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The ability to integrate information from different senses, and thereby facilitate detecting and localizing events, normally develops gradually in cat superior colliculus (SC) neurons as experience with cross-modal events is acquired. Here, we demonstrate that the portal for this experience-based change is association cortex. Unilaterally deactivating this cortex whenever visual-auditory events were present resulted in the failure of ipsilateral SC neurons to develop the ability to integrate those cross-modal inputs, even though they retained the ability to respond to them. In contrast, their counterparts in the opposite SC developed this capacity normally. The deficits were eliminated by providing cross-modal experience when cortex was active. These observations underscore the collaborative developmental processes that take place among different levels of the neuraxis to adapt the brain's multisensory (and sensorimotor) circuits to the environment in which they will be used., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Failure to attend to visual cues is a common consequence of visual cortex injury. Here, we report on a behavioural strategy whereby cross-modal (auditory-visual) training reinstates visuomotor competencies in animals rendered haemianopic by complete unilateral visual cortex ablation. The re-emergence of visual behaviours is correlated with the reinstatement of visual responsiveness in deep layer neurons of the ipsilesional superior colliculus (SC). This functional recovery is produced by training-induced alterations in descending influences from association cortex that allowed these midbrain neurons to once again transform visual cues into appropriate orientation behaviours. The findings underscore the inherent plasticity and functional breadth of phylogenetically older visuomotor circuits that can express visual capabilities thought to have been subsumed by more recently evolved brain regions. These observations suggest the need for reevaluating current concepts of functional segregation in the visual system and have important implications for strategies aimed at ameliorating trauma-induced visual deficits in humans.

The brain's ability to integrate information from different senses is acquired only after extensive sensory experience. However, whether early life experience instantiates a general integrative capacity in multisensory neurons or one limited to the particular cross-modal stimulus combinations to which one has been exposed is not known. By selectively restricting either visual-nonvisual or auditory-nonauditory experience during the first few months of life, the present study found that trisensory neurons in cat superior colliculus (as well as their bisensory counterparts) became adapted to the cross-modal stimulus combinations specific to each rearing environment. Thus, even at maturity, trisensory neurons did not integrate all cross-modal stimulus combinations to which they were capable of responding, but only those that had been linked via experience to constitute a coherent spatiotemporal event. This selective maturational process determines which environmental events will become the most effective targets for superior colliculus-mediated shifts of attention and orientation., (Copyright © 2015 the American Physiological Society.)

The ability to use cues from multiple senses in concert is a fundamental aspect of brain function. It maximizes the brain’s use of the information available to it at any given moment and enhances the physiological salience of external events. Because each sense conveys a unique perspective of the external world, synthesizing information across senses affords computational benefits that cannot otherwise be achieved. Multisensory integration not only has substantial survival value but can also create unique experiences that emerge when signals from different sensory channels are bound together. However, neurons in a newborn’s brain are not capable of multisensory integration, and studies in the midbrain have shown that the development of this process is not predetermined. Rather, its emergence and maturation critically depend on cross-modal experiences that alter the underlying neural circuit in such a way that optimizes multisensory integrative capabilities for the environment in which the animal will function.

The senses transduce different forms of environmental energy, and the brain synthesizes information across them to enhance responses to salient biological events. We hypothesize that the potency of multisensory integration is attributable to the convergence of independent and temporally aligned signals derived from cross-modal stimulus configurations onto multisensory neurons. The temporal profile of multisensory integration in neurons of the deep superior colliculus (SC) is consistent with this hypothesis. The responses of these neurons to visual, auditory, and combinations of visual-auditory stimuli reveal that multisensory integration takes place in real-time; that is, the input signals are integrated as soon as they arrive at the target neuron. Interactions between cross-modal signals may appear to reflect linear or nonlinear computations on a moment-by-moment basis, the aggregate of which determines the net product of multisensory integration. Modeling observations presented here suggest that the early nonlinear components of the temporal profile of multisensory integration can be explained with a simple spiking neuron model, and do not require more sophisticated assumptions about the underlying biology. A transition from nonlinear "super-additive" computation to linear, additive computation can be accomplished via scaled inhibition. The findings provide a set of design constraints for artificial implementations seeking to exploit the basic principles and potency of biological multisensory integration in contexts of sensory substitution or augmentation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Multisensory superior colliculus neurons in cats were found to retain substantial plasticity to short-term, site-specific experience with cross-modal stimuli well into adulthood. Following cross-modal exposure trials, these neurons substantially increased their sensitivity to the cross-modal stimulus configuration as well as to its individual component stimuli. In many cases, the exposure experience also revealed a previously ineffective or "silent" input channel, rendering it overtly responsive. These experience-induced changes required relatively few exposure trials and could be retained for more than 1 h. However, their induction was generally restricted to experience with cross-modal stimuli. Only rarely were they induced by exposure to a modality-specific stimulus and were never induced by stimulating a previously ineffective input channel. This short-term plasticity likely provides substantial benefits to the organism in dealing with ongoing and sequential events that take place at a given location in space and may reflect the ability of multisensory superior colliculus neurons to rapidly alter their response properties to accommodate to changes in environmental challenges and event probabilities.

