bluuebunny/crossref_metadata_2025 huggingface dataset:
Organization of the somatosensory cortex of the star‐nosed mole
Authors: Catania Kenneth C. , Kaas Jon H.
Published: January 2005

The nose of thestar‐nosed mole consists of a star‐like array of 22 fleshy appendages that radiate from the nostrils and are moved about to explore the environment. The surface of each appendage, or ray, is densely packed with bulbous receptor organs (Eimer's organs) that are highly responsive to tactile stimulation. Here, we report that these rays have corresponding morphological specializations in somatosensory cortex. Using a stain for the metabolic enzyme, cytochrome oxidase (CO), to reveal subdivisions of cortex, we disclosed a complex pattern of CO‐dense stripes or bands separated by sharp lines or septa of low CO staining. Multiunit microelectrode recordings of neural activity evoked by light tactile stimuli in somatosensory cortex of anesthetized moles allowed us to mark some of the bands and other CO‐dark regions with small electrolytic lesions and later relate recording results to the CO pattern. The results suggest that the primary somatosensory cortex, S1, has an unusual ventrolateral location and orientation with representations of mouth, nose rays, facial vibrissae, forepaw, and trunk in a rostrocaudal sequence. Within this presumptive S1, the 11 rays of the contralateral nose are represented as a rostral‐to‐caudal cortical pinwheel of 11 stripes. Cortex ventral to the primary set of stripes contains a second rostrocaudal representation of the rays as a mirror image of the first. This second set of stripes may be part of the second somatosensory area, S2. A third pattern of CO stripes appears to merge partially with caudal stripes of the first two patterns, so that a full pattern of 11 stripes is not obvious. This representation may correspond to the ventral somatosensory area, VS, of other mammals. An extensive area of cortex separated from the nose by a large septum was responsive to stimulation of the forelimb. Auditory cortex is unusually caudal in this mole, and the presumptive primary visual area is relatively small. These specializations of somatosensory cortex in star‐nosed moles may be more patent examples of the consequences of more general factors in brain development. The observations are consistent with the general rule that the terminations of sensory projections with discorrelated activity segregate. © 1995 Willy‐Liss, Inc.
Development of the hippocamposeptal projection in the rat
Authors: Linke Rüdiger , Pabst Thomas , Frotscher Michael
Published: January 2005

We analyzed the development of the hippocamposeptal projection and the morphology of the neurons giving rise to this projection. The fluorescent tracer Dil was injected into the septal region or the hippocampus in fixed brains of embryonic and early postnatal rats. Anterogradely labeled hippocampal axons first reached the septal region at E16. They ran along the midline of the brain, thereby approaching the medial septum. Axons to the lateral septum were first observed around E18/19. The lateral septum is partly innervated by collaterals of axons that travel to the medial septum. The projection to the lateral septal nuclei becomes more massive during early postnatal stages, whereas that to the medial septum becomes smaller. Cells in the medial septum retrogradely labeled by injection into the hippocampus were first observed at E18. Thus, the hippocamposeptal projection is established earlier than the septohippocampal projection.

The first hippocampal projection neurons are nonpyramidal neurons that appear to pioneer the pathway to the septum. Pyramidal cell axons follow this first cohort of axons into the medial septum. Pyramidal cells could be retrogadely labeled from the medial septum during the perinatal period but then diminished in number. At P10, only nonpyramidal cells were labeled by medial septal injections. This indicates that the pyramidal component of this projection is transient and is removed shortly after birth. However, as is known from ther studies, hippocampal pyramidal cells give rise to a powerful projection to the lateral septum in adult animals. Our results show that there is a considerable remodeling of the projection from the hippocampus to the septum during ontogenetic development. © 1995 Willy‐Liss, Inc.
Distribution and development of β‐adrenergic receptors in the rat olfactory bulb
Authors: Woo Cynthia C. , Leon Michael
Published: January 2005

Beta‐adrenergic stimulation appears to be involved in the establishment of both learned olfactory preferences and functional changes in the olfactory bulb of young rats. We examined the postnatal development of beta‐adrenergic receptors within the main olfactory bulb to determine the density and distribution of these receptors. To quantify beta‐adrenergic receptor density, olfactory bulb homogenates from postnatal day (PND) 1, 6, 12, and 19 rats were assessed for receptor binding with 125I‐iodopindolol. In addition, receptor autoradiography was performed with the selective P, antagonist ICI 89,406 and selective β2 antagonist ICI 118,551 on tissue sections from PND 1–30 rats to examine the distribution of the beta‐adrenergic receptor subtypes. We observed both an increase in receptor density with increasing age and the formation of distinct spatial distributions of the two beta receptor subtypes within the bulbar lamina. Beta‐adrenergic receptors were located in both deep and superficial layers of the bulb. Specifically, β1 receptors were present in the granule cell, internal plexiform and glomerular layers. β2 receptors were present in the granule cell, internal plexiform, external plexiform, and glomerular layers. High levels Of β2 receptors also were visible in the meningeal layers between the two bulbs. High densities of β1 and β2 adrenergic receptors were present within different sets of individual glomeruli by PND 12–19, and the number of these foci increased with age. The knowledge of beta‐noradrenergic receptor localization in the bulb may provide the basis for understanding the action of norepinephrine on neural processes in the developing olfactory bulb. © 1995 Wiley‐Liss, Inc.
Transient subcortical connections of inferior temporal areas TE and TEO in infant macaque monkeys
Authors: Webster Maree J. , Bachevalier Jocelyne , Ungerleider Leslie G.
Published: January 2005

