The use and abuse of wound care materials in the treatment of diabetic ulcerations.

With the ever-increasing availability of wound care materials for use in diabetic foot ulcerations, a thorough understanding of the indications and applications of these materials is important for wound-management success. The coupling of a lack of understanding of the interaction of wound care materials and the dynamic nature of wound-healing physiology may lead to a protracted healing course that may constitute an abuse of an otherwise useful adjunct to wound healing protocols. This article provides an overview of wound care products, their indications, and possible complications of inappropriate use.

Wound management in the diabetic foot.

The multiple opinions expressed in this Grand Rounds section make it clear that management of the diabetic patient with a foot wound is complex at best. Several significant points are repeated many times. The need for a detailed history and physical exam, accurate assessment of neurologic, vascular, metabolic status, and addressing the etiologic factor involved are all essential. All authors point to multispecialty integrated treatment protocols to produce the greatest success. Little mention is made of the use of topical agents to accelerate healing. This is due to the lack of unbiased studies, and the many available reports that demonstrate rapid healing when a complete and objective protocol is followed. The aims of this Grand Rounds are to stimulate interest in this important subject, and to provide the practitioner with a scaffold with which to build their own wound care management protocols.

Differential effects of peripheral manipulations on vibrissae-related patterns in the trigeminal brainstem.

The expression of galanin and neuropeptide Y (NPY) by primary afferent neurons, including those in the trigeminal (V) system, is markedly up-regulated after peripheral nerve damage and might be expected to influence the response of central somatosensory cells to such damage. In the present study, we assessed the effects of four manipulations that have been used to study development and maintenance of vibrissae-related patterns in the V system-nerve transection, whisker clipping, activity blockade with tetrodotoxin (TTX), and axoplasmic transport attenuation with vinblastine-upon the expression of galanin and NPY by V ganglion cells and their central axons in the V brainstem complex. Both neonatal transection of the infraorbital nerve (ION) and application of vinblastine to it resulted in a marked up-regulation of galanin and NPY in V ganglion cells and their central axon arbors in animals killed on postnatal day 6. Neither whisker clipping nor application of TTX to the ION produced such changes. Both ION transection and application of vinblastine to this nerve resulted in a loss of vibrissae-related cellular patterns in the brainstem, but TTX application and whisker clipping did not. These results raise the possibility that up-regulation of galanin and NPY may play a role in the disappearance of vibrissae-related cellular patterns in the brainstem of rats that sustain neonatal ION damage.

Effects of load inversion in cockroach walking.

To examine how walking patterns are adapted to changes in load, we recorded leg movements and muscle activities when cockroaches (Periplaneta americana) walked upright and on an inverted surface. Animals were videotaped to measure the hindleg femoro-tibial joint angle while myograms were taken from the tibial extensor and flexor muscles. The joint is rapidly flexed during swing and extended in stance in upright and inverted walking. When inverted, however, swing is shorter in duration and the joint traverses a range of angles further in extension. In slow upright walking, slow flexor motoneurons fire during swing and the slow extensor in stance, although a period of co-contraction occurs early in stance. In inverted walking, patterns of muscle activities are altered. Fast flexor motoneurons fire both in the swing phase and early in stance to support the body by pulling the animal toward the substrate. Extensor firing occurs late in stance to propel the animal forward. These findings are discussed within the context of a model in which stance is divided into an early support and subsequent propulsion phase. We also discuss how these changes in use of the hindleg may represent adaptations to the reversal of the effects of gravity.

Effects of postnatal blockage of cortical activity with tetrodotoxin upon lesion-induced reorganization of vibrissae-related patterns in the somatosensory cortex of rat.

Previous studies have shown that postnatal blockade of thalamocortical activity with either tetrodotoxin (TTX) or the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (APV) does not prevent the formation of vibrissae-related patterns. In the present study, blockade of cortical activity with TTX was combined with ablation of a row of vibrissae follicles or transection of the infraorbital nerve (ION, the trigeminal nerve branch that supplies the vibrissae follicles) to determine whether the cortical reorganization that follows these lesions in otherwise untreated animals was dependent upon neuronal activity that could be blocked with TTX. The results demonstrated that cortical TTX implants had no quantitative or qualitative effects upon the cortical reorganization that followed either vibrissae follicle cauterization or ION transection.

Effects of postnatal blockade of cortical activity with tetrodotoxin upon the development and plasticity of vibrissa-related patterns in the somatosensory cortex of hamsters.