In environments containing sensory events at competing locations, selecting a target for orienting requires prioritization of stimulus values. Although the superior colliculus (SC) is causally linked to the stimulus selection process, the manner in which SC multisensory integration operates in a competitive stimulus environment is unknown. Here we examined how the activity of visual-auditory SC neurons is affected by placement of a competing target in the opposite hemifield, a stimulus configuration that would, in principle, promote interhemispheric competition for access to downstream motor circuitry. Competitive interactions between the targets were evident in how they altered unisensory and multisensory responses of individual neurons. Responses elicited by a cross-modal stimulus (multisensory responses) proved to be substantially more resistant to competitor-induced depression than were unisensory responses (evoked by the component modality-specific stimuli). Similarly, when a cross-modal stimulus served as the competitor, it exerted considerably more depression than did its individual component stimuli, in some cases producing more depression than predicted by their linear sum. These findings suggest that multisensory integration can help resolve competition among multiple targets by enhancing orientation to the location of cross-modal events while simultaneously suppressing orientation to events at alternate locations.

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.

Single-neuron studies provide a foundation for understanding many facets of multisensory integration. These studies have used a variety of criteria for identifying and quantifying multisensory integration. While a number of techniques have been used, an explicit discussion of the assumptions, criteria, and analytical methods traditionally used to define the principles of multisensory integration is lacking. This was not problematic when the field was small, but with rapid growth a number of alternative techniques and models have been introduced, each with its own criteria and sets of implicit assumptions to define and characterize what is thought to be the same phenomenon. The potential for misconception prompted this reexamination of traditional approaches in order to clarify their underlying assumptions and analytic techniques. The objective here is to review and discuss traditional quantitative methods advanced in the study of single-neuron physiology in order to appreciate the process of multisensory integration and its impact.

Influences from the visual (AEV), auditory (FAES), and somatosensory (SIV) divisions of the cat anterior ectosylvian sulcus (AES) play a critical role in rendering superior colliculus (SC) neurons capable of multisensory integration. However, it is not known whether this is accomplished via their independent sensory-specific action or via some cross-modal cooperative action that emerges as a consequence of their convergence on SC neurons. Using visual-auditory SC neurons as a model, we examined how selective and combined deactivation of FAES and AEV affected SC multisensory (visual-auditory) and unisensory (visual-visual) integration capabilities. As noted earlier, multisensory integration yielded SC responses that were significantly greater than those evoked by the most effective individual component stimulus. This multisensory "response enhancement" was more evident when the component stimuli were weakly effective. Conversely, unisensory integration was dominated by the lack of response enhancement. During cryogenic deactivation of FAES and/or AEV, the unisensory responses of SC neurons were only modestly affected; however, their multisensory response enhancement showed a significant downward shift and was eliminated. The shift was similar in magnitude for deactivation of either AES subregion and, in general, only marginally greater when both were deactivated simultaneously. These data reveal that SC multisensory integration is dependent on the cooperative action of distinct subsets of unisensory corticofugal afferents, afferents whose sensory combination matches the multisensory profile of their midbrain target neurons, and whose functional synergy is specific to rendering SC neurons capable of synthesizing information from those particular senses.

