bluuebunny/crossref_metadata_2025 huggingface dataset:
Basal expression of the inducible transcription factors c‐Jun, JunB, JunD, c‐Fos, FosB, and Krox‐24 in the adult rat brain
Authors: Herdegen Thomas , Kovary Karla , Buhl Anja , Bravo Rodrigo , Zimmermann Manfred , Gass Peter
Published: January 2005

Jun, Fos, and Krox proteins are inducible transcription factors contributing to the control of gene expression. The elucidation of their individual expression patterns in the nervous system provides new insights into the ability of neurons to react with changes of gene expression to external stimulation under physiological or pathological conditions. The expression of c‐Jun, JunB, JunD, c‐Fos, FosB, and Krox‐24 was investigated in the brain of untreated male Sprague‐Dawley and female BDIX rats by immunocytochemistry using specific antibodies.

JunD immunoreactivity (IR) labeled the highest number of neurons, being present in almost all neurons of the brain. JunD was expressed at high levels in those areas that also exhibit c‐Jun, JunB, c‐Fos, and FosB‐IR, such as locus coeruleus, periolivary nuclei (ncl.), pontine and central gray, lateral lemniscal ncl., inferior and superior colliculi, leaflet of geniculate ncl., midline nuclei of thalamus, dorsomedial and paraventricular ncl. of hypothalamus, ncl. supraopticus, dorsolateral part of caudate putamen and lateral septal ncl. In contrast to the high number of JunD‐positive neurons, c‐Jun, JunB, c‐Fos, and FosB proteins were detected in rather low numbers of neurons in these brain areas; the rank of the number of immunopositive neurons was c‐Fos > JunB > c‐Jun > FosB. Particularly high levels of expression were observed for c‐Jun in medullary motoneurons, medial geniculate ncl., arcuate ncl., and dentate gyrus, and for JunB in the CA‐1 area of the hippocampus and islands of Calleja. The zinc finger protein Krox‐24 was expressed in many neurons of these brain areas, with only discrete Jun‐ and Fos‐IR; additionally, many intensely labeled nuclei were present in spinal ncl. of the trigeminal ventromedial ncl. of the hypothalamus and the CA‐1 area of the hippocampus. In the cerebellum, nuclear labeling was detected only for c‐Jun, JunD, and Krox‐24 in granule cells, JunD‐IR was also found in glial cells of gray matter and fiber tracts, whereas glial c‐Jun‐IR was observed only in fiber tracts. Apart from a weak JunD‐IR, some areas did not express Jun, Fos, and Krox proteins such as cuneate and gracile ncl., venterobasal. complex of thalamus, globus pallidum, and Purkinje cells of the cerebellum.

Our data indicate that inducible transcription factors of the fos, jun, and krox gene families show patterns of individual expression in untreated animals, thereby reflecting different mechanisms and/or thresholds for induction under physiological conditions. © 1995 Wiley‐Liss, Inc.
Brain‐derived neurotrophic factor‐transduced fibroblasts: Production of BDNF and effects of grafting to the adult rat brain
Authors: Lucidi‐Phillipi Carrie A. , Gage Fred H. , Shults Clifford W. , Jones Kevin R. , Reichardt Louis F. , Kang Un Jung
Published: January 2005

Local delivery of brain‐derived neurotrophic factor (BDNF) by genetically modified cells provides the unique opportunity to examine the effects of BDNF on adult dopaminergic and cholinergic neurons in vivo. Primary rat fibroblasts were genetically engineered to produce BDNF. Conditioned media from BDNF‐transduced fibroblasts supported embryonic chick dorsal root ganglion neurons as well as rat fetal mesencephalic neurons. BDNF‐transduced fibroblasts grafted to the rat brain survived and showed continued mRNA production for at least 2 weeks. The effects of BDNF‐transduced fibroblast grafts on the dopaminergic and cholinergic systems were then assessed. BDNF‐transduced fibroblasts grafted into the normal intact substantia nigra induced sprouting of tyrosine hydroxylase‐ and neurofilamentimmunoreactive fibers into the graft. Fibroblast grafts implanted into the normal intact striatum and midbrain as well as the 6‐hydroxydopamine‐lesioned brain did not induce sprouting of dopaminergic fibers; neither did they affect drug‐induced rotational behavior. BDNF‐transduced fibroblasts did, however, significantly increase the homovanillic acid/dopamine ratio when grafted into the normal midbrain. Following transection of the fimbriafornix, BDNF‐transduced fibroblasts grafted into the septum were unable to rescue the septal cholinergic population, as did nerve growth factor‐producing fibroblast grafts. Genetically modified fibroblast grafts may provide an effective, localized method of BDNF delivery in vivo to test biological effects of this factor on the central nervous system. © 1995 Wiley‐Liss, Inc.
Genetic control of retinal projections in inbred strains of albino mice
Authors: Rice Dennis S. , Williams Robert W. , Goldowitz Dan
Published: January 2005

