bluuebunny/crossref_metadata_2025 huggingface dataset:
Cells lacking ClpB display a prolonged shutoff phase of the heat shock response in Caulobacter crescentus
Authors: Simão Rita C. G. , Susin Michelle F. , Alvarez‐Martinez Cristina E. , Gomes Suely L.
Published: June 2005

The heat shock response in Caulobacter crescentus was previously shown to be positively regulated by the alternative sigma factor of RNA polymerase (RNAP) σ32, and negatively modulated by DnaK during the induction phase of the heat shock response but not during the recovery phase. In the present work we have investigated the involvement of the chaperone ClpB in the control of the heat shock response in C. crescentus. Data obtained indicated a role of ClpB in downregulation of heat shock protein (HSP) synthesis, as cells lacking this chaperone showed a prolonged shutoff phase of the heat shock response. In Escherichia coli, it has been proposed that the DnaK chaperone system switches transcription back to constitutively expressed genes through simultaneous reactivation of heat‐aggregated σ70, as well as sequestration of σ32 away from RNAP. In C. crescentus, results obtained with a clpB null mutant indicate that ClpB could be involved in the reactivation of the major sigma factor σ73. In support of this hypothesis, we showed that transcription directed from σ73‐dependent promoters is not switched back in the clpB null mutant during the recovery phase. Furthermore, we observed that resolubilization of heat‐aggregated σ73 is dependent on the presence of ClpB. Our findings also indicated that the absence of ClpB made cells more sensitive to heat shock and ethanol but not to other stresses, and unable to acquire thermotolerance.
Nursing Synchronization and Milk Ejection Failure as Maternal Strategies to Reduce Allosuckling in Pair‐Housed Sows (Sus scrofa domestica)
Authors: Illmann Gudrun , Pokorná Zuzana , Špinka Marek
Published: June 2005

Non‐offspring nursing (allosuckling) is costly for lactating females. It is reasonable to assume, therefore, that mechanisms have evolved to control the frequency of allosuckling. It is suggested that the synchronization of nursing between females could be such a mechanism. The aim of this study was to investigate whether nursing synchronization is related to the timing of nursing behaviour of paired sows and the behaviour of alien piglets in relation to allosuckling. Specifically, we predicted that: (i) nursing synchronization will increase if there is a real risk of allosuckling compared with a situation where there is none, (ii) nursing synchronization indeed reduces allosuckling and, therefore, those nursings with allosuckling attempts will be less closely synchronized than those without allosuckling attempts and (iii) in non‐synchronized nursings, the sows will more often employ another strategy to reduce allosuckling, namely, they will make the nursings non‐nutritive by not releasing milk. Ten pairs of sows and their litters were used in this study. For each pair, the two sows were housed individually until their litters were weaned; however, their litters had access to both sows from day 11 post‐partum. The behaviour of the 10 pairs of sows with their litters was videotaped for 6 h on days 10, 11, 17 and 24 post‐partum. The frequency of allosuckling attempts, non‐nutritive nursings and allosuckling during milk ejection was analysed for every pair for every day of observation. The observed frequency of nursing synchronization was high. The median interval between the start of a nursing within one pair of sows was 32 s. The first prediction was supported as synchronization became significantly tighter when piglets were given the possibility to allosuckle on day 11 [Cochran–Mantel–Haenszel (CMH) statistics, p < 0.0001]. The second prediction was also supported; the nursings were less closely synchronized when there were allosuckling attempts (CMH statistics, p < 0.05). Of all nursings, 36% had an allosuckling attempt; however, only 17% resulted in real allosuckling. Evidence in favour of the third prediction was also found as non‐nutritive nursings were more frequent in non‐synchronized nursings (CMH statistics, p < 0.05). Finally, real allosuckling during milk ejection was unrelated to the degree of nursing synchronization, as in less synchronized nursings, the sows responded to allosuckling attempts by not releasing milk. Our results suggest that sows are not able to completely suppress allosuckling; however, they can reduce its frequency through nursing synchronization and non‐nutritive nursings.
German Yellowjacket (Vespula germanica) Foragers Use Odors Inside the Nest to Find Carbohydrate Food Sources
Authors: Jandt Jennifer M. , Jeanne Robert L.
Published: June 2005

