Mindfulness meditation-related pain relief: evidence for unique brain mechanisms in the regulation of pain.

The cognitive modulation of pain is influenced by a number of factors ranging from attention, beliefs, conditioning, expectations, mood, and the regulation of emotional responses to noxious sensory events. Recently, mindfulness meditation has been found attenuate pain through some of these mechanisms including enhanced cognitive and emotional control, as well as altering the contextual evaluation of sensory events. This review discusses the brain mechanisms involved in mindfulness meditation-related pain relief across different meditative techniques, expertise and training levels, experimental procedures, and neuroimaging methodologies. Converging lines of neuroimaging evidence reveal that mindfulness meditation-related pain relief is associated with unique appraisal cognitive processes depending on expertise level and meditation tradition. Moreover, it is postulated that mindfulness meditation-related pain relief may share a common final pathway with other cognitive techniques in the modulation of pain.

Neurofilament proteins are preferentially expressed in descending output neurons of the cat the superior colliculus: a study using SMI-32.

Physiological studies indicate that the output neurons in the multisensory (i.e. intermediate and deep) laminae of the cat superior colliculus receive converging information from widespread regions of the neuraxis, integrate this information, and then relay the product to regions of the brainstem involved in the control of head and eye movements. Yet, an understanding of the neuroanatomy of these converging afferents has been hampered because many terminals contact distal dendrites that are difficult to label with the neurochemical markers generally used to visualize superior colliculus output neurons. Here we show that the SMI-32 antibody, directed at the non-phosphorylated epitopes of high molecular weight neurofilament proteins, is an effective marker for these superior colliculus output neurons. It is also one that can label their distal dendrites. Superior colliculus sections processed for SMI-32 revealed numerous labeled neurons with varying morphologies within the deep laminae. In contrast, few labeled neurons were observed in the superficial laminae. Neurons with large somata in the lateral aspects of the deep superior colliculus were particularly well labeled, and many of their secondary and tertiary dendrites were clearly visible. Injections of the fluorescent biotinylated dextran amine into the pontine reticular formation revealed that approximately 80% of the SMI-32 immunostained neurons also contained retrogradely transported biotinylated dextran amine, indicating that SMI-32 is a common cytoskeletal component expressed in descending output neurons. Superior colliculus output neurons also are known to express the calcium-binding protein parvalbumin, and many SMI-32 immunostained neurons also proved to be parvalbumin immunostained. These studies suggest that SMI-32 can serve as a useful immunohistochemical marker for detailing the somatic and dendritic morphology of superior colliculus output neurons and for facilitating evaluations of their input/output relationships.

Early establishment of adult-like nigrotectal architecture in the neonatal cat: a double-labeling study using carbocyanine dyes.

Virtually nothing is known about the ontogeny of substantia nigra, pars reticulata projections to the midbrain superior colliculus, even though this pathway is critical for the basal ganglia modulation of midbrain-mediated visuomotor behaviors. The present studies used the lipophilic carbocyanine dyes 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate and 1,1'-dioctodecyl-3,3,3',3'-tetramethylindodi, 4-chlorobenzenesulfonate salt to examine the crossed and uncrossed nigrotectal projections in neonatal cats, from parturition to 14 days postnatal (the technical limits of the tracing technique). In retrograde experiments, paired placement of the dyes in each superior colliculus produced numerous retrogradely-labeled nigrotectal neurons, with the uncrossed neurons far out numbering their crossed counterparts. No double-labeled neurons were observed, indicating that crossed and uncrossed nigrotectal neurons are segregated at birth. In anterograde experiments, dye placements into each substantia nigra, pars reticulata resulted in an iterative series of labeled patches, aligned medial-to-lateral across the intermediate and deep superior colliculus, a pattern reminiscent of the adult. Uncrossed neonatal axons had simple linear morphologies with few branch points; by contrast, crossed axons displayed more extensive terminal arbors that were distributed diffusely throughout the rostrocaudal extent of the contralateral superior colliculus In the final series of experiments, one dye was placed unilaterally in the substantia nigra, pars reticulata, while the second dye was positioned in the predorsal bundle, in order to bilaterally label superior colliculus output neurons. Although both crossed and uncrossed axons appeared to have contacted superior colliculus output neurons, crossed axons preferentially targeted the soma and proximal dendrites, whereas uncrossed terminals were distributed more distally. Throughout this early postnatal period, no significant changes in cellular morphologies or gross modification of terminal projection patterns were observed; however, the presence of growth cones in even the oldest animals studied suggests that the refinement of the nigrotectal projections extends well into postnatal life. Nevertheless, the segregation of crossed and uncrossed nigrotectal neurons into a highly organized afferent mosaic that has established synaptic contacts with superior colliculus output neurons indicates that many of the salient features characterizing nigrotectal projections are established prior to the onset of visual experience.

