bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional organization of auditory cortex in the Mongolian gerbil (Meriones unguiculatus). IV. Connections with anatomically characterized subcortical structures
Authors: Budinger Eike , Heil Peter , Scheich Henning 
Published: March 2003

AbstractThe subcortical connections of the four tonotopically organized fields of the auditory cortex of the Mongolian gerbil, namely the primary (AI), the anterior (AAF), the dorsoposterior (DP) and the ventroposterior field (VP), were studied predominantly by anterograde transport of biocytin injected into these fields. In order to allow the localization of connections with respect to subdivisions of subcortical auditory structures, their cyto‐, fibre‐ and chemoarchitecture was characterized using staining methods for cell bodies, myelin and the calcium‐binding protein parvalbumin. Each injected auditory cortical field has substantial and reciprocal connections with each of the three subdivision of the medial geniculate body (MGB), namely the ventral (MGv), dorsal (MGd) and medial division (MGm). However, the relative strengths of these connections vary: AI is predominantly connected with MGv, AAF with MGm and MGv, and DP and VP with MGd and MGv. The connections of at least AI and MGv are topographic: injections into caudal low‐frequency AI label laterorostral portions of MGv, whereas injections into rostral high‐frequency AI label mediocaudal portions of MGv. All investigated auditory fields send axons to the suprageniculate, posterior limitans, laterodorsal and lateral posterior thalamic nuclei, with strongest projections from DP and VP, as well as to the reticular and subgeniculate thalamic nuclei. AI, AAF, DP and VP project to all three subdivisions of the inferior colliculus, namely the dorsal cortex, external cortex and central nucleus ipsilaterally and to the dorsal and external cortex contralaterally. They also project to the deep and intermediate layers of the ipsilateral superior colliculus, with strongest projections from DP and VP to the lateral and basolateral amygdaloid nuclei, the caudate putamen, globus pallidus and the pontine nuclei. In addition, AAF and particularly DP and VP project to paralemniscal regions around the dorsal nucleus of the lateral lemniscus (DNLL), to the DNLL itself and to the rostroventral aspect of the superior olivary complex. Moreover, DP and VP send axons to the dorsal lateral geniculate nucleus. The differences with respect to the existence and/or relative strengths of subcortical connections of the examined auditory cortical fields suggest a somewhat different function of each of these fields in auditory processing.
Synaptic stimulation of nicotinic receptors in rat sympathetic ganglia is followed by slow activation of postsynaptic potassium or chloride conductances
Authors: Sacchi Oscar , Rossi Maria Lisa , Canella Rita 
Published: March 2003

AbstractTwo slow currents have been described in rat sympathetic neurons during and after tetanization of the whole preganglionic input. Both effects are mediated by nicotinic receptors activated by native acetylcholine (ACh). A first current, indicated as IAHPsyn, is calcium dependent and voltage independent, and is consistent with an IAHP‐type potassium current sustained by calcium ions accompanying the nicotinic synaptic current. The conductance activated by a standard synaptic train was ∼ 3.6 nS per neuron; it was detected in isolation in 14 out of a 52‐neuron sample. A novel current, IADPsyn, was described in 42/52 of the sample as a post‐tetanic inward current, which increased in amplitude with increasing membrane potential negativity and exhibited a null‐point close to the holding potential and the cell momentary chloride equilibrium potential. IADPsyn developed during synaptic stimulation and decayed thereafter according to a single exponential (mean τ = 148.5 ms) in 18 neurons or according to a two‐exponential time course (τ = 51.8 and 364.9 ms, respectively) in 19 different neurons. The mean peak conductance activated was ∼ 20 nS per neuron. IADPsyn was calcium independent, it was affected by internal and external chloride concentration, but was insensitive to specific blockers (anthracene‐9‐carboxylic acid, 9AC) of the chloride channels open in the resting neuron. It is suggested that gADPsyn represents a specific chloride conductance activatable by intense nicotinic stimulation; in some neurons it is even associated with single excitatory postsynaptic potentials (EPSCs). Both IAHP and IADPsyn are apparently devoted to reduce neuronal excitability during and after intense synaptic stimulation.
Identification of an opioid peptide secreted by rat embryonic mixed brain cells as a promoter of macrophage migration
Authors: Calvo Charles‐Félix , Cesselin François , Gelman Michèle , Glowinski Jacques 
Published: March 2003