Several previous studies have shown that postnatal blockade of thalamocortical activity with either tetrodotoxin (TTX) or the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovalerate (APV) does not prevent the formation of vibrissa-related patterns in the primary somatosensory cortex of rats. One limitation of these studies is that this pattern forms very shortly after birth in rats, and there may be only a very limited time over which it may be influenced by activity blockade. In the present study, the effect of activity blockade was evaluated in a more altricial rodent, the hamster. The present study showed that a pattern of thalamocortical afferents corresponding to the vibrissae is not observed until the fourth postnatal day in hamsters. Nevertheless, application of TTX-impregnated implants to the cortices of newborn hamsters had no qualitative or quantitative effect upon vibrissa-related patterns in the primary somatosensory cortices of these animals. Moreover, TTX implants did not prevent the changes in patterns that followed cauterization of a row of vibrissa follicles.

Postnatal blockade of cortical activity by tetrodotoxin does not disrupt the formation of vibrissa-related patterns in the rat's somatosensory cortex.

Neuronal activity has been shown to influence pattern formation in the visual system. In the present study, we determined whether or not this was also true in the somatosensory system by silencing the primary somatosensory cortex of rats with tetrodotoxin (TTX) for the first 7-11 days of life. Application of TTX during this period did not prevent the formation of the normal vibrissa-related pattern in S-I as visualized by either staining cortical sections for cytochrome oxidase, demonstration of the pattern with an antibody directed against serotonin, or labelling of thalamocortical axons with the carbocyanine dye, Di-I. These results indicate that neither peripherally evoked nor spontaneous activity are required for qualitatively normal pattern formation in the rat's primary somatosensory cortex.

Thalamic processing of vibrissal information in the rat. I. Afferent input to the medial ventral posterior and posterior nuclei.

Retrograde tracing with true blue (TB) and diamidino yellow (DY) and anterograde tracing with either wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) or Phaseolus vulgaris leucoagglutinin (PHA-L) were employed to investigate the projections from trigeminal nucleus principalis (PrV) and trigeminal subnucleus interpolaris (SpI) to their targets in the medial ventral posterior (VPM) and posterior (POm) nuclei of the thalamus. Many more cells in both PrV and SpI were labeled by tracer injections into VPM than into POm. Only a very small number of double-labeled neurons were observed in either PrV or SpI. However, a significantly higher percentage of SpI cells projected to POm or to both POm and VPM than was the case for PrV. Anterograde tracing with WGA-HRP showed that the projections from both PrV and SpI to VPM were much denser than those from the same nuclei to POm. Small injections of PHA-L into either PrV or SpI produced a focus of fairly dense labeling in VPM and much more diffuse terminal labeling in POm. These anatomical data provide evidence for two separate trigeminothalamic pathways, one originating from PrV and the second originating from SpI. Both of these pathways converge and diverge at the thalamic level. That is, information from the PrV pathway and from the SpI pathway are both provided to VPM in a morphologically restricted fashion and to POm in a morphologically widespread fashion.

Thalamic processing of vibrissal information in the rat: II. Morphological and functional properties of medial ventral posterior nucleus and posterior nucleus neurons.

Extracellular recording, intracellular recording, intracellular horseradish peroxidase injection, and receptive field mapping techniques were employed to evaluate the physiological and morphological properties of medial ventral posterior nucleus (VPM) and posterior nucleus (POm) neurons in normal adult rats. Overall, we physiologically characterized 148 VPM and 121 POm neurons. Over 82% of the VPM cells were excited only by deflection of one or more mystacial vibrissae, 10% were activated by displacement of guard hairs, and the remainder were either excited by indentation of the skin or were unresponsive. Less than 40% of the POm cells were activated by vibrissa deflection, 18% were excited by displacement of guard hairs, and another 17% were unresponsive. Most of the rest of the POm cells were excited by stimulation of skin, mucosa, or activation of muscle-related afferents. Small percentages of POm cells responded only to noxious stimulation, were classified as having a wide dynamic range, or were inhibited by peripheral stimulation. Electrical stimulation of either PrV or SpI activated most neurons in both VPM and POm. This excitation was almost invariably followed by a long-lasting hyperpolarization which was generally strong enough to prevent responses to either electrical stimuli delivered in the brainstem or mechanical stimulation of the periphery. The receptive fields of vibrissa-sensitive cells in POm were generally much larger than those of cells in VPM. Data obtained with extracellular recording indicated that VPM and POm cells responded to an average of 1.4 and 4.0 vibrissae, respectively. Intracellular recording from smaller samples of VPM and POm cells demonstrated the existence of inputs that were insufficient to produce spikes from the cell, but did yield epsp's. When both sub- and suprathreshold excitation were considered, the average number of vibrissa in the receptive field of a VPM cell was 2.7 and the value for POm cells became 7.8. HRP-filled neurons recovered in POm (N = 20) generally had much larger dendritic arbors than neurons in VPM (N = 31). For the former cells, the size of the dendritic tree was significantly correlated with the number of vibrissa to which the cell responded; for the latter neurons, it was not.