As part of a long‐term study designed to examine the ontogeny of visual memory in monkeys and its underlying neural circuitry, we have examined the subcortical connections of the inferior temporal cortex in infant monkeys and compared them to those previously described in adult monkeys (Webster et al. [1993] J. Comp. Neurol. 335:73–91). Inferior temporal areas TEO and TE were injected with wheat germ agglutinin conjugated to horseradish peroxidase and tritiated amino acids, respectively, or vice versa, in 1‐week‐old (N = 6) and 3–4‐year‐old (N = 6) Macaca mulatta, and the distributions of labeled cells and terminals were examined in subcortical structures. Although the connections of inferior temporal cortex with subcortical structures were found to be similar in infant and adult monkeys, several projections appear to undergo refinement during development. Quantitative analysis showed that (1) whereas the projection from TE to the superior colliculus is consistent (5 of 5 cases) and widespread in infants, it is less reliable (2 of 7 cases) and limited in areal extent in adults; (2) although the projections from TE to nucleus medialis dorsalis and the tail of the caudate are present in infants and adults, they are reduced in adults; and (3) TEO receives input from the dorsal lateral geniculate nucleus in both infants and adults, but the number of cells giving rise to this projection is lower in adults. There was also a suggestion that TE projects to nucleus paracentralis in infants (2 of 5 cases) but not in adults (0 of 7 cases). No differences between infants and adults were apparent in other subcortical connections, including those with the pulvinar, reticular nucleus, claustrum, and putamen. © 1995 Wiley‐Liss, Inc.
Distribution of calcitonin gene‐related peptide‐like immunoreactivity in the brain of the small‐spotted dogfish, scyliorhinus canicula L
Authors: Molist Pilar , Rodriguez‐Moldes Isabel , Batten Trevor F. C. , Anadon Ramon
Published: January 2005

The distribution of neuropeptides has been useful in comparing neuronal aggregates of elasmobranchs with those in other vertebrates. The distribution of calcitonin gene‐related peptide (CGRP)‐like immunoreactivity in the brain of the dogfish was examined with an antiserum to rat α‐CGRP. Western blot analysis confirms that our antiserum recognizes a single peptide in the dogfish brain very similar to mammalian CGRP. CGRP‐like immunoreactivity was located in discrete neuronal groups. CGRP‐like‐immunoreactive (CGRP‐ir) neurons were found in the motor nuclei III, IV, V, VI, VII, IX, and X of the brainstem motor column and in the octavolateral efferent neurons. In the isthmal region, two groups of CGRP‐ir neurons appeared in the parabrachial region and reticular substance. Three other CGRP‐ir cell groups were observed in the mesencephalon: in the ventral tegmental area, in the substantia nigra, and one widely scattered but numerous population in superficial layers of the optic tectum. In the diencephalon, CGRP‐ir cells were observed in the magnocellular preoptic nucleus and the organon vasculosum hypothalami. A population of CGRP‐ir cells was also observed in the entopeduncular nucleus in the impar telencephalon. CGRP‐ir fibers of central origin were widely distributed in the brain, but the most conspicuous areas were found in the ventral telencephalon, the hypothalamus, the mesencephalic lateral reticular area, and the dorsolateral isthmal region. The neurointermediate lobe of the hypophysis was also richly innervated by CGRP‐ir fibers. CGRP‐ir sensory fibers of cranial nerves IX and X and of dorsal spinal roots formed very conspicuous terminal fields in the lobus vagi and Cajal's nucleus commissuralis and in the dorsal region of the substantia gelatinosa, respectively. Comparison of the distribution of fibers and perikarya in dogfish and other vertebrates suggests that this CGRP‐ir system has been well conserved during evolution. © 1995 Wiley‐Liss, Inc.
Analysis of the retinas and optic nerves of achiasmatic belgian sheepdogs
Authors: Hogan Dale , Williams Robert W.
Published: January 2005

An autosomal recessive mutation carried in a family of black Belgian sheepdogs eliminates the optic chiasm—all retinal ganglion cell axons extend directly into the ipsilateral optic tract. One key issue we are trying to resolve is whether the retina or the chiasm is the principal site of mutant gene action. In this study, we have examined retinas of mutants to discover any associated changes in retinal structure.

Retinas of mutant animals are relatively normal. Inner and outer nuclear layers are qualitatively indistinguishable from those of normal dogs. The principal difference is that the area centralis of mutants is smaller and has a lower peak ganglion cell density than that of normal dogs (8,100 vs. 10,500/mm2, P < 0.05). This mutant phenotype is similar to that seen in retinas of Siamese cats and albino ferrets. Beyond area centralis, the central‐to‐peripheral gradient in ganglion cell density is normal in mutants. The size of the optic nerves, density of axons, and total number of axons do not differ between mutant and normal dogs.

One of three mutant dogs had a small abnormal optic chiasm. Retrograde labeling of ganglion cells demonstrated that the residual crossed projection originated from cells in a widespread region in nasal retina and not solely from the peripheral nasal region, as might be expected of an anti‐albino.