Mutations in the tyrosinase gene are often associated with a misrouting of retinal ganglion cell axons at the optic chiasm. In albinos, tyrosinase activity is lost and some ganglion cell axons that would normally project into the ipsilateral optic tract instead cross midline and project into the contralateral tract. The developmental mechanisms that cause this modification in neuronal connectivity are unknown. In this study, we screened six diverse strains of albino mice (strains 129, A, AKR, BALB/c, C57BL/6‐c/c, and CD‐1) to discover genetically determined variations and possible gene loci that might affect the severity of the albino decussation abnormality. Ganglion cells were retrogradely labeled with horseradish peroxidase, and the ipsilaterally and contralaterally projecting cells were counted. The average number of ipsilaterally projecting ganglion cells in the six albino strains varies from 1,000 to 1,300. Despite this variation, 1.8–1.9% of the total population projects ipsilaterally in each strain. In comparison, 2.8% project ipsilaterally in the pigmented strain, C57BL/6‐+/+. However, the percentage of displaced, ipsilaterally projecting cells varies substantially among albino strains‐from a low of 4% in strain CD‐1 to a high of nearly 10% in C57BL/6‐c/c. We conclude that even with large differences in genetic background and in absolute numbers of ganglion cells, there is no appreciable variation in the magnitude of decussation error among albino mice. The consistent effect of null alleles at tyrosinase suggests a comparably tight linkage between the biochemical activity of this enzyme and the mechanisms that control decussation phenotype. © 1995 Wiley‐Liss, Inc.
Cellular distribution of iron, transferrin, and ferritin in the hypotransferrinemic (Hp) mouse brain
Authors: Dickinson Thomas K. , Connor James R.
Published: January 2005

Hypotransferrinemic (Hp) mice have a point mutation or small deletion in the transferrin (Tf) gene, resulting in defective splicing of precursor Tf mRNA. Hp animals produce 1% of normal Tf levels and require supplemental serum or purified Tf for survival. Because of the lack of endogenous brain Tf, we examined regional and cellular distributions of iron and iron regulatory proteins (Tf and ferritin) in selected brain regions of Hp mice. The regional distribution of iron, Tf, and ferritin in Hp brain was similar to normal except for the pattern of iron staining in hippocampus. The cellular distribution of iron, ferritin, and Tf was similar between Hp and normal animals. The predominant cell type, staining for Tf and iron was oligodendrocytes. Qualitative observations suggest that the number of cells staining for iron was similar between Hp and normal mice, whereas the number of Hp Tf‐positive cells was reduced. Ferritin immunostaining was similar in both cases. However, ferritin‐positive cells were preominantly astrocytes, an observation unique to mice among species studied previously. Western blot analysis revealed that Tf present in HP brain was of exogenous origin (from supplemental injections). Presumably, Tf transports the iron found in Hp oligodendrocytes. These data demonstrate that, despite reduced endogenous Hp brain Tf, iron and plasma Tf migrate or are transported to the appropriate cells (oligodendrocytes), bringing into question the role of endogenous brain Tf in extracellular iron transport.
Lateral superior olive projections to the inferior colliculus in normal and unilaterally deafened ferrets
Authors: Moore David R. , Russell F. Anne , Cathcart Nicki C.
Published: January 2005

We have examined the projection from the lateral superior olive (LSO) to the inferior colliculus (IC) in the ferret, with particular interest in the laterality of the projection and in the effects of unilateral cochlear removal in infancy. Large or small deposits of the retrograde tracer wheat germ agglutininhorseradish peroxidase (WGA‐HRP) were made in the IC of anesthetized adult ferrets that either were normally hearing or had been unilaterally deafened in infancy (P5 or P25). After 2 days, the ferrets were perfused, and frontal sections of the brainstem were treated with tetramethyl benzidine. For large deposits of WGA‐HRP, equal numbers of labelled neurons were found evenly spread through both LSOs. Smaller deposits of WGA‐HRP produced four results that contrasted with previous reports on the cat. First, many more labelled neurons were found in the contralateral than in the ipsilateral LSO. Second, the relative number of labelled neurons in each LSO was independent of whether the deposits were in the ventral or in the dorsal IC. Third, the total number of labelled LSO neurons was independent of whether the deposits were in the ventral or in the dorsal IC. Fourth, the proportion of ipsilateral to contralateral labelled neurons was slightly higher in the medial LSO than in the lateral LSO. Ventral IC deposits resulted in more labelled neurons in the medial LSO, and dorsal IC deposits resulted in more labelled neurons in the lateral LSO, as expected. Neonatal cochlear removal did not change any of these results. We conclude that, in the ferret, the organization of the crossed and uncrossed projections from the LSO to the IC differs from that of the cat, and any similarity with the optic chiasm is not obvious. © 1995 Wiley‐Liss, Inc.
Dopaminergic innervation of the telencephalon of the pigeon (Columba livia): A study with antibodies against tyrosine hydroxylase and dopamine
Authors: Wynne Brigitte , Güntürkün Onur
Published: January 2005

The dopaminergic structures in the telencephalon of the pigeon were investigated with antisera against glutaraldehyde‐conjugated dopamine (DA) and tyrosine hydroxylase (TH). Our goal was to describe the morphological patterns of the labelled axons and to provide a detailed map of the density and regional distribution of the dopaminergic innervation in relation to cytoarchitectonic areas.

DA‐ and TH‐like fibers reached their highest density in the paleostriatum augmentatum and the lobus parolfactorius of the basal ganglia. The paleostriatum primitivum was characterized by a dichotomous DA‐positive innervation with a diffuse fiber network contacting en passant granular cells and a more specific input that completely wrapped up large cells, which probably represent relay neurons. Two distinct DA‐positive pathways could be followed back from the forebrain leading to the dopaminergic cell groups of the nucleus tegmenti pedunculopontinus pars lateralis and the area ventralis tegmentalis. The primary sensory areas of the visual, auditory, somatosensory, and trigeminal systems within the forebrain of the pigeon were virtually devoid of DA‐like fibers and demonstrated only TH‐positive axons, probably of a noradrenergic nature. Among the limbic structures, the neostriatum caudolaterale (a possible equivalent of the mammalian prefrontal cortex), the septum, the nucleus accumbens, and parts of the archistriatum were heavily labelled by DA‐like axons.

