Responses to innocuous,but not noxious,somatosensory stimulation by neurons in the ferret superior colliculus

The intermediate and deep layers of the superior colliculus (SC) are known for their role in initiating orienting behaviors. To direct these orienting functions, the SC of some animals (e.g., primates, carnivores) is dominated by inputs from the distance senses (vision, audition). In contrast, the rodent SC relies more heavily on non-visual inputs, such as touch and nociception, possibly as an adaptive response to the proximity of dangers encountered during their somatosensory-dominant search behaviors. The ferret (a carnivore) seems to employ strategies of both groups: above ground they use visual/auditory cues, but during subterranean hunting ferrets must rely on non-visual signals to direct orienting. Therefore, the present experiments sought to determine whether the sensory inputs to the ferret SC reveal adaptations common to functioning in both environments. The results showed that the ferret SC is dominated (63%; 181/286) by visual/auditory inputs (like the cat), rather than by somatosensory inputs (as found in rodents). Furthermore, tactile responses were driven primarily from hair-receptors (like cats), not from the vibrissae (as in rodents). Additionally, while a majority of collicular neurons in rodents respond to brief noxious stimulation, no such neurons were encountered in the ferret SC. A small proportion (4%; 13/286) of the ferret SC neurons were responsive to long-duration (> 5s) noxious stimulation, but further tests could not establish these responses as nociceptive. Collectively, these data indicate that the ferret SC is best adapted for the animal's visual/acoustically guided activities and most closely resembles the SC of its phylogenetic relative, the cat.     

Orienting our view of the superior colliculus: specializations and general functions

The mammalian superior colliculus (SC) and its non-mammalian homolog, the optic tectum are implicated in sensorimotor transformations. Historically, emphasis on visuomotor functions of the SC has led to a popular view that it operates as an oculomotor structure rather than a more general orienting structure. In this review, we consider comparative work on the SC/optic tectum, with a particular focus on non-visual sensing and orienting, which reveals a broader perspective on SC functions and their role in species-specific behaviors. We highlight several recent studies that consider ethological context and natural behaviors to advance knowledge of the SC as a site of multi-sensory integration and motor initiation in diverse species.     

Neural substrates of sensory-guided locomotor decisions in the rat superior colliculus

Deciding in which direction to move is a ubiquitous feature of animal behavior, but the neural substrates of locomotor choices are not well understood. The superior colliculus (SC) is a midbrain structure known to be important for controlling the direction of gaze, particularly when guided by visual or auditory cues, but which may play a more general role in behavior involving spatial orienting. To test this idea, we recorded and manipulated activity in the SC of freely moving rats performing an odor-guided spatial choice task. In this context, not only did a substantial majority of SC neurons encode choice direction during goal-directed locomotion, but many also predicted the upcoming choice and maintained selectivity for it after movement completion. Unilateral inactivation of SC activity profoundly altered spatial choices. These results indicate that the SC processes information necessary for spatial locomotion, suggesting a broad role for this structure in sensory-guided orienting and navigation.     

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses.     

Tonic Descending Influences on Cat Spinal Cord Dorsal Horn Neurons

The extent and nature of tonic supraspinal influences was determined on cat spinal cord dorsal horn neurons that received both noxious (radiant heat) and nonnoxious (hair movement) inputs or only a nonnoxious input. The former cells receive a tonic inhibition that descends in the dorsolateral funiculi and which is selective for the noxious input. The latter neurons are under a tonic facilitation.     

Reorganization of the Connectivity of Cortical Field DZ in Congenitally Deaf Cat

Psychophysics and brain imaging studies in deaf patients have revealed a functional crossmodal reorganization that affects the remaining sensory modalities. Similarly, the congenital deaf cat (CDC) shows supra-normal visual skills that are supported by specific auditory fields (DZ-dorsal zone and P-posterior auditory cortex) but not the primary auditory cortex (A1). To assess the functional reorganization observed in deafness we analyzed the connectivity pattern of the auditory cortex by means of injections of anatomical tracers in DZ and A1 in both congenital deaf and normally hearing cats. A quantitative analysis of the distribution of the projecting neurons revealed the presence of non-auditory inputs to both A1 and DZ of the CDC which were not observed in the hearing cats. Firstly, some visual (areas 19/20) and somatosensory (SIV) areas were projecting toward DZ of the CDC but not in the control. Secondly, A1 of the deaf cat received a weak projection from the visual lateral posterior nuclei (LP). Most of these abnormal projections to A1 and DZ represent only a small fraction of the normal inputs to these areas. In addition, most of the afferents to DZ and A1 appeared normal in terms of areal specificity and strength of projection, with preserved but smeared nucleotopic gradient of A1 in CDCs. In conclusion, while the abnormal projections revealed in the CDC can participate in the crossmodal compensatory mechanisms, the observation of a limited reorganization of the connectivity pattern of the CDC implies that functional reorganization in congenital deafness is further supported also by normal cortico-cortical connectivity.     