Prior work has shown that yellowjacket waSPS remember food odors and use them as cues when foraging. There is also evidence they have mechanisms to recruit nest mates to highly rewarding food sources, as naïve individuals are more likely to go to food sources with scents similar to those visited by nest mates. We asked whether recruitment requires behavioral stimulation by returning foragers, as in honey bees, or if sampling the food source inside the nest is sufficient. We tested this by eliminating the behavior of returning foragers by inserting a scented sugar solution directly into a Vespula germanica nest. Exiting foragers were given a choice of the test scent and a control scent. WaSPS were more likely to choose the test scent. We conclude that behavioral interactions with returning foragers are not necessary to stimulate nest mates to associate an odor with a food source and search for a resource bearing that odor, and that experience with the scented reward inside the nest is sufficient to achieve this result.
Is Male Cohabitation Costly for Females of the Spider Stegodyphus lineatus (Eresidae)?
Authors: Erez Tamar , Schneider Jutta M. , Lubin Yael
Published: June 2005

Reproductive interests of females and males can vary over a number of issues, including the number of matings and the occurrence and duration of mate guarding and cohabitation. The mating system of the spider Stegodyphus lineatus (Eresidae) is characterized by an exceptional sexual conflict where males induce females to remate by committing infanticide. Females experience high costs because of this male strategy, while males benefit. During the mating season, males tend to stay with females for several days. We examined whether this male strategy of cohabitation is also disadvantageous for females of S. lineatus. A field experiment revealed that male presence in a female's nest negatively affected her body condition, whereas cohabiting males gained weight because they fed on prey caught in webs of females. As a response, females did not renew their webs when males were present. Thus, females with a cohabiting male experienced the combined cost of prey loss and loss of time available for foraging. These costs are expected to increase with every additional cohabiting male. Mated females behaved more aggressively toward males than did virgin females. This behavior may be interpreted as an adaptive response to reduce mating costs.
Time Learning and Anticipatory Activity in Groups of Arctic Charr
Authors: Brännäs Eva , Berglund Ulf , Eriksson Lars‐Ove
Published: June 2005

Time learning and anticipatory activity were studied in five groups of 16–17 Arctic charr (Salvelinus alpinus) using self‐feeding devices with individual recognition (PIT (Passive Integrated Transponders)‐tags). The fish were kept under a LD 12:12 h cycle and periods of free access to the food were alternated with periods of time‐limited (2 h) access to food. Self‐feeding activity was significantly related to the light period in unrestricted conditions while related to the feeding periods during time‐limited access to food. The fish learned to concentrate their feeding activity to the restricted mealtime (>50% of the daily self‐feeding activity) within 10 d. The food anticipatory activity, measured as an increased self‐feeding activity before the feeding time and as aggressive interactions close to the trigger, was significant in both cases. The dominant individuals increased the trigger activity in advance of the time‐restricted reward period and subdominant individuals approached the trigger also in advance, inducing aggressive interactions. Thus, anticipating and learning a temporally predictable food source was pronounced in groups of self‐feeding Arctic charr.
Formation of an Olfactory Search Image for Explosives Odours in Sniffer Dogs*
Authors: Gazit Irit , Goldblatt Allen , Terkel Joseph
Published: June 2005

The term ‘search image’ refers to an animal's heightened ability to detect a specific cryptic prey, after experience with that prey. Formulated in 1960 by Tinbergen (Archives Neerlandaises de zoologie, vol. 13, pp. 265–343), the search image concept has been the subject of much research, albeit almost entirely based on visual search cues in birds of prey. Given the theoretical and practical importance of this concept for foraging or searching in general, we set out to investigate whether dogs could form olfactory search images for explosive odours. Seven experienced explosives detector dogs were first tested for their ability to detect 30 g of the explosives 2,4,6‐trinitrotoluene (TNT), RDX + polyisobutylene + di(2‐ethylhexyl)sebacate + fuel oil (C4) or pentaerythritol tetranitrate (PETN) placed in various containers randomly distributed along a 300‐m limestone track. In consecutive stages of the experiment, we altered the relative percentages of the three explosives. The results showed that the percentage of TNT containers detected by the dogs increased in trials that followed placing of a high percentage of TNT relative to other explosives and decreased in trials that follwed placing of a relatively low percentage of TNT containers. The percentage detection of C4 and PETN was not influenced by their relative abundance at any stage. Overall, these results suggest that dogs can form an olfactory search image that might aid in prey/target detection.
Learning in realistic networks of spiking neurons and spike‐driven plastic synapses
Authors: Mongillo Gianluigi , Curti Emanuele , Romani Sandro , Amit Daniel J.
Published: June 2005

