The formation of a cortical somatotopic map.

The primary somatosensory cortex of small rodents is an isomorphic representation of the body surface. Similar representations are characteristic of the subcortical pathways, leading from the periphery to the cortex, and these representations develop in a sequence that begins at the periphery, and that ends in the cortex. Furthermore, central representations at all levels of the neural axis are altered by perinatal perturbations of the peripheral surface. This has led to the hypothesis that the periphery plays an instructional role in the formation of central neuronal structures. The morphology of this discrete organization has been examined thoroughly during the development of the thalamocortical projections. The mechanism(s) that underlies the formation of these representations remains unclear although some recent evidence suggests the involvement of activity-dependent processes that are modulated by 5-HT.

The formation of afferent patterns in the somatosensory cortex of the neonatal rat.

In the rat, the clustered pattern of thalamocortical afferent terminals to the "barrel field" portion of primary somatosensory cortex replicates the arrangement of vibrissae on the face, and the pattern of the terminals can be altered by the removal of vibrissae on the face, and the pattern of the terminals can be altered by the removal of vibrissae at birth (Killackey et al., '76). These patterns of terminals were studied using enzyme succinic dehydrogenase (SDH) because in somatosensory cortex the activity levels of SDH closely correspond to the patterns of thalamocortical afferent terminals. The present experiments show that the pattern of high SDH segmentation in the portion of layer IV of somatosensory cortex that is related to the vibrissae develops during postnatal Day 3 through 6. Activity related to the centers of individual clusters is first visible, with indistinct boundaries. At later times the edges of individual clusters become apparent. Further, in animals with Row C of vibrissae removed at birth, the abnormal SDH segmentation in somatosensory cortex develops with a time course similar to that of normal animals. At ages when edge boundaries are first distinct, a fused band corresponding to the removed row of vibrissae is present. Thus the aberrant organization seen in the adult cortex is the result of an abnormal initial development, not a later reorganization from a normal pattern. And indeed, vibrissae removal at Day 5 or 6 does not result in an aberrant cortical SDH pattern. Finally, after removal of all five rows of mystacial vibrissae at birth, the cortical SDH pattern seen at postnatal Days 6 and 7 consists of five bands in place of the normally present five rows of clusters. This may indicate that closer relationships exist between vibrissae within one row than vibrissae in adjacent rows.

Vibrissae representation in subcortical trigeminal centers of the neonatal rat.

In the neonatal rat differential activity levels of the metabolic enzyme succinic dehydrogenase (SDH) reveal intricately detailed sgementation in the neuropil of the spinal and principal trigeminal nuclei of the brainstem and in the ventrobasal complex of the thalamus. The segmentation occurs in the portions of these nuclei that electrophysiological evidence has indicated to be related to the mystacial vibrissae and sinus hairs on the face of the rat. Indeed, the pattern of segmentation in each nucleus replicates the topographic distribution of the vibrissae and sinus hairs. Further, within the spinal trigeminal nucleus, there appear to be two distinct representations of the vibrissae, one in the subnucleus caudalis and a second in the subnucleus interpolaris. Examination of these patterns of segmentation indicates that the large mystacial vibriaase and sinus hairs on the face of the young rat are somatotopically represented three times within the trigeminal complex, as straight cylinders of neuropil, and once in the ventrobasal complex, as curved cylinders of neuropil. Neonatal vibrissae damage leads to an aberrant organization of the segmentation in the spinal trigeminal nucleus and the ventrobasal complex. In the spinal trigeminal nucleus, the SDH activity in areas associated with damaged vibrissae is of a lower than normal density, and patterns are indistinct. However, rows of clusters associated with the adjacent normal vibrissae are apparent and appear to be enlarged. In the ventrobasal complex, vibrissae damage results in bands of normal density SDH activity where rows of segmented clusters would normally be present. Comparison of these data to the cortical data in the previous paper (Killackey and Belford, '79) indicates that cortical and nuclear structures can have aspects of their development controlled by similar mechanisms.