Nitric oxide (NO) containing (nitrergic) interneurons are well-positioned to convey the cortical influences that are crucial for multisensory integration in superior colliculus (SC) output neurons. However, it is not known whether nitrergic interneurons are in this position early in life, and might, therefore, also play a role in the functional maturation of this circuit. In the present study, we investigated the postnatal developmental relationship between these two populations of neurons using Beta-nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH) histochemistry and SMI-32 immunocytochemistry to label presumptive interneurons and output neurons, respectively. SMI-32 immunostained neurons were proved to mature and retained immature anatomical features until approximately 8 postnatal weeks. In contrast, nitrergic interneurons developed more rapidly. They had achieved their adult-like anatomy by 4 postnatal weeks and were in a position to influence the dendritic elaboration of output neurons. It is this dendritic substrate through which much of the cortico-collicular influence is expressed. Double-labeling experiments showed that the dendritic and axonal processes of nitrergic interneurons already apposed the somata and dendrites of SMI-32 labeled neurons even at the earliest age examined. The results suggest that nitrergic interneurons play a role in refining the cortico-collicular projection patterns that are believed to be essential for SC output neurons to engage in multisensory integration and to support normal orientation responses to cross-modal stimuli.

Sensory integration is a characteristic feature of superior colliculus (SC) neurons. A recent neural network model of single-neuron integration derived a set of basic biological constraints sufficient to replicate a number of physiological findings pertaining to multisensory responses. The present study examined the accuracy of this model in predicting the responses of SC neurons to pairs of visual stimuli placed within their receptive fields. The accuracy of this model was compared to that of three other computational models (additive, averaging and maximum operator) previously used to fit these data. Each neuron's behavior was assessed by examining its mean responses to the component stimuli individually and together, and each model's performance was assessed to determine how close its prediction came to the actual mean response of each neuron and the magnitude of its predicted residual error. Predictions from the additive model significantly overshot the actual responses of SC neurons and predictions from the averaging model significantly undershot them. Only the predictions of the maximum operator and neural network model were not significantly different from the actual responses. However, the neural network model outperformed even the maximum operator model in predicting the responses of these neurons. The neural network model is derived from a larger model that also has substantial predictive power in multisensory integration, and provides a single computational vehicle for assessing the responses of SC neurons to different combinations of cross-modal and within-modal stimuli of different efficacies.

For thousands of years science philosophers have been impressed by how effectively the senses work together to enhance the salience of biologically meaningful events. However, they really had no idea how this was accomplished. Recent insights into the underlying physiological mechanisms reveal that, in at least one circuit, this ability depends on an intimate dialogue among neurons at multiple levels of the neuraxis; this dialogue cannot take place until long after birth and might require a specific kind of experience. Understanding the acquisition and usage of multisensory integration in the midbrain and cerebral cortex of mammals has been aided by a multiplicity of approaches. Here we examine some of the fundamental advances that have been made and some of the challenging questions that remain.

Much of the information about multisensory integration is derived from studies of the cat superior colliculus (SC), a midbrain structure involved in orientation behaviors. This integration is apparent in the enhanced responses of SC neurons to cross-modal stimuli, responses that exceed those to any of the modality-specific component stimuli. The simplest model of multisensory integration is one in which the SC neuron simply sums its various sensory inputs. However, a number of empirical findings reveal the inadequacy of such a model; for example, the finding that deactivation of cortico-collicular inputs eliminates the enhanced response to a cross-modal stimulus without eliminating responses to the modality-specific component stimuli. These and other empirical findings inform a computational model that accounts for all of the most fundamental aspects of SC multisensory integration. The model is presented in two forms: an algebraic form that conveys the essential insights, and a compartmental form that represents the neuronal computations in a more biologically realistic way.

Multisensory integration refers to the process by which the brain synthesizes information from different senses to enhance sensitivity to external events. In the present experiments, animals were reared in an altered sensory environment in which visual and auditory stimuli were temporally coupled but originated from different locations. Neurons in the superior colliculus developed a seemingly anomalous form of multisensory integration in which spatially disparate visual-auditory stimuli were integrated in the same way that neurons in normally reared animals integrated visual-auditory stimuli from the same location. The data suggest that the principles governing multisensory integration are highly plastic and that there is no a priori spatial relationship between stimuli from different senses that is required for their integration. Rather, these principles appear to be established early in life based on the specific features of an animal's environment to best adapt it to deal with that environment later in life.

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.

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.