Although our analysis does not rule out the retina as a site of mutant gene action, the modest differences between mutant and normal retinas suggest that the mutation either acts outside the retina or exerts a highly specific effect on ganglion cell trajectories alone. © 1995 Wiley‐Liss, Inc.
Organization of the colliculo‐suprageniculate pathway in the cat: A wheat germ agglutinin‐horseradish peroxidase study
Authors: Katoh Yoshimitsu Y. , Benedek György
Published: January 2005

A wheat germ‐agglutinated horseradish peroxidase (WGA‐HRP) tracing technique was used to label the cell bodies of neurons in the superior colliculus that send projections into the visually sensitive region of the suprageniculate nucleus (Sg) in the feline thalamus. After determination of the position of the Sg by detecting characteristic single‐unit responses to moving visual stimuli, WGA‐HRP was injected into the Sg in five pentobarbital‐anesthetized cats. The animals were than sacrificed, and serial frozen sections of the midbrain were processed for the demonstration of peroxidase activity.

A total of 2,736 WGA‐HRP‐stained neurons were located within the ipsilateral superior colliculus (SC), and a few labeled cells were consistently found bilaterally in the external nuclei of the inferior colliculus. In each cat, a small but significant fraction of the labeled cells were encountered contralateral to the injection.

Medial SC neurons tended to project to the posterior Sg, and lateral SC neurons tended to project to more rostral Sg. However, labeled cells were distributed homogeneously along the rostrocaudal extent of the SC, indicating the absence of a well defined topographic relationship. Nor was the Sg injection site location related to the laminar distribution of SC projection neurons. In all cases, the majority of the labeled cells were found in layer IV (49.0%), with fewer cells in layers III (17.5%), layer V (20.0%), and layer VI (11.8%). No labeled cells were located in layer I, although a few were located in the deep part of layer II.

Five types of SC projection cells were distinguished morphologically. Of the 258 labeled cells that could be characterized, 25% were stellate cells, 25% vertical cells, 20% granular cells, 17% triangular cells, and 12% horizontal cells. The average diameter of 226 cells ranged between 8 and 47 μm. We conclude that a mixed population of SC cells projects to the Sg; the morphological heterogeneity and the distribution of these cells suggests that several functionally different pathways may be involved in the colliculothalamic pathway and in the processing of visual input in the SC. © 1995 Wiley‐Liss, Inc.
Expression of FGF‐2 and FGF receptor type 1 in the adult rat brainstem: Effect of colchicine
Authors: Grothe Claudia , Janet Thierry
Published: January 2005

In the adult rat brainstem, neuronal subpopulations of several motor and sensory nuclei display basic fibroblast growth factor (bFGF or FGF‐2) immunoreactivity (IR; Grothe et al. J. Comp. Neurol. 305:328–336). In the present study we demonstrate that FGF‐2‐IR correlates with staining for the high‐affinity FGF‐receptor 1. Intracerebroventricular injection of colchicine leads to the disappearance or substantial reduction of FGF‐2‐IR in the hypoglossal, facial, trigeminal motor, trochlear, and mesencephalic trigeminal nuclei. In contrast, FGF‐2‐IR appears in many perikarya of the red nucleus and the medial nucleus of the trapezoid body, whereas in control rats both nuclei showed immunostained fibers and almost no immunoreactive cell bodies. This dramatic change of FGF‐2‐IR could be explained by the ability of colchicine to block fast axonal transport. Cranial nuclei may internalize FGF‐2 at the periphery via high‐affinity receptors and retrogradely transport the molecule to their perikarya. The red nucleus and the medial nucleus of the trapezoid body may synthesize FGF‐2 and provide the growth factor to afferent or efferent neurons. The presence of FGF‐2 mRNA in brainstem extract and the absence of the FGF‐2 transcript in extracts of the hypoglossal nucleus corroborate this suggestion.

The effect of colchicine on FGF‐2‐IR in the brainstem nuclei suggests that FGF‐2 could be specifically retrogradely transported in other cranial nuclei, in addition to the hypoglossal system. Together with the ability of FGF‐2 to stimulate neuronal survival, this result strongly supports the hypothesis that FGF‐2 is acting as a neurotrophic factor on specific central neuron populations. © 1995 Wiley‐Liss, Inc.
Inputs from identified jaw‐muscle spindle afferents to trigeminothalamic neurons in the rat: A double‐labeling study using retrograde HRP and intracellular biotinamide
Authors: Luo Pifu , Dessem Dean
Published: January 2005

Projections from physiologically identified jaw‐muscle spindle afferents onto trigeminothalamic neurons were studied in the rat. Trigeminothalamic neurons were identified by means of retrograde transport of horseradish peroxidase from the ventroposteromedial nucleus of the thalamus. Labeled neurons were found contralaterally in the supratrigeminal region (Vsup), the trigeminal principal sensory nucleus, the ventrolateral part of the trigeminal subnucleus oralis, the spinal trigeminal subnuclei interpolaris and caudalis, the reticular formation, and an area ventral to the trigeminal motor nucleus (Vmo) and medial to the trigeminal principal sensory nucleus (AVM). Jaw‐muscle spindle afferents were physiologically identified by their increased firing during stretehing of the jaw muscles and intracellularly injected with biotinamide. Axon collaterals and boutons from jaw‐muscle spindle afferents were found in Vmo; Vsup; the dorsomedial part of the trigeminal principal sensory nucleus (Vpdm); the dorsomedial part of the spinal trigeminal subnuclei oralis, interpolaris (Vidm) and caudalis; the parvicellular reticular formation (PCRt); and the mesencephalic trigeminal nucleus. Trigeminothalamic neurons in Vsup, Vpdm, Vidm, PCRt, and AVM were associated with axon collaterals and boutons from intracellularly stained jaw‐muscle spindle afferents. Trigeminothalamic neurons in Vsup, Vpdm, Vidm, and PCRt were closely apposed by one to 14 intracellularly labeled boutons from jaw‐muscle spindle afferents, suggesting a powerful input to some trigeminothalamic neurons. These data demonstrate that muscle length and velocity feedback from jaw‐muscle spindle afferents is projected to the contralateral thalamus via multiple regions of the trigeminal system and implicates these pathways in the projection of trigeminal proprioceptive information to the cerebral cortex. © 1995 Wiley‐Liss, Inc.
Differences in the connectivity of rat pudendal motor nuclei as revealed by retrograde transneuronal transport of wheat germ agglutinin
Authors: Peshori Kavita R. , Erichsen Jonathan T. , Collins William F.
Published: January 2005

