bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dexterity in adult monkeys following early lesion of the motor cortical hand area: the role of cortex adjacent to the lesion
Authors: Rouiller E.M. , Yu X.H. , Moret V. , Tempini A. , Wiesendanger M. , Liang F. 
Published: March 2003

AbstractInfant monkeys were subjected to unilateral lesions of the motor cortex (mainly its hand representation). After maturation, they showed normal use of the contralateral hand for global grip movements. However, as compared with the ipsilateral hand, precision grip tasks requiring relatively independent finger movements were performed with less dexterity, particularly if adjustments of the wrist position were necessary. The purpose of this study was to investigate mechanisms which may be responsible for the rather well, although not complete, preservation of manipulative behaviour of these adult monkeys. To this end, the hand representations were mapped bilaterally with intracortical microstimulation in the mature monkeys, and the dexterity of both hands assessed quantitatively in a precision grip task. The behavioural effects of reversible inactivations of the primary (M1) and supplementary (SMA) motor cortical areas were then tested. The following were found. (i) The hand contralateral to the lesion exhibited subtle but significant dexterity deficits, as compared with the ipsilateral hand; the deficit was essentially for complex movements requiring dissociation of the thumb–index finger pinch from the other digits, involving also an arm rotation. (ii) Reversible inactivation of the M1 hand representation in the intact hemisphere dramatically impaired dexterity of the opposite hand without affecting the ipsilateral hand (contralateral to the early lesion). (iii) A relatively complete hand representation was found to occupy a new territory, medial to the old lesion. (iv) The role of this new displaced representation was crucial for the preserved dexterity of the opposite hand, as evidenced by its functional inactivation. In contrast, inactivation of both SMA cortices did not interfere with the manipulative behaviour. It is thus concluded that the preserved functional capacity of manipulations with the hand opposite the early lesion can be essentially attributed to a cortical reorganization around the old lesion. Under the present experimental conditions, contributions from either the SMA or the intact M1 appear not to be crucial.
Deafferentation up‐regulates the expression of the mGlu1a metabotropic glutamate receptor protein in the olfactory bulb
Authors: Casabona G. , Catania M.V. , Storto M. , Ferraris N. , Perroteau I. , Fasolo A. , Nicoletti F. , Bovolin P. 
Published: March 2003

AbstractChemical lesion of olfactory neuroepitheium induced an up‐regulation of the mGlu1a metabotropic glutamate receptor protein in the olfactory bulb, as shown by Western blot analysis. At 2 days after the lesion, the increase in the receptor protein was associated with an increase in mGlu1a mRNA levels; in contrast, at longer times after the lesion (16 days), mRNA levels were reduced in spite of the high expression of the receptor protein, perhaps as a result of product‐inhibition of mGlu1 gene expression. Immunohistochemical analysis showed that the increase in mGlu1a induced by olfactory denervation was confined to the glomeruli, which occupy the external portion of the olfactory bulb. Within these structures, mGlu1a receptors are mainly localized on the distal dendrites of mitral cells, which are innervated by the glutamatergic axons of the olfactory nerve.These results demonstrate that the expression of mGlu1a receptors is up‐regulated in response to glutamatergic deafferentation, supporting a role for this particular receptor subtype in the physiology of synaptic transmission.
Behavioural effects of subthalamic nucleus lesions in the hemiparkinsonian marmoset (Callithrix jacchus)
Authors: Henderson J.M. , Annett L.E. , Torres E.M. , Dunnett S.B. 
Published: March 2003

