bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between intracerebral gamma oscillations and slow potentials in the human sensorimotor cortex
Authors: Szurhaj William , Labyt Etienne , Bourriez Jean‐Louis , Kahane Philippe , Chauvel Patrick , Mauguière François , Derambure Philippe
Published: August 2006

Changes in sensorimotor rhythms (mu, beta and gamma) and movement‐related cortical potentials (MRCPs) are both generated principally by the contralateral sensorimotor areas during the execution of self‐paced movement. They appear to reflect movement control mechanisms, which remain partially unclear. With the aim of better understanding their sources and significance, we recorded MRCPs and sensorimotor rhythms during and after self‐paced movement using intracerebral electrodes in eight epileptic subjects investigated by stereoelectroencephalography. The results showed that: (i) there is a strong spatial relationship between the late components of movement − the so‐called motor potential (MP) and post‐movement complex (PMc) – and gamma event‐related synchronization (ERS) within the 40–60 Hz band, as the MP/PMc always occurred in contacts displaying gamma ERS (the primary sensorimotor areas), whereas mu and beta reactivities were more diffuse; and (ii) MPs and PMc are both generated by the primary motor and somatosensory areas, but with distinct sources. Hence, this could mean that kinesthesic sensory afferences project to neurons other than those firing during the pyramidal tract volley. The PMc and low gamma ERS represent two electrophysiological facets of kinesthesic feedback from the joints and muscles involved in the movement to the sensorimotor cortex. It could be suggested that gamma oscillations within the 40–60 Hz band could serve to synchronize the activities of the various neuronal populations involved in control of the ongoing movement.
Molecular characterization of adult mouse subventricular zone progenitor cells during the onset of differentiation
Authors: Bonnert Timothy P. , Bilsland James G. , Guest Paul C. , Heavens Robert , McLaren Donna , Dale Charlotte , Thakur Matthew , McAllister George , Munoz‐Sanjuan Ignacio
Published: August 2006

Adult mouse subventricular zone (SVZ) neural progenitor cells (NPCs) retain the capacity to generate multiple lineages in vitro and in vivo. Thus far, the mechanisms involved in the regulation of these cells have not been well elucidated. We have carried out RNA profiling of adult SVZ cell cultures undergoing differentiation, to identify pathways that regulate progenitor cell proliferation and to define a set of transcripts that can be used as molecular tools in the drug discovery process. We carried out a stepwise stratification of the results to identify transcripts specifically enriched in NPCs and validated some of these using comparative literature analysis, quantitative polymerase chain reaction and immunological techniques. The results show a set of transcription factors, secreted molecules and plasma membrane markers that are differentially regulated during differentiation. Pathway analysis highlights alterations in insulin growth factor, Wnt and transforming growth factor β signalling cascades. Further characterization of these components could provide greater insight into the mechanisms involved in the regulation of neurogenesis in the adult brain.
Distribution of TRPC1 receptors in dendrites of rat substantia nigra: a confocal and electron microscopy study
Authors: Martorana Alessandro , Giampà Carmela , DeMarch Zena , Viscomi Maria Teresa , Patassini Stefano , Sancesario Giuseppe , Bernardi Giorgio , Fusco Francesca R.
Published: August 2006

Transient receptor potential channels (TRPC) are plasma membrane, non‐selective cationic channels and have been proposed as candidates involved in the regulation of cellular Ca2+ influx. The expression, at mRNA level, of several TRPCs has been demonstrated recently in dopaminergic neurons of the substantia nigra (SN). The aim of the present study was to characterize the expression of TRPC1, at a protein level, in the substantia nigra neurons and non‐excitable cells of Wistar rats. Single‐label immunohistochemistry and double‐label immunofluorescence were used to study the expression of TRPC1 among substantia nigra dopamine neurons and cellular processes using antibodies against tyrosine hydroxylase (TH), substance P (SP), enkephalin, synaptophysin, vesicular glutamate transporter‐2 (Vglut‐2), microtubule associated protein‐2 and metabotropic glutamate receptor 1 (mGluR1). Moreover, the ultrastructural localization of TRPC1 was investigated by means of electron microscopy. A set of dual label experiments was also performed to investigate the presence of TRPC1 among glial cells. Our results showed that TRPC1 is localized mainly in dendritic processes of dopamine neurons, whereas a relatively small percentage of neuronal somata display a light TRPC1 immunoreactivity. Such results were confirmed by our electron microscopy observations. Our study demonstrates, for the first time, a coexpression of TRPC1 and mGluR1 receptors in dendrites of the substantia nigra dopaminergic neurons. Such observation reinforces the concept of an involvement of TRPC1 in mGluR1‐mediated excitatory inputs in rat dopamine neurons.
Early neural activity and dendritic growth in turtle retinal ganglion cells
Authors: Mehta Vandana , Sernagor Evelyne
Published: August 2006