Bilateral coordinated activation of pudendal motoneurons is an essential component of penile reflexes in male rats. However, little is known about the intraspinal organization of these reflexes. In the present study, retrograde transneuronal transport of wheat germ agglutinin (WGA) was used to examine the organization of spinal motoneurons and putative interneurons mediating penile reflexes in adult male rats. Injection of WGA into the ventral bulbospongiosus muscle resulted in direct retrograde labeling of motoneurons in the ipsilateral dorsomedial (DM) nucleus and transneuronal labeling of ipsilateral and contralateral DM motoneurons. Motoneurons in the ipsilateral and contralateral dorsolateral (DL) nuclei were not labeled. WGA‐labeled putative interneurons were observed bilaterally, primarily in the ventromedial spinal gray matter extending dorsally to the central canal and the dorsal gray commissure. The number of transneuronally labeled putative interneurons increased with longer survival times. Injection of WGA into the ischiocavernosus muscle resulted in direct retrograde labeling of motoneurons in the medial subdivision of the ipsilateral DL nucleus. However, no WGA labeling was detected in motoneurons in the lateral subdivision of the ipsilateral DL nucleus, the contralateral DL nucleus, or the DM nuclei at any of the survival times studied (1–7 days). Only a small number of transneuronally labeled putative interneurons was observed in the ventrolateral gray matter at longer survival times (3–7 days). Thus, marked differences were observed between the DM and DL nuclei with respect to the transneuronal transport of WGA. These results are discussed with respect to the organization of the spinal circuits that mediate pudendal motor reflexes. © 1995 Wiley‐Liss, Inc.
Retinal ganglion cells in normal hamsters and hamsters with novel retinal projections. I. Number, distribution, and size
Authors: Métin Christine , Irons W. Andrew , Frost Douglas O.
Published: January 2005

We examined the number, spatial distribution, and size of ganglion cells in the retinae of normal Syrian hamsters and hamsters with retinal projections to the auditory and somatosensory nuclei of the thalamus, induced by neonatal surgery. As revealed by retrograde filling with horseradish peroxidase, there are about 64,600 contralaterally projecting retinal ganglion cells (RGCs) and 1,700 ipsilaterally projecting RGCs in the retinae of normal adult hamsters. Contralaterally projecting RGCs are distributed throughout the retina and have two local density peaks located within a central streak of high RGC density that is oriented approximately along the nasal‐temporal axis. RGC density falls above and below the central streak, with a steeper gradient towards the upper retina. Ipsilaterally projecting RGCs are diffusely distributed within a crescent at the inferotemporal retinal periphery and are most dense at the internal border of the crescent. The soma diameter of contralaterally projecting RGCs ranges from 6 to 25 μm; the diameter distribution is unimodal, with a peak in the 10–13 μm range and is skewed toward smaller values, with an elongated tail towards higher values. Contralaterally projecting RGCs tend to be smaller in regions of higher density. Ipsilaterally projecting RGCs tend to be larger than contralaterally projecting RGCs both globally and within the temporal crescent, and their size distributions tend to be less regular and less well related to local density.

The retinae of neonatally operated hamsters with novel retinal projections to the auditory and somatosensory systems contain about one‐fourth the normal number of contralaterally projecting RGCs, whose relative density distribution is approximately normal despite the drastic reduction of absolute RGC density. The range and distribution of RGC soma diameters are similar in normal and neonatally operated hamsters, and, in operated as in normal hamsters, contralaterally projecting RGC somata tend to be smaller in regions of higher density.

Our results in normal hamsters suggest a role for intraretinal mechanisms in the determination of RGC size. Our findings in neonatally operated hamsters suggest that, despite the reduced number of RGCs in these animals, the same types of RGCs are found in the retinae of normal and neonatally operated hamsters. © 1995 Wiley‐Liss, Inc.
Dynorphin opioid inhibition of cocaine‐induced, D1 dopamine receptor‐mediated immediatem‐early gene expression in the striatum
Authors: Steiner Heinz , Gerfen Charles R.
Published: January 2005