Nonlinear visuoauditory integration in the mouse superior colliculus

Sensory information from different modalities is processed in parallel, and then integrated in associative brain areas to improve object identification and the interpretation of sensory experiences. The Superior Colliculus (SC) is a midbrain structure that plays a critical role in integrating visual, auditory, and somatosensory input to assess saliency and promote action. Although the response properties of the individual SC neurons to visuoauditory stimuli have been characterized, little is known about the spatial and temporal dynamics of the integration at the population level. Here we recorded the response properties of SC neurons to spatially restricted visual and auditory stimuli using large-scale electrophysiology. We then created a general, population-level model that explains the spatial, temporal, and intensity requirements of stimuli needed for sensory integration. We found that the mouse SC contains topographically organized visual and auditory neurons that exhibit nonlinear multisensory integration. We show that nonlinear integration depends on properties of auditory but not visual stimuli. We also find that a heuristically derived nonlinear modulation function reveals conditions required for sensory integration that are consistent with previously proposed models of sensory integration such as spatial matching and the principle of inverse effectiveness.     

Different Stimuli,Different Spatial Codes: A Visual Map and an Auditory Rate Code for Oculomotor Space in the Primate Superior Colliculus

Maps are a mainstay of visual, somatosensory, and motor coding in many species. However, auditory maps of space have not been reported in the primate brain. Instead, recent studies have suggested that sound location may be encoded via broadly responsive neurons whose firing rates vary roughly proportionately with sound azimuth. Within frontal space, maps and such rate codes involve different response patterns at the level of individual neurons. Maps consist of neurons exhibiting circumscribed receptive fields, whereas rate codes involve open-ended response patterns that peak in the periphery. This coding format discrepancy therefore poses a potential problem for brain regions responsible for representing both visual and auditory information. Here, we investigated the coding of auditory space in the primate superior colliculus(SC), a structure known to contain visual and oculomotor maps for guiding saccades. We report that, for visual stimuli, neurons showed circumscribed receptive fields consistent with a map, but for auditory stimuli, they had open-ended response patterns consistent with a rate or level-of-activity code for location. The discrepant response patterns were not segregated into different neural populations but occurred in the same neurons. We show that a read-out algorithm in which the site and level of SC activity both contribute to the computation of stimulus location is successful at evaluating the discrepant visual and auditory codes, and can account for subtle but systematic differences in the accuracy of auditory compared to visual saccades. This suggests that a given population of neurons can use different codes to support appropriate multimodal behavior.     

Sensory experience and the formation of a computational map of auditory space in the brain.

The basic wiring of the brain is first established before birth by using a variety of molecular guidance cues. These connections are then refined by patterns of neural activity, which are initially generated spontaneously and subsequently driven by sensory experience. In the superior colliculus, a midbrain nucleus involved in the control of orienting behaviour, visual, auditory, and tactile inputs converge to form superimposed maps of sensory space. Maps of visual space and of the body surface arise from spatially ordered projections from the retina and skin, respectively. In contrast, the map of auditory space is computed within the brain by tuning the neurons to different localization cues that result from the acoustical properties of the head and ears. Establishing and maintaining the registration of the maps in the face of individual differences in the size and relative positions of different sense organs is an activity-dependent process in which the synaptic circuits underlying the auditory representation are modified and calibrated under the influence of both auditory and visual experience. BioEssays 1999;21:900-911.     