AbstractConditioned media from embryonic mixed cells from the rat brain were used in a chemotaxis assay to look for potential chemotactic activity which could account for the infiltration of the developing central nervous system (CNS) by macrophage precursors. The most potent chemotactic activity was found in the conditioned medium from E17 mixed brain cells (E17‐CM). Based upon checkerboard analysis, this activity was shown to be chemotactic rather than chemokinetic. This chemoattraction was not restricted to brain macrophages (BM) because it was as pronounced on bone marrow‐derived macrophages. The implication of a peptide compound in this activity was suggested by its resistance to heat as well as acid treatments, and by its sensitivity to aminopeptidase M digestion. In agreement with the opioid nature of the peptide, not only naloxone, but also the delta opioid receptor antagonist ICI‐174 reduced the migration of BM in response to E17‐CM by 60%. This migratory activity was no longer effective when pertussis toxin‐treated BM were used. When the chemotactic effects of selective opioid agonists were compared to that of E17‐CM, DPDPE, the delta agonist, was the most efficient in attracting BM. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis indicated that delta as well as other known opioid receptors were expressed in both BM and E17 mixed brain cells. Finally, a Met‐enkephalin‐like reactivity was found by RIA in the E17‐CM. Altogether, these observations suggest that a delta‐like opioid peptide released from embryonic mixed brain cells could be responsible for the infiltration of the developing CNS by macrophages precursors.
Synaptically released 5‐HT modulates the activity of tonically discharging neuronal populations in the rostral ventral medulla (RVM)
Authors: Piguet Pascale , Stoeckel Marie‐Elisabeth , Schlichter Rémy 
Published: March 2003

AbstractThere is substantial evidence for an important modulating role of monoamines (catecholamines and serotonin, 5‐HT) in the rostral ventral medulla (RVM), a region which plays an important role in cardiovascular and nociceptive functions. We investigated in slices the role of endogenous monoamines in the synaptic control of the activity of rat RVM neuronal populations using intracellular recordings in the lateral RVM plus lateral aspect of nucleus paragigantocellularis lateralis. A triple‐labelling protocol allowed us to identify the location of impaled neurons and their eventual monoaminergic phenotype within the serotonergic and catecholaminergic populations of the RVM. Focal electrical stimulation revealed the existence of a functional monoaminergic input onto RVM neurons which was mediated by endogenous 5‐HT acting at inhibitory 5‐HT1A receptors but did not involve noradrenergic neurotransmission. The slow 5‐HT‐mediated inhibitory postsynaptic potential (IPSP) was only observed in the regularly discharging neurons, which were found to be neither catecholaminergic nor serotonergic. The synaptic release of 5‐HT was, itself, under an inhibitory control involving GABAA (γ‐aminobutyric acid) receptors. Moreover, we characterized the effect of the 5‐HT‐releasing agent fenfluramine on this functional 5‐HT‐mediated synaptic transmission. Our results show that the effect of fenfluramine is biphasic consisting of an initial prolongation of the serotonergic IPSP followed by a decrease in amplitude. Our data provide a basis for the previously reported inhibitory effects of exogenously applied serotonin agonists/antagonists on the autonomic functions controlled by the RVM. This 5‐HT pathway, which functionally links the serotonergic and catecholaminergic regions, might play an important role in cardiovascular and nociceptive functions.
Running and cocaine both upregulate dynorphin mRNA in medial caudate putamen
Authors: Werme Martin , Thorén Peter , Olson Lars , Brené Stefan 
Published: March 2003