AbstractRecent studies in non‐human primates support a role for the subthalamic nucleus in the expression of parkinsonian symptomatology, and it has been proposed that subthalamic lesions may provide a surgical treatment for the symptoms of Parkinson’s disease in humans. We have applied a broad range of behavioural tests to characterize the effects of lesions of the subthalamic nucleus on parkinsonian symptoms in the unilateral 6‐hydroxydopamine (6‐OHDA) lesioned marmoset (Callithrix jacchus). Thirteen marmosets were trained on a battery of behavioural tasks that were conducted at regular intervals before and after surgery. All received unilateral 6‐OHDA lesions to the medial forebrain bundle. Seven animals were then given an additional N‐methyl‐d‐aspartate lesion of the ipsilateral subthalamic nucleus, whereas the remaining six animals received a variety of control or sham lesions to the nucleus. The 6‐OHDA lesions induced a strong ipsilateral bias in head position; mild–moderate ipsilateral rotation spontaneously and after injection of saline or amphetamine; and contralateral rotation after injection of apomorphine. Hemineglect was evident as delayed initiation of reaches on the contralateral side on the staircase reaching task. Additional subthalamic lesions significantly reversed the bias in head position from ipsilateral to contralateral and decreased neglect as evidenced by improved latencies to initiate reaching on the contralateral side at the staircase. However, deficits in skilled movements persisted in the subthalamic nucleus lesion group in that they did not complete the staircase task any faster than the control group and remained impaired on another task which required reaching into tubes. These behavioural effects demonstrate that excitotoxic lesioning of the subthalamic nucleus can ameliorate some, but not all, parkinsonian‐like deficits in the unilateral 6‐OHDA lesioned marmoset.
Focal ischaemia of the rat brain elicits an unusual inflammatory response: early appearance of CD8+ macrophages/microglia
Authors: Jander Sebastian , Schroeter Michael , D’Urso Donatella , Gillen Clemens , Witte Otto W. , Stoll Guido 
Published: March 2003

AbstractCerebral ischaemia leads to profound glial activation and leukocyte infiltration into the infarct area. In this study, we provide evidence for a dual macrophage response in focal ischaemic lesions of the rat brain. We show that a considerable proportion of macrophages in the ischaemic lesions express the CD8αβ heterodimer to date only described on CD8+ T cells. As known from other lesion paradigms, CD4+ macrophages were also present. Interestingly, CD8‐ and CD4‐expressing macrophages formed two non‐overlapping subpopulations. CD8+ macrophages reached their maximum during the first week with pronounced downregulation thereafter whereas CD4+ cells persisted at high levels into the second week. In contrast to cerebral ischaemia, macrophages in the spleen and in Wallerian degeneration after optic nerve axotomy expressed CD4, but not CD8. In experimental autoimmune encephalomyelitis, CD8 was mainly associated with T cells and very weakly detectable on some ramified cells resembling activated microglia. In conclusion, we show that cerebral ischaemia triggers an unusual inflammatory response characterized by the appearance of CD8+/CD4– macrophages that might exert specific functions in the pathogenesis of ischaemic brain damage.
Cytokines promote the survival of mouse cranial sensory neurones at different developmental stages
Authors: Horton Antony R. , Bartlett Perry F. , Pennica Diane , Davies Alun M. 
Published: March 2003

AbstractTo investigate when the neurotrophic cytokines ciliary neurotrophic factor (CNTF), leukaemia inhibitory factor (LIF), oncostatin‐M (OSM), interleukin‐6 (IL‐6) and cardiotrophin‐1 (CT‐1) act on developing sensory neurones and whether they co‐operate with neurotrophins in regulating neuronal survival, we studied the in vitro trophic effects of these factors on two well‐characterized populations of cranial sensory neurones at closely staged intervals throughout embryonic development. The cutaneous sensory neurones of the trigeminal ganglion, which show an early, transient survival response to BDNF and NT3 before becoming NGF‐dependent, were supported by CNTF, LIF, OSM and CT‐1 during the late fetal period, several days after the neurones become NGF‐dependent. At this stage of development, these cytokines promoted the survival of a subset of NGF‐responsive neurones. The enteroceptive neurones of the nodose ganglion, which retain dependence on BDNF throughout fetal development, were supported throughout their development by CNTF, LIF, OSM and CT‐1, and displayed an additional survival response to IL‐6 in the late fetal period. These findings indicate that populations of sensory neurones display different developmental patterns of cytokine responsiveness and show that embryonic trigeminal neurones pass through several phases of differing neurotrophic factor survival requirements.
Kinetics of AMPA‐type glutamate receptor channels in rat caudate‐putamen neurones show a wide range of desensitization but distinct recovery characteristics
Authors: Jahn K. , Bufler J. , Franke C. 
Published: March 2003