Organization of the Connections between the Parietal Associative Zone and the Primary Sensory Zones in the Cat Neocortex

In acute experiments on cats, we studied the impulse activity of 262 neurons of the parietal associative zone (PAZ, field 5). Among them, 129 cells [100 silent units and 29 units generating background activity (BA)] were identified as output neurons, while 133 cells with the BA were interneurons of the intrinsic cortical neuronal circuits. Electrical stimulation of the primary visual, auditory, or somatosensory cortices evoked no impulse responses in silent output PAZ neurons, while output neurons with the BA and interneurons (more than 65 and 80% of the cell units, respectively) generated clear responses (more frequently, phasic). Stimulation of the auditory and visual cortices exerted mostly inhibitory effects, while stimulation of the somatosensory cortex provided mostly excitatory influences. The ratios of neurons generating primary excitatory and inhibitory responses to stimulation of the visual, auditory, and somatic cortices were 0.3:1, 0.6:1, and 3.2:1, respectively. More than 95% of the field-5 neurons were influenced from the primary sensory zones via di- and/or polysynaptic pathways. Monosynaptic excitatory inputs from the visual cortex were identified for 3.8% of interneurons and 6.9% of output PAZ neurons; for the auditory cortical inputs, the respective figures were 1.7 and 3.5%. Monosynaptic connections with the somatic cortex were found only for 4% of the interneurons under study. It has been concluded that interaction of heteromodal signals coming to the PAZ via the corticopetal and associative inputs occurs on neurons of all the cortical layers.     

Minimal Hodgkin–Huxley type models for different classes of cortical and thalamic neurons

We review here the development of Hodgkin–Huxley (HH) type models of cerebral cortex and thalamic neurons for network simulations. The intrinsic electrophysiological properties of cortical neurons were analyzed from several preparations, and we selected the four most prominent electrophysiological classes of neurons. These four classes are “fast spiking” “regular spiking” “intrinsically bursting” and “low-threshold spike” cells. For each class, we fit “minimal” HH type models to experimental data. The models contain the minimal set of voltage-dependent currents to account for the data. To obtain models as generic as possible, we used data from different preparations in vivo and in vitro, such as rat somatosensory cortex and thalamus, guinea-pig visual and frontal cortex, ferret visual cortex, cat visual cortex and cat association cortex. For two cell classes, we used automatic fitting procedures applied to several cells, which revealed substantial cell-to-cell variability within each class. The selection of such cellular models constitutes a necessary step towards building network simulations of the thalamocortical system with realistic cellular dynamical properties.     

Reward-dependent gain and bias of visual responses in primate superior colliculus

Eye movements are often influenced by expectation of reward. Using a memory-guided saccade task with an asymmetric reward schedule, we show that visual responses of monkey SC neurons increase when the visual stimulus indicates an upcoming reward. The increase occurred in two distinct manners: (1) reactively, as an increase in the gain of the visual response when the stimulus indicated an upcoming reward; (2) proactively, as an increase in anticipatory activity when reward was expected in the neuron's response field. These effects were observed mostly in saccade-related SC neurons in the deeper layer which would receive inputs from the cortical eye fields and the basal ganglia. These results, together with recent findings, suggest that the gain modulation may be determined by the inputs from both the cortical eye fields and the basal ganglia, whereas the anticipatory bias may be derived mainly from the basal ganglia.     

Hebbian mechanisms help explain development of multisensory integration in the superior colliculus: a neural network model

The superior colliculus (SC) integrates relevant sensory information (visual, auditory, somatosensory) from several cortical and subcortical structures, to program orientation responses to external events. However, this capacity is not present at birth, and it is acquired only through interactions with cross-modal events during maturation. Mathematical models provide a quantitative framework, valuable in helping to clarify the specific neural mechanisms underlying the maturation of the multisensory integration in the SC. We extended a neural network model of the adult SC (Cuppini et?al., Front Integr Neurosci 4:1?C15, 2010) to describe the development of this phenomenon starting from an immature state, based on known or suspected anatomy and physiology, in which: (1) AES afferents are present but weak, (2) Responses are driven from non-AES afferents, and (3) The visual inputs have a marginal spatial tuning. Sensory experience was modeled by repeatedly presenting modality-specific and cross-modal stimuli. Synapses in the network were modified by simple Hebbian learning rules. As a consequence of this exposure, (1) Receptive fields shrink and come into spatial register, and (2) SC neurons gained the adult characteristic integrative properties: enhancement, depression, and inverse effectiveness. Importantly, the unique architecture of the model guided the development so that integration became dependent on the relationship between the cortical input and the SC. Manipulations of the statistics of the experience during the development changed the integrative profiles of the neurons, and results matched well with the results of physiological studies.     