The development of vibrissae representation in subcortical trigeminal centers of the neonatal rat.

In every station of the trigeminal system of the young rat, the segmented activity of the mitochondrial enzyme succinic dehydrogenase (SDH) clearly delineates the representation of the mystacial vibrissae. In the trigeminal complex of the medulla, three parallel representation can be seen, two in the spinal trigeminal nucleus and one in the principal trigeminal nucleus. In the next station, the ventrobasal complex of the thalamus, a single representation occurs. Likewise, layer IV of somatosensory cortex contains one representation of the vibrissae. Further, neonatal damage to the mystacial vibrissae results in anomalies within each representation. The present study delineates both the normal development of subcortical trigeminal stations and the aberrant organization seen after vibrisse removal. The results of a similar study on somatosensory cortex (Killackey and Belford, '79) and the present data allow the comparison of the development of each of the five vibrissae representations in the trigeminal system. In the brainstem, each of the three trigeminal complex representations are present at birth, although the pattern becomes more distinct over the first several days of life. Interestingly, vibrissae removal at birth induces an aberrant pattern that is distinct by postnatal Day 3. Although details are not equally discernible in each representation, the abnormalities appear to be similar. The SDH segmentation in the ventrobasal complex develops during postnatal Days 1 through 4. At Day 1, portions of the matrix of high density SDH activity break up into bands. Clusters can be discerned within these bands on Day 2. By Day 4 the pattern is sharply delineated. Vibrissae removal at birth results in anomalies that are a part of the initial development of segmentation, not a later reorganization. Comparison of the present data with that of our previous studies indicates that there is a sequential development of the central somatosensory structures related to the vibrissae, beginning with the most peripheral station. Further, there are many similarities in the development of each station. There are also differences which are particularly important in comparing the trigeminal nuclei with the later stations. The unique features in the abnormal development of the trigeminal nuclei are likely due to their direct connections with the periphery.

Efferent connections of the brainstem trigeminal complex with the facial nucleus of the rat.

The sensory surface of the face of the rat is topographically represented in the brainstem trigeminal complex (Nord, '67), and in parallel with this the underlying facial musculature is also represented in a topographic fashion in the facial nucleus (Papez, '27; Martin and Lodge, '77; Watson and Sakae, '78). It has been recently reported that in the young rat three distinct representations of the vibrissae are present in the sensory portion of the brainstem trigeminal complex (Belford and Killackey, '79). Within this perspective, the specific connectivity between the brainstem trigeminal complex and the facial nucleus was investigated in adult rats by Fink-Heimer technique. The two major sensory nuclei of the brainstem trigeminal complex, the spinal trigeminal nucleus and the principal sensory nucleus, differ in their projection patterns to the facial nucleus. While the principal sensory nucleus sends sparse projections to the ipsilateral lateral and dorsal subdivisions of the facial nucleus, the spinal trigeminal nucleus send differential projections to various subdivisions of the facial nucleus depending on their origin with respect to three cytoarchitectonically different subnuclei that compose the spinal trigeminal nucleus. It is concluded that the magnocellular portion of subnucleus caudalis projects rather heavily to the ipsilateral lateral subdivision of the facial nucleus, while the projections from the subnucleus interpolaris are sparser and distributed more widely to parts of the lateral, dorsal and intermediate subdivisions of the facial nucleus ipsilaterally. In contrast to ipsilateral facial projections from the rest of the brainstem trigeminal complex, the projections from the subnucleus oralis of the spinal trigeminal nucleus are bilateral and confined to the intermediate subdivision of the facial nucleus. However, ipsilateral projections of the subnucleus oralis are denser than the the very sparse contralateral projections. In addition to the facial projections from the brainstem trigeminal complex, projections from the upper portions of the cervical cord to the medial subdivision of the facial nucleus were observed. These projections ar bilateral, and those fibers destined for the contralateral medial subdivision cross over below the level of the pyramidal decussation.

Fine structural survey of the rat's brainstem sensory trigeminal complex.