Abstractα‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐type glutamate receptor channels of rat caudate‐putamen neurones were studied by ultrafast application of agonists to outside‐out vesicles taken from medium‐sized spiny neurones in thin slices. Upon application of 10 m m glutamate for 50 ms, fast rising and desensitizing currents were activated. Ten to 90% rise time values were ≈ 0.5 ms. Dose–response studies revealed an EC50 of 0.63 m
m glutamate. In double logarithmic coordinates, the curve had a maximal slope between 1.33 and 1.85 at low concentrations, indicating at least two binding sites for glutamate. Rise time increased with low agonist concentrations, whereas desensitization kinetics showed only a weak dependence on concentration. The time constant of desensitization was fitted with one exponential and ranged between 2 and 11 ms, with a mean of 6.19 ± 2.31 ms (n = 239). Following brief glutamate pulses (1 ms) currents decayed with time constants of 2.7 ± 0.23 ms (n = 12). Recovery from desensitization was investigated by double‐pulse experiments. Recovery time constants fell in two subgroups with respective mean values of 110.6 ± 14.2 ms (n = 8) and 288.6 ± 33.2 ms (n = 8). By adding low glutamate concentrations to the bath solution, predesensitization of AMPA‐type receptors without channel opening could be shown. A 50% reduction in control amplitude was achieved with 5.2 ± 2.1 μm (n = 22) glutamate in the background. We hypothesize a circular reaction scheme with at least two binding sites for glutamate to describe activation, desensitization and recovery from desensitization in rat caudate‐putamen neurones.
N‐Syndecan and HB‐GAM (Heparin‐Binding Growth‐Associated Molecule) associate with early axonal tracts in the rat brain
Authors: Kinnunen Anu , Kinnunen Tarja , Kaksonen Marko , Nolo Riitta , Panula Pertti , Rauvala Heikki 
Published: March 2003

AbstractHeparin‐Binding Growth‐Associated Molecule (HB‐GAM)/pleiotrophin is an 18 kDa extracellular matrix‐ and cell‐surface‐associated protein shown to enhance neurite outgrowth of perinatal forebrain neurones in vitro. The heparan sulphate proteoglycan N‐syndecan (
Raulo et al. 1994
) has been isolated as a receptor/coreceptor for the HB‐GAM. We have investigated, whether HB‐GAM and N‐syndecan could have a similar role in neurite outgrowth and axon guidance in early axonal tracts of brain. In the present study N‐syndecan was found to be spatiotemporally associated with the developing axonal tracts already on embryonic day 9 in rat, as revealed by coexpression with class III β‐tubulin, which is one of the earliest neuronal markers (
Easter et al. 1993
;Brittis et al. 1995
). Later, N‐syndecan and HB‐GAM were detected in the first afferent serotonergic projections arising from the pontine raphe nuclei. The expression pattern of HB‐GAM peaked in the developing rhombencephalon at embryonic stage (E) 13–14. At the same time, N‐syndecan was expressed in the developing raphe neurones growing neurites towards the diencephalon along HB‐GAM immunoreactive pathways. When rhombencephalic neurones were cultured on decreasing concentrations of substrate‐bound HB‐GAM, E13 neurones showed a significantly better neurite outgrowth response than E11, E16 or E18 neurones. The neurite outgrowth of raphe neurones in vitro was inhibited by adding soluble heparin or N‐syndecan into the culture medium, whereas addition of chondroitin sulphate had no effect. In a simple pathway assay, E13 raphe neurones selectively preferred attaching and growing neurites on pathways containing HB‐GAM as compared with regions containing either laminin or fibronectin alone. Our results suggest that HB‐GAM may function as a developmentally regulated cue for rhombencephalic neurones that possess N‐syndecan on their cell membrane.
Long‐lasting increased pain sensitivity in rat following exposure to heroin for the first time
Authors: Laulin Jean‐Paul , Larcher Agnès , Célèrier Evelyne , Moal Michel Le , Simonnet Guy 
Published: March 2003

AbstractAcute dependence, defined as a precipitation of somatic signs by an antagonist, may occur after a single administration of an opiate drug. Because hyperalgesia is a consistent sign of the withdrawal syndrome, we tested the effectiveness of heroin, an opiate used by addicts, to induce pain facilitation even after a first exposure to the drug. In opiate‐naive rats, subcutaneous injection of heroin induced analgesia followed by allodynia, a decrease in pain threshold. This latter phenomenon was observed in the absence of noxious stimuli and lasted several days. An N‐methyl‐d‐aspartate (NMDA) receptor antagonist, MK‐801 prevented such long‐lasting allodynia. These results suggest that allodynia is an early sign reflecting neural plasticity associated with the development of dependence.
The cerebral metabolic effects of manipulating glutamatergic systems within the basal forebrain in conscious rats
Authors: Browne Susan E. , Muir Janice L. , Robbins Trevor W. , Page Keith J. , Everitt Barry J. , McCulloch James 
Published: March 2003