A direct projection from superior colliculus to substantia nigra pars compacta in the cat.

Dopaminergic neurons exhibit a short-latency, phasic response to unexpected, biologically salient stimuli. The midbrain superior colliculus also is sensitive to such stimuli, exhibits sensory responses with latencies reliably less than those of dopaminergic neurons, and, in rat, has been shown to send direct projections to regions of the substantia nigra and ventral tegmental area containing dopaminergic neurons (e.g. pars compacta). Recent electrophysiological and electrochemical evidence also suggests that tectonigral connections may be critical for relaying short-latency (<100 ms) visual information to midbrain dopaminergic neurons. By investigating the tectonigral projection in the cat, the present study sought to establish whether this pathway is a specialization of the rodent, or whether it may be a more general feature of mammalian neuroanatomy. Anterogradely and retrogradely transported anatomical tracers were injected into the superior colliculus and substantia nigra pars compacta, respectively, of adult cats. In the anterograde experiments, abundant fibers and terminals labeled with either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin were seen in close association with tyrosine hydroxylase-positive (dopaminergic) somata and processes in substantia nigra pars compacta and the ventral tegmental area. In the retrograde experiments, injections of biotinylated dextran amine into substantia nigra produced significant retrograde labeling of tectonigral neurons of origin in the intermediate and deep layers of the ipsilateral superior colliculus. Approximately half of these biotinylated dextran amine-labeled neurons were, in each case, shown to be immunopositive for the calcium binding proteins, parvalbumin or calbindin. Significantly, virtually no retrogradely labeled neurons were found either in the superficial layers of the superior colliculus or among the large tecto-reticulospinal output neurons. Taken in conjunction with recent data in the rat, the results of this study suggest that the tectonigral projection may be a common feature of mammalian midbrain architecture. As such, it may represent an additional route by which short-latency sensory information can influence basal ganglia function.

Quantitative assessment of developing afferent patterns in the cat inferior colliculus revealed with calbindin immunohistochemistry and tract tracing methods.

The central nucleus of the inferior colliculus (CNIC) is comprised of an orderly series of fibrodendritic layers. These layers include integrative circuitry for as many as 13 different ascending auditory pathways, each tonotopically ordered. Calcium-binding proteins, such as calbindin-D28k (CB), may be useful neurochemical markers for specific subsets of afferent input in these layers and their spatial organization that are developmentally regulated. In this study, CB-immunohistochemistry was used to examine 1-42 postnatal-day-old kitten and adult cat CNIC and anterograde tracers were used to label afferent projections from the lateral superior olivary nucleus (LSO) to the CNIC at similar ages. A distinct axonal plexus that is CB-immunopositive is described. This CB-afferent compartment is present at birth and persists throughout the ages examined. Already at birth, the CB-immunostained plexus in kitten CNIC is organized into discrete bands that are approximately 75 microm thick and 500 microm long. In adult CNIC, the periodic banded pattern of CB-immunostained fibers is similar to that in kittens albeit bands are thicker (145 microm) and longer (700 microm). Growth in band thickness in adult cat appears proportional to growth of the IC, whereas length of the dense CB-immunostained bands is somewhat more focused in the central region of fibrodendritic layers. The banded pattern of the CB-immunostained plexus is well correlated with the location and dimension of afferent projections from the LSO in newborn kitten labeled with carbocyanine dye, 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate and in adult cat labeled with wheat germ agglutinin conjugated with horseradish peroxidase. The results reveal a neurochemical marker for one type of synaptic compartment in CNIC layers, banding, that is organized before hearing onset in kittens, but that may undergo some postnatal pruning.

Covariant maturation of nocifensive oral behaviour and c-fos expression in rat superior colliculus.