The multisensory (deep) layers of the superior colliculus (SC) play an important role in detecting, localizing, and guiding orientation responses to salient events in the environment. Essential to this role is the ability of SC neurons to enhance their responses to events detected by more than one sensory modality and to become desensitized ('attenuated' or 'habituated') or sensitized ('potentiated') to events that are predictable via modulatory dynamics. To identify the nature of these modulatory dynamics, we examined how the repetition of different sensory stimuli affected the unisensory and multisensory responses of neurons in the cat SC. Neurons were presented with 2HZ stimulus trains of three identical visual, auditory, or combined visual–auditory stimuli, followed by a fourth stimulus that was either the same or different ('switch'). Modulatory dynamics proved to be sensory-specific: they did not transfer when the stimulus switched to another modality. However, they did transfer when switching from the visual–auditory stimulus train to either of its modality-specific component stimuli and vice versa. These observations suggest that predictions, in the form of modulatory dynamics induced by stimulus repetition, are independently sourced from and applied to the modality-specific inputs to the multisensory neuron. This falsifies several plausible mechanisms for these modulatory dynamics: they neither produce general changes in the neuron's transform, nor are they dependent on the neuron's output. [ABSTRACT FROM AUTHOR]

The operation of our multiple and distinct sensory systems has long captured the interest of researchers from multiple disciplines. When the Society was founded 50 years ago to bring neuroscience research under a common banner, sensory research was largely divided along modalityspecific lines. At the time, there were only a few physiological and anatomical observations of the multisensory interactions that powerfully influence our everyday perception. Since then, the neuroscientific study of multisensory integration has increased exponentially in both volume and diversity. From initial studies identifying the overlapping receptive fields of multisensory neurons, to subsequent studies of the spatial and temporal principles that govern the integration of multiple sensory cues, our understanding of this phenomenon at the single-neuron level has expanded to include a variety of dimensions. We now can appreciate how multisensory integration can alter patterns of neural activity in time, and even coordinate activity among populations of neurons across different brain areas. There is now a growing battery of sophisticated empirical and computational techniques that are being used to study this process in a number of models. These advancements have not only enhanced our understanding of this remarkable process in the normal adult brain, but also its underlying circuitry, requirements for development, susceptibility to malfunction, and how its principles may be used to mitigate malfunction. [ABSTRACT FROM AUTHOR]

The ability to integrate information across multiple senses enhances the brain’s ability to detect, localize, and identify external events. This process has been well documented in single neurons in the superior colliculus (SC), which synthesize concordant combinations of visual, auditory, and/or somatosensory signals to enhance the vigor of their responses. This increases the physiological salience of crossmodal events and, in turn, the speed and accuracy of SC-mediated behavioral responses to them. However, this capability is not an innate feature of the circuit and only develops postnatally alter the animal acquires sufficient experience with covariant crossmodal events to form links between their modality-specific components. Of critical importance in this process are tectopetal influences from association cortex. Recent findings suggest that, despite its intuitive appeal, a simple generic associative rule cannot explain how this circuit develops its ability to integrate those crossmodal inputs to produce enhanced multisensory responses. The present neurocomputational model explains how this development can be understood as a transition from a default state in which crossmodal SC inputs interact competitively to one in which they interact cooperatively. Crucial to this transition is the operation of a learning rule requiring coactivation among tectopetal afferents for engagement. The model successfully replicates findings of multisensory development in normal cats and cats of either sex reared with special experience. In doing so, it explains how the cortico-SC projections can use crossmodal experience to craft the multisensory integration capabilities of the SC and adapt them to the environment in which they will be used. [ABSTRACT FROM AUTHOR]

Neurons in the superior colliculus (SC) integrate cross-modal inputs to generate responses that are more robust than to either input alone, and are frequently greater than their sum (superadditive enhancement). Previously, the principles of a real-time multisensory transform were identified and used to accurately predict a neuron's responses to combinations of brief flashes and noise bursts. However, environmental stimuli frequently have more complex temporal structures that elicit very different response dynamics than previously examined. The present study tested whether such stimuli (i.e., pulsed) would be treated similarly by the multisensory transform. Pulsing visual and auditory stimuli elicited responses composed of higher discharge rates that had multiple peaks temporally aligned to the stimulus pulses. Combinations pulsed cues elicited multiple peaks of superadditive enhancement within the response window. Measured over the entire response, this resulted in larger enhancements than expected given enhancements elicited by non-pulsed ("sustained") stimuli. However, as with sustained stimuli, the dynamics of multisensory responses to pulsed stimuli were highly related to the temporal dynamics of the unisensory inputs. This suggests that the specific characteristics of the multisensory transform are not determined by the external features of the cross-modal stimulus configuration; rather the temporal structure and alignment of the unisensory inputs is the dominant driving factor in the magnitudes of the multisensory product. [ABSTRACT FROM AUTHOR]