后掩蔽效应对大棕蝠下丘神经元声反应的影响

以回声定位蝙蝠为模式动物,采用在体动物细胞外单位记录法,研究了后掩蔽效应对下丘神经元声反应的影响。结果显示,部分神经元(38％,12／31)对测试声刺激的反应明显受到掩蔽声的抑制,其后掩蔽效应强弱与掩蔽声和测试声的相对强度差(inter-stimulus level difference,SLD),以及测试声与掩蔽声之间的间隔时间(inter-stimulus onset asynchrony,SOA)有关：当掩蔽声强度升高或测试声强度降低时,后掩蔽效应增强;而SOA的缩短,亦可见后掩蔽效应增强。另外,相当数量的神经元(52%,16／31)对测试声刺激的反应并不受掩蔽声的影响,其中有的神经元只有在特定SLD和SOA时,才表现出后掩蔽效应。而少数下丘神经元(10％,3／31)在特定SLD和SOA时,掩蔽声对测试声反应有易化作用。上述结果表明,部分下丘神经元参与了声认知活动中的后掩蔽形成过程,推测下丘神经元在定型声反应特性中,对掩蔽声诱导的兴奋前抑制性输入与测试声诱导的兴奋性输入之间的时相性动态整合起关键作用。     

Development and organization of multimodal representation in cat superior colliculus

The present paper examines developmental and organizational parallels between visual and nonvisual cells in the cat superior colliculus (SC). An attempt is made to relate these developmental and organizational features to the role the SC plays in orientation behavior. In young kittens visually guided behavior is virtually nonexistent and requires many weeks to develop. Similarly, kitten SC cells are unresponsive to visual stimuli until at least 7 days after birth, and it is only after many weeks that SC cells behave as do those of the adult. In contrast to the development of visual cells, however, some neurons responsive to somatic stimuli are present in the SC on the day of birth, and cells responsive to acoustic stimuli appear several days later. Thus, the sequence in which modality represenstation appears in the cat SC parallels the developmental chronology of the use of different sensory cues for orientation. These data indicate that the functional roles of the visual, somatic, and acoustic representations may be similar. The finding that the organization of the somatic representation in the SC is similar to, and in register with, the visual representation is consistent with this possibility. It is suggested that the SC can utilize cues from a variety of modalities in order to facilitate appropriate orientation behavior.     

Contrast gain control in auditory cortex

The auditory system must represent sounds with a wide range of statistical properties. One important property is the spectrotemporal contrast in the acoustic environment: the variation in sound pressure in each frequency band, relative to the mean pressure. We show that neurons in ferret auditory cortex rescale their gain to partially compensate for the spectrotemporal contrast of recent stimulation. When contrast is low, neurons increase their gain, becoming more sensitive to small changes in the stimulus, although the effectiveness of contrast gain control is reduced at low mean levels. Gain is primarily determined by contrast near each neuron's preferred frequency, but there is also a contribution from contrast in more distant frequency bands. Neural responses are modulated by contrast over timescales of ～100?ms. By using contrast gain control to expand or compress the representation of its inputs, the auditory system may be seeking an efficient coding of natural sounds.     

Genomic homology of the domestic ferret with cats and humans

We used chromosome paints from both the domestic cat and humans to directly establish chromosomal homology between the genome of these species and the domestic ferret. The chromosome painting data indicate that the ferret has a highly conserved karyotype closer to the ancestral carnivore karyotype than that of the cat. The cat chromosome paints revealed 22 homologous autosomal regions in the ferret genome: 16 ferret chromosomes were hybridized by a single cat paint, while 3 ferret chromosomes were hybridized by two cat paints. In situ hybridization combined with banding showed that ferret Chromosome (Chr) 1 = cat A2p/C2, Chr 2 = F2/C1q, and Chr 3 = A2q/D2. Five ferret chromosomes are homologous to single arms of cat chromosomes: ferret 4 = A1q, 5 = B1q, 6 = C1p, 10 = A1p, and 12 = B1p. The human chromosome paints revealed 32 + XY homologous regions in the ferret genome: 9 ferret chromosomes were each hybridized by a single human paint, 7 by two paints, 3 by three paints. The 10 ferret chromosomes hybridized by multiple human paints produced the following associations: ferret 1 = human 19/3/21, 2 = 8q/2q, 3 = 10/7, 5 = 8/4, 8 = 15/14, 9 = 10/12/22, 11 = 20/2, 12 = 8/4, 14 = 12/22/18, 18 = 19/16. We present an index of genomic diversity, Z, based on the relative number of conserved whole chromosome and chromosome segments as a preliminary statistic for rapid comparison between species. The index of diversity between human-ferret (Z = 0.812) is slightly less than human-cat (Z = 0.843). The homology data presented here allow us to transfer gene mapping data from both cats and humans to the ferret. Received: 21 December 1999 / Accepted: 30 May 2000     