Injections of formalin into the rodent paw elicit a rapid orientation of the head and mouth to the source of discomfort, followed by licking and biting the injected area. Previous work has shown this response is dependent on the integrity of the midbrain superior colliculus. The present experiments were initiated to examine the ontogeny of this oral nocifensive reaction and to determine whether it is correlated with the functional maturation of collicular responses to noxious stimuli (as indicated by c-fos immunohistochemistry). Rat pups at various postnatal ages received formalin injections in either the hindpaw or perioral regions. Behaviour was videotaped, and after 120 min, animals were killed and the brain and spinal cord processed for Fos-like immunoreactivity. Uninjected controls were treated identically. Formalin-induced oral responses following injections into the hindpaw and the expression of Fos in the superior colliculus were virtually absent until 10 days postnatal, despite the presence of Fos-like immunoreactivity in many other structures (e.g. spinal cord, parabrachial area, periaqueductal grey). In contrast, animals from day 1 were able to use limbs to localise the perioral injection site. From day 10 onward, there was a progressive increase in oral nocifensive behaviours and Fos expression in the superior colliculus. Our observations are consistent with the hypothesis that the normal elaboration of pain-induced oral behaviour is initiated only after a functionally active superior colliculus has developed, and support previous observations that link the colliculus particularly with oral nocifensive behaviours.

Corticotectal and corticostriatal projections from the frontal eye fields of the cat: an anatomical examination using WGA-HRP.

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.

Distribution of the calcium-binding proteins calbindin D-28K and parvalbumin in the superior colliculus of adult and neonatal cat and rhesus monkey.

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.

Parallel analyses of nociceptive neurones in rat superior colliculus by using c-fos immunohistochemistry and electrophysiology under different conditions of anaesthesia.

Multiple sensory inputs to the superior colliculus (SC) play an important role in guiding head and eye movements toward or away from biologically significant stimuli. Much is now known about the visual, auditory, and somatosensory response properties of SC neurones that mediate these behavioural reactions. Rather less is known about the responses of SC neurones to noxious stimuli, and thus far, most of this information has been obtained in anaesthetised animals. Therefore, the purpose of the present study was to use the c-fos immunohistochemical technique and standard extracellular electrophysiology as parallel measures of nociceptive activity in the SC under different conditions of anaesthesia. In unanaesthetised animals, experimental and control treatments induced a qualitatively similar pattern of Fos-like immunoreactivity (FLI) in the SC, which was quantitatively related to the severity or biologic salience of the treatment; thus, baseline control < control injections of saline < a nonpainful stressor (immobilisation) < noxious injections of formalin. Compared with baseline levels, urethane and avertin anaesthesia induced FLI expression in the SC intermediate layers, although the FLI response to both noxious stimulation and control conditions was differentially suppressed in different layers of the SC by anaesthesia. Parallel electrophysiologic recordings found that anaesthesia was associated with high levels of spontaneous activity in the SC intermediate layers, often in neurones which were also nociceptive. High rates of background spike activity were also induced in the SC intermediate layers by noxious stimulation in chronically recorded awake animals. Although these results point to some differences between the nociceptive responses of SC neurones in anaesthetised and unanaesthetised animals, both data sets support the view that there are different populations of nociceptive neurones in the rodent SC that may be related to different adaptive functions of pain.

Visual response properties and visuotopic representation in the newborn monkey superior colliculus.

Visual response properties and visuotopic representation in the newborn monkey superior colliculus. J. Neurophysiol. 78: 2732-2741, 1997. Visually responsive neurons were recorded in the superior colliculus (SC) of the newborn rhesus monkey. The receptive fields of these neurons were larger than those in the adult, but already were organized into a well-ordered map of visual space that was very much like that seen in mature animals. This included a marked expansion of the representation of the central 10 degrees of the visual field and a systematic foveal to peripheral increase in receptive field size. Although newborn SC neurons had longer response latencies than did their adult counterparts, they responded vigorously to visual stimuli and exhibited many visual response properties that are characteristic of the adult. These included surround inhibition, within-field spatial summation, within-field spatial inhibition, binocularity, and an adult-like ocular dominance distribution. As in the adult, SC neurons in the newborn preferred a moving visual stimulus and had adult-like selectivities for stimulus speed. The developmentally advanced state of the functional circuitry of the newborn monkey SC contrasts with the comparative immaturity of neurons in its visual cortex. It also contrasts with observations on the state of maturation of the newborn SC in other developmental models (e.g., cat). The observation that extensive visual experience is not necessary for the development of many adult-like SC response properties in the monkey SC may help explain the substantial visual capabilities shown by primates soon after birth.