The fine structural organization of the principal sensory trigeminal nucleus was compared with that of the spinal trigeminal nucleus (subnuclei oralis, interpolaris, and the deep layers of caudalis) in adult albino rats. Direct comparisons indicate similarities between all of the subdivisions of the brainstem trigeminal complex both in the major morphological classes of neurons present and in basic patterns of synaptic connections. Major differences between the several subdivisions occur in the relative numbers and distribution of the different cell types. The spinal trigeminal nucleus is distinguished by more numerous large (22-40 micron) polygonal neurons which give rise to long straight primary dendrites. Both the perikaryal surface and the thick primary dendrites of many of these cells are densely innervated by synaptic terminals. Especially large cells of this type are a prominent feature of subnucleus oralis. By contrast, the principal sensory nucleus is distinguished by its high density of small to medium-sized (8-20 micron) round or ovoid neurons. These smaller neurons tend to receive a sparse axosomatic innervation. In addition to these differences the spinal trigeminal neuropil is distinguished by the striking manner in which it is broken up by large rostrocaudally oriented bundles of myelinated axons. Proximal dendrites of polygonal and fusiform neurons often wrap around these large axon bundles. Morphologically heterogeneous populations of synaptic terminals with round vesicles (R terminals) and terminals with predominantly flattened vesicles (F terminals) occur in all of the subdivisions of the trigeminal complex. Both types of terminal make primarily axodendritic synapses, but both also make axosomatic synapses, and axospinous synapses with somatic as well as dendritic spines. In addition, axoaxonic synaptic contacts from F terminals onto large R terminals are seen in all subdivisions. Convincing examples of presynaptic dendrites were not observed in any of the brainstem subdivisions. Synaptic glomeruli, characteristic groupings of dendrites and synaptic terminals, are found throughout the brainstem trigeminal complex. The dendritic elements in these glomeruli tend to be small-diameter dendrites, spines, and large, spinelike appendages. Within the glomerulus these elements are postsynaptic to a single large R terminal and may also be postsynaptic to smaller F terminals. In addition, axoaxonic synaptic contacts from the F terminals onto the R terminal are a consistent feature of trigeminal synaptic glomeruli.(ABSTRACT TRUNCATED AT 400 WORDS)

The organization of the neonatal rat's brainstem trigeminal complex and its role in the formation of central trigeminal patterns.

The present study delimits the relationship of primary trigeminal afferents to their targets, the brainstem trigeminal nuclei of the neonatal rat. Previously, the brainstem trigeminal complex of the rat has been subdivided on the basis of either cytoarchitectonics or patterns of succinic dehydrogenase activity into the principal sensory nucleus and the three subnuclei of the spinal trigeminal nucleus, oralis, interpolaris, and caudalis. In this paper, we demonstrate that each of these subdivisions can also be identified by its pattern of primary trigeminal afferents. In addition, we demonstrate that the terminations of these afferents are distributed in a punctate fashion which correlates with vibrissae-related patterns of histochemical staining. Further, vibrissae removal in the neonatal rat at any age studied results in a corresponding deafferentation of both the principal sensory nucleus and all subnuclei of the spinal trigeminal nucleus. This same procedure has a graded, age-dependent effect on the vibrissae-related pattern of cytochrome oxidase staining in somatosensory cortex. On this basis, we conclude that vibrissae-related pattern formation in the central trigeminal system can be best understood in terms of a single "sensitive" period for the entire system. We hypothesize that this is the period during which an interaction normally occurs between primary trigeminal afferents and target neurons of the principal sensory nucleus.

The organization and mutability of the forepaw and hindpaw representations in the somatosensory cortex of the neonatal rat.