It is commonly believed that the ability to integrate information from different senses develops according to associative learning principles as neurons acquire experience with co-active cross-modal inputs. However, previous studies have not distinguished between requirements for co-activation versus co-variation. To determine whether cross-modal co-activation is sufficient for this purpose in visual-auditory superior colliculus ( SC) neurons, animals were reared in constant omnidirectional noise. By masking most spatiotemporally discrete auditory experiences, the noise created a sensory landscape that decoupled stimulus co-activation and co-variance. Although a near-normal complement of visual-auditory SC neurons developed, the vast majority could not engage in multisensory integration, revealing that visual-auditory co-activation was insufficient for this purpose. That experience with co-varying stimuli is required for multisensory maturation is consistent with the role of the SC in detecting and locating biologically significant events, but it also seems likely that this is a general requirement for multisensory maturation throughout the brain. [ABSTRACT FROM AUTHOR]

Development of multisensory integration capabilities in superior colliculus (SC) neurons was examined in cats whose visual-auditory experience was restricted to a circumscribed period during early life (postnatal day 30-8 months). Animals were periodically exposed to visual and auditory stimuli appearing either randomly in space and time, or always in spatiotemporal concordance. At all other times animals were maintained in darkness. Physiological testing was initiated at ˜2 years of age. Exposure to random visual and auditory stimuli proved insufficient to spur maturation of the ability to integrate cross-modal stimuli, but exposure to spatiotemporally concordant cross-modal stimuli was highly effective. The multisensory integration capabilities of neurons in the latter group resembled those of normal animals and were retained for 16 months in the absence of subsequent visual-auditory experience. Furthermore, the neurons were capable of integrating stimuli having physical properties differing significantly from those in the exposure set. These observations suggest that acquiring the rudiments of multisensory integration requires little more than exposure to consistent relationships between the modality-specific components of a cross-modal event, and that continued experience with such events is not necessary for their maintenance. Apparently, the statistics of cross-modal experience early in life define the spatial and temporal filters that determine whether the components of cross-modal stimuli are to be integrated or treated as independent events, a crucial developmental process that determines the spatial and temporal rules by which cross-modal stimuli are integrated to enhance both sensory salience and the likelihood of eliciting an SC-mediated motor response. [ABSTRACT FROM AUTHOR]

Non-technical summary The superior colliculus (SC) is a subcortical brain structure critically involved in the production of eye and head movements to novel or salient visual cues. But to accomplish its function, an input from visual cortex also is required. Because visual cortex projects directly to the SC, this route is typically viewed as the predominant way by which cortex exerts higher-level control over SC-mediated behaviours. However, anatomical studies suggest that other multi-neuronal circuits through the basal ganglia, a collection of interconnected structures involved in decision making, might provide an alternative way for cortex to influence the SC. The present study provides physiological evidence for such an alternative route and affords additional insights into how the brain initiates and controls movements in response to visual cues. Such knowledge could be important for developing therapies to lessen the effects of visual deficits in patients experiencing loss of function following head trauma or stroke. [ABSTRACT FROM AUTHOR]

The multisensory integration capabilities of superior colliculus neurons emerge gradually during early postnatal life as a consequence of experience with cross-modal stimuli. Without such experience neurons become responsive to multiple sensory modalities but are unable to integrate their inputs. The present study demonstrates that neurons retain sensitivity to cross-modal experience well past the normal developmental period for acquiring multisensory integration capabilities. Experience surprisingly late in life was found to rapidly initiate the development of multisensory integration, even more rapidly than expected based on its normal developmental time course. Furthermore, the requisite experience was acquired by the anesthetized brain and in the absence of any of the stimulus-response contingencies generally associated with learning. The key experiential factor was repeated exposure to the relevant stimuli, and this required that the multiple receptive fields of a multisensory neuron encompassed the cross-modal exposure site. Simple exposure to the individual components of a cross-modal stimulus was ineffective in this regard. Furthermore, once a neuron acquired multisensory integration capabilities at the exposure site, it generalized this experience to other locations, albeit with lowered effectiveness. These observations suggest that the prolonged period during which multisensory integration normally appears is due to developmental factors in neural circuitry in addition to those required for incorporating the statistics of cross-modal events; that neurons learn a multisensory principle based on the specifics of experience and can then apply it to other stimulus conditions; and that the incorporation of this multisensory information does not depend on an alert brain. [ABSTRACT FROM AUTHOR]