Response properties of corticotectal and corticostriatal neurons in the posterior lateral suprasylvian cortex of the cat.

Lateral suprasylvian cortex (LS) is an important source of visual projections to both the striatum and superior colliculus. Although these two LS efferent systems are likely to be involved in different aspects of visual processing, little is known about their functional properties. In the present experiments, 86 neurons in halothane-anesthetized, paralyzed cats were recorded along the posterior aspects of the medial and lateral banks of LS (PMLS and PLLS). Neurons were selected for analysis on the basis of antidromic activation from electrodes chronically implanted in the superior colliculus and caudate nucleus. The segregated nature of corticostriatal and corticotectal neurons was apparent; in no instance could a neuron be antidromically activated from both the superior colliculus and the caudate nucleus. Many common features were revealed between corticotectal and corticostriatal neurons; the majority of neurons in both populations were binocular and contralaterally dominant, showed similar responses to stationary flashed light, and expressed within-field spatial summation and surround inhibition. However, a number of information-processing features distinguished between corticotectal and corticostriatal neurons; the former were generally tuned to lower velocities than were the latter, and, for a given eccentricity in visual space, corticotectal neurons had smaller receptive fields than did corticostriatal neurons. Moreover, most corticotectal neurons displayed a marked preference for movements toward temporal visual space, whereas corticostriatal neurons revealed no specialization for a particular direction of movement. In addition, whereas corticotectal neurons were selective for receding stimuli, corticostriatal neurons were selective for approaching stimuli. The presence of these two corticofugal pathways is discussed in relation to their presumptive functional roles in the facilitation of attentive and orientation behaviors.

A simple enzyme histochemical method for the simultaneous demonstration of acetylcholinesterase and monoamine oxidase in fixed-frozen sections.

We describe an enzyme histochemical technique for the simultaneous demonstration of acetylcholinesterase (AChE) and monoamine oxidase (MAO) (Types A, B, or A+B) in fixed-frozen sections. Several regions in the mesencephalon and brainstem were examined for both somatic and neuropil labeling. The results obtained are equivalent or superior to those obtained using previous methods for the individual localization of these enzymes. The simultaneous visualization of AChE and MAO in the same section allows the relationship of the two enzymes to be easily assessed with brightfield microscopy.

Nociceptive neurones in rat superior colliculus. I. Antidromic activation from the contralateral predorsal bundle.

Accumulating evidence suggests that the rodent superior colliculus (SC) plays as important a role in avoidance and defensive behaviours as it does in orientation and approach. These two complementary behaviours are associated with two anatomically segregated tectofugal output pathways, such that orientation and approach are mediated by the crossed descending projection, whereas avoidance and defence are subserved via the uncrossed projection. Because nociceptive neurones in the SC have been presumed to participate in withdrawal or defensive behaviours, it has been proposed that they have direct access only to the uncrossed efferent pathway. However, in certain behavioural situations, the most adaptive response to injury, or to a painful object in prolonged contact with the skin, is to orient towards the source of discomfort so that the skin can be licked and/or the offending object removed. Presumably then, nociceptive as well as low-threshold neurones would have access to the crossed descending pathway in order to initiate such behaviours. Determining whether or not this is the case was the objective of the present study. Both nociceptive-specific (82%) and wide-dynamic-range (18%) SC neurones were identified using long-duration (up to 6 s), frankly noxious mechanical and thermal stimuli in urethane-anaesthetised Long-Evans hooded rats. The majority (85.7%) of the nociceptive neurones encountered were located within the intermediate layers, which corresponds with the location of the cells-of-origin of the crossed descending projection. Nearly half (44.9%) were activated antidromically from electrical stimulation of the crossed descending pathway at a site in the brainstem below its decussation. The mean conduction velocity of these nociceptive output neurones was 9.02 m/s, which corresponds well to previous estimates of conduction velocity in the crossed tecto-reticulo-spinal tract. These data demonstrate that a significant proportion of nociceptive neurones in the rat SC have axons that project to the contralateral brainstem via the crossed descending projection. Nociceptive neurones could, therefore, effect orientation responses to noxious stimuli via similar output pathways that low-threshold neurones utilize to initiate orientation to innocuous stimuli.

Nociceptive neurones in rat superior colliculus. II. Effects of lesions to the contralateral descending output pathway on nocifensive behaviours.

