bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attention to pain localization and unpleasantness discriminates the functions of the medial and lateral pain systems
Authors: Kulkarni B. , Bentley D. E. , Elliott R. , Youell P. , Watson A. , Derbyshire S. W. G. , Frackowiak R. S. J. , Friston K. J. , Jones A. K. P. 
Published: June 2005

AbstractFunctional imaging studies have identified a matrix of structures in the brain that respond to noxious stimuli. Within this matrix, a division of function between sensory‐discriminative and affective responses has so far been demonstrated by manipulating either pain intensity or unpleasantness under hypnosis in two different normal volunteer groups studied on separate occasions. Our study used positron emission tomography (PET) to demonstrate this division of function under more natural conditions in a healthy group of volunteers, using a CO2 laser to provide nociceptive stimuli that selectively activate A‐delta and C‐fibres without contamination by touch sensations. We measured the differential cerebral responses to noxious and innocuous laser stimuli during conditions of selective attention to either the unpleasantness or location of the stimuli. Attention to location increased responses in the contralateral (right) primary somatosensory and inferior parietal cortices. This result implies that these components of the lateral pain system are concerned mainly with the localization of pain. In contrast, attention to unpleasantness increased responses in bilateral perigenual cingulate and orbitofrontal cortices, contralateral (right) amygdala, ipsilateral (left) hypothalamus, posterior insula, M1 and frontal pole. These areas comprise key components of the medial pain and neuroendocrine systems and the results suggest that they have a role in the affective response to pain. Our results indicate the importance of attentional effects on the pattern of nociceptive processing in the brain. They also provide the first clear demonstration, within a single experiment, of a major division of function within the neural pain matrix.
The chemokine CCL2 modulates Ca2+ dynamics and electrophysiological properties of cultured cerebellar Purkinje neurons
Authors: Van Gassen K. L. I. , Netzeband J. G. , De Graan P. N. E. , Gruol D. L. 
Published: June 2005

AbstractThe chemokine CCL2 is produced at high levels in the central nervous system (CNS) during infection, injury, neuroinflammation and other pathological conditions. Cells of the CNS including neurons and glia express receptors for CCL2 and these receptors may contribute to a signaling system through which pathologic conditions in the CNS are communicated. However, our understanding of the consequences of activation of chemokine signaling in the CNS is limited, especially for neurons. In many cell types, chemokine signaling alters intracellular Ca2+ dynamics. Therefore, we investigated the potential involvement of this mechanism in neuronal signaling activated by CCL2. In addition, we examined the effects of CCL2 on neuronal excitability. The studies focused on the rat cerebellar Purkinje neuron, an identified CNS neuronal type reported to express both CCL2 and its receptor, CCR2. Immunohistochemical studies of Purkinje neurons in situ confirmed that they express CCR2 and CCL2. The effect of exogenous application on Purkinje neurons was studied in a cerebellar culture preparation. CCL2 was tested by micropressure or bath application, at high concentrations (13–100 nm) to simulate conditions during a pathologic state. Results show that Purkinje neurons express receptors for CCL2 and that activation of these receptors alters several neuronal properties. CCL2 increased resting Ca2+ levels, enhanced the Ca2+ response evoked by activation of metabotropic glutamate receptor 1 and depressed action potential generation in the cultured Purkinje neurons. Passive membrane properties were unaltered. These modulatory effects of CCL2 on neuronal properties are likely to contribute to the altered CNS function associated with CNS disease and injury.
A bipotent neural progenitor cell line cloned from a cerebellum of an adult p53‐deficient mouse generates both neurons and oligodendrocytes
Authors: Tominaga Mitsutoshi , Honda Shinya , Okada Atsumasa , Ikeda Akifumi , Kinoshita Seiji , Tomooka Yasuhiro 
Published: June 2005