The present study demonstrates that the primary somatosensory cortex of the rat contains a map of the entire body surface that is discernible with a routine anatomical staining technique, the succinic dehydrogenase reaction. The overall proportions of this map are relatively constant from rat to rat and very similar to those reported in previous physiological investigations (Welker: Brain Res. 26:259-275, '71, J. Comp. Neurol. 166:173-190, '76). We found 67% of the map to be related to the head of the rat, 15% to the forelimb, 14% to the trunk, and 4% to the hindlimb. Within the forelimb and hindlimb representations, there is a consistent internal organization that can be related to specific peripheral structures (digits or palm pads). Further, damage to either the periphery or the nerves innervating these regions on the day of birth produces disruptions in the normal pattern, but damage on day 6 or later does not. We interpret these results as indicating that the role of the periphery in organizing central neuronal structures during development previously demonstrated for the trigeminal system extends to the entire rat somatosensory system. Comparison of the present results with physiological studies of adult cortical maps after peripheral damage suggests to us that different substrates underlie the changes reported in the adult.

Ontogenetic change in the distribution of callosal projection neurons in the postcentral gyrus of the fetal rhesus monkey.

In the postcentral gyrus of the mature rhesus monkey the distribution of callosal projection neurons is discontinuous. The density of callosal projection neurons, which are mainly located in the supragranular layers, varies both within and across cytoarchitectonic areas (Killackey et al., '83). In the present study, we investigated the ontogeny of corpus callosum projections of the postcentral gyrus in five fetal rhesus monkeys, ranging in age from embryonic day (E) 108 to E 133. Multiple large injections of horseradish peroxidase that involved the underlying white matter were made into the postcentral gyrus of one hemisphere and the distribution of labeled neurons in the ipsilateral thalamus and the other hemisphere was determined. The pattern of thalamic label indicated that the tracer was effectively transported from all portions of the postcentral gyrus. We found that the areal distribution pattern of labeled callosal projection neurons varied at the different fetal ages. At early fetal ages (E 108, E 111, and E 119) callosal projection neurons were continuously distributed throughout the postcentral gyrus. As in the adult animal, the vast majority of labeled callosal projection neurons were found in the supragranular layers, although a few labeled cells were located in the infragranular layers. From the earliest age, there was regional variation in the width of the band of labeled supragranular callosal projection neurons. The difference between the precentral and postcentral gyrus was most obvious, but there was also a difference between anterior and posterior portions of the postcentral gyrus. The first indication of some discontinuity in the distribution of callosal projection neurons was noted at E 126. By E 133, approximately 1 month before birth, the distribution of callosal projection neurons appeared remarkably mature. On E 119 aggregations of anterograde label could be detected in restricted portions of the posterior postcentral gyrus beneath the cortical layers. By E 133 anterograde label was found within the cortical layers (most densely in layer IV) in these regions of the postcentral gyrus. Thus, the emergence of the discrete pattern of callosal projection neurons appears to be temporally correlated with the ingrowth of callosal afferents. On the basis of these observations, as well as those of others (discussed in the text), we propose that the ontogenetic changes in the distribution of callosal projection neurons reflect the unique strategy employed by cortical projection neurons in establishing their patterns of connectivity. It is hypothesized that this strategy may involve multiple processes.

Development of order in the rat trigeminal system.

The trigeminal system of the rat is characterized by a high degree of order. The pattern of the distribution of vibrissae follicles on the face is replicated at each synaptic station between face and somatosensory cortex (Belford and Killackey, '80). The present study details the development of the trigeminal nerve, its intrinsic organization, and its relationship with its peripheral and central targets. We have observed that at early embryonic ages (E12 and E13) the trigeminal ganglion neurons grow out in straight lines without crossing, and the distance between these neurons and their peripheral and central targets is very short. We have found that fibers reach the periphery before follicle formation is first detectable (E14). At all ages, the trigeminal fibers show a marked tendency to fasciculate. After the development of the pattern of vibrissae follicles on the face, the pattern of fasciculation within the nerve can be clearly related to the rows of vibrissae and the buccal pad. This peripherally related order in the nerve was experimentally verified by injecting horseradish peroxidase into the follicles of individual rows and selectively sectioning portions of the nerve. Further, we provide evidence that the discrete brainstem pattern reflecting vibrissae distribution develops after organization is detectable in the nerve and in a temporal sequence from lateral to medial, which replicates the developmental sequence of vibrissae follicles from ocular to nasal on the face. This sequence is detectable in both the distribution of afferent terminals as measured with succinic dehydrogenase histochemistry and of horseradish peroxidase back-labeled trigeminothalamic relay cells. We interpret our results as suggesting that a number of factors may play a role in the establishment of specific neuronal topographies in the rodent trigeminal system.