A wealth of evidence implicates the crossed descending projection from the superior colliculus (SC) in orientation and approach behaviours directed towards novel, non-noxious stimuli. In our preceding paper, we identified a population of nociceptive neurones in the rat SC that have axons that project to the contralateral brainstem via this output pathway. The purpose of the present study was, therefore, to evaluate the prediction that the crossed descending projection of the SC is also involved in the control of orientation and approach movements of the head and mouth made during the localisation of persistent noxious stimuli. An independent-groups design was used to test the effects of interrupting the contralateral descending projection from the SC on the behavioural reactions elicited by noxious mechanical stimuli presented to the tail and hindpaws. In different groups of animals, a microwire knife was used to cut the contralateral descending fibres at two different locations: (1) a sagittal cut at the level of the dorsal tegmental decussation; (2) a bilateral coronal cut of the predorsal bundle at the level of the medial pontine reticular formation. Retrograde anatomical tracing techniques were then used to evaluate the effectiveness of the cuts and to assess possible involvement of non-collicular fibre systems in both lesioned and control animals. Additional behavioural procedures were performed to test for general neurological status and responsiveness of animals to non-noxious stimuli. Anatomical tracing data indicated that the largest population of neurones with fibres severed by both cuts were the cells-of-origin of the contralateral descending projection in the intermediate white layer of the SC. Behavioural results showed that significantly more animals in both lesion groups failed to locate and bite a mechanical clip placed on the tail. Instead of switching to motor behaviours to localise and remove noxious stimuli, they persisted with defensive reactions, which included freezing, vocalisation or forward and backward escape. In contrast, when the clip was placed on the hindpaws, it was successfully localised by most lesioned and control animals; however, lesioned animals had reliably longer latencies and spent less time in close contact with the clip. Consistent with the established role of the contralateral descending projection in non-noxious orientation, lesioned animals also showed orienting deficits to a range of non-noxious sensory stimuli. These data suggest that, under certain behavioural circumstances, nociceptive information from the SC is integral to the elaboration of orienting and approach movements of the head and mouth elicited by persistent noxious stimuli.

Extrinsic and intrinsic connections of the cat's lateral suprasylvian visual area.

The lateral suprasylvian visual area (LS) is known to have numerous interconnections with visual cortical areas as well as with subcortical structures implicated in visually-guided behaviors. In contrast, little data is available regarding connections within the LS itself. In order to obtain information about intra-areal connections and to re-investigate LS connectivity with various cortical and subcortical areas, the traces (biocytin or WGA-HRP) was injected into various loci along the medial and lateral banks of the LS. The anterograde tracer, biocytin injections into both medial and lateral bank produced label contained within the respective bank that extended rostrally and caudally from the infection site. In addition, following medical bank injections, considerable label was distributed throughout the fundus and, to a lesser extent, in the lateral bank. In contrast, no label could be detected in the medial bank after lateral bank injections, and, although label was observed in the fundus, it was restricted to the most lateral aspects. Moderate labeling could be observed in the medial bank following the tracer injection into the most rostral aspect of the lateral bank. It is likely that input derived from various visual cortical areas which project to the medial bank of the LS has access to this intra-areal circuitry. This may provide a route by which visual cortical information can be relayed to other cortical and subcortical structures involved in visually-guided behaviors such as the anterior ectosylvian visual cortex, striatum, and the deep layers of the superior colliculus, despite the fact that these structures themselves do not receive substantial direct projections from the visual cortical areas that are associated with the medial bank. Examination of the laminar location of the cells-of-origin of striate and extrastriate projections to LS using retrograde trace, WGA-HRP, revealed that the supragranular laminae of areas 17, 18 and 19 were the source of LS afferents whereas afferents from the other cortical areas (e.g., 20a, 20b, 21a, 21b, 7 and anterior ectosylvian visual area) were from both supra- and infragranular laminae. In addition, all LS subregions received intra-areal afferent projections from all LS cortical laminae. Thus, although rather clear hierarchical relationship between LS and visual cortical areas appears to exist, the interconnections among LS subregions provide no clear evidence of simple hierarchical relationships between regions LS or may have feed-forward and feed-back pathways.

Corticostriatal and corticotectal projections from visual cortical areas 17, 18 and 18a in the pigmented rat.