AbstractHere we report developmental characteristics of a clonal cell line 2Y‐3t established from a multifocal neoplasm that arose in a cerebellum of an adult p53‐deficient mouse. The tumorigenicity of the line was not observed in soft agar assay or in nude mouse assay. In serum‐containing medium, 2Y‐3t cells were epithelial‐like in morphology and were mitotic. When they were cultured in serum‐free medium, the expressions of neural stem and/or progenitor cell markers were decreased. Concomitantly, the expressions of neuronal and oligodendrocyte markers were increased in concert with morphological differentiation, and DNA synthesis ceased. None of astrocyte markers were detected under these culture conditions. Double‐labelling studies revealed that two cell populations coexisted, expressing neuronal or oligodendrocyte markers. Triiodothyronine (T3) increased the oligodendrocyte population when 2Y‐3t cells were cultured in serum‐free medium. Recloning of the line gave rise to three types of subclones. Sixteen subclones were capable of generating both neurons and oligodendrocytes, four subclones were capable of generating only neurons and one subclone was capable of generating only oligodendrocytes. Thus, 2Y‐3t cells have characteristics of bipotent neural progenitor cells capable of generating both neurons and oligodendrocytes. In addition, the line expressed mRNA for Pax‐2 and had GAD67‐positive cells when cultured in serum‐free medium. However, none of the mRNAs for Zic‐1, Math1, zebrin or Calbindin‐D28k were detected, suggesting that the 2Y‐3t line might generate the GABAergic interneuron lineage of the mouse cerebellum.
Dopaminergic regulation of orexin neurons
Authors: Bubser Michael , Fadel Jim R. , Jackson Lela L. , Meador‐Woodruff James H. , Jing Deqiang , Deutch Ariel Y. 
Published: June 2005

AbstractOrexin/hypocretin neurons in the lateral hypothalamus and adjacent perifornical area (LH/PFA) innervate midbrain dopamine (DA) neurons that project to corticolimbic sites and subserve psychostimulant‐induced locomotor activity. However, it is not known whether dopamine neurons in turn regulate the activity of orexin cells. We examined the ability of dopamine agonists to activate orexin neurons in the rat, as reflected by induction of Fos. The mixed dopamine agonist apomorphine increased Fos expression in orexin cells, with a greater effect on orexin neurons located medial to the fornix. Both the selective D1‐like agonist, A‐77636, and the D2‐like agonist, quinpirole, also induced Fos in orexin cells, suggesting that stimulation of either receptor subtype is sufficient to activate orexin neurons. Consistent with this finding, combined SCH 23390 (D1 antagonist)–haloperidol (D2 antagonist) pretreatment blocked apomorphine‐induced activation of medial as well as lateral orexin neurons; in contrast, pretreatment with either the D1‐like or D2‐like antagonists alone did not attenuate apomorphine‐induced activation of medial orexin cells. In situ hybridization histochemistry revealed that LH/PFA cells rarely express mRNAs encoding dopamine receptors, suggesting that orexin cells are transsynaptically activated by apomorphine. We therefore lesioned the nucleus accumbens, a site known to regulate orexin cells, but this treatment did not alter apomorphine‐elicited activation of medial or lateral orexin neurons. Interestingly, apomorphine failed to activate orexin cells in isoflurane‐anaesthetized animals. These data suggest that apomorphine‐induced arousal but not accumbens‐mediated hyperactivity is required for dopamine to transsynaptically activate orexin neurons.
Differential modulation of anterior cingulate cortical activity by afferents from ventral tegmental area and mediodorsal thalamus
Authors: Onn Shao‐Pii , Wang Xiao‐Bin 
Published: June 2005

AbstractA distinct increase in cell firing activity is reported in prefrontal cortex during working memory tasks. The afferents that modulate this activity are not yet identified. Using in vivo intracellular recording and labelling of prefrontal cortical pyramidal neurons in anaesthetized rats, we systematically evaluated the influences of afferent projections arising from the ventral tegmental area (VTA) and mediodorsal thalamus (MD) by phasic electrical stimulation with a range of stimulus frequencies. Both VTA‐ and MD‐responsive pyramidal neurons exhibited extensive intracortical axon arborization. Neither single shocks to the VTA at 0.2 Hz, nor low frequency trains of stimuli at 1–4 Hz (< 5 Hz) interrupted the periodicity of membrane bistability in bistable pyramidal neurons. However, high‐frequency VTA‐train stimulation (10–50 Hz) interrupted the bistability, and produced sustained membrane depolarizations accompanied by intense tonic firing in a frequency‐dependent manner. Electrical stimulation of MD (10–50 Hz) did not produce sustained activity in the same PFC neurons. Thus, the sustained activity induced by high‐frequency VTA trains is input selective. This effect of VTA‐train stimulation was attenuated by systemic injection of the D1 receptor antagonist, SCH 23390, and blocked by acute dopamine (DA) depletion produced via α‐methyl‐para‐tyrosine pre‐treatment, suggesting that sustained cortical activity is mediated by DA. Chemical stimulation of VTA via intra‐VTA infusion of NMDA induced sustained activity similar to VTA‐train stimulation. Thus, while both VTA‐ and MD‐responsive pyramidal neurons exhibited extensive intracortical axon arborization, VTA synapses (as opposed to MD synapses) may be critically positioned in the dendritic arborizations of anterior cingulate cortical pyramidal neurons, which may allow their modulation of sustained activity in prefrontal bistable neurons.
Loss of zolpidem efficacy in the hippocampus of mice with the GABAA receptor γ2 F77I point mutation
Authors: Cope D. W. , Halbsguth C. , Karayannis T. , Wulff P. , Ferraguti F. , Hoeger H. , Leppä E. , Linden A.‐M. , Oberto A. , Ogris W. , Korpi E. R. , Sieghart W. , Somogyi P. , Wisden W. , Capogna M. 
Published: June 2005