We have used simulations to study the learning dynamics of an autonomous, biologically realistic recurrent network of spiking neurons connected via plastic synapses, subjected to a stream of stimulus–delay trials, in which one of a set of stimuli is presented followed by a delay. Long‐term plasticity, produced by the neural activity experienced during training, structures the network and endows it with active (working) memory, i.e. enhanced, selective delay activity for every stimulus in the training set. Short‐term plasticity produces transient synaptic depression. Each stimulus used in training excites a selective subset of neurons in the network, and stimuli can share neurons (overlapping stimuli). Long‐term plasticity dynamics are driven by presynaptic spikes and coincident postsynaptic depolarization; stability is ensured by a refresh mechanism. In the absence of stimulation, the acquired synaptic structure persists for a very long time. The dependence of long‐term plasticity dynamics on the characteristics of the stimulus response (average emission rates, time course and synchronization), and on the single‐cell emission statistics (coefficient of variation) is studied. The study clarifies the specific roles of short‐term synaptic depression, NMDA receptors, stimulus representation overlaps, selective stimulation of inhibition, and spike asynchrony during stimulation. Patterns of network spiking activity before, during and after training reproduce most of the in vivo physiological observations in the literature.
Neuronal mechanisms underlying control of a brain–computer interface
Authors: Hinterberger Thilo , Veit Ralf , Wilhelm Barbara , Weiskopf Nikolaus , Vatine Jean‐Jacques , Birbaumer Niels
Published: June 2005

Brain–computer interfaces (BCIs) enable humans or animals to communicate or control external devices without muscle activity using electric brain signals. The BCI used here is based on self‐regulation of slow cortical potentials (SCPs), a skill that most people and paralyzed patients can acquire with training periods of several hours up to months. The neurophysiological mechanisms and anatomical sources of SCPs and other event‐related brain potentials have been described but the neural mechanisms underlying the self‐regulation skill for the use of a BCI are unknown. To uncover the relevant areas of brain activation during regulation of SCPs, the BCI was combined with functional magnetic resonance imaging. The electroencephalogram was recorded inside the magnetic resonance imaging scanner in 12 healthy participants who learned to regulate their SCP with feedback and reinforcement. The results demonstrate activation of specific brain areas during execution of the brain regulation skill allowing a person to activate an external device; a successful positive SCP shift compared with a negative shift was closely related to an increase of the blood oxygen level‐dependent response in the basal ganglia. Successful negativity was related to an increased blood oxygen level‐dependent response in the thalamus compared with successful positivity. These results may indicate learned regulation of a cortico‐striatal‐thalamic loop modulating local excitation thresholds of cortical assemblies. The data support the assumption that human subjects learn the regulation of cortical excitation thresholds of large neuronal assemblies as a prerequisite for direct brain communication using an SCP‐driven BCI. This skill depends critically on an intact and flexible interaction between the cortico‐basal ganglia‐thalamic circuits.
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

Functional 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

The 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

Here 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

Orexin/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

A 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

Zolpidem 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

Emotional 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

The 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

It 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

The ‘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

We 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

Ischemic 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.
Sexual dimorphisms in the effect of low‐level p25 expression on synaptic plasticity and memory
Authors: Ris L. , Angelo M. , Plattner F. , Capron B. , Errington M. L. , Bliss T. V. P. , Godaux E. , Giese K. P.
Published: June 2005