Trigeminal projections to the superior colliculus of the rat.

The deep layers of the rodent superior colliculus contain a vibrissae-related organization that is in "spatial register" with the overlying visuotopic organization (Dräger and Hubel, '76). The distribution of vibrissae-related afferents and their cells of origin were determined with a number of anatomical techniques. The brainstem trigeminal complex afferents to the superior colliculus terminate in the lateral portions of the strata album intermediate and griseum profundum and, to a lesser degree, in deep portions of the stratum griseum intermediate. The cells giving rise to these afferents are located mainly in the ventral portions of the contralateral principal sensory nucleus, subnucleus oralis, and subnucleus interpolaris. The majority of tectal projection cells are found in subnucleus interpolaris, and the fewest in the principal sensory nucleus. Further, the density of projection cells in the three components of the brainstem trigeminal complex can be correlated with the density of their projections to the superior colliculus. The afferents from the somatosensory cortex terminate in a continuous band in the strata album intermediate and griseum intermediate. The cells of origin of this projection are located in layer Vb of the agranular zones of the ipsilateral somatosensory cortex. The present results suggest that the organization of trigeminal afferents to the deep portion of the superior colliculus is similar to that of the visual afferents to the superficial laminae. Further, the results suggest that observations on the nature of afferent termination pattern should be made with care, considering both the techniques employed and the idiosyncrasies of the local neuropil.

The sensitive period in the development of the trigeminal system of the neonatal rat.

In previous studies we have described vibrissae-related segmentation in the brainstem, thalamus, and cortex of the neonatal rat. Using succinic dehydrogenase (SDH) histochemistry, we delineated the time course in development of the normal segmentation at each level of the trigeminal system and the aberrant segmentation resulting from follicle damage at birth (Killackey and Belford, '79; Belford and Killackey, '79a, b). The present study examines the aberrant patterns that result from damage to the vibrissae follicles at different ages, comparing the patterns at the different levels of the trigeminal system. The present study indicates a number of similarities between the central representations of the vibrissae. First, the patterns are similar within each of the three representations in the trigeminal nuclei for removal at a given age in a particular animal. These changes include a decrease in SDH density but a maintenance of normal row widths. Second, the patterns are similar within both the ventrobasal complex and layer IV of somatosensory cortex for removal at a given age in a particular animal. These changes include a fusion of individual clusters into bands, and a decrease in band width, but maintenance of normal SDH density. Third, the effects of damage to a row of vibrissae follicles at different ages are graded. Earlier damage produces more marked aberrations. Fourth, for all of the structures, the transition between bands and clusters occurs with damage at the same age. Further, the last age at which damage produces aberrant patterns is Day 3 for all of the structures. Thus, the data suggest that there is one sensitive period for pattern alteration in the entire central trigeminal system.

The ontogeny of the distribution of callosal projection neurons in the rat parietal cortex.

The ontogeny of callosal projection neurons in the rat parietal cortex was examined using the retrograde and anterograde transport of horseradish peroxidase (HRP), as well as Golgi and Nissl stains. From postnatal day 0 (PND 0) to early PND 4, the callosal projection neurons are distributed as two continuous horizontal bands of cells which extend throughout the subplate in layers Va and Vc-upper VIa. Neurons within the cortical plate (CP), however, do not transport HRP from a contralateral injection site until PND 3 to early PND 4, when a few cells at the lower CP border are generally labeled. However, by late on PND 4, and more consistently by PND 5, several changes in the distribution of callosal projection neurons take place. First, cells at all levels of the CP become labeled in a sequential fashion, from the lower border upward. Second, gaps, or areas devoid of HRP, become apparent in layer IV of the barrel field area. Third, in the cortical areas containing the gaps, as well as in other areas which are destined not to be callosally connected in the adult, there is a noticeable decrease in the number of cells labeled with HRP. This decrease continues through PND 15 and possibly into adulthood. The foregoing developmental events are compared to cortical maturation as seen in both Golgi- and Nissl-stained material. By PND 15, the basic adult pattern of callosal projection neurons is established. The neurons reside mainly in layers III and Va, with fewer in layers II and Vc-upper VIa, and fewer still in the other cortical layers. They are aligned in vertical arrays in discrete areas of the cortex.