Neurons in the striatum that project to the substantia nigra contain the opioid peptide dynorphin. Stimulation of D1 dopamine receptors results in increased expression of mRNA encoding dynorphin as well as expression of immediate‐early genes such as c‐fos in these neurons. Levels of dynorphin vary in different regions of the normal rat striatum, being highest in ventral and medial striatum. In a prior study, we have shown that both regional and temporal patterns of c‐fos induction following treatment with the indirect dopamine receptor agonist cocaine are inversely related to those of dynorphin expression. These results suggested that dynorphin is involved in regulating the responsiveness of these neurons to dopamine input. In the present experiments, we examined such a potential role for dynorphin by analyzing the influence of the dynorphin (kappa opioid receptor) agonist spiradoline on immediate‐early gene induction by cocaine, and we determined that this immediate‐early gene response is mediated by D1 dopamine receptors located in the striatum. As a marker of neuron activation, expression of c‐fos and zif 268 immediate‐early genes was assessed with quantitative in situ hybridization histochemistry. Results showed that (1) intrastriatal infusion of the D1 dopamine receptor antagonist SCH‐23390 (2.5–250 pmol) resulted in a dose‐dependent blockade of immediate‐early gene induction by cocaine (30 mg/kg); (2) systemic administration of the kappa opioid receptor agonist spiradoline (0.5–10.0 mg/kg) decreased cocaine‐induced expression of c‐fos and zif 268 mRNAs in striatum in a dose‐dependent manner; (3) intrastriatal infusion of spiradoline (1–50 nmol) also suppressed immediate‐early gene induction by cocaine, demonstrating that kappa opioid receptors located in the striatum mediate such an effect; and (4) systemic and intrastriatal administration of spiradoline also affected immediate‐early gene expression in cortex. These results demonstrate that, in striatum, immediate‐early gene induction by cocaine is a D1 dopamine receptor‐mediated process that is inhibited by activation of kappa opioid receptors. Therefore, these findings suggest that the striatal dynorphin opioid system acts directly and/or indirectly to inhibit dopamine input to striatonigral neurons through kappa opioid receptor‐mediated processes in the striatum. © 1995 Wiley‐Liss, Inc.
Thalamic distribution of projection neurons to the primary motor cortex relative to afferent terminal fields from the globus pallidus in the macaque monkey
Authors: Inase Masahiko , Tanji Jun
Published: January 2005

To examine quantitatively the pathway from the internal segment of the globus pallidus to the primary motor cortex through the thalamus, we compared the distribution of thalamocortical neurons projecting to the motor cortex with the distribution of afferent terminal fields from the pallidum in the ventrolateral nuclear group of the thalamus in four Japanese monkeys by using the anterograde and retrograde double‐labeling method. In each monkey, different fluorescent retrograde tracers (Fast Blue and Diamidino Yellow) were injected separately into the distal and proximal forelimb areas of the primary motor cortex after physiological mapping with intracortical microstimulation. In the same individual monkeys, an anterograde tracer, wheatgerm agglutinin conjugated to horseradish peroxidase, was injected into the internal segment of the globus pallidus after the forelimb part was identified physiologically.

A small group of projection neurons to the distal and proximal representations of the motor cortex were found in the terminal fields from the pallidum, but a majority of the projection neurons were distributed outside the terminal area in the thalamus. These results confirm the existence of the pathway from the pallidum through the thalamus to the primary motor cortex, but also indicate that the primary motor cortex receives its major thalamic inputs from outside of the pallidal projection area, and that the pallidum sends its major outputs to nonprimary motor areas through the thalamus. © 1995 Wiley‐Liss, Inc.
Distribution of GAD‐like immunoreactivity in the retina and central visual system of Rana pipiens
Authors: Tyler Christopher J. , Fite Katherine V. , Devries Geert J.
Published: January 2005

Immunohistochemistry was used to survey the distribution of glutamic acid decarboxylase (GAD), the synthesizing enzyme for gamma‐aminobutyric acid (GABA), throughout the visual system of the frog Rana pipiens. GAD‐like immunoreactivity (GAD‐LI) was assessed in the retina, in primary retinorecipient targets, and in thalamic nuclear groups postsynaptic to primary retinal terminal zones. Within the retina, the inner plexiform layer displayed intense GAD‐LI, but immunoreactivity was absent in the ganglion cell layer (GCL). Putative amacrine, bipolar, and horizontal cell somata were also labeled.

Centrally, GAD‐LI was observed in all primary visual nuclei. Dense, GAD‐like immunoreactive punctate structures (puncta), presumably terminals, were observed in the pretectal nucleus lentiformis mesencephali, posterior thalamic neuropil, and uncinate neuropil. GADlike immunoreactive puncta were noted in several laminae of the optic tectum, with the highest concentrations located within the 9th and 8th laminae. Moderate numbers of GAD‐like immunoreactive puncta were found in the mesencephalic nucleus of the basal optic root, and two thalamic neuropils—corpus geniculatum and neuropil of Bellonci. The ventrolateral area, posterocentral nucleus, and posterolateral nucleus all contained sparse amounts of GAD‐LI.

These observations suggest that GABA plays an important physiological role in all central visual areas of Rana pipiens. © 1995 Wiley‐Liss, Inc.
Precocious invasion of the optic stalk by transient retinopetal axons
Authors: Reese B. E. , Geller S. F.
Published: January 2005

This study demonstrates that the fetal optic nerve contains a conspicuous population of transient retinopetal axons. Implants of the carbocyanine dye, DiI, were made into the retina or diencephalon of fetal ferrets to label the retinopetal axons retrogradely or anterogradely, respectively, and sections were immunostained for β‐tubulin to label the early differentiating axons in the optic nerve.