AbstractZolpidem is a hypnotic benzodiazepine site agonist with some γ‐aminobutyric acid (GABA)A receptor subtype selectivity. Here, we have tested the effects of zolpidem on the hippocampus of γ2 subunit (γ2F77I) point mutant mice. Analysis of forebrain GABAA receptor expression with immunocytochemistry, quantitative [3H]muscimol and [35S] t‐butylbicyclophosphorothionate (TBPS) autoradiography, membrane binding with [3H]flunitrazepam and [3H]muscimol, and comparison of miniature inhibitory postsynaptic current (mIPSC) parameters did not reveal any differences between homozygous γ2I77/I77 and γ2F77/F77 mice. However, quantitative immunoblot analysis of γ2I77/I77 hippocampi showed some increased levels of γ2, α1, α4 and δ subunits, suggesting that differences between strains may exist in unassembled subunit levels, but not in assembled receptors. Zolpidem (1 µm) enhanced the decay of mIPSCs in CA1 pyramidal cells of control (C57BL/6J, γ2F77/F77) mice by ∼ 60%, and peak amplitude by ∼ 20% at 33–34 °C in vitro. The actions of zolpidem (100 nm or 1 µm) were substantially reduced in γ2I77/I77 mice, although residual effects included a 9% increase in decay and 5% decrease in peak amplitude. Similar results were observed in CA1 stratum oriens/alveus interneurons. At network level, the effect of zolpidem (10 µm) on carbachol‐induced oscillations in the CA3 area of γ2I77/I77 mice was significantly different compared with controls. Thus, the γ2F77I point mutation virtually abolished the actions of zolpidem on GABAA receptors in the hippocampus. However, some residual effects of zolpidem may involve receptors that do not contain the γ2 subunit.
What is said or how it is said makes a difference: role of the right fronto‐parietal operculum in emotional prosody as revealed by repetitive TMS
Authors: Van Rijn Sophie , Aleman André , Van Diessen Eric , Berckmoes Celine , Vingerhoets Guy , Kahn René S. 
Published: June 2005

AbstractEmotional signals in spoken language can be conveyed by semantic as well as prosodic cues. We investigated the role of the fronto‐parietal operculum, a somatosensory area where the lips, tongue and jaw are represented, in the right hemisphere to detection of emotion in prosody vs. semantics. A total of 14 healthy volunteers participated in the present experiment, which involved transcranial magnetic stimulation (TMS) in combination with frameless stereotaxy. As predicted, compared with sham stimulation, TMS over the right fronto‐parietal operculum differentially affected the reaction times for detection of emotional prosody vs. emotional semantics, showing that there is a dissociation at a neuroanatomical level. Detection of withdrawal emotions (fear and sadness) in prosody was delayed significantly by TMS. No effects of TMS were observed for approach emotions (happiness and anger). We propose that the right fronto‐parietal operculum is not globally involved in emotion evaluation, but sensitive to specific forms of emotional discrimination and emotion types.
The opioid fentanyl affects light input, electrical activity and Per gene expression in the hamster suprachiasmatic nuclei
Authors: Vansteensel Mariska J. , Magnone Maria Chiara , Van Oosterhout Floor , Baeriswyl Stéphanie , Albrecht Urs , Albus Henk , Dahan Albert , Meijer Johanna H. 
Published: June 2005

