bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortically driven Fos induction in the striatum is amplified by local dopamine D2‐class receptor blockade
Authors: Berretta Sabina , Sachs Zohar , Graybiel Ann M. 
Published: March 2003

AbstractDopamine D2‐class receptors have been shown to control the excitability of striatal neurons in response to cortical activation. It has been unclear, however, whether such receptors could regulate the number of striatal neurons activated by cortical stimulation, and thus affect the population response of the striatum to its cortical inputs. We used Fos induction as a readout to measure the ensemble response of striatal neurons to localized stimulation of the frontal cortex and tested for the effects of D2‐class dopamine receptor blockade on this response. In freely moving rats, we stimulated the frontal cortex by local epidural application of a dose of a GABAA receptor antagonist (picrotoxin) just threshold for inducing Fos in the striatum. We combined this treatment with D2‐class dopamine receptor antagonist treatments at dose levels also just threshold for inducing Fos, using either (i) systemic haloperidol or (ii) intrastriatal (–)sulpiride. Both systemic and intrastriatal blockade of D2‐class receptors sharply increased the numbers of striatal neurons exhibiting cortically evoked Fos induction. These findings suggest that local activation of intrastriatal D2‐class dopamine receptors can regulate the number of striatal neurons responsive to cortical inputs, thus dynamically shaping the flow of information through the striatum.
Dopamine cells in nigral grafts differentiate prior to implantation
Authors: Sinclair Simon R. , Fawcett James W. , Dunnett Stephen B. 
Published: March 2003

AbstractThe yield of surviving dopamine cells in nigral grafts is typically low. It is unclear whether the dopamine neurons that do survive are postmitotic at the time of implantation, or are precursor cells that differentiate into dopamine neurons following transplantation in the host brain. We have therefore compared the survival of dopamine neurons in grafts that have been labelled with BrdU at different times prior to or following implantation in order to identify those cells that undergo final cell division at each stage of the procedure. Seven groups of rats were prepared with unilateral nigrostriatal lesions. Three groups received nigral grafts derived from E14 embryos labelled with BrdU in utero on either E12, E13 or E14 days of embryonic age (the E14 injection made 2 h prior to preparation of the graft cell suspension). Three further groups received nigral grafts from untreated E14 embryos, and then dividing cells within the grafts were labelled by injection of BrdU into the host lateral ventricle, 2 h, 1 day or 2 days after implantation (equivalent to E14, E15 and E16 days of embryonic age). The control group received standard (unlabelled) E14 grafts. Five weeks after the transplantation surgery, the host brains were processed using double immunohistochemical techniques to detect tyrosine hydroxylase (TH)‐positive neurons which had incorporated BrdU. In the grafts labelled with BrdU prior to implantation, there was an increasing proportion of double‐labelled cells (out of the total TH‐positive cells surviving in the grafts) with birth dates on E12, E13 and E14 (1%, 12% and 10% per day, respectively). By contrast, grafts labelled following implantation, although containing many dividing neurons, had very few of these BrdU‐labelled cells expressing a dopaminergic phenotype; <  1% surviving TH‐positive cells were double‐labelled from the 2 h post‐transplant injection, and <  0.1% from each subsequent injection. This suggests not only that the great majority of TH‐positive neurons in nigral grafts were already differentiated at the time of implantation, but also that transplantation of E14 ventral mesencephalic tissue either kills dopaminergic precursors or (more likely in our opinion) prevents their differentiation into a dopaminergic phenotype. Precursor cells that would differentiate into dopaminergic neurons beyond E14 if left in situ in the intact ventral mesencephalon do not readily differentiate into mature dopamine neurons following transplantation. If we are to enhance yields of functional dopamine‐rich transplants, then we must identify strategies both to protect predifferentiated dopamine neurons in the grafts and to promote differentiation of a dopaminergic phenotype in precursor cells that continue to divide within the grafts following transplantation into an adult host environment.
Selective sensitivity of early postmitotic retinal cells to apoptosis induced by inhibition of protein synthesis
Authors: Rehen S. K. , Neves D. D. C. , Fragel‐Madeira L. , Britto L. R. G. , Linden R. 
Published: March 2003