A transient projection from the trigeminal brainstem complex to the superficial layers of the hamster's superior colliculus.

Anterograde tracing with the carbocyanine dye, Di-I, was used to describe the normal postnatal development of the projection from the trigeminal (V) brainstem complex to the superior colliculus (SC) in hamster. In adult hamsters, this projection is completely restricted to the deep laminae, primarily the stratum album intermedium. Trigeminal fibers were present in the SC by the day of birth, and at this time, they terminated mainly in the deep layers. However, labelled fibers also extended into the superficial laminae (the stratum griseum superficiale and stratum opticum) reaching as far as the SC surface. Trigeminal projections to the superficial SC laminae were visible as late as postnatal day (P-) 6, but were absent by P-8. During the period when V axons were present in the superficial SC laminae, they could not be detected in the dorsal lateral geniculate nucleus.

Development of the occipital corticotectal projection in the hamster.

Anterograde and retrograde labelling with the carbocyanine dye, Di-I, was used to assess the development of the visual cortical projection to the superior colliculus (SC) in pre- and postnatal hamsters. Posterior cortical axons arrive in the SC on postnatal (P-) day one (the first 24 hours after birth = P-0) and begin to arborize in the superficial laminae (the stratum griseum superficiale [SGS] and stratum opticum [SO]) within one day after they enter the tectum. Over succeeding days, the density of the projection increases and numerous labelled fibers are visible throughout the depth of the SGS and SO. Beginning on P-6, there is a decrease in the density of labelled fibers in the upper SGS and by P-10, the laminal distribution of the occipital corticotectal pathway appears adult-like. Anterograde tracing with Di-I also revealed the presence of a few corticotectal fibers that crossed the midline in both the SC and posterior commissures to terminate mainly in the superficial tectal laminae contralateral to the injection site. Crossed corticotectal fibers were visible in hamsters aged between P-3 and P-12. Retrograde tracing with Di-I in hamsters killed between P-3 and P-12 demonstrated that both the ipsilateral and crossed corticotectal projections arose exclusively from pyramidal cells in developing lamina V.

Organization of the projections from the trigeminal brainstem complex to the superior colliculus in the rat and hamster: anterograde tracing with Phaseolus vulgaris leucoagglutinin and intra-axonal injection.

Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and intra-axonal recording and injection techniques were employed to describe the projection from the trigeminal (V) brainstem complex to the deep laminae of the superior colliculus (SC) in the hamster and the rat. The organization of these projections was the same in the two species. Deposits of PHA-L into V nucleus principalis (PrV) produced labelled axons and boutonlike swellings in the lower stratum griseum intermediale (SGI) and upper stratum album intermedium (SAI) in the SC bilaterally. Plots of boutonlike swellings indicated that the terminals of this projection were arrayed in clusters. Nucleus principalis also projected to the stratum griseum profundum (SGP) and stratum album profundum (SAP). This deeper projection did not terminate in clusters and it was most prominent in the lateral SC. The ipsilateral PrV-SC projection appeared to arise mainly from axons that recrossed the midline at the level of the SC commissure. Reconstruction of individual PHA-L labelled fibers demonstrated that single axons gave rise to terminals on both sides of the midline. Deposits of PHA-L into V subnucleus interpolaris (SpI) yielded results that were identical to those obtained with PrV injections with one exception: none of these deposits produced any labelled terminals in the ipsilateral SC. Deposits of PHA-L into V subnucleus caudalis (SpC) produced only sparse labelling in SC. Most labelled swellings were located in the SGP and SAP and they were visible only in the SC contralateral to the PHA-L injection site. Single axons arising from cells in SpI were recorded and injected with horseradish peroxidase (HRP) in the hamster's SC. These fibers all responded to stimulation of multiple mystacial vibrissae and gave rise to 2-5 clusters of bouton-like swellings in the lower SGI and upper SAI.