AbstractPhysical activities such as long‐distance running can be habit forming and associated with a sense of well‐being to a degree that justifies comparison with drug‐induced addictive behaviours. To understand molecular similarities and dissimilarities controlling these behaviours in humans we compared the effects of running in running wheels to the effects of chronic cocaine or morphine administration on mRNA levels in brain reward pathways in the inbred Fischer and Lewis rat strains. These strains are both inbred from the Sprague–Dawley strain; Lewis rats display a higher preference towards addictive drugs and running than do Fischer rats. After chronic cocaine or running a similar increase of dynorphin mRNA in medial caudate putamen was found in the Lewis rat, suggesting common neuronal adaptations in this brain region to both cocaine and running. Fischer and Lewis rats both responded to cocaine with increased dynorphin mRNA levels in medial caudate putamen. However, only Lewis rats increased dynorphin mRNA after running, possibly reflecting the much higher degree of running by the Lewis strain as compared to the Fischer strain. Moreover, the running‐induced upregulation of dynorphin mRNA was blocked by the opioid receptor antagonist naloxone. We suggest that running increases dynorphin mRNA by a mechanism that involves endogenous opioids. The voluntary wheel‐running model in rats might be used to study natural reward and compulsive behaviours and possibly also to screen candidate drugs for treatment of compulsive disorders.
Stage of specification of the spinal cord and tectal projections from cortical grafts
Authors: Pinaudeau Cécile , Gaillard Afsaneh , Roger Michel 
Published: March 2003

AbstractIn order to determine the embryonic age at which the hodological phenotype developed by neocortical cells is specified, we have examined the spinal or tectal projections developed by embryonic (E) grafts of presumptive frontal or occipital neocortex placed into the frontal or occipital neocortex of newborn host rats. Grafts of E13, E14 and E16 cells of the frontal cortex transplanted into the occipital cortex of newborns are capable of developing and maintaining in adulthood a spinal cord axon. Grafts of E12 cells do not project to the spinal cord but send fibres to the superficial layers of the tectum. In addition, following transplantation into the frontal cortex, early embryonic (E12) cells from the presumptive occipital cortex are capable of differentiating into neurons with spinal cord projection but are practically incapable of developing a tectal projection. When grafted at E14 into the frontal cortex, occipital cells lose the capacity to project to the spinal cord but become able to send fibres to the tectum. Taken together, these findings indicate that young (E12) embryonic frontal and occipital cortical cells are competent to subsequently differentiate into neurons projecting to the spinal cord or tectum according to instructive signals available in the cortical territory where they complete their development. By E13/E14, some cortical cells are specified and their capacity to contact targets that are not appropriate to their embryonic origin is much reduced. These findings are consistent with the notion that cortical specification involves progressive restriction in cell multipotentiality and fate specification toward region‐specific phenotypes.
Regulation of NGF‐family ligands and receptors in adulthood and senescence: correlation to degenerative and regenerative changes in cutaneous innervation
Authors: Bergman Esbjörn , Ulfhake Brun , Fundin Bengt T. 
Published: March 2003

AbstractDuring development, a highly differential neurotrophin dependency is reported for various types of nerve endings in the whisker follicle. To what extent these dependencies extend and play a role in adulthood is largely unresolved. We show here, using in situ hybridization and immunohistochemistry that the expression of neurotrophins and trk/p75 receptors persists in adulthood. As suggested by their expression profiles, many classes of cutaneous nerve endings disclose similar ligand–receptor dependencies in adult animals as during development, while other populations appear to switch their dependency. Furthermore, our data suggest that sensory endings that have a high turnover due to mechanical wear and tear, e.g. Merkel cell–neurite complexes at the level of ring sinus show a more complex ligand–receptor expression phenotype than do endings with a less vulnerable location, e.g. the Merkel cell–neurite complexes at the rete ridge collar. Thus, neurotrophin‐3 (NT3)/trkA signalling is suggested to be important for a continuous terminal plasticity of Merkel cell–neurite complexes at the level of ring sinus in adulthood. Evidence supporting a role for neurotrophin signalling in maintaining the adult cutaneous innervation also comes from the close correlation between altered ligand–receptor expression(s) and axonal/terminal aberrations in senescence. Thus, an ageing‐related decrease in target neurotrophin expression, notably NT3 and NT4, results in a site‐specific loss of sensory terminals concomitant with an aberrant growth of regenerating/sprouting axons into new target fields. Ageing of the cutaneous innervation, manifested in degenerative and regenerative events, seems strongly associated with changes in neurotrophic interactions between sensory neurons and target tissues.
Aberrant trajectory of entorhino‐dentate axons in the mutant Shaking Rat Kawasaki: a DiI‐labelling study
Authors: Woodhams Peter L. , Terashima Toshio 
Published: March 2003