Regions of the visual cortex and the deep layers of the superior colliculus (SC) have been suggested to be functionally linked via an 'indirect' pathway through the basal ganglia. The present report demonstrates projections from the striate (area 17) and extrastriate (areas 18 and 18a) visual cortex in Long-Evans hooded rats to the striatum (ST) and SC with anterograde (biocytin) and retrograde (WGA-HRP and fluorescent dyes) tracers. Biocytin injections into each cortical area produced markedly different patterns of labeling in ST and SC. Injections into area 17 resulted in a dense labeling in the superficial layers of SC, with little labeling present in the deep layers of SC or ST. In contrast, injections into area 18a, which produced marked labeling in the deep layers of SC with moderate in the superficial layers, resulted in dense labeling in the caudal two-thirds of the dorsal region of ST; injections into area 18 produced numerous terminals mainly in the deep layers of SC and in the rostral two-thirds of the dorsal aspect of ST. WGA-HRP injections into ST resulted in numerous retrogradely labeled pyramidal neurons in areas 18 and 18a, but only a few labeled neurons were observed in area 17. Corticostriatal neurons in extrastriate visual cortex were distributed predominantly in layer V, with smaller numbers in layers II and III, whereas corticotectal neurons were located only in layer V of both the striate and extrastriate visual cortex. Although corticostriatal and corticotectal neurons were intermingled in layer V, no double-labeled neurons were observed following injections of different fluorescent dyes into ST and SC. It appears, therefore, that: 1) the major source of visual input to both ST and the deep layers of SC in the rat arises not from the primary visual cortex but from extrastriate visual areas; and that 2) the projections from the extrastriate visual area to ST and SC originate from different populations of corticofugal neurons.

Response properties of nociceptive and low-threshold neurons in rat trigeminal pars caudalis.

There is little doubt that trigeminal nociceptive neurons play a critical role in signaling the presence of harmful, or potentially harmful, orofacial stimuli. Unfortunately, there is only a limited understanding of how these neurons code such stimuli and whether this code is maintained in those structures responsible for generating overt reactions. The present series of experiments were designed to quantitatively document the response properties of nociceptive neurons in the rat trigeminal pars caudalis using the same electrical and innocuous and/or noxious mechanical and thermal stimuli employed in the characterization of nociceptive neurons with orofacial receptive fields in the rat superior colliculus. Neurons were classified as either low-threshold mechanoreceptive, wide-dynamic-range, or nociceptive-specific (type I, II) depending on their responsiveness to these stimuli. Nociceptive pars caudalis neurons (92/135, 68%) had receptive field organizations and input fibers (as indicated by latencies to electrical stimuli) quite different from those of low-threshold neurons (43/135, 32%). Nociceptive stimulus-response relationships for the population of wide-dynamic-range and nociceptive-specific type I neurons to contact heat stimuli were positively accelerating power functions with exponents of 3.9 and 4.4, respectively. This contrasted sharply with the low-threshold component of wide-dynamic-range neurons which was a negatively accelerating power function with an exponent of 0.7. All categories of nociceptive neurons also responded vigorously to cold stimuli. The thresholds of both hot and cold stimuli were often below psychophysical estimates of thermal pain, suggesting that "nociceptive" neurons process far more information than that required to signal potentially harmful stimuli. The fundamental similarities in nociceptive properties in pars caudalis and other structures of the central nervous system suggest that there is little transformation of the information encoded at successive levels of the neuraxis. This is consistent with the idea that the functional role of nociceptive neurons is reflected more in which circuits they are integrated and less in differences in their physiological properties.

Functional development of a central visual map in cat.

1. The onset of visual activity in the superficial layers of the cat superior colliculus begins abruptly at about 6 days postnatal (DPN), just before natural eye opening. Despite the presence of many inactive sites at this time, the systematic nature of the superior colliculus visuotopy is already evident. The number of inactive sites across the horizontal dimension of the superficial layers decreases rapidly so that by 9-10 DPN most sites are visually responsive. 2. Initially, visual activity is restricted to the topmost portion of the superficial gray layer, where W-cell terminals predominate, but rapidly extends down to include Y-cell territory at 10 DPN. 3. In contrast to what might have been expected based on earlier behavioral observations, there was no physiological evidence for a central-to-peripheral gradient in the development of the superior colliculus visuotopy. Rather, the entire visual field is well represented long before the expression of any visually initiated behaviors. 4. In contrast to the rapidity of the appearance and organization of the visual representation in superficial layers, deep layers remain refractory to visual stimuli for weeks.