Organization of the projection from the superficial to the deep layers of the hamster's superior colliculus as demonstrated by the anterograde transport of Phaseolus vulgaris leucoagglutinin.

Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) was employed to describe the projection from the superficial to the deep layers of the hamster's superior colliculus (SC). Deposits of PHA-L in the stratum griseum superficiale (SGS) resulted in labelled terminal swellings in the stratum opticum and all of the deep laminae (the stratum griseum intermediate [SGI], stratum albumin intermedium [SAI], stratum griseum profundum [SGP], and stratum albumin profundum [SAP]). Labelled terminals were also visible in the periaqueductal gray (PAG). Reconstructions of individual axons showed that many collateral in the deep laminae arose from axons that projected to targets outside the colliculus. The projection from the superficial to the deep laminae had a loose topographic organization, and the trajectories of interlaminar axons were generally deflected laterally from "projection" lines that were orthogonal to the SC surface. Physiological recording and receptive field mapping were used to determine actual projection lines, which connect neurons in the superficial and deep layers that have receptive fields with the same elevation. These projection lines closely matched the trajectory of the pathway from the superficial to the deep laminae.

Distribution of visual callosal projection neurons in hamsters subjected to transection of the optic radiations on the day of birth.

The optic radiations of hamsters were transected on the day of birth and visual callosal projections in these animals were traced using retrograde transport of either horseradish peroxidase (HRP) or the fluorescent tracers True blue (TB) or Diamidino yellow (DY) when the animals reached maturity (greater than 45 days of age). In the hemisphere ipsilateral to the neonatal lesion, the distribution of callosal cells was markedly altered. These neurons were almost completely restricted to a continuous band in lower lamina V and the upper portion of layer VI. Anterograde HRP transport to the deafferented hemisphere also revealed an abnormal distribution of callosal terminals. The band of labelling that is located along the 17-18a border in the normals was much broader than is normally the case. In the hemisphere contralateral to the lesion, the distributions of callosal cells and terminals were essentially normal. Labelled neurons were located in the infragranular layers (primarily lower layer V and the upper part of lamina VI) throughout area 17 and also in layers II-IV in the 17-18a border region. Anterograde labelling was visible in layers V and VI throughout the mediolateral extent of the dorsal posterior neocortex and supragranular labelling was restricted to the lateral portion of area 17 and medial 18a. These results suggest that the normal thalamic projection to the visual cortex is necessary for the establishment of the strip of supragranular callosal projection neurons which is normally located in the 17-18a border region, but not for the establishment (or maintenance) of callosal projections by large numbers of neurons in the infragranular laminae. They show further that neonatal transection of the optic radiations results in reduction in the correspondence between the distributions of callosal cells and terminals in the deafferented hemisphere.

The structural and functional characteristics of striate cortical neurons that innervate the superior colliculus and lateral posterior nucleus in hamster.

Intracellular recording and horseradish peroxidase injection techniques were used to structurally and functionally characterize the striate cortical neurons in hamster that projected to the superior colliculus and/or lateral posterior nucleus of the thalamus. With two exceptions, the receptive field properties and morphological characteristics of the neurons antidromically activated from the colliculus and lateral posterior nucleus were quite similar. Striate corticotectal and striate cortico-lateral posterior neurons generally had non-oriented receptive fields which gave either "on-off' or no responses to flashed stimuli. Only a small number (less than 5%) were orientation selective, but about one-third were directionally selective. Most of the cells preferred movement with an upward component. Most striate corticotectal and cortico-lateral posterior cells responded to a wide range of stimulus velocities and exhibited little spatial summation. With the possible exception of two cells, all the projection neurons we recovered were large lamina V pyramidal cells whose apical dendrites extended to and branched extensively in layer I. All had extensive (in some cases over 1 mm) tangential axon collaterals, primarily in layers V and/or VI. The electrophysiological experiments also demonstrated that some (50% of a sample of 20 cells) corticotectal neurons also sent an axon collateral to the lateral posterior nucleus. Finally, our recordings showed that many (56% of a sample of 27 neurons) cells which could be antidromically activated from the lateral posterior nucleus, but not the superior colliculus had response latencies which exceeded those of almost all the cells which could be antidromically activated from the tectum. Retrograde transport of diamidino yellow and true blue confirmed the electrophysiological result that individual cortical neurons projected to both the superior colliculus and lateral posterior nucleus. These experiments showed that 20% of the striate cortical cells that projected into colliculus also sent an axon collateral to the lateral posterior nucleus.