AbstractThe Shaking Rat Kawasaki (SRK) is a neurological mutant that exhibits abnormalities of cell migration and lamination, with many similarities to the mouse reeler mutant. We recently used lamina‐specific antibody staining to show that despite severe aberrations in the laminar organization of the SRK dentate gyrus, the entorhinal terminal field in the outer dentate molecular layer appeared relatively normal (Woodhams & Terashima, 1999, J. Comp. Neurol. 409 p57). However, neurofilament immunostaining suggested that entorhino‐dentate afferents take an abnormal trajectory in reaching their appropriate targets, the granule cells dendrites. In the present study, anterograde tracing with the carbocyanine dye 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (DiI) has been used to delineate directly the path that entorhinal axons take to the dentate gyrus, confirming that in SRK entorhinal axons do indeed reach their appropriate terminal fields in the molecular layer, with laminar segregation between projections from the lateral and medial entorhinal cortices. However, these fibres fail to cross the hippocampal fissure between the subiculum and the dentate gyrus, coursing instead parallel to it until they curve round the deepest point of the fissure in field CA3. Similar findings were seen in the murine reeler mutant. Insertion of DiI crystals into the entorhinal cortex of neonatal rats also retrogradely labelled the developmentally transient Cajal–Retzius cells at the hippocampal fissure; these survive for longer in SRK than in normal littermates. The presence of a marked astrogliosis at the SRK hippocampal fissure may play a part in determining the abnormal trajectory taken by entorhino‐dentate afferents in this mutant.
Single‐cell mRNA expression of HCN1 correlates with a fast gating phenotype of hyperpolarization‐activated cyclic nucleotide‐gated ion channels (Ih) in central neurons
Authors: Franz Oliver , Liss Birgit , Neu Axel , Roeper Jochen 
Published: March 2003

AbstractHyperpolarization‐activated currents (Ih) are key players in shaping rhythmic neuronal activity. Although candidate genes for Ih channels have been cloned (HCN1–HCN4), the subunit composition of different native Ih channels is unknown. We used a combined patch‐clamp and qualitative single‐cell reverse transcription multiplex polymerase chain reaction (RT‐mPCR) approach to analyse HCN1–4 coexpression profiles in four neuronal populations in mouse CNS. Coexpression of HCN2, HCN3 and HCN4 mRNA was detected in single neurons of all four neuronal cell types analysed. In contrast, HCN1 mRNA was detected in neocortical and hippocampal pyramidal neurons but not in dopaminergic midbrain and thalamocortical neurons. HCN1 expression was correlated with significantly faster activation kinetics on the level of individual neurons. Semiquantitative single‐cell RT‐mPCR analysis demonstrated that HCN1 mRNA expression is at least eightfold higher in cortical neurons than subcortical neurons. We show that single neurons possess complex coexpression patterns of Ih candidate genes. Alternative expression of HCN1 is likely to be an important molecular determinant to generate the different neuronal Ih channel species adapted to tune either subcortical or cortical network activity.
Early postnatal maturation of GABAA‐mediated inhibition in the brainstem respiratory rhythm‐generating network of the mouse
Authors: Ritter B. , Zhang W. 
Published: March 2003

AbstractIt is well established that GABAA‐mediated postsynaptic potentials are excitatory in many brain regions during embryonic and early postnatal life. The pre‐Bötzinger complex (PBC) in the brainstem is an essential component of the respiratory rhythm‐generating network, where GABAA‐mediated inhibition plays a critical role in generating a stable respiratory rhythm in adult animals. In the present study, using the perforated patch technique, we investigated the maturation of GABAA receptor‐mediated effects on rhythmically active PBC neurons and on the motor output in slice preparations from P0–15 neonatal mice. The reversal potential of GABAA receptor‐mediated current (EGABA‐A) switched from depolarizing to hyperpolarizing within the first postnatal week. EGABA‐A was −13.7 ± 9.8 mV at P0, then it changed to −44.8 ± 7.0 mV at P2 and −71.5 ± 6.8 mV at P4. Perfusion of bicarbonate‐free saline has no detectable influence on EGABA‐A, indicating that a lack of Cl– extrusion during P0–3 is mainly responsible for early GABAA‐ergic excitation. At the network level, blockade of GABAA receptors with bicuculline did not significantly change the frequency of rhythmic bursts recorded from hypoglossal nerve roots before P3, whereas it increased the coefficient of variation. After P3, bicuculline increased burst frequency with little effect on the coefficient of variation. Thus, chloride‐mediated inhibition, which appears in PBC neurons after P3, coincides with the appearance of GABAA‐mediated modulation of the respiratory rhythm. GABAA receptor‐activated inhibition may therefore be necessary for frequency modulation in the respiratory network beginning on the fourth postnatal day in the mouse brainstem.
Programmed cell death in the developing human telencephalon
Authors: Rakic Sonja , Zecevic Nada 
Published: March 2003