A highly characteristic morphological feature of the catecholaminergic innervation was the presence of “baskets,” which are constituted by TH‐ and DA‐positive fibers coiled up around large perikarya, so that the surrounded somata were virtually visible by the presence of labelled axons. The density of basket and nonbasket type innervations seemed to be independently regulated, so that each forebrain structure could be characterized by a mixture consisting of the individual degrees of these two features.

Our results demonstrate that the dopaminergic innervation of the forebrain of the pigeon is widespread but shows important regional variations. Similar to mammals, associative and motor structures are heavily innervated by dopaminergic fibers, whereas sensory areas are dominated by their noradrenergic input. The basket and nonbasket type innervations observed in virtually all of these subdivisions of the telencephalon may indicate the presence of two main classes of catecholaminergic afferents with different mechanisms of modulation of forebrain activity patterns. © 1995 Wiley‐Liss, Inc.
Innervation of nonmystacial vibrissae in the adult rat
Authors: Fundin B. T. , Arvidsson J. , Rice F. L.
Published: January 2005

Vibrissal follicle‐sinus complexes (F‐SCs) in the mystacial pad of rodents are heavily innervated by different types of sensory nerve endings. One site in mystacial F‐SCs, the inner conical body (ICB), is uniquely well innervated only in those species, such as the rat, that rhythmically whisk their mystacial vibrissae. In this study, we examined the innervation of rat nonmystacial F‐SCs, which are not whisked. Supraorbital, posteroorbital, lateral cervical, median cervical, submental, and carpal forelimb F‐SCs were cut on a cryostat and were either prepared for anti‐human protein gene product (PGP 9.5) immunofluorescence or stained using the Winkelmann silver technique. Much of the innervation of the nonmystacial F‐SCS is similar to that of mystacial F‐SCs. All are innervated by a large deep vibrissal nerve (DVN) and several smaller superficial vibrissal nerves (SVNs). As in the mystacial pad, the SVNs show a distribution of Merkel and free nerve endings qualitatively similar to the rete ridge collar of all the nonmystacial F‐SCs as well as provide circumferentially oriented endings to the ICBs to all but median‐cervical and carpal F‐SCs. Not only was the ICB innervation relatively sparse in median‐cervical and rpal F‐SCs, but a large portion of the carpal ICB innervation also ascended from the DVNs, which make only a small, ICB contribution in other locations. Similar to mystacial pad F‐SCs, the DVNs provided Merkel and lanceolate endings to the level of the ring sinus as well as reticular and irregular lanceolate‐like endings to the level of the cavernous sinus. However, all but the posteroorbital F‐SCs have relatively few lanceolate endings. Carpal F‐SCs also have relativiely few ring‐sinus Merkel endings, which are diffusely distributed, are limited to the superficial portion of the outer root sheath. They also lack reticular and irregular lanceolate‐like endings in the cavernous sinus. However, carpal F‐SCs have a unique set of corpuscular endings in the ICB, ring sinus, and cavernous sinus that are rrely seen in other F‐SCs. PGP 9.5 immunofluorescence also revealed two sets of fine‐caliber profiles at the level of the ICB and ring sinus that were not previously seen in mystacial F‐SCs. Athough there was no correlation between ICB innervation and whisking, the regional variations in F‐SC innervation suggest that functional differences may exist between vibrissae at different locations in the body. © 1995 Wiley‐Liss, Inc.
Projection of jaw‐muscle spindle afferents to the caudal brainstem in rats demonstrated using intracellular biotinamide
Authors: Luo Pifu , Wong Richard , Dessem Dean
Published: January 2005

Intracellular staining with biotinamide was used to study the axonal projection and synaptic morphology of rat jaw‐muscle spindle afferents. Intracellular recordings in the mesencephalic trigeminal nucleus (Vme) were identified as spindle afferent responses by their increased firing during stretching of the jaw‐elevator muscles. Biotinamide‐stained axon collaterals with boutons were found in the trigeminal motor nucleus (Vmo), Vme, the region dorsal to Vmo including the supratrigeminal region, the dorsomedial portion of the trigeminal principal sensory nucleus, and the dorsomedial part of the rostral spinal trigeminal subnucleus oralis. Additional, previously undescribed projections of jaw‐muscle spindle afferents were found to the dorsomedial portiori of the caudal spinal trigeminal subnucleus oralis (Vodm), the dorsomedial part of the spinal trigeminal subnucleus interpolaris (Vidm), the caudal parvicellular reticular formation, laminae IV and V of the spinal trigeminal subnucleus caudalis (Vc), and the dorsal division of the medullary reticular field. Labeled spindle boutons in Vodm formed predominately axodendritic synapses. Some of these boutons received presynaptic inputs from unlabeled P‐type boutons containing clear, spherical, or flattened vesicles. In Vidm, labeled collaterals and boutons were densely clustered into glomerular‐like structures. Labeled boutons in Vidm made axodendritic, axosomatic, and axoaxonic synapses and received synaptic contacts from unlabeled boutons containng clear, spherical, or flat and pleomorphic vesicles. Unlabeled presynaptic boutons in Vidrn occasionally contained dense core vesicles. Labeled boutons in Vc mainly formed synaptic contacts with large diameter dendrites. This projection of jaw‐muscle spindle afferents to caudal brainstem regions may play a significant role in masticatory‐muscle stretch reflexes and in the integration of trigeminal proprioceptive information and its transmission to higher centers. © 1995 Wiley‐Liss, Inc.
Anatomical demonstration of vagal input to nicotinamide acetamide dinucleotide phosphate diaphorase‐positive (nitrergic) neurons in rat fundic stomach
Authors: Berthoud Hans‐Rudolf
Published: January 2005

Recent pharmacological evidence suggests that the nonadrenergic, noncholinergic (NANC) vagal inhibitory input responsible for receptive relaxation of the fundic stomach is mediated by nitric oxide‐synthesizing enteric neurons. To demonstrate anatomically such direct vagal inputs to neurochemically identified enteric neurons, we utilized the nicotinamide acetamide dinucleotide phosphate (NADPH)‐diaphorase histochemical reaction in conjunction with selective anterograde labeling of vagal efferents or afferents.