Subcortical projections of area 17 in the anophthalmic mouse.

Anterograde and retrograde tracing methods were used to compare the subcortical projections of area 17 in ZRDCT-an, anophthalmic mice with those of sighted C57BL mice. In both groups, area 17 projected to the dorsocaudal striatum, the reticular, lateral and lateral posterior nuclei, the dorsal and vental lateral geniculate nuclei, the zona incerta, the anterior and posterior pretectal nuclei, the stratum griseum superficiale of the superior colliculus and the dorsolateral pons. Occasional labeled fibers in both groups were also seen in the ventrobasal nucleus, but it was not clear whether or not any axons terminated in this region. The projections to the superior colliculus and dorsal lateral geniculate nucleus were analyzed in greater detail. In both normals and blind mice the striate corticotectal projection arose from cells in layer V and that to the geniculate from neurons in lamina VI. The topographic organizations of these projections in the two groups were indistinguishable. The striate corticotectal projection to the colliculus in the anophthalmic mice did appear to terminate more dorsally in the stratum griseum superficiale than that in sighted animals. These data demonstrate that a signal from the retina is not required for either the restriction of 'visual' cortical axons to their normal subcortical targets or the achievement of normal topography within those target nuclei.

Projections to the cardioinhibitory region of the nucleus ambiguus of rat.

The nucleus ambiguus is a brainstem structure which sends projections through the vagus nerve to the viscera, primarily heart, lung, and gut. The anatomical relationship between the nucleus ambiguus and other brain structures has not been elucidated nor has the cardiac region been identified physiologically in rats. We have attempted to clarify which areas of the nucleus ambiguus are cardioinhibitory and to determine other regions of the brain which send direct projections to this physiologically identified cardiac region. Stimulating electrodes were positioned stereotaxically in the medulla of anesthetized rats. Small currents were passed through the electrodes to locate regions in the ventrolateral medulla which slowed heart rate. In each rat, the area found was small (less than 200 micron in diameter), very specific, and located in the rostral portion of the nucleus ambiguus. Micro-quantities of horseradish peroxidase were then iontophoretically ejected into this brainstem area; 24-72 hours following the HRP injection, the rats were processed for HRP reaction product using the tetramethybenzidine method. The major brain area which sent projections to the rostral nucleus ambiguus was the ipsilateral medial subnucleus of the solitary tract. A few labeled cells were found in the ipsilateral ventrolateral subnucleus of the solitary tract, parabrachial complex, the paraventricular nucleus of the hypothalamus, and the contralateral nucleus ambiguus. Control injections in reticular areas surrounding the rostral nucleus ambiguus showed no label in the medial solitary nucleus.

Anatomical and functional organization of pathway from superior colliculus to lateral posterior nucleus in hamster.

A series of anatomical (autoradiographic and horseradish peroxidase, HRP) and electrophysiological experiments were carried out to determine the organization of the pathway from the superior colliculus (SC) to the lateral posterior nucleus (LP) in the hamster. Small, electrophoretic HRP deposits restricted to LP labeled numerous cells in both the ipsilateral and contralateral colliculus. Over 95% of the labeled cells were located in the lower one-half of the stratum griseum superficiale (SGS) and the upper stratum opticum (SO). A number of different morphological cell types contributed axons to the tecto-LP pathway. The receptive-field properties of antidromically activated tecto-LP neurons were delineated using extracellular single-unit recording techniques. Ninety-eight percent of the tecto-LP cells recorded were isolated in the SGS and SO. All tecto-LP cells responded more vigorously to moving than to flashed stimuli, one-third were directionally selective, and one-third exhibited some degree of speed selectivity. The responses of tecto-LP neurons did not differ appreciably from those of superficial layer collicular cells that could not be antidromically activated by LP shocks. Small pressure injections or electrophoretic deposits of [3H]leucine into sites with known retinotopy in the superficial collicular laminae were used to determine whether or not the tecto-LP projection in hamster was topographically organized. Injections anywhere in the SGS and SO yielded dense label in almost all of the caudal (LPc) and rostrolateral (LPrl) subnuclei of LP, ipsilaterally, and sparser labeling in these same subnuclei, contralaterally. No injection produced significant labeling in the rostromedial (LPrm) subnucleus. Our autoradiographic data gave no indication of any topographic order in the tecto-LP projection. Electrophysiological methods were also used to map the tecto-LP projection. Multiple stimulating microelectrodes were positioned at physiologically defined sites in the SGS, and single cells were recorded in LP, ipsilaterally. Threshold currents for activation of LP cells from different collicular sites were then compared with the angular separation of SC and LP receptive-field centers. No significant correlation between these two variables was noted, again indicating a lack of topographic organization in the tecto-LP projection. The receptive-field properties of individual LP neurons (n = 211) were also assessed and correlated with subnuclear location and responsivity to SC shocks.(ABSTRACT TRUNCATED AT 400 WORDS)