AbstractThe suprachiasmatic nuclei (SCN) contain a major circadian pacemaker, which is regulated by photic and nonphotic stimuli. Although enkephalins are present in the SCN, their role in phase regulation of the pacemaker is largely unknown. The opioid agonist fentanyl, a homologue of morphine, is an addictive drug that induces phase shifts of circadian rhythms in hamsters. We observed that these phase shifts are blocked by naloxone, which is a critical test for true opioid receptor involvement, and conclude that opioid receptors are the sole mediators of the actions of fentanyl on the circadian timing system. A strong interaction between opioids and light input was shown by the ability of fentanyl and light to completely block each other's phase shifts of behavioural activity rhythms. Neuronal ensemble recordings in vitro provide first evidence that SCN cells show direct responses to fentanyl and react with a suppression of firing rate. Moreover, we show that fentanyl induces a strong attenuation of light‐induced Syrian hamster Period 1 (shPer1) gene expression during the night. During the subjective day, we found no evidence for a role of shPer1 in mediation of fentanyl‐induced phase shifts. Based on the present results, however, we cannot exclude the involvement of shPer2. Our data indicate that opioids can strongly modify the photic responsiveness of the circadian pacemaker and may do so via direct effects on SCN electrical activity and regulation of Per genes. This suggests that the pathways regulating addictive behaviour and the circadian clock intersect.
The reinforcing effects of chronic d‐amphetamine and morphine are impaired in a line of memory‐deficient mice overexpressing calcineurin
Authors: Biala Grazyna , Betancur Catalina , Mansuy Isabelle M. , Giros Bruno 
Published: June 2005

AbstractIt has recently emerged that there is a commonality in the molecular mechanisms underlying long‐term neuronal changes in drug addiction and those mediating synaptic plasticity associated with learning and memory. In the hippocampus, the calcium–calmodulin‐dependent protein phosphatase calcineurin plays a pivotal role in the molecular mechanisms that underlie learning and memory functions. Transgenic mice that express an active form of calcineurin specifically in forebrain structures have previously been shown to have a deficit in the transition from short‐ to long‐term memory. Here, we investigated the involvement of calcineurin in the motivational effects of amphetamine and morphine using this line of transgenic mice (CN98). Our results showed that amphetamine and morphine did not induce conditioned place preference in calcineurin‐mutant mice, whereas food remained an efficient reinforcer. In addition, behavioural sensitization to these two drugs, as measured by horizontal locomotion, was disturbed in the transgenic mice. In contrast, neither the horizontal locomotion in response to acute d‐amphetamine or morphine nor the somatic signs of morphine withdrawal were affected in calcineurin mutant mice compared to their wild‐type littermates. Our data indicate that calcineurin‐mediated protein dephosphorylation in the hippocampus is involved in the long‐term effects of drugs of abuse without influencing the motivational response to a natural reward or the physical component of opioid withdrawal. The present results emphasize the essential role of hippocampal‐dependent learning and memory in the development of drug addiction.
A neural signature of colour and luminance correspondence in bistable apparent motion
Authors: Sterzer Philipp , Kleinschmidt Andreas 
Published: June 2005

AbstractThe ‘correspondence problem’ refers to the ambiguity of apparent motion (AM) paths if several similar objects are displaced across successive displays. We investigated the effect of intrinsic object properties such as colour and luminance on AM paths, and used functional magnetic resonance imaging to localize neural correlates of correspondence matching in visual cortical regions. Human subjects looked at an AM display where two dots in diagonally opposite corners of an implicit rectangle were flashed in alternation with two dots in the other two corners, yielding spontaneous alternations between horizontal and vertical AM. The dots differed in colour or luminance, or were identical. Neural activity was analysed as a function of whether the perceived AM path matched the dots' colour or luminance, and was also compared to activity during bistable AM displays without correspondence cues. When AM paths matched colour and luminance cues, activity in early visual cortex was the same as during perception of uncued displays, whereas it was suppressed when perceived AM paths violated colour or luminance cues. Colour‐sensitive extrastriate cortex (V4 complex) transiently activated whenever AM perception switched from a pattern violating colour correspondence to one consistent with colour. We propose that the neural correlate of correspondence in early visual cortex reflects regulatory mechanisms that flexibly gate early visual feature processing in accord with an overriding perceptual decision. Conversely, activation of feature‐selective extrastriate regions depends on the type of cue used for correspondence matching and may reflect the salience of percepts that match in colour and motion.
Involvement of the nitric oxide–cyclic GMP pathway and neuronal nitric oxide synthase in ATP‐induced Ca2+ signalling in cochlear inner hair cells
Authors: Shen Jing , Harada Narinobu , Nakazawa Hiroko , Yamashita Toshio 
Published: June 2005