Approximately 30% of all myenteric neurons of the fundic myenteric plexus stained positive for NADPH diaphorase, and the principal recipient of axonal projections from NADPH diaphorase‐positive neurons was the circular muscle layer. In a group of animals showing the most complete labeling of vagal efferent preganglionics with the carbocyanine dye DiA, quantitative analysis of the half of the ventral fundic wall closer to the greater curvature revealed that 46.8% ± 4.4% of all myenteric neurons received some degree of vagal contacts and that 30.5% ± 6.6% of such vagally contacted neurons were also NADPH diaphorase positive. In another group of rats with the most successful selective labeling of vagal afferents through DiI injections into the left nodose ganglion, analysis of select ganglia throughout the ventral fundic wall revealed that, of a total of 454 neurons with vagal afferent contacts, 34.8% ± 2.8% were NADPH diaphorase positive.

These findings support the view that, in the fundic stomach, some vagal preganglionic efferents terminate on nitric oxide‐synthesizing neurons that, in turn, project to and relax the external smooth muscle layers. Furthermore, vagal afferent endings also contact NADPH diaphorase‐positive neurons, suggesting the possibility of local axon reflexes originating from smooth muscular in‐series tension receptors and terminating on nitrergic neurons of the myenteric plexus. © 1995 Wiley‐Liss, Inc.
Ascending projections of the posterior nucleus of the hypothalamus: PHA‐L analysis in the rat
Authors: Vertes Robert P. , Crane Alison M. , Colom Luis V. , Bland Brian H.
Published: January 2005

With the exception of a report by R. B. Veazey, D. G. Amaral, and W. M. Cowan (1982, J. Comp. Neurol. 207:135–156) that examined the projections of the posterior hypothalamic area in the monkey by using the autoradiographic technique, the ascending projections of the posterior nucleus (PH) of the hypothalamus have not been systematically examined in any species. The present report describes the ascending projections of PH in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris ‐leucoagglutinin (PHA‐L). The major ascending route for PH fibers is the medial forebrain bundle. PH fibers project densely to several subcortical and cortical sites. The subcortical sites are the subthalamus/hypothalamus (zona incerta, the supramammillary nucleus, lateral, perifornical, dorsal, and anterior nuclei/areas), the thalamus (lateroposterior, laterodorsal, parafascicular, reuniens, paraventricular, central medial, paracentral, central lateral and intermediodorsal nuclei), the amygdala (central, lateral, and medial nuclei), the septal area (bed nucleus of atria terminalis, medial and lateral septum), and the basal forebrain (horizontal/vertical limbs of diagonal band nuclei and lateral preoptic area). The cortical sites are the perirhinal, insular, frontal (lateral agranular), prelimbic, and infralimbic cortices.

The diversity of PH projections to subcortical and cortical “limbic‐related” sites and to several structures with direct input to the hippocampus (supramammillary nucleus, reuniens, paraventricular and laterodorsal nuclei of the thalamus, medial and lateral septum, and perirhinal cortex) suggest that the PH may serve a critical role in various components of emotional behavior, including mnemonic processes associated with significant emotional events. © 1995 Wiley‐Liss, Inc.
Visual areas in the dorsal and medial extrastriate cortices of the marmoset
Authors: Rosa Marcello G. P. , Schmid Leisa M.
Published: January 2005

To define the number and limits of the visual areas in the primate extrastriate cortex, the visuotopy of the dorsal convexity and medial wall was studied by electrophysiological recordings in five marmosets anaesthetised with sufentanil and nitrous oxide and paralysed with pancuronium bromide. We identified five visuotopic representations in and around the densely myelinated zone between visual area 2 (V2) and the posterior parietal cortex. Most of the densely myelinated zone is formed by the homologue of the owl monkey's dorsomedial area (DM); thus, we also termed this area DM in the marmoset. Within DM, the lower quadrant representation is continuous, with central vision represented laterally, peripheral vision medially, the horizontal meridian caudally, and the vertical meridian rostrally. In contrast, the upper quadrant representation is split, with the central portion represented at the lateral edge of DM on the dorsal surface, and the periphery along the midline. Two other visual field representations, corresponding to the dorsointermediate area (DI) and to a new subdivision termed the dorsoanterior area (DA), are also densely myelinated but can be distinguished from DM based on the separation of the bands of Baillerger and visual topography. In addition, a homologue of the medial visual area (M) was identified. Our results reveal a highly complex visuotopy in primate cortex, with local discontinuities in representation and borders between areas that are often not coincident with either the horizontal or the vertical meridian. The topography of the dorsal extrastriate cortex in the marmoset strongly suggests that both visual area 3 (V3) and the parieiooccipital area (PO) of other primates are portions of a single visuotopic representation, DM, and calls into question the, existence of visual areas with partial or quadrantic representations of the visual field. © 1995 Wiley‐Liss, Inc.
Vitronectin receptor expression and distribution at the photoreceptor‐retinal pigment epithelial interface
Authors: Anderson Don H. , Johnson Lincoln V. , Hageman Gregory S.
Published: January 2005