Dye implants into the optic nerve head, but not the retinal periphery, retrogradely labeled somata in the ventrolateral diencephalon, provided the implants were made before embryonic day (E) 30. When dye implants were made into the ventrolateral diencephalon, these same retinopetal axons were anterogradely labeled, coursing through the optic nerve but never invading the retina. The axons course as 2–5 fascicles from their cells of origin and turn laterally to enter the optic nerve where it joins the future hypothalamus. The retinopetal cells can be retrogradely labeled as early as E20, before optic axons have left the retina.

The optic nerve and fiber layer are immunoreactive for β‐tubulin on E24 and thereafter, whereas on E20 and E22, they are immunonegative. Yet at these early embryonic ages, immunopositive fascicles of axons course from the diencephalon into the optic stalk, confirming the precocious nature of the retinopetal projection. Implants of dye made into the future optic nerve head at these very early stages also retrogradely label retinopetal cells in the future chiasmatic region. These cells are distributed primarily on the side ipsilateral to the midline, but a few can be found contralateral to it. Both these, as well as the retinopetal axons arising from the ventrolateral diencephalon, may serve a transient guidance function for later developing optic axons. © 1995 Wiley‐Liss, Inc.
Opioid precursor gene expression in the human hypothalamus
Authors: Sukhov Renat R. , Walker Lary C. , Rance Naomi E. , Price Donald L. , Young W. Scott
Published: January 2005

Using in situ hybridization histochemistry, we studied the distribution of neurons that express preproopiomelanocortin (pre‐POMC), preprodynorphin (pre‐PDYN), and preproenkephalin (pre‐PENK) gene transcripts within the human hypothalamus and surrounding structures. Of the three opioid systems, pre‐POMC neurons have the most restricted distribution. Pre‐POMC cells are most numerous in the infundibular nucleus and retrochiasmatic area of the mediobasal hypothalamus; a few labeled cells are present within the boundaries of the ventromedial nucleus and infundibular stalk. Pre‐POMC message was not found in the limited samples of structures adjacent to the hypothalamus.

In contrast to neurons that express pre‐POMC, neurons expressing pre‐PDYN and pre‐PENK are more widely represented throughout the hypothalamus and extrahypothalamic structures. However, pre‐PDYN and pre‐PENK cells differ from one another in distribution. Pre‐PDYN message is especially abundant in neurons of the tuberal and mammillary regions, with a distinct population of labeled cells in the premammillary nucleus and dorsal posterior hypothalamus. Pre‐PDYN gene expression also is found in neurons of the dorsomedial nucleus, ventromedial nucleus, caudal magnocellular portion of the paraventricular nucleus, dorsolateral supraoptic: nucleus, tuberomammillary nucleus, caudal lateral hypothalamus, and retrochiasmatic area. In structures immediately adjacent to the hypothalamus, pre‐PDYN neurons were observed in the caudate nucleus, putamen, cortical nucleus of the amygdala, and bed nucleus of the stria terminalis.

Pre‐PENK neurons occur in varying numbers in all hypothalamic nuclei except the mammillary bodies. The chiasmatic region is particularly rich in pre‐PENK neurons, with the highest packing density in the intermediate nucleus [the intermediate nucleus (Braak and Braak [1987] Anat. Embryol. 176:315–330) has also been termed the sexually dimorphic: nucleus of the preoptic area (SDA‐POA; Swaab and Fliers [1985] Science 228:1112–1115) or the interstitial nucleus of the anterior hypothalamus 1 (Allen et al. [1989] J. Neurosci. 9:497–506)], dorsal suprachiasmatic nucleus, medial preoptic area, and rostral lateral hypothalamic area. Pre‐PENK neurons are numerous in the infundibular nucleus, ventromedial nucleus, dorsomedial nucleus, caudal parvicellular portion of the paraventricular nucleus, tuberomammillary nucleus, lateral hypothalamus, and retrochiasmatic area. Only a few lightly labeled cells were found in the periphery of the supraoptic nucleus and lateral tuberal nucleus. In areas adjacent tothe hypothalamus, cells that contain pre‐PENK message occur in the nucleus basalis of Meynert, central nucleus of amygdala, bed nucleus of the stria terminalis, caudate nucleus, and putamen. The differential distribution of pre‐POMC, pre‐PDYN, and pre‐PENK neurons in the human hypothalamus suggests that these three opioid systems influence hypothalamic functions in quite different ways. © 1995 Wiley‐Liss, Inc.
Frog prohormone convertase PC2 mRNA has a mammalian‐like expression pattern in the central nervous system and is colocalized with a subset of thyrotropin‐releasing hormone‐expressing neurons
Authors: Pu Le‐Ping , Hayes William P. , Mill John F. , Ghose Shubroto , Friedman Theodore C. , Loh Y. Peng
Published: January 2005