Organization of corticocortical connections in the parietal cortex of the rat.

An analysis based on Nissl, anterograde degeneration, and succinic dehydrogenase histochemical techniques reveals that there are two distinct regions of parietal cortex which are characterized by different cytoarchitectonic features and anatomical connections. The "granular" cortical zone possesses a well-defined fourth layer composed of small, densely-packed cells, receives dense projections from the ventral posterior nucleus of the thalamus, and is essentially free of callosal inputs. "Agranular" cortical areas which surround or lie embedded within the granular zone lack a well-defined fourth layer, receive sparse projection from the ventral posterior nucleus, but send and receive extensive callosal projections. These findings suggest that thalamic and callosal projections to the parietal cortex maintain a pattern of areal segregation. The granular cortical zone, which apparently corresponds to SmI, projects ipsilaterally to motor cortex, SmII, and adjacent agranular areas. The superficial layers of the granular cortex also project heavily upon the underlying layer V. This intracortical projection is not organized in discrete clusters within the "barrel field" cortex. This suggests that the specialized organization of thalamic afferents and granule cells within the "barrel field" is not maintained in the intracortical circuitry of this region.

Areal and laminar organization of corticocortical projections in the rat somatosensory cortex.

The present study examines patterns of connectivity between the primary somatosensory cortex of the rat (SI) and surrounding cortical areas also implicated in the processing of somatosensory information. The impetus for the study was the recent reports of major differences in the organization of cortex lateral and caudal to the SI in two other rodent species; the mouse (Carvell and Simons, '86: Somatosens. Res. 3:213-237; '87: J. Comp. Neurol. 265:409-427) and the grey squirrel (Krubitzer et al., '86: J. Comp. Neurol 250: 403-430). Corticocortical connections between the somatosensory areas of the rat parietal cortex were examined by using the combined retrograde and anterograde transport of horseradish peroxidase as well as the retrograde transport of fluorescent tracers. Tracer injections were made into different locations within SI and dysgranular cortex as well as into more lateral regions of parietal cortex. The tangential patterns of distribution both of callosal connections and of cytochrome oxidase activity together provided points of reference in determining the relation between injection sites and the resultant patterns of label. The results indicate that two distinct somatosensory areas, SI and the dysgranular cortex, are interconnected with a further lateral somatosensory area referred to as the second somatosensory area (SII). These projections are organized in a topographic fashion, which we interpret as evidence for a single representation of the body surface in SII. The three somatosensory areas each exhibit unique laminar patterns of ipsilateral corticocortical projection neurons and terminations. In SI, projection neurons are found mainly in layers II, III, and Va, and terminations are largely restricted to the infragranular layers. In the dysgranular cortex, projection neurons and terminations are found in all layers except layer I in which only terminal label is detectable and layer Vb in which notably fewer neurons are labelled. In SII, projection neurons and terminations are found in all layers except layer I and are particularly dense in lower layer III and layer IV. Further, whereas the laminar and areal distributions of ipsilateral and contralateral corticocortical projections largely overlap in both SI and the dysgranular cortex, in SII they tend to be areally segregated. Neurons projecting bilaterally to both ipsilateral and contralateral somatosensory cortex were equally rare in all three somatosensory areas. These results are discussed in relation to the organization of SII in other rodent species, and it is concluded that in the rat, like the mouse, cortex lateral and caudal to SI contains a single representation of the body surface.