AbstractWe recently demonstrated that extracellular adenosine 5′‐triphosphate (ATP) induced nitric oxide (NO) production in the inner hair cells (IHCs) of the guinea pig cochlea, which inhibited the ATP‐induced increase in the intracellular Ca2+ concentrations ([Ca2+]i) by a feedback mechanism [Shen, J., Harada, N. & Yamashita, T. (2003) Neurosci. Lett., 337, 135–138]. We herein investigated the role of the NO–cGMP pathway and neuronal NO synthase (nNOS) in the ATP‐induced Ca2+ signalling in IHCs using the Ca2+‐sensitive dye fura‐2 and the NO‐sensitive dye DAF‐2. Fura‐2 fluorescence‐quenching experiments with Mn2+ showed that ATP triggered a Mn2+ influx. L‐NG‐nitroarginine methyl ester (L‐NAME), a nonspecific NOS inhibitor, accelerated the ATP‐induced Mn2+ influx while S‐nitroso‐N‐acetylpenicillamine (SNAP), a NO donor, suppressed it. 1H‐[1,2,4]oxadiazole[4,3‐a] quinoxalin‐1‐one, an inhibitor of guanylate cyclase, and KT5823, an inhibitor of cGMP‐dependent protein kinase, enhanced the ATP‐induced [Ca2+]i increase. 8‐Bromoguanosine‐cGMP, a membrane‐permeant analogue of cGMP mimicked the effects of SNAP. Moreover, the effects of 7‐nitroindazole, a selective nNOS inhibitor, mimicked the effects of L‐NAME regarding both the enhancement of the ATP‐induced Ca2+ response and the attenuation of NO production. Immunofluorescent staining of nNOS using a single IHC revealed that nNOS was distributed throughout the IHCs, but enriched in the apical region of the IHCs as shown by intense staining. In conclusion, the ATP‐induced Ca2+ influx may be the principal source for nNOS activity, which may interact with P2X receptors in the apical region of IHCs. Thereafter, NO can be produced and conversely inhibits the Ca2+ influx via the NO–cGMP–PKG pathway by a feedback mechanism.
Microsphere embolism‐induced cortical cholinergic deafferentation and impairments in attentional performance
Authors: Craft Tara K. S. , Mahoney John H. , DeVries A. Courtney , Sarter Martin 
Published: June 2005

AbstractIschemic events have been hypothesized to play a critical role on the pathogenesis of dementia and the acceleration of cognitive impairments. This experiment was designed to determine the consequences of microvascular ischemia on the cortical cholinergic input system and associated attention capacities. Injections of microspheres (≈50 µm diameter; ≈5000 microspheres/100 µL) into the right common carotid artery of rats served as a model of microvascular ischemia and resulted in decreases in the density of cholinergic fibers in the ipsilateral medial prefrontal cortex and frontoparietal areas. Furthermore, dense astrogliosis, indicated by glial fibrillary acidic protein (GFAP) immunohistochemistry, was observed in the globus pallidus, including the areas of origin of cholinergic projections to the cortex. Fluoro‐Jade B staining indicated that loss of neurons in the cortex was restricted to areas of microsphere‐induced infarcts. Attentional performance was assessed using an operant sustained attention task; performance in this task was previously demonstrated to reflect the integrity and activity of the cortical cholinergic input system. Embolized animals' performance was characterized by a decrease in the animals' ability to detect signals. Their performance in non‐signal trials remained unaffected. The residual density of cholinergic axons in prefrontal and frontoparietal areas correlated with the animals' performance. The present data support the hypothesis that microvascular ischemia results in loss of cortical cholinergic inputs and impairs associated attentional performance. Microsphere embolism represents a useful animal model for studying the role of interactions between microvascular disorder and impaired forebrain cholinergic neurotransmission in the manifestation of cognitive impairments.