The prohormone convertase (PC2) is expressed in the mammalian central nervous system (CNS) and has been shown to play an important role in the processing of certain neuropeptide precursors and prohormones at paired basic residues. Amphibian PC2 cDNA was recently cloned for the frog Xenopus laevis, and both its sequence and its pituitary expression pattern were shown to be very similar to those of mammalian PC2. To investigate further the function of PC2 in the vertebrate CNS, we used in situ hybridization histochemistry to localize the distribution of cells expressing PC2 mRNA in the frog brain and the spinal cord. The distribution of PC2‐expressing cells was also compared with that of cells expressing thyrotropin‐releasing hormone (TRH) mRNA or peptide. PC2‐expressing cells were detected in specific nuclei that were widely distributed in the frog CNS. In forebrain, telencephalic PC2 mRNA was found in the olfactory bulb, pallium, striatum, amygdala, and septum, and diencephalic PC2 mRNA was seen in the preoptic area, thalamus, and hypothalamus. More posteriorly, PC2 cells were localized to midbrain tegmentum, the torus semicircularis, and the optic tectum, as well as the cerebellum, brainstem, and spinal cord. Despite this wide distribution, steady‐state levels of PC2 mRNA were clearly different in various brain nuclei. Regions with higher levels showed good correspondence to areas shown by others in frog to contain large numbers of neuropeptideexpressing cells, including TRH cells. On the other hand, not all brain areas with high levels of TRH mRNA had high levels of PC2 mRNA. Localization studies combining in situ hybridization and immunocytochemistry showed that, at least in optic tectum and brainstem, PC2 mRNA and pro‐TRH peptide coexist. These findings suggest that pro‐TRH is processed by PC2 in some, but possibly not all, brain regions. Thus, different converting enzymes may be involved in pro‐TRH processing in different brain regions. © 1995 Wiley‐Liss, Inc.
Differential expression of mGluR5 metabotropic glutamate receptor mRNA by rat striatal neurons
Authors: Testa Claudia M. , Standaert David G. , Landwehrmeyer G. Bernhard , Penney John B. , Young Anne B.
Published: January 2005

Metabotropic glutamate receptors (mGluRs) mediate the effects of glutamate neurotransmission on intracellular second messenger systems. Among the seven distinct mGluR receptor isoforms currently identified, the mGluR5 isoform is expressed particularly prominently in the striatum, where it may contribute to neuronal plasticity, motor behaviors, and excitotoxic injury. mGluR5 mRNA expression in striatal enkephalinergic, somatostatinergic, and cholinergic neurons was examined using double label in situ hybridization techniques. mGluR5 expression is abundant in a large number of medium‐sized striatal cells but is absent in a significant minority of neurons. Double label in situ hybridization with 35S‐dATP‐ and digoxygenin‐dUTP‐tailed oligonucleotide probes demonstrated that mGluR5 message is highly expressed by enkephalinergic striatal neurons but is not detectable in cholinergic or somatostatin interneurons. In addition, some nonenkephalin, presumably substance P, neurons were also strongly labeled for mGluR5. The differential expression of mGluR5 in striatal projection neurons vs. interneurons may contribute to the selective vulnerability of these neurons to disease processes. © 1995 Wiley‐Liss, Inc.
Neuropeptide receptors in developing and adult rat spinal cord: An in vitro quantitative autoradiography study of calcitonin gene‐related peptide, neurokinins, μ‐opioid, galanin, somatostatin, neurotensin and vasoactive intestinal polypeptide receptors
Authors: Kar S. , Quirion R.
Published: January 2005

A number of neuroactive peptides including calcitonin gene‐related peptide (CGRP), substance P, neurokinin B, opioids, somatostatin (SRIF), galanin, neurotensin and vasoactive intestinal polypeptide (VIP) have been localized in adult rat spinal cord and are considered to participate either directly and/or indirectly in the processing of sensory, motor and autonomic functions. Most of these peptides appear early during development, leading to the suggestion that peptides, in addition to their neurotransmitter/neuromodulator roles, may possibly be involved in the normal growth and maturation of the spinal cord. To provide an anatomical substrate for a better understanding of the possible roles of peptides in the ontogenic development of the cord, we investigated the topographical profile as well as variation in densities of [125I]hCGRPα, [125I]substance P/neurokinin‐1 (NK‐1), [125I]eledoisin/neurokinin‐3 (NK‐3), [125I]FK 33–824 ([D‐Ala2, Me‐Phe4, Met(O)ol5]enkephalin)/μ‐opioid, [125I]galanin, [125I]T0D8‐SRIF14 (an analog of sornatostatin), [125I]neurotensin and [125I]VIP binding sites in postnatal and adult rat spinal cord using in vitro quantitative receptor autoradiography. Receptor binding sites recognized by each radioligand are found to be distributed widely during early stages of postnatal development and then to undergo selective modification to attain their adult profile of distribution during the third week of postnatal development. The apparent density of various receptor sites, however, are differently regulated depending on the lamina and the stage of development studied. For example, the density of μ‐opioid binding sites, following a peak at postnatal day 4 (N), declines gradually in almost all regions of the spinal cord with the increasing age of the animal [125I]substance P/NK‐1 binding sites, on the other hand, show very little variation until P14 and then subsequently decrease as the development proceeds. In the adult rat, most of these peptide receptor binding sites are localized in relatively high amounts in the superficial laminae of the dorsal horn. To varying extents, moderate to low density of various peptide receptor binding sites are also found to be present in the ventral horn, intermediolateral cell column and around the central canal. Taken together, these results suggest that each receptor‐ligand system is regulated differently during development and may each uniquely be involved in cellular growth, differentiation and in maturation of the normal neural circuits of the spinal cord, Furthermore, the selective localization of various receptor binding sites in adult rat spinal cord over a wide variety of functionally distinct regions reinforces the neurotransmitter/ modulator roles of these peptides in sensory, motor and autonomic functions associated with the spinal cord. © 1995 Wiley‐Liss, Inc.
Development of glycinergic cells and puncta in nuclei of the superior olivary complex of the postnatal ferret
Authors: Henkel Craig K. , Brunso‐Bechtold Judy K.
Published: January 2005