Converging cortical influences from the anterior ectosylvian sulcus and the rostral lateral suprasylvian sulcus were shown to have a multisensory-specific role in the integration of sensory information in superior colliculus (SC) neurons. These observations were based on changes induced by cryogenic deactivation of these cortico-SC projections. Thus, although the results indicated that they played a critical role in integrating SC responses to stimuli derived from different senses (i.e., visual-auditory), they played no role in synthesizing its responses to stimuli derived from within the same sense (visual-visual). This was evident even in the same multisensory neurons. The results suggest that very different neural circuits have evolved to code combinations of cross-modal and within-modal stimuli in the SC, and that the differences in multisensory and unisensory integration are likely caused by differences in the configuration of each neuron's functional inputs rather than to any inherent differences among the neurons themselves. The specificity of these descending influences was also apparent in the very different ways in which they affected responses to the component cross-modal stimuli and their actual integration. Furthermore, they appeared to target only multisensory neurons and not their unisensory neighbors. [ABSTRACT FROM AUTHOR]

Individual superior colliculus (SC) neurons integrate information from multiple sensory sources to enhance their physiological response. The response of an SC neuron to a cross-modal stimulus combination can not only exceed the best component unisensory response but can also exceed their arithmetic sum (i.e., superadditivity). The present experiments were designed to investigate the temporal profile of multisensory integration in this model system. We found that cross-modal stimuli frequently shortened physiological response latencies (mean shift, 6.2 ms) and that response enhancement was greatest in the initial phase of the response (the phenomenon of initial response enhancement). The vast majority of the responses studied evidenced superadditive computations, most often at the beginning of the multisensory response. [ABSTRACT FROM AUTHOR]

It is well established that superior colliculus (SC) multisensory neurons integrate cues from different senses; however, the mechanisms responsible for producing multisensory responses are poorly understood. Previous studies have shown that spatially congruent cues from different modalities (e.g., auditory and visual) yield enhanced responses and that the greatest relative enhancements occur for combinations of the least effective modality-specific stimuli. Although these phenomena are well documented, little is known about the mechanisms that underlie them, because no study has systematically examined the operation that multisensory neurons perform on their modality-specific inputs. The goal of this study was to evaluate the computations that multisensory neurons perform in combining the influences of stimuli from two modalities. The extracellular activities of single neurons in the SC of the cat were recorded in response to visual, auditory, and bimodal visual-auditory stimulation. Each neuron was tested across a range of stimulus intensities and multisensory responses evaluated against the null hypothesis of simple summation of unisensory influences. We found that the multisensory response could be superadditive, additive, or subadditive but that the computation was strongly dictated by the efficacies of the modality-specific stimulus components. Superadditivity was most common within a restricted range of near-threshold stimulus efficacies, whereas for the majority of stimuli, response magnitudes were consistent with the linear summation of modality-specific influences. In addition to providing a constraint for developing models of multisensory integration, the relationship between response mode and stimulus efficacy emphasizes the importance of considering stimulus parameters when inducing or interpreting multisensory phenomena. [ABSTRACT FROM AUTHOR]

Multisensory neurons and their ability to integrate multisensory cues develop gradually in the midbrain [i.e., superior colliculus (SC)]. To examine the possibility that early sensory experiences might play a critical role in these maturational processes, animals were raised in the absence of visual cues. As adults, the SC of these animals were found to contain many multisensory neurons, the large majority of which were visually responsive. Although these neurons responded robustly to each of their cross-modal inputs when presented individually, they were incapable of synthesizing this information. These observations suggest that visual experiences are critical for the SC to develop the ability to integrate multisensory information and lead to the prediction that, in the absence of such experience, animals will be compromised in their sensitivity to cross-modal events. [ABSTRACT FROM AUTHOR]