AbstractIn previous work we showed that apoptosis in retinal tissue from developing rats can be induced by inhibition of protein synthesis (Rehen et al. 1996, Development, 122, 1439–1448). Here we show that recent postmitotic cells are the cells sensitive to apoptosis triggered by blockade of protein synthesis. To label all proliferating cells in the retina, a series of injections of the nucleotide analogue, bromo‐deoxy‐uridine (BrdU, 60 mg/kg b.w.), was given in rat pups. Then, explants of the retina were incubated in vitro with the inhibitor of protein synthesis anisomycin (1.0–3.2 μg/mL) for 1 day to induce apoptosis. Detection of apoptotic bodies under differential interference contrast microscopy was combined with immunocytochemistry for BrdU, proliferating cell nuclear antigen (PCNA) or for various markers of retinal cell differentiation. Despite the large number of BrdU‐ and PCNA‐labelled cells in the tissue, the vast majority of the cells that underwent apoptosis were postmitotic cells which have left the mitotic cycle 3–4 days before. However, these cells were not labelled with antibodies to calretinin, calbindin, rhodopsin or to a Muller glial cell marker, suggesting that these are early postmitotic neurons. We suggest that during migration and initial differentiation, the apoptotic machinery is blocked by suppressor proteins, thus allowing recent postmitotic cells to find their final positions and differentiate while protected from apoptosis.
Adenosine suppresses protein kinase A‐ and C‐induced enhancement of glutamate release in the hippocampus
Authors: Bouron Alexandre 
Published: March 2003

AbstractCultured hippocampal neurons from neonatal rats were used to investigate the effect of adenosine on the release of glutamate. Spontaneous tetrodotoxin‐resistant miniature excitatory postsynaptic currents (mEPSCs) through AMPA receptor channels were recorded by means of the whole‐cell patch‐clamp technique. Adenosine (50 μm) reversibly reduced the frequency of mEPSCs by ∼ 50–60%, but did not change their amplitudes. The protein kinase A inhibitor Rp‐cyclic adenosine monophosphate (100–150 μm) did not block the adenosine‐dependent reduction of the mEPSC frequency, showing that adenosine is not depressing synaptic transmission via a protein kinase A (PKA)‐dependent mechanism. The D1 dopamine agonist SKF‐38393 (250 μm), forskolin (5 μm) and 8Br‐cAMP (2 mm), known to activate the cAMP/PKA‐dependent signalling pathway, all enhanced the mEPSC frequency. A subsequent application of adenosine (50 μm) strongly reduced the potentiation produced by any one of these three drugs. It also reversed protein kinase C (PKC)‐dependent stimulation of glutamate release induced by phorbol myristate acetate (100 nm). Taken together, adenosine not only inhibits the spontaneous release of glutamate independently of protein kinases A and C but also reverses the enhancement of exocytosis produced by protein kinases A and C activators.
Induction of stable long‐term depression in vivo in the hippocampal–prefrontal cortex pathway
Authors: Takita Masatoshi , Izaki Yoshinori , Jay Thérèse M. , Kaneko Hidekazu , Suzuki Shinya S. 
Published: March 2003

AbstractWe studied excitatory field potentials in the medial prefrontal cortex (mPFC, prelimbic area) to electrostimulation of the ventral hippocampus (CA1/subicular region) in the anaesthetized rat. Nine hundred stimulus trains (5 pulses at 250 Hz) applied at 1 Hz to the ventral hippocampus significantly and persistently depressed the amplitude and maximal slope (∼ 55% for each index) of the prelimbic field potentials, but did not change the latency of the maximal slope or peak negativity. Twelve stimulus trains (50 pulses at 250 Hz) applied subsequently at 0.1 Hz restored the depression back to control level, and this reversible depression was maintained for at least 13 h. Cumulative depressive effects on the prelimbic field potential amplitude and maximal slope were observed upon addition of stimulus trains in the hippocampus. An important implication of the results is that the direct pathway from the hippocampus to the mPFC in the rat retains long‐term depression (LTD) as a neuroplastic form in vivo. This form could cooperate with long‐term potentiation (LTP) and such a bi‐directional synaptic plasticity in the prefrontal cortex contributes to how cortical neural networks store information.
Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination
Authors: Nait‐Oumesmar Brahim , Decker Laurence , Lachapelle François , Avellana‐Adalid Virginia , Bachelin Corinne , Van Evercooren Anne Baron‐. 
Published: March 2003