A comparison of visual callosal organization in normal, bilaterally enucleated and congenitally anophthalmic mice.

Visual callosal connections were examined using the horseradish peroxidase (HRP) technique in normal, neonatal and adult C57BL mice, and in adults of this strain which were bilaterally enucleated within 12 h of birth. In addition, callosal connections were also delineated in two strains of congenitally anophthalmic mice, ZRDCT-an and orJ. Material from 129/J mice served as controls for the latter strain. In normal adults anterograde labelling and HRP labelled cells were visible primarily at the borders of area 17. In the 17-18a border region, labelled neurons were located primarily in layers II-III and V. In the medial striate cortex, a small number of labelled cells were present, primarily in lamina VI. Anterograde HRP labelling in the normal adults was also located primarily at the borders of area 17. At the 17-18a border, it was very heavy in layers V and VI, somewhat lighter in layer IV, and fairly dense in layers II-III and the lower half of lamina I. Labelling indicative of anterograde HRP transport was also visible in lowermost lamina V and layer VI across the entire mediolateral extent of area 17. In normals injected with HRP on postnatal day 2 and perfused 24 h later, callosal neurons were distributed throughout the dorsal posterior neocortex, primarily in layers V and VI. Only a very few labelled cells were visible in the supragranular laminae. In adult mice blinded at birth, the zone of callosal cells and terminals extended much further into area 17 than in normals, but aside from the anterograde labelling in layer VI and lowermost lamina V, the medial one-third of the striate cortex was still for the most part devoid of callosal cells and fibers. The laminar distributions of the labelled cells and anterograde transport in the blinded animals were the same as in the normal mice. In both strains of anophthalmic mice the pattern of callosal connections was unlike that in either the normals or neonatal enucleates. In the caudal "visual" cortex, callosal cells and anterograde transport indicative of terminal labelling were visible primarily in the 17-18a border area. Rostrally, however, they were both distributed in multiple (two-three) patches within area 17. Serial reconstructions demonstrated that these patches tended to be aligned in stripes which ran parallel to the 17-18a border. One of these was always located at the 17-18a border, and here the laminar distribution of labelled cells and anterograde labelling was the same as in the normals.(ABSTRACT TRUNCATED AT 400 WORDS)

Neonatal superior collicular lesions alter visual callosal development in hamster.

Visual callosal connections were examined using autoradiographic (ARG) and horseradish peroxidase (HRP) techniques in normal adult hamsters, and in adults subjected to ablation of the superficial tectal laminae at birth. Additional ARG and HRP experiments were carried out in hamsters 1-27 days of age in order to describe the normal development of this pathway. Neonatal collicular lesions, which deprived visual cortical neurons of a major terminal zone in the midbrain, substantially altered the visual callosal pathway. In the lesioned animals, the numbers of supragranular callosal cells in the 17-18a border region and lamina VI callosal neurons in medial area 17 were significantly greater than normal. The ARG experiments demonstrated additional clearcut abnormalities in the visual callosal pathway of the lesioned hamsters. First, the mediolateral extent of the supragranular callosal zone around the 17-18a border was increased. Secondly, dense label was visible over lower layer V and lamina VI throughout area 17. Finally, labelling in lamina I could also be observed across the entire mediolateral extent of area 17. Experiments in the developing hamsters suggested that some of the abnormalities observed in the lesioned animals may have resulted from the maintenance of normally transient developmental states. During the first postnatal week, both callosal cells and anterograde labelling were evenly distributed throughout the dorsal posterior neocortex, but only in the subplate region. During the second postnatal week, supragranular callosal cells were also labelled in both medial and lateral area 17, but from their first appearance, they were always most numerous in the 17-18a border region. At the same time callosal axons invaded the supragranular laminae, but only near the 17-18a border. By the end of the second postnatal week, the visual callosal pathway was very similar to that in the adult.