It had previously been shown that influences from two cortical areas, the anterior ectosylvian sulcus (AES) and the rostral lateral suprasylvian sulcus (rLS), play critical roles in rendering superior colliculus (SC) neurons capable of synthesizing their cross-modal inputs. The present studies examined the consequences of selectively eliminating these cortical influences on SC-mediated orientation responses to cross-modal stimuli. Cats were trained to orient to a low-intensity modality-specific cue (visual) in the presence or absence of a neutral cue from another modality (auditory). The visual target could appear at various locations within 45° of the midline, and the stimulus effectiveness was varied to yield an average of correct orientation responses of approximately 45%. Response enhancement and depression were observed when the auditory cue was coupled with the target stimulus: A substantially enhanced probability in correct responses was evident when the cross-modal stimuli were spatially coincident, and a substantially decreased response probability was obtained when the stimuli were spatially disparate. Cryogenic blockade of either AES or rLS disrupted these behavioral effects, thereby eliminating the enhanced performance in response to spatially coincident cross-modal cues and degrading the depressed performance in response to spatially disparate cross-modal cues. These disruptive effects on targets contralateral to the deactivated cortex were restricted to multisensory interactive processes. Orientation to modality-specific targets was unchanged. Furthermore, the pattern of orientation errors was unaffected by cortical deactivation. These data bear striking similarities to the effects of AES and rLS deactivation on multisensory integration at the level of individual SC neurons. Presumably, eliminating the critical influences from AES or rLS cortex disrupts SC multisensory synthesis that, in turn, disables SC-mediated multisensory orientation behaviors. [ABSTRACT FROM AUTHOR]

The distribution of the calcium-binding proteins calbindin D-28K and parvalbumin was examined in newborn and adult superior colliculus of cat and rhesus monkey using immunohistochemical techniques. In adult animals of both species, calbindin-immunoreactive neurons had a three-tiered arrangement: one band was present in the upper aspects of the superficial laminae, a second in the intermediate laminae, and a third in the deep laminae. The intermediate tier was less obvious in the monkey, whereas the deep tier was less pronounced in the cat. Parvalbumin-immunoreactive neurons had a complementary distribution to calbindin-immunoreactive neurons within these laminae in both species, although the segregation of calbindin immunoreactivity and parvalbumin immunoreactivity in the superficial laminae was not as precise in the monkey as it was in the cat. At birth, calbindin immunoreactivity in the newborns of both species was remarkably mature, with its three-tiered distribution clearly evident. By contrast, parvalbumin immunoreactivity was distinctly different in the newborn cat than in the newborn monkey: whereas parvalbumin immunoreactivity in the newborn monkey was already very similar to its adult-like pattern, the pattern in the newborn cat was quite immature. The superficial laminae of the newborn cat were virtually devoid of parvalbumin immunoreactivity, and, although the intermediate laminae displayed robust parvalbumin-immunoreactive neuropil, comparatively fewer parvalbumin-immunoreactive neurons were observed. Conspicuously few in number were the large multipolar neurons in the intermediate laminae, which give rise to the descending efferents to the brainstem. However, parvalbumin-immunoreactive neurons were present within the deep laminae, suggesting a ventral-to-dorsal maturational gradient in parvalbumin expression that parallels the ventral-to-dorsal gradient of neurogenesis. The differences in parvalbumin immunoreactivity observed between these two species at parturition are consistent with the advanced visual and visuomotor capabilities of the newborn monkey and the absence of visually related behaviors in the newborn cat. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Corticofugal projections from the frontal eye fields (FEF) are believed to access the superior colliculus (SC) directly (i.e., monosynaptically) and indirectly (i.e., multisynaptically) through the basal ganglia. The present results suggest that these two pathways are derived from largely segregated populations of corticofugal neurons. Furthermore, while the different subregions of the FEF from which these pathways originate have different termination patterns in the basal ganglia (i.e., striatum, ST), they share a common termination pattern in the SC. Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the two major subdivisions of the FEF (presylvian and cruciate sulci) resulted in dense label in both the ST (bilaterally) and the SC (ipsilaterally). Corticostriatal labeling was found in the caudal part of the head of the caudate nucleus (heaviest ipsilaterally), with labeling from cruciate injections located ventromedial to that produced by presylvian injections. Only presylvian injections resulted in labeling in the putamen. Retrograde tracing experiments demonstrated that both presylvian and cruciate corticostriatal projections originated from neurons in lamina III and the upper aspects of lamina V. An additional but small group of presylvian corticostriatal projections was found in lamina VI. Corticotectal terminal labeling was restricted to the deep laminae of the SC and was derived exclusively from lamina V neurons in cortex. They differed from their corticostriatal counterparts in laminar/sub-laminar location and in soma sizes. [ABSTRACT FROM AUTHOR]