p25, a degradation product of p35, has been reported to accumulate in the forebrain of patients with Alzheimer's disease. p25 as well as p35 are activators of cyclin‐dependent kinase 5 (Cdk5) although p25/Cdk5 and p35/Cdk5 complexes have distinct properties. Several mouse models with high levels of p25 expression exhibit signs of neurodegeneration. On the contrary, we have shown that low levels of p25 expression do not cause neurodegeneration and are even beneficial for particular types of learning and memory [Angelo et al., (2003) Eur J. Neurosci., 18, 423–431]. Here, we have studied the influence of low‐level p25 expression in hippocampal synaptic plasticity and in learning and memory for each sex separately in two different genetic backgrounds (129B6F1 and C57BL/6). Surprisingly, we found that low‐level p25 expression had different consequences in male and female mutants. In the two genetic backgrounds LTP induced by a strong stimulation of the Schaffer's collaterals (four trains, 1‐s duration, 5‐min interval) was severely impaired in male, but not in female, p25 mutants. Furthermore, in the two genetic backgrounds spatial learning in the Morris water maze was faster in female p25 mutants than in male transgenic mice. These results suggest that, in women, the production of p25 in Alzheimer's disease could be a compensation for some early learning and memory deficits.
Characterization of organotypic ventral mesencephalic cultures from embryonic mice and protection against MPP+ toxicity by GDNF
Authors: Jakobsen B. , Gramsbergen J. B. , Møller Dall A. , Rosenblad C. , Zimmer J.
Published: June 2005

We characterized organotypic ventral mesencephalic (VM) cultures derived from embryonic day 12 (E12) mice (CBL57/bL6) in terms of number of dopaminergic neurons, cell soma size and dopamine production in relation to time in vitro and tested the effects of 1‐methyl‐4‐phenylpyridinium (MPP+) and glial derived neurotrophic factor (GDNF) to validate this novel culture model. Dopamine production and dopaminergic neuron soma size increased dramatically with time in vitro, whereas the number of dopamine neurons declined by approximately 30% between week 1 and week 2, which was further reduced after week 4. GDNF treatment (100 ng/mL) increased dopaminergic neuron soma size (up to 43%) and DOPAC production (approximately three‐fold), but not the number of dopamine neurons in control cultures. One‐week‐old cultures were more vulnerable to MPP+, than three‐week‐old cultures. The EC50 for dopamine depletion after 2 days exposure and 15 days of recovery were 0.6 and 7 µm, respectively. Both pre‐treatment and post‐treatment with GDNF are important to obtain maximal protection against MPP+ toxicity. In one‐week‐old cultures (5 µm MPP+, 2 days) GDNF provided potent neuroprotection with dopamine contents reaching control levels and number of tyrosine hydroxylase (TH)+ cells up to 80% of control, but in three‐week‐old cultures (10 µm MPP+, 2 days) the protective potential of GDNF was markedly reduced. Long recovery periods after MPP+ exposure are required to distinguish between reversible or irreversible toxic and/or trophic effects.
Neuroanatomical correlates of voluntary inhibition of accommodation/vergence under monocular open‐loop viewing conditions
Authors: Richter H. O. , Andersson J. , Schneider H. , Långström B.
Published: June 2005

The purpose of this work is to identify human neural circuits involved in inhibition of accommodation/vergence by contrasting the cortical functions subservient to negative voluntary accommodation/vergence (NVA) with those evoked by active fixation in darkness (FIX). Five subjects with normal corrected acuity were studied using positron emission tomography and the HO bolus technique. The dominant right eye viewed a laser speckle pattern (633 nm) whose direction and velocity of motion were determined by the refractive state of the eye. The speckle pattern was presented at a distance of 1.8 m (0.55 D). The non‐dominant eye was patched. Subjects performed two tasks counterbalanced for order effects: (i) attempted fixation on the remembered target in darkness with the dominant eye open and ‘fixating’; and (ii) voluntary reduction of the laser speckle flow during each alternate 20‐s epoch when a convex +2.0 D lens was placed in front of the right eye causing the speckle pattern to move downwards at 3 °/s. Comparison of the condition of NVA with the condition of FIX indicated widespread occipital activation. Decreases in absolute regional cerebral blood flow occurred in the superior parietal cortex (BA 5), frontal cortex (BA 8 and 10) and within the postcentral/precentral gyrus (BA 1/2/3/4) bilaterally where deactivation clusters eclipsed the presumed neck and shoulder areas. Negative accommodation/vergence appears to be driven by a reduction of parasympathetic tone, and has the effect of shutting down brain regions known to be involved in regulating visual search as well as a centrally controlled eye–head–neck–shoulder motor programme responsible for posturing gaze.
Loss of forebrain cholinergic neurons and impairment in spatial learning and memory in LHX7‐deficient mice
Authors: Fragkouli Apostolia , Hearn Catherine , Errington Mick , Cooke Sam , Grigoriou Maria , Bliss Tim , Stylianopoulou Fotini , Pachnis Vassilis
Published: June 2005