Laser scanning confocal microscopy was employed to map the distribution of integrin immunoreactivity at the photoreceptor‐retinal pigment epithelial (RPE) interface of the primate retina, and to determine its relationship to the actin cytoskeleton. Immunolabeling using a polyclonal antibody to the human vitronectin receptor (VnR), a heterodimer containing the αv subunit in combination with either the β3 or β5 subunits, is detected primarily on the apical surface of the retinal pigment epithelium (RPE) in vivo and in vitro. It is also associated with the photoreceptor inner and outer segment cell surfaces. In contrast, immunolabeling using a polyclonal antibody to the human fibronectin receptor (FnR), a heterodimer containing the α5 and β1 subunits, is detected principally on the basolateral surface of the RPE and is virtually absent in photoreceptors. A partial three‐dimensional reconstruction of the anti‐VnR labeling pattern in cone photoreceptors reveals cell surface labeling that originates at the level of the myoid just distal to the outer limiting membrane. It extends distally toward the ellipsoid and terminates at the level of the cone outer segment. Approximately 20–22 immunoreactive foci are distributed evenly around the perimeter of the cone ellipsoid. These foci correspond in number and location to the calycal processes that protrude from the distal portion of the ellipsoid. A double‐labeling procedure, employing VnR antibody and a fluorescently labeled phallotoxin (phalloidin), was used to identify regions of VnR co‐distribution with filamentous actin (F‐actin). One such region includes the VnR‐immunoreactive foci at the margins of the cone inner segments and the actin cables that course through the photoreceptor ellipsoid and terminate within the calycal processes. A second zone of co‐distribution coincides with the actin‐containing, circumferential bundle at the lateral borders of the RPE cells, and a third zone is associated with the apical microvilli of the RPE that ensheath cone outer segments. In order to help identify the specific subunits underlying VnR (αvβ3/5) immunoreactivity, Northern blots of retinal‐RPE RNA were probed with α32P‐cDNAs to the human αv, β3, and β5 subunits and additional immunolocalization studies were performed using integrin human α or β subunit‐specific antisera. The results from these studies strongly suggest that one or more integrins, containing the αv and/or β5 subunits, are expressed by the photoreceptors and RPE. It thus appears likely that an integrin(s) from the cytoadhesin family located on the plasma membranes of these cells participates in some adhesion‐related event(s) at the interface between the neurol retina and the RPE. © 1995 Wiley‐Liss, Inc.
Variability and partial synchrony of the cell cycle in the germinal zone of the early embryonic cerebral cortex
Authors: Reznikov Kyrill , Van Der Kooy Derek
Published: January 2005

Cell cycle parameters were estimated using the cumulative 3H‐thymidine S‐phase labeling and percentage of labeled mitoses methods in the embryonic day 14 and 15 germinal zone of the rat cerebral cortex. The shortest cell cycle time was seen in the dorsal neocortex and the longest in the lateral neocortex and fimbria (the latter also had a low growth fraction). No differences were observed in cell cycle times between the cells in the ventricular and subventricular zone in the same neocortical region. The results suggest gradients of lengthening cell cycle times extending ventrolaterally and ventromedially from the dorsomedial neocortex. Although a majority of proliferating cells in individual cortical regions seem to belong to one population in terms of cell kinetics, several pieces of evidence suggest some heterogeneity: the asymmetric shapes of the percentages of labeled mitoses curves, the small population of cells that become pyknotic. Groups of DNA‐synthesizing nuclei that were ectopically located in the inner half of the ventricular zone also indicate the existence of different subpopulations of neuroepithelial cells. In addition, after a pulse injection of 3H‐thymidine the germinal zone is characterized by alternating clusters of heavily and lightly labeled cell nuclei that may reflect the simultaneous passage of a clusters of clel through the same portion of S‐phase. We suggest that partial cell cycle synchrony within groups of ventricular cells may explain the presence of these iterative cell kinetic patterns in the developing cortex. © 1995 Wiley‐Liss, Inc.
Auditory thalamocortical pathways defined in monkeys by calcium‐binding protein immunoreactivity
Authors: Molinari M. , Dell'Anna M. E. , Rausell E. , Leggio M. G. , Hashikawa T. , Jones E. G.
Published: January 2005

This study investigated differentiation of Macaca fuscata auditory thalamus into chemically defined nuclei forming relays to auditory cortical areas. The thalamus was stained immunocytochemically for parvalbumin and 28 kDa calbindin in normals and in brains in which retrogradely transported tracers were injected into middle layers of auditory cortical areas or applied to the cortical surface.

Parvalbumin‐ and calbindin‐immunoreactive cells show a complementary distribution in ventral, anterodorsal, post and magriocellular medial geniculate nuclei. The ventral nucleus has a high density of parvalbumin cells and few calbindin cells, and the anterodorsal nucleus has a high density of parvalbumin cells and moderate numbers of calbindin cells. Both nuclei have a dense parvalbumin‐immunoreactive neuropil formed by terminations of fibers ascending in the brachium of the inferior colliculus. The posterodorsal nucleus has approxi mately equal proportions of parvalbumin and calbindin cells; neuropil staining is weak but contains terminations of calbindin‐immunoreactive fibers ascending in the midbrain tegmenturn. The magnocellular nucleus contains domains of parvalbumin and calbindin cells.

Parvalbumin cells in the ventral nucleus project to a central core of auditory cortex with densest parvalbumin immunoreactivity. Those in anterodorsal and posterodorsal nuclei project to surrounding auditory fields with less dense parvalbumin immunoreactivity; those in the magnocellular nucleus project widely to auditory and other fields.