Abstract N‐methyl‐d‐aspartate (NMDA) and non‐NMDA receptor‐mediated manipulations of the cortical cholinergic input arising from the basal forebrain differentially affect cognitive function. We used [14C]‐2‐deoxyglucose autoradiography in conscious rats to map the effects of excitatory amino acid agonist infusions into the nucleus basalis magnocellularis (NBM) on cerebral functional activity, as reflected by local rates of glucose utilization. Acute stimulation of NBM neurones by local infusion of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA), 15 min before glucose use measurement, resulted in glucose use reductions in nine cortical regions innervated by NBM efferents including prefrontal, frontal, sensorimotor and cingulate cortices. NMDA infusions altered glucose use in two cortical areas. Both AMPA and NMDA markedly increased glucose use in the striatum and globus pallidus, with concomitant perturbations in striato‐pallidal projection targets including the substantia nigra, entopeduncular nucleus, subthalamic nucleus and lateral habenular nucleus. In contrast, the GABAA agonist muscimol did not affect glucose use in the NBM or neocortical regions, but induced glucose use increases in several subcortical nuclei including the substantia nigra and entopeduncular nucleus.The delayed effects of excitotoxic lesions were assessed 3 weeks after basal forebrain infusions of AMPA, NMDA, ibotenate or quisqualate. Statistically significant glucose use changes only occurred in the hypothalamus after NMDA, and the NBM after ibotenate infusions, although reduced cortical metabolism was apparent following AMPA‐induced lesions of the NBM. Results support a dissociation between the functional sequelae of NMDA and non‐NMDA receptor‐mediated events in the basal forebrain, and long‐term compensatory functional adaptation following cortical denervation.
Pattern formation in the cerebellum of murine embryonic stem cell chimeras
Authors: Hawkes Richard , Faulkner‐Jones Beverly , Tam Patrick , Tan Seong‐Seng 
Published: March 2003

AbstractThe cerebellar cortex is subdivided into an elaborate, stereotyped array of transverse zones and parasagittal stripes. It has been speculated that (i) all Purkinje cells derive from 10 to 20 precursors allocated early in embryogenesis and (ii) that pattern formation is based on cell lineage restriction in the founder pool. These hypotheses have been tested by clonal analysis of embryonic stem cell chimeras. Neither speculation is supported: the analysis suggests that Purkinje cells derive from a founder population of > 102 precursors, and that neither cerebellar transverse developmental boundaries nor parasagittal stripes have a clonal origin. We conclude that early lineage restriction plays no role in cerebellar pattern formation.
Functional magnetic resonance imaging of a human auditory cortex area involved in foreground–background decomposition
Authors: Scheich Henning , Baumgart Frank , Gaschler‐Markefski Birgit , Tegeler Carola , Tempelmann Claus , Heinze Hans J. , Schindler Frank , Stiller Detlef 
Published: March 2003

AbstractAuditory foreground–background decomposition is a pattern recognition process which combines simultaneous and sequential grouping in complex sound sequences. Using functional magnetic resonance imaging with reduced scanner noise and stimulation through a new type of earphones, we investigated the possibility that this process activates topographically distinct areas of human auditory cortex. A basic matching‐to‐sample task with variable tones (sequential grouping) caused significant activity in three separate landmark‐related territories on the supratemporal plane. A similar task in the presence of a strongly masking acoustic background pattern to challenge simultaneous grouping led to the distinction of the subterritory in which foreground signal‐related or task‐related signal properties were exclusively seen. In contrast to the remainder of territories the level of activity and the periodicity of the signal time‐course was resistant to the masking influence of the background.This suggests that auditory foreground–background decomposition involves a specialized non‐primary auditory cortex field. Generally, the findings demonstrate functional parcellation of auditory cortex for which the evidence in humans, in contrast to other primates, is only indirect to date.
Characterization of perforant path lesions in rodent models of memory and attention
Authors: Kirkby D.L. , Higgins G.A. 
Published: March 2003