The diversity of our senses conveys many advantages; it enables them to compensate for one another when needed, and the information they provide about a common event can be integrated to facilitate its processing and, ultimately, adaptive responses. These cooperative interactions are produced by multisensory neurons. A well-studied model in this context is the multisensory neuron in the output layers of the superior colliculus (SC). These neurons integrate and amplify their cross-modal (e.g., visual-auditory) inputs, thereby enhancing the physiological salience of the initiating event and the probability that it will elicit SC-mediated detection, localization, and orientation behavior. Repeated experience with the same visual-auditory stimulus can also increase the neuron's sensitivity to these individual inputs. This observation raised the possibility that such plasticity could be engaged to restore visual responsiveness when compromised. For example, unilateral lesions of visual cortex compromise the visual responsiveness of neurons in the multisensory output layers of the ipsilesional SC and produces profound contralesional blindness (hemianopia). The possibility that multisensory plasticity could restore the visual responses of these neurons, and reverse blindness, was tested in the cat model of hemianopia. Hemianopic subjects were repeatedly presented with spatiotemporally congruent visual-auditory stimulus pairs in the blinded hemifield on a daily or weekly basis. After several weeks of this multisensory exposure paradigm, visual responsiveness was restored in SC neurons and behavioral responses were elicited by visual stimuli in the previously blind hemifield. The constraints on the effectiveness of this procedure proved to be the same as those constraining SC multisensory plasticity: whereas repetitions of a congruent visual-auditory stimulus was highly effective, neither exposure to its individual component stimuli, nor to these stimuli in non-congruent configurations was effective. The restored visual responsiveness proved to be robust, highly competitive with that in the intact hemifield, and sufficient to support visual discrimination. • Unilateral blindness can be rehabilitated by multisensory training. • Training stimuli must be arranged in spatiotemporally congruent assemblies. • The training protocol is effective in human and non-human animals. • The midbrain superior colliculus is believed to support recovered vision. [ABSTRACT FROM AUTHOR]

The multisensory integration capabilities of superior colliculus (SC) neurons are normally acquired during early postnatal life and adapted to the environment in which they will be used. Recent evidence shows that they can even be acquired in adulthood, and require neither consciousness nor any of the reinforcement contingencies generally associated with learning. This process is believed to be based on Hebbian mechanisms, whereby the temporal coupling of multiple sensory inputs initiates development of a means of integrating their information. This predicts that co-activation of those input channels is sufficient to induce multisensory integration capabilities regardless of the specific spatiotemporal properties of the initiating stimuli. However, one might expect that the stimuli to be integrated should be consonant with the functional role of the neurons involved. For the SC, this would involve stimuli that can be localized. Experience with a non-localizable cue in one modality (e.g., ambient sound) and a discrete stimulus in another (e.g., a light flash) should not be sufficient for this purpose. Indeed, experiments with cats reared in omnidirectional sound (effectively masking discrete auditory events) reveal that the simple co-activation of two sensory input channels is not sufficient for this purpose. The data suggest that experience with the kinds of cross-modal events that facilitate the role of the SC in detecting, locating, and orienting to localized external events is a guiding factor in this maturational process. Supported by NIH grants NS 036916 and EY016716. [ABSTRACT FROM AUTHOR]

Although there are many perceptual theories that posit particular maturational profiles in higher-order (i.e., cortical) multisensory regions, our knowledge of multisensory development is primarily derived from studies of a midbrain structure, the superior colliculus. Therefore, the present study examined the maturation of multisensory processes in an area of cat association cortex [i.e., the anterior ectosylvian sulcus (AES)] and found that these processes are rudimentary during early postnatal life and develop only gradually thereafter. The AES comprises separate visual, auditory, and somatosensory regions, along with many multisensory neurons at the intervening borders between them. During early life, sensory responsiveness in AES appears in an orderly sequence. Somatosensory neurons are present at 4 weeks of age and are followed by auditory and multisensory (somatosensory-auditory) neurons. Visual neurons and visually responsive multisensory neurons are first seen at 12 weeks of age. The earliest multisensory neurons are strikingly immature, lacking the ability to synthesize the cross-modal information they receive. With postnatal development, multisensory integrative capacity matures. The delayed maturation of multisensory neurons and multisensory integration in AES suggests that the higher-order processes dependent on these circuits appear comparatively late in ontogeny. [ABSTRACT FROM AUTHOR]