The identification of the genetic determinants specifying neuronal networks in the mammalian brain is crucial for the understanding of the molecular and cellular mechanisms that ultimately control cognitive functions. Here we have generated a targeted allele of the LIM‐homeodomain‐encoding gene Lhx7 by replacing exons 3–5 with a LacZ reporter. In heterozygous animals, which are healthy, fertile and have no apparent cellular deficit in the forebrain, b‐galactosidase activity reproduces the pattern of expression of the wild‐type Lhx7 locus. However, homozygous mutant mice show severe deficits in forebrain cholinergic neurons (FCNs), while other classes of forebrain neurons appear unaffected. Using the LacZ reporter as a marker, we show that in LHX7‐deficient mice FCN progenitors survive but fail to generate cholinergic interneurons in the striatum and cholinergic projection neurons in the basal forebrain. Analysis of behaviour in a series of spatial and non‐spatial learning and memory tasks revealed that FCN ablation in Lhx7 mutants is associated with severe deficits in spatial but only mild impairment of non‐spatial learning and memory. In addition, we found no deficit in long‐term potentiation in mutant animals, suggesting that FCNs modulate hippocampal function independently of its capacity to store information. Overall our experiments demonstrate that Lhx7 expression is required for the specification or differentiation of cholinergic forebrain neurons involved in the processing of spatial information.
Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse control
Authors: Winstanley Catharine A. , Baunez Christelle , Theobald David E. H. , Robbins Trevor W.
Published: June 2005

Although the subthalamic nucleus (STN) is involved in regulating motor function, and inactivation of this structure relieves the motor symptoms in Parkinsonian patients, recent data indicate that corticosubthalamic connections are involved in both the regulation of attention and the ability to withhold from responding. Considerable evidence suggests that the neural circuitry underlying such behavioural disinhibition or impulsive action can be at least partially dissociated from that implicated in impulsive decision‐making and it has been suggested that the tendency to choose impulsively is related to the ability to form and use Pavlovian associations. To explore these hypotheses further, STN‐lesioned rats were tested on the delay‐discounting model of impulsive choice, where impulsivity is defined as the selection of a small immediate over a larger delayed reward, as well as in a rodent autoshaping paradigm. In contrast to previous reports of increased impulsive action, STN lesions decreased impulsive choice but dramatically impaired the acquisition of the autoshaping response. When the STN was lesioned after the establishment of autoshaping behaviour, lesioned subjects were more sensitive to the omission of reward, indicative of a reduction in the use of Pavlovian associations to control autoshaping performance. These results emphasize the importance of the STN in permitting conditioned stimulus–unconditioned stimulus associations to regulate goal‐seeking, a function which may relate to the alterations in impulsive choice observed in the delay‐discounting task. These data bear a striking similarity to those observed after lesions of the orbitofrontal cortex and are suggestive of an important role for corticosubthalamic connections in complex cognitive behaviour.
A kind of auditory ‘primitive intelligence’ already present at birth
Authors: Carral Vanessa , Huotilainen Minna , Ruusuvirta Timo , Fellman Vineta , Näätänen Risto , Escera Carles
Published: June 2005

‘Primitive intelligence’ in audition refers to the capacity of the auditory system to adaptatively model the acoustic regularity and react neurophysiologically to violations of such regularity, thus supporting the ability to predict future auditory events. In the present study, event‐related brain potentials to pairs of tones were recorded in 11 human newborns to determine the infants' ability to extract an abstract acoustic rule, the direction of a frequency change. Most of the pairs (standard,P = 0.875) were of ascending frequency (i.e. the second tone higher than the first), while the remaining pairs (deviant,P = 0.125) were of descending frequency (the second tone being lower). Their frequencies varied among seven levels to prevent discrimination between standard and deviant pairs on the basis of absolute frequencies. We found that event‐related brain potentials to deviant pairs differed in amplitude from those to standard pairs at 50–450 ms from the onset of the second tone of a pair, indicating the infants' ability to represent the abstract rule. This finding suggests the early ontogenetic origin of ‘primitive intelligence’ in audition that eventually may form a prerequisite for later language acquisition.