SEP topographies elicited by innocuous and noxious sural nerve stimulation. II. Effects of stimulus intensity on topographic pattern and amplitude

The effects of innocuous and noxious sural nerve stimulation on the SEP scalp topography were examined in 15 human subjects. This analysis focused on the 6 stable periods (i.e., consecutive time points where the topography did not change) that were identified in the companion paper (Dowman 1994). Stable period 1 (SP1: 58–90 msec post stimulus), SP4 (178–222 msec) and SP5 (223–277 msec) showed amplitude-stimulus intensity relationships that are similar to those of neurons involved in the sensory-discriminative aspects of innocuous somatosensation. The SP1 topographic pattern showed little or no change across the innocuous and noxious stimulus levels, which together with the amplitude data suggests that SP1 is largely generated by neurons involved in innocuous somatosensation. The SP4 topographic pattern did not change appreciably across the innocuous and noxious stimulus levels, but its aplitude decreased with increasing noxious stimulation. These data suggest that SP4 is generated by neurons involved in innocuous somatosensation and that noxious inputs inhibit these cells. There were differences in the SP5 topographic patterns evoked at the innocuous and the noxious stimulus levels, which suggest SP5 also receives a contribution from neurons involved in noxious somatosensation. SP3 (135–157 msec) and SP6 (282–339 msec) are probably generated by neurons involved in noxious somatosensation. The topographic patterns of both were different at innocuous and noxious levels. SP3's amplitude-stimulus intensity function suggests that it is generated by neurons that respond to noxious inputs in a non-graded fashion. The amplitude and offset latency of SP6 increased with increasing noxious stimulation, which suggests that SP6 is generated by neurons that respond to noxious inputs in a graded fashion.     

Multisensory integration in the superior colliculus: a neural network model

Neurons in the superior colliculus (SC) are known to integrate stimuli of different modalities (e.g., visual and auditory) following specific properties. In this work, we present a mathematical model of the integrative response of SC neurons, in order to suggest a possible physiological mechanism underlying multisensory integration in SC. The model includes three distinct neural areas: two unimodal areas (auditory and visual) are devoted to a topological representation of external stimuli, and communicate via synaptic connections with a third downstream area (in the SC) responsible for multisensory integration. The present simulations show that the model, with a single set of parameters, can mimic various responses to different combinations of external stimuli including the inverse effectiveness, both in terms of multisensory enhancement and contrast, the existence of within- and cross-modality suppression between spatially disparate stimuli, a reduction of network settling time in response to cross-modal stimuli compared with individual stimuli. The model suggests that non-linearities in neural responses and synaptic (excitatory and inhibitory) connections can explain several aspects of multisensory integration.     

Morphological and physiological study of afferent projections of the posterolateral thalamic nucleus in rats

It was shown by the method of retrograde axonal transport of horseradish peroxidase that the posterolateral thalamic nucleus (NPL) in rats receives considerable ascending projections from the superior colliculus (SC), the dorsal part of the lateral geniculate body (LGB), and the pretectal region (PT) and smaller projections from n. ventralis posterior (VP) and n. ventralis lateralis (VL) of the thalamus, the ventral part of LGB, the zona incerta, and anterior hypothalamus. The most marked descending projections run into NPL from area 18A of the cortex and the dentate fascia of the hippocampus, whereas inputs from cortical areas 18, 20, 7, 29c, 17, and 36 are less marked. In electrophysiological experiments with peripheral stimulation of visual, auditory, and somatosensory systems, polysensory convergence and interaction between signals from these systems were studied during isolated and simultaneous presentation of heterosensory stimuli. Of 229 neurons tested, 134 (58.5%) responded to at least one of the stimuli mentioned. Among monomodal neurons (53 of 134) there were some cells which responded to visual (77.4%) and somatic (22.6%) stimulation; neurons which responded only to acoustic stimulation were not found in the nucleus. As far as polymodal neurons (81 of 134) responding to two or three sensory stimuli are concerned, the most effective inputs of these units were visual and somatosensory. Interaction between stimuli acting on polymodal neurons was expressed as mutual inhibition or facilitation of responses; opposite effects could be observed on the various components of these responses.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 168–176, March–April, 1984.