? Second, how are signals converted from different sensory modalities into commands in a common motor frame of reference? Last, how are the motor command signals found in the superior colliculus transformed into those needed by the motor neuron pools innervating the extraocular muscles?     

A computational study of multisensory maturation in the superior colliculus (SC)

Multisensory neurons in cat SC exhibit significant postnatal maturation. The first multisensory neurons to appear have large receptive fields (RFs) and cannot integrate information across sensory modalities. During the first several months of postnatal life RFs contract, responses become more robust and neurons develop the capacity for multisensory integration. Recent data suggest that these changes depend on both sensory experience and active inputs from association cortex. Here, we extend a computational model we developed (Cuppini et al. in Front Integr Neurosci 22: 4-6, 2010) using a limited set of biologically realistic assumptions to describe how this maturational process might take place. The model assumes that during early life, cortical-SC synapses are present but not active and that responses are driven by non-cortical inputs with very large RFs. Sensory experience is modeled by a "training phase" in which the network is repeatedly exposed to modality-specific and cross-modal stimuli at different locations. Cortical-SC synaptic weights are modified during this period as a result of Hebbian rules of potentiation and depression. The result is that RFs are reduced in size and neurons become capable of responding in adult-like fashion to modality-specific and cross-modal stimuli.     

Visual deprivation alters the development of cortical multisensory integration

It has recently been demonstrated that the maturation of normal multisensory circuits in the cortex of the cat takes place over an extended period of postnatal life. Such a finding suggests that the sensory experiences received during this time may play an important role in this developmental process. To test the necessity of sensory experience for normal cortical multisensory development, cats were raised in the absence of visual experience from birth until adulthood, effectively precluding all visual and visual-nonvisual multisensory experiences. As adults, semichronic single-unit recording experiments targeting the anterior ectosylvian sulcus (AES), a well-defined multisensory cortical area in the cat, were initiated and continued at weekly intervals in anesthetized animals. Despite having very little impact on the overall sensory representations in AES, dark-rearing had a substantial impact on the integrative capabilities of multisensory AES neurons. A significant increase was seen in the proportion of multisensory neurons that were modulated by, rather than driven by, a second sensory modality. More important, perhaps, there was a dramatic shift in the percentage of these modulated neurons in which the pairing of weakly effective and spatially and temporally coincident stimuli resulted in response depressions. In normally reared animals such combinations typically give rise to robust response enhancements. These results illustrate the important role sensory experience plays in shaping the development of mature multisensory cortical circuits and suggest that dark-rearing shifts the relative balance of excitation and inhibition in these circuits.     

Visual,auditory and somatosensory convergence in output neurons of the cat superior colliculus: multisensory properties of the tecto-reticulo-spinal projection

Summary A select population of superior colliculus (SC) neurons receives and integrates information from the visual, auditory and somatosensory systems. Determining which SC neurons comprise this population and where they send their multisensory messages is important in understanding the functional impact of the SC on attentive and orientation behavior. One of the major routes by which the SC influences these behaviors is the tecto-reticulo-spinal tract, a descending pathway that plays an integral role in the orientation of the eyes, ears and head. Of the 182 tecto-reticulo-spinal neurons (TRSNs) encountered in the present study, almost all (94%) responded to sensory stimuli and the overwhelming majority (84%) were multisensory. The present results demonstrate that the TRSN serves as an important link among the different sensory systems and provides a substrate through which they may gain access to the circuitry mediating orientation behavior.     

Transient pauses in delay-period activity of superior colliculus neurons

A feature of neurons in the mammalian superior colliclus (SC) is the robust discharge of action potentials preceding the onset of rapid eye movements called saccades. The burst, which commands ocular motoneurons, is often preceded by persistent, low-level activity, likely reflecting neuronal processes such as target selection, saccade selection and preparation. Here, we report on a transient pause in persistent activity of SC neurons. We trained monkeys to make or withhold saccades based on the shape of a centrally located cue. We found that after the cue changed shape, there was a measurable pause in persistent activity of SC neurons, even though the cue was located well outside the response field of the neurons. We show here that this pause is not a simple, transient inhibitory drive from neurons representing the central visual field. Rather, the occurrence of the pause depends on the occurrence of saccades made much later in the trial. The characteristics of the pause such as magnitude or duration are not predictable from the task condition, rather the occurrence of the pause across the SC neuronal population varies with whether a saccade is made much later in the trial. We developed a model that accounts for our results and makes testable predictions about the effects of signals related to inhibition in SC neuronal populations.     

Location of saccade-related neurons in the macaque superior colliculus

Summary The locations of saccade-related neurons were studied in the superior colliculi of two adult rhesus monkeys (Macaco, mulatta) by placing marking lesions at the sites of physiologically characterized cells and comparing these histologically identified sites with the collicular laminae and acetylcholinesterase (AChE)-rich patches. Three major conclusions were drawn on the basis of 39 histologically identified sites at which saccade-related neurons were recorded. First, saccade-related neurons were distributed from the ventral half of the optic layer through the deep gray layer, and were most concentrated in the intermediate gray and white layers. Second, there was a clear relationship between the discharge characteristics of these saccade-related neurons and the depths at which they were found. Neurons having presaccadic bursts, defined as clipped and partially-clipped, tended to be encountered more dorsally, and neurons that did not have bursts (undipped) were encountered more ventrally. Although cells having different discharge characteristics seemed to be organized along a dorsoventral axis, there was no compelling evidence that these properties were specified by their laminar locations. Third, there was no clear correlation between the locations of saccade-related neurons and the distribution of individual AChE-rich patches. Saccade-related cells were found both in the caudal superior colliculus where patches were located and in the rostral superior colliculus where patches were not found; both within and between the two tiers of AChE-rich patches in the caudal superior colliculus; and both within and between individual AChE-rich patches. However, the depth-level at which saccade-related neurons occurred generally matched the region bounded by the two tiers of AChE-rich patches in the intermediate and deep layers, and the dorsal and ventral extent of saccade-related neurons was the same as that of the AChE-rich patches.     

Audio-visual multisensory integration in superior parietal lobule revealed by human intracranial recordings

Intracranial recordings from three human subjects provide the first direct electrophysiological evidence for audio-visual multisensory processing in the human superior parietal lobule (SPL). Auditory and visual sensory inputs project to the same highly localized region of the parietal cortex with auditory inputs arriving considerably earlier (30 ms) than visual inputs (75 ms). Multisensory integration processes in this region were assessed by comparing the response to simultaneous audio-visual stimulation with the algebraic sum of responses to the constituent auditory and visual unisensory stimulus conditions. Significant integration effects were seen with almost identical morphology across the three subjects, beginning between 120 and 160 ms. These results are discussed in the context of the role of SPL in supramodal spatial attention and sensory-motor transformations.