AbstractProgrammed cell death (PCD) in the form of apoptosis is recognized as one of the central events in the development of the central nervous system. To study the time of onset, extent and distribution of PCD in the human telencephalon, embryos and fetuses from 4.5 to 27 gestational weeks (g.w.) were examined using the TUNEL (TdT‐mediated dUTP‐biotin nick‐end labelling) in situ method. At 4.5 g.w. sparse TUNEL(+) nuclei were observed in the ventricular zone of the neural tube. With the formation of the cortical plate at 7–8 g.w., TUNEL(+) nuclei were seen in all developmental layers of the cortical anlage, as well as in the subcortical regions such as the ganglionic eminence and the internal capsule. The proliferative zones (the ventricular zone, the subventricular zone and the ganglionic eminence) contained the majority of all apoptotic nuclei observed in each specimen. However, the apoptotic index was highest in the subplate zone and in layer I. Double‐labelling experiments suggested that neuronal precursors were the main population of cells undergoing PCD in the first trimester of gestation, whereas glial cells probably start dying around midgestation. The onset of labelling of microglial cells and apoptotic nuclei were synchronous, indicating the involvement of microglia in PCD. In conclusion, two distinct types of PCD were observed during human telencephalic development: embryonic apoptosis, which was synchronous with proliferation and migration of neuronal cells and probably not related to establishment of neuronal circuitry, and fetal apoptosis, which coincided with differentiation and synaptogenesis, and therefore may be related to the development of axonal‐target connectivity.
α1‐Adrenergic receptor‐induced slow rhythmicity in nonrespiratory cervical motoneurons of neonatal rat spinal cord
Authors: Morin Didier , Bonnot Agnès , Ballion Bérangère , Viala Denise 
Published: March 2003

AbstractPrevious studies have reported that the α1‐adrenergic system can activate spinal rhythm generators belonging to the central respiratory network. In order to analyse α1‐adrenergic effects on both cranial and spinal motoneuronal activity, phenylephrine (1–800 μm) was applied to in vitro preparations of neonatal rat brainstem–spinal cord. High concentration of phenylephrine superfusion exerted multiple effects on spinal cervical outputs (C2–C6), consisting of a lengthening of respiratory period and an increase in inspiratory burst duration. Furthermore, in 55% of cases a slow motor rhythm recorded from the same spinal outputs was superimposed on the inspiratory activity. However, this phenylephrine‐induced slow motor rhythm generated at the spinal level was observed neither in inspiratory cranial nerves (glossopharyngeal, vagal and hypoglossal outputs) nor in phrenic nerves. Whole‐cell patch‐clamp recordings were carried out on cervical motoneurons (C4–C5), to determine first which motoneurons were involved in this slow rhythm, and secondly the cellular events underlying direct phenylephrine effects on motoneurons. In all types of motoneurons (inspiratory and nonrespiratory) phenylephrine induced a prolonged depolarization with an increase in neuronal excitability. However, only nonrespiratory motoneurons showed additional rhythmic membrane depolarizations (with spiking) occurring in phase with the slow motor rhythm recorded from the ventral root. Furthermore the tonic depolarization produced in all motoneurons results from an inward current [which persists in the presence of tetrodotoxin (TTX)] associated with a decrease in neuron input conductance, with a reversal potential varying as a Nernstian function of extracellular K+ concentration. Our results indicate that the α1‐adrenoceptor activation: (i) affects both the central respiratory command (i.e. respiratory period and inspiratory burst duration) and spinal inspiratory outputs; (ii) induces slow spinal motor rhythmicity, which is unlikely to be related to the respiratory system; and (iii), increases motoneuronal excitability, probably through a decrease in postsynaptic leak K+ conductance.