The distribution of glycine‐immunopositive cells and axonal endings was studied in the adult and early postnatal ferret superior olive. As in other species, the most prominent glycine‐immunopositive cell group in the adult ferret superior olive was the medial nucleus of the trapezoid body. Other darkly immunostained cells were present, although more scattered, in most periolivary regions, including the lateral and ventral trapezoid body nuclei. In the lateral superior olivary nuclei, glycine‐immunopositive cells were intermingled with immunonegative cells. A comparable population of cells in the ipsilateral lateral superior olivary nucleus was retrogradely labeled in cases with unilateral injections of tritiated glycine in the inferior colliculus. Glycine‐immunopositive puncta were widely distributed in the neuropil in most periolivary regions, including dense accumulations in the dorsomedial periolivary region and ventral and lateral nuclei of the trapezoid body. In the lateral and medial superior olivary nuclei, immunopositive puncta were distributed around the principal cells in characteristic perisomatic halos.

In postnatal ferrets, immunopositive cell bodies were first observed by postnatal day 7 and were distributed in regions comparable to regions in the adult, with the exception that immunopositive cells in the lateral superior olivary nucleus did not appear until about postnatal day 28. There was diffuse staining in the neuropil in principal and periolivary nuclei by postnatal day 7. During the third postnatal week, the immunostaining in the neuropil began to take on a more granular appearance and immunopositive puncta could be seen by postnatal day 35. In the lateral and medial superior olivary nuclei, the earliest distribution of immunostaining in the neuropil was nonuniform, being greater in the high‐frequency, medial, and ventral regions, respectively. The density gradient in these areas was gradually eliminated over the next 2 postnatal weeks as immunostained processes and endings appeared over greater portions of the nuclei. © 1995 Wiley‐Liss, Inc.
Developmental changes in epitope accessibility as an indicator of multiple states of an immunoglobulin‐like neural cell adhesion molecule
Authors: Denburg Jeffrey L. , Caldwell Robert T. , Marner Joyce M.
Published: January 2005

Cell surface molecules with restricted spatial and temporal distributions are good candidates for mediators of the cell‐cell interactions that are necessary for the development of the nervous system. A monoclonal antibody (MAb 23A7) was produced that selectively and transiently labeled a limited subset of axons in the chick embryo spinal cord. Determination of the N‐terminal amino acid sequence and immunoprecipitation experiments demonstrated that the 23A7 antigen is identical to Bravo/Nr‐CAM, a previously described cell adhesion molecule with immunoglobulin‐like domains (E. J. de la Rosa, J. F. Kayyem, J. M. Roman, Y.‐D. Stierhof, W. J. Dreyer, and U. Schwartz [1989] J. Cell Biol. 111:3087–3096; M. Grumet, V. Mauro, M. P. Goon, G. M. Edelman, and B. A. Cunningham [1991] J. Cell Biol. 113:1399–1412).

The temporal distribution of the 23A7 antigen is unusual in that, immunohistochemically, MAb 23A7 binding greatly decreases after 7 days of development, whereas Western blot analysis indicates increasing levels of the antigen until 17 days of development. In contrast, an antiserum against purified Nr‐CAM, which also binds only to the 23A7 antigen, labels nearly all the axons in the tissue throughout all the later stages of development. These anomalous observations are apparently not the result of differential sensitivity of the 23A7 epitope to fixation, the use of suboptimal concentrations of the MAb, or selective MAb binding to a subset of Bravo/Nr‐CAM molecules produced by alternative splicing of the transcript or by posttranslational modification. These findings could indicate the existence of multiple states of Bravo/Nr‐CAM, which during development, vary in the accessibility of their extracellular domains to the MAb. This suggests the existence of multiple conformation or aggregation states of this cell adhesion molecule, each of which might be performing a different function. © 1995 Wiley‐Liss, Inc.
Patterning of local intracortical projections within the vibrissae representation of rat primary somatosensory cortex
Authors: Hoeflinger Brian F. , Bennett‐Clarke Carol A. , Chiaia Nicolas L. , Killackey Herbert P. , Rhoades Robert W.
Published: January 2005

Anterograde and retrograde tracing with biotinylated dextran amine and Phaseolus vulgaris leukoagglutinin was used to assess projection patterns within the vibrissae representation of the rat's primary somatosensorycortex (S‐I). Large and small injections of either tracer into the center of the vibrissae representation yielded dense anterograde and retrograde labelling throughout much of the tangential extent of the vibrissae representation within S‐I. In all layers, the pattern and extent of retrograde and anterograde label was in rough congruence. The organization of this labelling varied across cortical layers. In layers II and III, labelled fibers extended away from injection sites in all directions and yielded a uniform pattern, which decreased in density with increasing distance from the tracer injection. There was a tendency for labelling to be more extensive along the representation of the row of vibrissae follicles that included the injection site than across rows. There was also a tendency for anterograde labelling to be more extensive in the direction of the representation of follicles more rostral on the face than that injected. In lamina IV, both labelled fibers and cells were restricted for the most part to the septa regions between the barrels. However, a small number of retrogradely labelled neurons were also located in the barrels (approximately one‐ninth of the number found in the septa). The pattern observed in laminae II–III was repeated in layers V and VI. In these laminae, there was no evidence of a pattern of intracortical connections related to the vibrissae representation in overlying lamina IV. © 1995 Wiley‐Liss, Inc.