Injections of middle cortical layers label a large majority of parvalbumin cells in the ventral, anterodorsal, or posterodorsal nuclei and in the magnocellular nucleus. Superficial deposits label calbindin cells only, usually in more than one nucleus, implying a widespread projection system. © Wiley‐Liss, Inc.
Factors influencing mossy fiber collateral sprouting in organotypic slice cultures of neonatal mouse hippocampus
Authors: Coltman B. W. , Earley E. M. , Shahar A. , Dudek F. E. , Ide C. F.
Published: January 2005

Collateral sprouting of dentate granule cell axons, the mossy fibers, occurs in response to denervation, kindling, or excitotoxic damage to the hippocampus. Organotypic slice culture of rodent hippocampal tissue is a model system for the controlled study of collateral sprouting in vitro. Organotypic roller‐tube cultures were prepared from hippocampal slices derived from postnatal day 7 mice. The Timm heavy metal stain and densitometry were used to assay the degree of mossy fiber collateral sprouting in the molecular layer of the hippocampal dentate gyrus. Factors influencing mossy fiber collateral sprouting were time in culture, positional origin of the slice culture along the septotemporal axis of the hippocampus, and presence of attached subicular‐entorhinal cortical tissues. Collateral sprouting in the molecular layer was first detected after 6 days in culture and increased steadily thereafter. By 2 weeks considerable sprouting was apparent, and at 3 weeks intense sprouting was observed within the molecular layer. An intrinsic septal‐to‐temporal gradient of collateral sprouting was apparent at 14 days in culture. To determine whether differential damage to the mossy fibers was the basis for the differences in collateral sprouting along the septotemporal axis, we made complete transections of the mossy fiber projection as it exited the dentate hilus at various levels along the septotemporal axis; no differences were found on subsequent collateral sprouting in the dentate molecular layer. Timm‐stained hippocampal cultures with an attached entorhinal cortex, a major source of afferent innervation to the dentate granule cells, displayed significantly less collateral sprouting at 10 days in culture compared to that in cultures from adjacent sections without attached subicular‐entorhinal tissues present. Thus, time in culture, position along the septotemporal axis, and presence of afferent cortical tissues influence aberrant neurite collateral sprouting in organotypic slice cultures of neonatal mouse hippocampus. © Wiley‐Liss, Inc.
Vasopressin binding in the cerebral cortex of the mongolian gerbil is reduced by transient cerebral ischemia
Authors: Vallet Philippe , Bouras Constantin , Barberis Claude , Dreifuss Jean Jacques , Dubois‐Dauphin Michel
Published: January 2005

In Mongolian gerbils, the content of vasopressin in the cerebral cortex, the striatum, and the hypothalamus is increased after induction of acute cerebral ischemia. We used an iodinated vasopressin analogue and light microscopic autoradiography to study the distribution of vasopressin V1 receptors in the brain of adult male gerbils and to evaluate the effects of a transient bilateral cerebral ischemia (6 minutes) on the density of this receptor population. The animals were killed immediately or 10, 30, or 100 hours after transient bilateral occlusion of the common carotid arteries.

In control animals, specific [125I]‐VPA binding sites were present in various structures of the brain (olfactory bulb, anterior olfactory nucleus, lateral septum, bed nucleus of the stria terminalis, median preoptic area, ventral pallidum, substantia innominata, amygdala, thalamus, hypothalamic mammillary nuclei, superior colliculus, subiculum, central gray, nucleus of the solitary tract, hypoglossal nucleus). The strongest labeling was detected in the cerebral cortex, layers 5–6. After 30–100 hours of survival time following ischemia there was a marked decrease in [125I]‐VPA binding site density in these cerebral cortex layers. To a lesser degree, a decrease was also detected in the lateral septal nucleus. In contrast, labeling in other noncortical structures remained unchanged. All animals with 100 hours recovery showed a loss of cells in hippocampus (CA1 layer) and striatum. In addition, ischemia induced concomitant and proliferative changes in cortical and hippocampal astrocytes assessed by glial fibrillary acid protein immunoreactivity. These observations indicate a role for vasopressin in the cerebral cortex either on neurons or on glial cells and the modulation of vasopressin receptor expression by transient cerebral isehemia. © Wiley‐Liss, Inc.
Comparison of the topology and growth rules of motoneuronal dendrites
Authors: Dityatev Alexander E. , Chmykhova Nadejda M. , Studer Lorenz , Karamian Olga A. , Kozhanov Valery M. , Clamann H. Peter
Published: January 2005

The complexity, shape, and branching modes of the dendrites of spinal motoneurons were compared in cat, rat, and frog using topological analysis and growth models. The complexity of motoneuronal dendrites, measured as the mean number of terminal segments, varied significantly among samples and was related to contractile properties of innervated motor units. Despite this variation, all mature motoneurons having a mean number of terminal segments per dendrite greater than ten (up to 24. 3) exhibited a narrow range of values of coefficients describing the symmetry of tree shapes (0.42–0.47). This implies low variability in the topological shape of motoneuronal dendrites of different animals. This similarity of tree shapes proved to be a result of the similarity of growth rules. The growth of the dendrites could be described to a first approximation by a two‐parameter (Q and S) model called the QS model and by a multitype Markovian model. The estimation of parameters of the QS model, in which parameter Q is related to the probability of branching of intermediate segments, revealed that Q was equal or close to 0, implying that branching of dendrites is restricted to terminal segments. The estimates of the parameter S, which describes whether the probability of branching increases (S < 0) or decreases (S > 0) exponentially with segment order, were positive. This was in agreement with the results of estimation of probabilities of branching provided by the Markovian model, which showed that the branching probabilities decreased with segment order in an exponential manner in most of the neurons studied.