AbstractEarly stage Alzheimer's disease (AD) pathology is associated with neurodegeneration of systems within the temporal cortex, e.g. the entorhinal cortex, perforant pathway and hippocampus. The perforant pathway provides the major neuronal input to the hippocampus from the entorhinal cortex and thus relays multimodal sensory information derived from cortical zones into the hippocampus. The earliest symptoms of AD include cognitive impairments, e.g. deficits in short‐term memory and attention. Consequently, we have investigated the effect of bilateral knife cut lesions to the perforant path on cognition in rats using models measuring primarily short‐term memory (operant delayed match to position task), attention (serial five‐choice reaction time task) and spatial learning (Morris water maze). Rats receiving bilateral perforant path lesions showed normal neurological function and a mild hyperactivity. The lesion produced little effect on attention assessed using the five‐choice task. In contrast, animals with equivalent lesions showed a robust delay‐dependent deficit in the delayed match to position task. Spatial learning in the water maze task was also severely impaired. The delay‐dependent deficit in the match to position task was not reversed by tacrine (3 mg/kg) pretreatment. The present data support a selective impairment of cognitive function following perforant path lesions that was confined to mnemonic rather than attentional processing. These findings complement primate and human studies identifying a critical role of the perforant pathway and associated temporal lobe structures in declarative memory. Degeneration of the perforant pathway is likely to contribute to the mnemonic deficits characteristic of early AD. The failure of tacrine to ameliorate these deficits may be relevant to an emerging clinical literature suggesting that cholinomimetic therapies improve attentional rather than mnemonic function in AD.
Localization of a G protein Gi2 in the cilia of rat ependyma, oviduct and trachea
Authors: Shinohara Haruo , Asano Tomiko , Kato Kanefusa , Kameshima Takamichi , Semba Reiji 
Published: March 2003

AbstractIn previous studies, the localization of a pertussis toxin‐sensitive G protein was demonstrated in ependymal cilia, but the identification of the subtype of G protein was inconsistent. To clarify this issue, we studied the localization of Goα, Gi1α, Gi3α and Gi2α in the ciliated ependymal cells and in the cilia of some other tissues of rats using specific antibodies. The cilia of the ependymal cells that line the ventricular cavity of the brain were intensely immunoreactive for Gi2α, but not for Goα, Gi1α or Gi3α. Immunoblot analysis demonstrated higher levels of Gi2α in the ependymal cilia‐rich pellet than in the motor area of the parietal cortex. At the ultrastructural level, the immunoreactivity specific for Gi2α was found predominantly in the cilia, but rarely in the microvilli or the basal bodies of ependymal cells. In cross‐sections, the immunoreactivity specific for Gi2α was observed only in cell membranes, in particular, in the inner electron‐dense leaflet of the trilaminar structure. In addition to that in the ependymal cilia, such specific localization of Gi2α was observed in the motile cilia in other tissues, including the oviduct and trachea. By contrast, the stereocilia in the ductus deferens were not immunopositive for Gi2α. These findings suggest that Gi2 might play an important role in the signal transduction in ciliary membrane‐associated function(s) of the ependymal cells, oviduct and trachea.
Increased flexibility and selectivity in spatial learning of transgenic mice ectopically expressing the neural cell adhesion molecule L1 in astrocytes
Authors: Wolfer David P. , Mohajeri Hasan M. , Lipp Hans‐Peter , Schachner Melitta 
Published: March 2003

AbstractThe expression of the neural cell adhesion molecule L1 is altered by neuronal activity and promotes neurite outgrowth in vitro. To study the effects of L1 on learning and synaptic plasticity, transgenic mice have been created which express L1 ectopically in glial fibrillary acidic protein (GFAP) expressing astrocytes. Ninety mice, including GFAP‐L1‐transgenic mice from two genetic backgrounds and their littermates, were tested for swimming navigation learning in the Morris water maze according to a standardized protocol. While learning the position of an invisible target platform and also relearning its position after relocation, GFAP‐L1‐transgenic mice spent a greater fraction of their swim time in the target quadrant. Moreover, they showed a more rapid improvement of escape performance during the first day of training. Factor analysis revealed that this difference in swimming pattern could not be explained by non‐cognitive factors. Factor analysis also revealed that, during a probe trial, the GFAP‐L1‐transgenic mice spent comparatively less time in the old target quadrant than predicted by the increased searching they had shown during acquisition learning. Hence, ectopic expression of L1 by astrocytes in mice appears to be linked to a factor which increases behavioural flexibility and selectivity while learning and relearning, but concomitantly may lead to a relative reduction of spatial retention.