AbstractIdentifying a source of cells with the capacity to generate oligodendrocytes in the adult CNS would help in the development of strategies to promote remyelination. In the present study, we examined the ability of the precursor cells of the adult mouse subventricular zone (SVZ) to differentiate into remyelinating oligodendrocytes. After lysolecithin‐induced demyelination of the corpus callosum, progenitors of the rostral SVZ (SVZa) and the rostral migratory pathway (RMS), expressing the embryonic polysialylated form of the neural cell adhesion molecule (PSA‐NCAM), increased progressively with a maximal expansion occurring after 2 weeks. This observation correlated with an increase in the proliferation activity of the neural progenitors located in the SVZa and RMS. Moreover, polysialic acid (PSA)‐NCAM‐immunoreactive cells arizing from the SVZa were detected in the lesioned corpus callosum and within the lesion. Tracing of the constitutively cycling cells of the adult SVZ and RMS with 3H‐thymidine labelling showed their migration toward the lesion and their differentiation into oligodendrocytes and astrocytes but not neurons. These data indicate that, in addition to the resident population of quiescent oligodendrocyte progenitors of the adult CNS, neural precursors from the adult SVZ constitute a source of oligodendrocytes for myelin repair.
Nitric oxide stimulates cGMP formation in rat optic nerve axons, providing a specific marker of axon viability
Authors: Garthwaite Giti , Goodwin David A. , Garthwaite John 
Published: March 2003

AbstractA major transduction pathway for nitric oxide (NO) is stimulation of soluble guanylyl cyclase and the generation of cyclic GMP (cGMP). In the central nervous system, the NO–cGMP pathway has previously been associated primarily with synapses, particularly glutamatergic synapses. We report here that NO caused a large increase in the levels of cGMP in a central white matter tract devoid of synapses, namely in the rat isolated optic nerve. Cyclic GMP immunohistochemistry indicated that this response was confined to the axons. Accordingly, nerves previously subjected to 1 h of oxygen/glucose deprivation, which leads to irreversible axonal damage, displayed an 80% reduction in their subsequent capacity to generate cGMP in response to NO and a corresponding reduction in the numbers of cGMP‐immunostained axons. Protection of the axon cGMP response against this insult was achieved by omission of Ca2 +  or Na +  from the incubation medium, and by the pharmacological agents tetrodotoxin, lamotrigine, BW619C89 and BW1003C87, all of which protect axonal structure from oxygen/glucose deprivation‐induced damage. The results suggest that the NO–cGMP pathway has a hitherto unsuspected function in the optic nerve. Additionally, the expression of NO‐stimulated guanylyl cyclase in optic nerve axons provides a simple, sensitive and specific marker of their functional integrity that is likely to be valuable in investigating the mechanisms responsible for axon degeneration in ischaemia and other conditions.
Altered synaptic clustering of GABAA receptors in mice lacking dystrophin (mdx mice)
Authors: Knuesel Irene , Mastrocola Mario , Zuellig Richard A. , Bornhauser Beat , Schaub Marcus C. , Fritschy Jean‐Marc 
Published: March 2003

AbstractDystrophin is selectively localized in the postsynaptic density of neurons in cerebral cortex, hippocampus and cerebellum. Here, we show by double‐immunofluorescence staining that dystrophin is extensively colocalized with GABAA receptor subunit clusters in these brain regions. To determine the relevance of this observation, we investigated in mdx mice, which provide a model of Duchenne muscular dystrophy, whether the absence of dystrophin affects the synaptic clustering of GABAA receptors. A marked reduction in the number of clusters immunoreactive for the α1 and α2 subunits was observed in, respectively, cerebellum and hippocampus of mdx mice, but not in striatum, which is normally devoid of dystrophin. Furthermore, these alterations were not accompanied by a change in gephyrin staining, although gephyrin is colocalized with the majority of GABAA receptor clusters in these regions. These results indicate that dystrophin may play an important role in the clustering or stabilization of GABAA receptors in a subset of central inhibitory synapses. These deficits may underlie the cognitive impairment seen in Duchenne patients.
Mapping of somatosensory cortices with functional magnetic resonance imaging in anaesthetized macaque monkeys
Authors: Hayashi Toshihiro , Konishi Seiki , Hasegawa Isao , Miyashita Yasushi 
Published: March 2003