Individual axon morphology and thalamocortical topography in developing rat somatosensory cortex.

The morphology of individual thalamocortical axons in developing rat primary somatosensory cortex was studied using lipophilic tracers. Anterograde labeling with lipophilic dyes demonstrated a topographical organization of thalamocortical projections exiting the thalamus as early as embryonic day (E) 16; retrograde labeling studies demonstrated topography of these projections as they reached the cortex as early as E18. At E17, axons course tangentially within the intermediate zone and turn or branch near the deepest layer of cortex (layer VIb), suggesting the presence of guidance cues in this region. Axons appear to grow and branch progressively within layers VIb and VIa during the following days; axons in the intermediate zone may give rise to radially directed branches. Individual axons appear to grow steadily and progressively into the cortex, with the leading front of axons at the transition zone between the cortical plate (CP) and the differentiating cortical layers. At birth (P0), thalamocortical axons extend radially through layers VIa and V and emit branches within these layers; some axons reach the CP. By P1, layer IV has begun to differentiate and axons begin to form a few simple branches in the vicinity of the layer IV cells. Over the ensuing week, axons generate more branches within layer IV, but the tangential extent of individual axon arbors does not exceed the width of a barrel. By P7, individual axons overlap within barrel clusters, and individual axons span the width of a cluster. These observations indicate that thalamic afferents develop by progressive growth of arbors that remain spatially restricted, rather than by overbranching and retracting arbors.

Phenotypic characterisation of respecified visual cortex subsequent to prenatal enucleation in the monkey: development of acetylcholinesterase and cytochrome oxidase patterns.

Prenatal bilateral enucleation induces cortex, which normally would have become striate cortex, to follow a default developmental pathway and to take on the cytoarchitectonic appearance of extrastriate cortex (default extrastriate cortex, Dehay et al. [1996] J. Comp. Neurol. 367:70-89). We have investigated if this manipulation influences the cortical expression of acetylcholinesterase (AChE) and cytochrome oxidase (CO). Early enucleation (before embryonic day 81; E81) had only minor effects on the distribution of AChE and CO in the striate cortex. In animals that underwent operation, the striate cortex CO blobs were significantly more closely spaced on the operculum compared with the calcarine. After early enucleation, there was a periodic distribution of CO dense patches in default extrastriate cortex. These CO patches had a center-to-center spacing that was considerably smaller than that of CO stripes in normal area V2, but was somewhat larger than that of the CO blobs in striate cortex. Although the CO stripes characteristic of normal area V2 could not be detected, there were some high-frequency CO patches, similar to those found in default extrastriate cortex. Early enucleation caused a failure to form the transient AChE bands running perpendicular to the striate border, which are normally present in the fetus and early neonate. Late enucleation did not alter AChE expression in extrastriate cortex. The relatively minor effects of early enucleation in the reduced striate cortex contrast with the changes in expression of these enzymes in extrastriate cortex, which accompany large shifts in the location of the striate border. This suggests a massive reorganisation of cortical phenotype in extrastriate cortex.

Ascending auditory projections to the inferior colliculus in the adult gerbil, Meriones unguiculatus.

Ascending auditory projections to the inferior colliculus (IC) of the adult gerbil were studied using the retrograde transport of horseradish peroxidase. Our results indicate that in gerbils, the IC receives afferent projections from most brainstem auditory nuclei. A strong contralateral projection originates in the cochlear nuclear complex (CN). A smaller but consistent projection from all three divisions of ipsilateral CN is also present. The medial superior olive (MSO), superior parolivary nucleus, and ventral nucleus of the lateral lemniscus all maintain ipsilateral projections to the IC. Bilateral projections arise from the lateral superior olive, lateral nucleus of the trapezoid body, and dorsal nucleus of the lateral lemniscus. Previous investigations in other mammalian species provide conflicting data concerning the magnitude of a direct ipsilateral projection from CN to the IC. Our quantitative data indicate that the ipsilateral projection from CN in the gerbil is nearly one third as large as the projection from ipsilateral MSO. The projection from contralateral CN is six times larger than the MSO projection. The distribution of labeled cells across the rostrocaudal extent of MSO and the three divisions of the cochlear nuclear complex are presented.