The QS and Markovian models involve different assumptions about the sequence and timing of branching events, and selection of the best model can provide insight into details of dendritic outgrowth. Extensive simulation of tree outgrowth using a Markovian model revealed significant differences between simulated trees and real dendrites, particularly with regard to variability of the number of terminals and to symmetry. In contrast, the QS model provided a good fit to the mean values and standard deviations of basic topological parameters. This model is adequate to describe the shape of mature motoneurorial dendrites. It implies that dendritic branches have many opportunities to bifurcate during the whole time of development and that bifurcating potency of a branch is a function of the number and position of other branches of that dendrite. Combined with analysis of metrical properties such as lengths of segments, the QS model can assist in a quantitative analysis of development and plasticity. © 1995 Wiley‐Liss, Inc.
A comparison of the antidiarrheal and some other pharmacological effects of clonidine, lidamidine, and loperamide in the rat
Authors: Lal Harbans , Shearman Gary T.
Published: January 2005

Clonidine, lidamidine, and loperamide each inhibited castor oil‐induced diarrhea in the rat. Clonidine and lidamidine, but not loperamide, also induced diuresis but at doeses above those producing antidiarrheal activity. Clonidine and lidamidine, but not loperamide, produced autonomic and central effects including piloerection, hypotonia, exopthalmus and ataxia at doeses similar to those producing antidiarrheal activity. These data suggest that only loperamide possesses selective antidiarrheal activity.
Suppression of insulin‐induced prolactin secretion in man by nomifensine
Authors: Masala Antonic , Alagna Sergio , Rovasio Pier Paolo , Rassu Sergio
Published: January 2005

In 12 healthy male volunteers we studied the effect of nomifensine, an inhibitor of endogenous catecholamine reuptake, on insulin‐induced prolactin and growth hormone (GH) secretion. The effect of the drug on TRH‐induced prolactin secretion was also studied. Nomifansine was able to suppress completely the insulin‐stimulated prolaction secretion, whereas no effect on GH secretion was observed. TRH‐induced prolactin secretion was uninfluenced by the drug.
Thyroliberin (TRH)‐induced shaking behavior in rats: Inhibition by antinociceptive compounds
Authors: Kruse Hansjoerg , Moeller Juergen
Published: January 2005

The influence of 49 compounds, among them 12 analgesics, on “wet dog” shaking (WDS) induced by thyroliberin (TRH) in rats has been investigated. WDS was dose dependently reduced by all of the analgesics and by 20 of the other drugs. The following compounds were the most active (ED50 values in parentheses): clonidine (5.4 μg/kg), fentanyl (9.6 μg/kg), oxotremorine (21 μg/kg), apomorphine (0.25 mg/kg), amphetamine (0.30 mg/kg), tetrabenazine (0.38 mg/kg), morphine (0.78 mg/kg), chlorpromazine (1.0 mg/kg), and ergotamine (1.2 mg/kg). Both agonists and antagonists of noradrenergic, dopaminergic, serotonergic, and GABA‐ergic functions were inhibitors of WDS, and antinociceptive activity was shared by most of the effective drugs.

Thus, WDS or head‐shaking induced by TRH must be considered to be an expression of headache rather than such other causes as heat gain mechanisms or tremor induction. Prevention of TRH‐induced WDS may be used as a test of analgesic activity.
Attenuation of conflict‐induced suppression by clonidine: Indication of anxiolytic activity
Authors: Kruse Hansjoerg , Dunn Robert W. , Theurer Karin L. , Novick William J. , Shearman Gary T.
Published: January 2005

Clonidine was tested in a conflict‐induced suppression paradigm (bar pressing for food reward suppressed by electric foot shock) in rats. This drug significantly and dose dependently (25–100 μg/kg) both increased punished responding and decreased unpunished responding. Clonidine at 200 μg/kg had no effect on punished bar pressing, although it markedly inhibited unpunished responding due to sedation. The effect of clonidine on shock‐suppressed lever pressing was prevented by yohimbine 5 mg/kg and partially antagonized by phenoxybenzamine 2.5 mg/kg but was not significantly altered by phenoxybenzamine 1 mg/kg, atropine 5 mg/kg, methysergide 5 mg/kg, or naloxone 10 mg/kg.

This activity of clonidine does not seem to be due to its analgesic or food intake‐increasing properties. It may be a true anxiolytic effect, brought about by presynaptic stimulation of noradrenergic neurons which could result in an inhibitory influence on the locus coeruleus.
Dopaminergic activity of some simplified ergoline derivatives
Authors: Euvrard Catherine , Ferland Louise , Fortin Michel , Oberlander Claude , Labrie Fernand , Boissier Jacques R.
Published: January 2005

The dopamine (DA) agonist activity of new simplified ergoline derivatives (RU 27849, RU 28251, and RU 28306) was studied in comparison with bromocriptine. In contrast to bromocriptine, the three compounds were weak displacers of 3H‐dihydroergocriptine or 3H‐spiroperidol binding from bovine anterior pituitary or rat striatal membrane sites and weak inhibitors of prolactin secretion in anterior pituitary cells in culture. Similarly to bromocriptine, they did not induce changes in either the basal or the DA‐induced stimulation of the adenylate cyclase activities. In vivo, the three derivatives, at a low dose, increased plasma prolactin levels, decreased striatal DA turnover, and increased striatal acetylcholine content, as did bromocriptine. Furthermore, in 6‐OHDA‐lesioned rats, these molecules, like bromocriptine, induced an intense contralateral circling behavior. From their effectiveness in these different tests, the potencies of these new ergoline derivatives can be ranked in the following order : N‐propyl > N‐methyl > N‐H.
Influence of age on isolation stress‐stimulated carcinogen‐metabolizing enzymes of rats
Authors: Capel I. D. , Jenner M. , Dorrell H. M. , Williams D. C.
Published: January 2005