AbstractFunctional magnetic resonance imaging (fMRI) in macaque monkeys is emerging as a potent candidate to bridge the gap between data from human fMRI studies and data from anatomy, electrophysiology and lesion studies in monkeys. The primary (SI) and secondary (SII) somatosensory cortices are the principal regions for somatosensory information processing and contain systematic representations of the body surface map (somatotopy). To examine the functional organization of the somatosensory cortices in anaesthetized macaque monkeys with fMRI, we asked whether focal and differential activation could be observed in SI and SII in response to tactile stimulation with two parameters: body sides (right and left) and body regions (hand and face). We found that changes in stimulus parameters elicited differential focal activation in both SI and SII in two ways. First, the hand and face stimulation activated SI and SII in the contralateral, but not in the ipsilateral, hemisphere. Second, the hand and face stimulation differentially activated two adjacent regions in both SI and SII. These fMRI results appear to correlate with previous mapping studies by other methods in the macaque somatosensory cortices. This study shows the feasibility of fMRI studies in mapping multiple sensory areas in monkeys by which we can distinguish between adjacent functionally distinct regions.
Molecular Characterization and In Situ Localization Of A Full‐Length Cyclic Nucleotide‐Gated Channel In Rat Brain
Authors: Strijbos Paul J. L. M. , Pratt Gerard D. , Khan Shahid , Charles Ian G. , Garthwaite John 
Published: March 2003

AbstractIon channels gated directly by cyclic nucleotides are required for the transduction of sensory signals in photoreceptor cells and olfactory cells. Cyclic nucleotide‐gated (CNG) channels may also be expressed in the central nervous system because partial transcripts that share homology with CNG channels have been found therein. We have now isolated and cloned a full‐length CNG channel cDNA from adult rat brain. The sequence is identical to that of the α‐subunit originally found in the olfactory epithelium (CNCα3). In situ hybridization, using probes specific for the CNCα3 mRNA, suggest that this channel is expressed widely in the rat brain, albeit mostly at relatively low levels. Certain neuronal populations, however, such as deep cerebellar nuclei, olfactory bulb mitral cells and cerebellar Purkinje neurons, appeared specially enriched. The study demonstrates for the first time that a full‐length CNG channel mRNA is expressed in the brain, supporting the possibility that CNG channels are involved in central neural communication and plasticity. The sequence reported in this paper has been deposited in the GenBank data base (accession no. AF126808).
Expression of nonclassical MHC class I (RT1‐U) in certain neuronal populations of the central nervous system
Authors: Lidman Olle , Olsson Tomas , Piehl Fredrik 
Published: March 2003

AbstractMajor histocompatibility complex (MHC) class I genes consist of classical (Ia) and nonclassical (Ib) types. Recently, a set of structurally similar MHC class Ib genes in the rat, denoted RT1‐U, was described. We here demonstrate expression of RT1‐U mRNA using highly stringent oligonucleotide in situ hybridization in several different neuronal populations, including different motor nuclei and the substantia nigra in the rat MHC (c) and (n) haplotypes under normal conditions. The expression pattern for β2‐microglobulin mRNA was almost identical. In contrast, neuronal expression of classical MHC class I (RT1‐A) was low. Interestingly, after mechanical nerve injury, glial cells predominantely upregulated expression of RT1‐A, whereas neuronal expression of RT1‐U remained unchanged. Neuronal expression of nonclassical MHC class I may thus be important for immune surveillance in the nervous system.
α‐Gustducin expression in the vomeronasal organ of the mouse
Authors: Zancanaro Carlo , Caretta Carla Mucignat , Merigo Flavia , Cavaggioni Andrea , Osculati Francesco 
Published: March 2003

AbstractThe expression of α‐gustducin, a G protein α subunit involved in bitter and sweet taste transduction, was investigated in chemosensory tissues of adult mice. By immunohistochemistry, α gustducin was absent in the olfactory neuroepithelium. Instead, α gustducin was expressed in a subset of bipolar cells in the proliferative zone of the vomeronasal neuroepithelium as well as in taste buds. Northern blot analysis confirmed the presence of α gustducin in isolated vomeronasal organs. Moreover, immunohisto‐ chemistry revealed the expression of α gustducin in scattered cells of the nasal respiratory epithelium. These results show for the first time that α gustducin is expressed in chemosensory tissue outside the alimentary tract, suggesting that common transduction mechanisms could be shared by apparently unrelated chemosensory tissues.
Cyclical changes in endogenous levels of oestrogen modulate the induction of LTD and LTP in the hippocampal CA1 region
Authors: Good Mark , Day Mark , Muir Janice L. 
Published: March 2003