Ascending projections to the inferior colliculus following unilateral cochlear ablation in the neonatal gerbil, Meriones unguiculatus.

We evaluated the consequences of neonatal cochlear destruction upon ascending projections to the inferior colliculi. Unilateral cochlear ablations were performed in both neonatal and adult gerbils. Four to 12 months later, the inferior colliculus (IC) was examined physiologically and injected unilaterally with horseradish peroxidase (HRP). The number of labeled cells was determined bilaterally in all three divisions of cochlear nucleus (CN) and in the medial superior olive (MSO). In both experimental groups, transneuronal changes within the deafferented CN were greater in the ventral divisions than in the dorsal division. On the unoperated side the magnitude of projections from CN to the inferior colliculi was altered in animals lesioned as neonates. Following HRP injections into the IC on the unoperated side, the number of ipsilaterally labeled cells in CN (unoperated side) was significantly greater in the neonatal experimental group than in adult experimental and control animals. These anatomical changes were accompanied by increased ipsilaterally evoked excitatory activity recorded in the IC on the unoperated side. Following HRP injections into the IC on the ablated side, the number of contralaterally labeled cells in CN (unoperated side) was significantly reduced in animals lesioned as neonates as compared with control animals. The number of labeled cells in ipsilateral MSO was not significantly different across groups. Our interpretation is that unilateral cochlear ablation in neonatal gerbils results in an increase in the magnitude of ipsilateral projections and a decrease in the magnitude of contralateral projections from CN on the unoperated side to the inferior colliculi. These data suggest that the normal pattern of innervation of the IC results, in part, from interactions among afferent projections.

Laminar and areal differences in the origin of the subcortical projection neurons of the rat somatosensory cortex.

Fluorescent retrograde tracing techniques were employed in a double-labelling paradigm to determine the distribution of corticospinal, corticotectal, and corticotrigeminal projection neurons in layer Vb of the adult and neonatal rat somatosensory cortex. The double-labelling paradigm allowed a direct comparison of the cortical distribution of neurons projecting to each target and identification of neurons projecting to more than one target. In the adult rat, each population of projection neurons was found to have a unique laminar and/or areal distribution. Corticospinal projection neurons were located throughout the width of layer Vb in the medial granular portion of somatosensory cortex, while corticotrigeminal projection neurons were distributed throughout the width of layer Vb in the more laterally located dysgranular portion of somatosensory cortex. Corticotectal projection neurons were located more superficially in layer Vb than either corticospinal or corticotrigeminal projection neurons and found scattered throughout both dysgranular and granular somatosensory cortex. Each combination of subcortical injections also resulted in double labelling a small percentage of uniquely distributed neurons. These distribution differences coupled with measurements of cell size allowed us to identify the parent population of the dual projection neurons. Subpopulations of corticotectal neurons also project to the brainstem trigeminal complex and to the spinal cord. Subpopulations of corticotrigeminal neurons also project to the spinal cord, and a proportion of corticotrigeminal neurons projects to at least two targets within the brainstem trigeminal complex (nucleus principalis and subnucleus interpolaris). In the adult rat, corticospinal neurons (as defined by either laminar position or somal size) did not appear to give off collaterals to either the superior colliculus or brainstem trigeminal complex. In the neonatal rat, double-labelled neurons which project to both the spinal cord and the tectum are distributed throughout the full width of layer Vb, rather than restricted to the superficial portion of the layer as in the adult rat. Further, it appears as if the ontogenetic change in the laminar distribution of corticospinal and tectal projection neurons is achieved by mechanisms of selective process elimination rather than cell death. These results are discussed in terms of both the developmental factor which may contribute to the discrete distribution of cortical projection neurons found in the adult and the functional significance of bifurcating projection neurons.