Rats aged 6, 12, 24, 36, and 52 weeks were subjected to social isolation for 4 days, while littermates housed in groups of six for the same period served as controls. The isolation treatment resulted in a 2‐fold increase in the serum corticosterone level of all except the youngest animals in whom the hormone level was greater than 4 times that of their age‐matched controls. Hepatic microsomal protein was highest in the 24‐week‐old rats and lowest in the rats aged 52 weeks. The levels of most of the enzymes measured were lowest in the 6‐ and 52‐week‐old animals. No significant differences in microsomal protein, cytochrome P450, epoxide hydrolase, UDPGA transferase, or glutathione transferase were observed between the isolated and control animals. The stress treatment increased aryl hydrocarbon hydroxylase levels of the rats aged 6, 36, and 52 weeks by 100%, 50%, and 33% respectively. The microsomes prepared from livers of isolated 6‐week‐old animals catalyzed the binding of significantly higher amounts of [3H]‐benzo(a)pyrene to DNA than controls.
The clinical relevance of opiate receptor research
Authors: Smith Andrew P. , Loh Horace H.
Published: January 2005

Recent progress in opiate receptor research of particular relevance to clinicians is discussed. A simple binding assay, which in itself is valuable in allowing rapid screening of new compounds for opiate activity, has been the basis of these studies. Extensive mapping of opiate receptors in subcortical brain regions has provided important insights into the neuronal pathways involved in analgesia, while physical and chemical characterization of these receptors has led to a simple means of distinguishing agonists from antagonists. The existence of multiple receptors suggests that the analgetic effects of the opiates may be dissociated from other effects, and studies of tolerance and dependence indicate that they too may be dissociable from analgesia. Purification of the receptors, at last a reasonable possibility, may lead to new ways to promote or inhibit analgesia.
Antagonism of baclofen's effects on rat striatal 5‐HT metabolism: A model for 5‐HT agonistic properties?
Authors: Waldmeier Peter C. , Fehr Bruno
Published: January 2005

The increase in the rat striatal concentration of 5‐hydroxyindoleacetic acid (5‐HIAA) elicited by baclofen was antagonized by the 5‐HT antagonists pipamperone (10/30 mg/kg i.p.), cyproheptadine (30 mg/kg i.p.), methiothepin (1 mg/kg i.p.), and GP 50 302 (1/3 mg/kg i.p.), but not by cinanserin (1–30 mg/kg i.p.), pizotifen (1–10 mg/kg i.p.), spiroperdol (0.1–1 mg/kg i.p.), or haloperidol (0.1–1 mg/kg i.p.). The 5‐HT agonists, m‐chlorophenylpiperazine (1 mg/kg i.p.) and MK 212 (3/10 mg/kg i.p.) also showed an antagonistic effect. Methysergide (5–20 mg/kg i.p.) and quipazine (2.5/5 mg/kg i.p.) were previously shown to act similarly, whereas mianserin (5–20 mg/kg i.p.) was inactive and methergoline at lower doses (0.25–0.5 mg/kg i.p.) increased the effect of baclofen, which was reversed at higher doses (1 mg/kg i.p.). The alterations by these compounds of the 5‐HT increase elicited by baclofen were more or less similar; however, they were less clear‐cut and occurred at higher doses. These interactions were not the result of interferences of the compounds with the absorption, distribution, or metabolism of baclofen nor with its effect on the nigrostriatal dopaminergic system, since the increase in dopamine concentrations it caused was not affected by any of the compounds. A comparison of our results with published data on the antagonism of 5‐hydroxytryptophan‐induced head twitches, on spiroperidol or 5‐HT displacement, on 5‐HT‐stimulated adenylate cyclase, and with electrophysiological results suggests that the antagonistic effect of compounds interfering with the 5‐HIAA elevating action of baclofen is not related to 5‐HT receptor blocking properties of these drugs, Instead, it seems to be much more related to 5‐HT agonists properties. It is speculated that this model might reveal presynaptic agonistic properties of drugs, but more data are needed to confirm or reject this.
The cardiovascular effects in dogs of two N‐Di‐Alkyl substituted analogs of dopamine and dopamine
Authors: Maixner W. , Long J. P. , Wright C. B. , Cannon J. G.
Published: January 2005

The cardiovascular effects of two N‐di‐alkyl substituted analogs of dopamine and dopamine were tested in the dog. Intravenous administration of N, N‐diethyldopamine (DEDA) decreased mean arterial pressure, heart rate, and mildly depressed cardiac output. Intravenously administered N, N‐dipropyldopamine (DPDA) decreased mean arterial pressure, heart rate, and total peripheral vascular resistance. Both compounds inhibited reflex sympathetic responses produced by a bilateral common carotid occlusion. Femoral artery injections of DEDA or DPDA produced biphasic responses. A transient increase in femoral bed vascular resistance was followed by a decrease in femoral bed vascular resistance sensitive to alpha adrenoceptor antagonism. In contrast to DEDA and DPDA, intravenously administered dopamine increased cardiac output and heart rate while reducing arterial pressure and total peripheral vascular resistance. Femoral artery injections of dopamine resulted in a dose‐dependent constrictor response which was antagonized by alpha receptor blockade. These data demonstrate that DEDA and DPDA induce different cardiovascular responses from dopamine.