AbstractThe present study investigated the effects of naturally fluctuating endogenous levels of oestrogen on the induction and maintenance of long‐term potentiation (LTP) and long‐term depression (LTD) in the CA1 region of the hippocampus. Using an anaesthetized in vivo preparation, the results showed that the induction of LTP was augmented during the pro‐oestrous stage of the oestrous cycle. In contrast to LTP, however, the induction of paired‐pulse LTD was severely attenuated during pro‐oestrous, but was clearly manifested by rats during met/dioestrous and oestrous stages of the cycle. These findings are discussed with reference to: (i) the modulatory effects of oestrogen on N‐methyl‐d‐aspartate (NMDA) receptor function and γ‐aminobutyric acid (GABA) neurotransmission in the hippocampus; and (ii) the functional implications that such cyclical changes in synaptic plasticity have for learning and memory processes supported by the hippocampus.
Visual response augmentation in cat (and macaque) LGN: potentiation by corticofugally mediated gain control in the temporal domain
Authors: Cudeiro Javier , Rivadulla Casto , Grieve Kenneth L. 
Published: March 2003

AbstractVisual responses of neurons are dependent on the context of a stimulus, not only in spatial terms but also temporally, although evidence for temporally separate visual influences is meagre, based mainly on studies in the higher cortex. Here we demonstrate temporally induced elevation of visual responsiveness in cells in the lateral geniculate nucleus (LGN) of cat and monkey following a period of high intensity (elevated contrast) stimulation. This augmentation is seen in 40–70% (monkey–cat) of cells tested and of all subtypes. Peaking at ∼ 3 min following the period of intense stimulation, it can last for 10–12 min and can be repeated and summed in time. Furthermore, it is dependent on corticofugal input, is seen even when high contrast stimuli of orthogonal orientation are used and therefore results from a/any prior increase in activity in the retino‐geniculo‐striate pathway. We suggest that this reflects a general mechanism for control of visual responsiveness; both a flexible and dynamic means of changing effectiveness of thalamic activity as visual input changes, but also a mechanism which is an emergent property of the thalamo‐cortico‐thalamic loop.
Evidence for functional compartmentalization of trigeminal muscle spindle afferents during fictive mastication in the rabbit
Authors: Westberg K. ‐G. , Kolta A. , Clavelou P. , Sandström G. , Lund J. P. 
Published: March 2003

AbstractPrimary afferent neurons innervating muscle spindles in jaw‐closing muscles have cell bodies in the trigeminal mesencephalic nucleus (NVmes) that are electrically coupled and receive synapses. Each stem axon gives rise to a peripheral branch and a descending central branch. It was previously shown that some spikes generated by constant muscle stretch fail to enter the soma during fictive mastication. The present study examines whether the central axon is similarly controlled. These axons were functionally identified in anaesthetized and paralysed rabbits, and tonic afferent firing was elicited by muscle stretch. For the purpose of comparison, responses were recorded extracellularly both from the somatic region and from the central axon in the lateral brainstem. Two types of fictive masticatory movement patterns were induced by repetitive stimulation of the masticatory cortex and monitored from the trigeminal motor nucleus. Field potentials generated by spike‐triggered averaging of action potentials from the spindle afferents were employed to determine their postsynaptic effects on jaw‐closing motoneurons. Tonic firing of 32% NVmes units was inhibited during the jaw‐opening phase, but spike frequency during closing was almost equal to the control rate during both types of fictive mastication. A similar inhibition occurred during opening in 83% of the units recorded along the central branch. However, firing frequency in these was significantly increased during closing in 94%, probably because of the addition of antidromic action potentials generated by presynaptic depolarization of terminals of the central branch. These additional spikes do not reach the soma, but do appear to excite motoneurons. The data also show that the duration and/or frequency of firing during the bursts varied from one pattern of fictive mastication to another. We conclude that the central axons of trigeminal muscle spindle afferents are functionally decoupled from their stem axons during the jaw‐closing phase of mastication. During this phase, it appears that antidromic impulses in the central axons provide one of the inputs from the masticatory central pattern generator (CPG) to trigeminal motoneurons.