Early neural activity, both prenatal spontaneous bursts and early visual experience, is believed to be important for dendritic proliferation and for the maturation of neural circuitry in the developing retina. In this study, we have investigated the possible role of early neural activity in shaping developing turtle retinal ganglion cell (RGC) dendritic arbors. RGCs were back‐labelled from the optic nerve with horseradish peroxidase (HRP). Changes in dendritic growth patterns were examined across development and following chronic blockade or modification of spontaneous activity and/or visual experience. Dendrites reach peak proliferation at embryonic stage 25 (S25, one week before hatching), followed by pruning in large field RGCs around the time of hatching. When spontaneous activity is chronically blocked in vivo from early embryonic stages (S22) with curare, a cholinergic nicotinic antagonist, RGC dendritic growth is inhibited. On the other hand, enhancement of spontaneous activity by dark‐rearing (Sernagor & Grzywacz (1996)Curr. Biol., 6, 1503–1508) promotes dendritic proliferation in large‐field RGCs, an effect that is counteracted by exposure to curare from hatching. We also recorded spontaneous activity from individual RGCs labelled with lucifer yellow (LY). We found a tendency of RGCs with large dendritic fields to be spontaneously more active than small‐field cells. From all these observations, we conclude that immature spontaneous activity promotes dendritic growth in developing RGCs.
FGF‐2‐induced cell proliferation stimulates anatomical, neurophysiological and functional recovery from neonatal motor cortex injury
Authors: Monfils Marie‐H. , Driscoll Ira , Kamitakahara Holly , Wilson Brett , Flynn Corey , Teskey G. Campbell , Kleim Jeffrey A. , Kolb Bryan
Published: August 2006

Infant rats treated with basic fibroblast growth factor‐2 (FGF‐2) after postnatal day (P)10 motor cortical injury, show functional improvement in adulthood relative to those that do not receive FGF‐2. In this study we used a combination of behavioural, immunohistochemical, electrophysiological, electron microscopic and teratological approaches to investigate possible mechanisms by which FGF‐2 may influence functional recovery. We show that subcutaneous injections of FGF‐2 following bilateral lesions to the motor cortex at P10 in the rat leads to filling of the lesion area with migrating neuroblasts and cycling cells. We assessed the functionality of this tissue in adulthood, and show that cells from the filled region spontaneously fire and form synapses. Behavioural analysis shows enhanced motor performance in the FGF‐2‐treated lesion rats in comparison to vehicle‐treated lesion rats, and this improvement is reversed by removal of the tissue from the previously lesioned area or by blocking cortical regeneration by embryonic treatment with bromodeoxyuridine (BrdU). The results show that FGF‐2 stimulates filling of the lesion cavity with cells after neonatal motor cortex lesions, that the new tissue has anatomical and physiological properties similar to control tissue, and that the filled region supports motor behaviour.
Decision‐making and Weber's law: a neurophysiological model
Authors: Deco Gustavo , Rolls Edmund T.
Published: August 2006

We describe an integrate‐and‐fire attractor model of the decision‐related activity of ventral premotor cortex (VPC) neurons during a vibrotactile frequency comparison task [Romo et al. (2004)Neuron, 41, 165–173]. Populations of neurons for each decision in a biased competition attractor network receive a bias input that depends on the firing rates of VPC neurons that code for the two vibrotactile frequencies. The firing rate of the neurons in whichever attractor wins, reflects the sign of the difference in the frequencies (Δf) being compared but not the absolute frequencies. However, the transition from the initial spontaneous firing state to one of the two possible attractor states depends probabilistically on the difference of the vibrotactile frequencies scaled by the base frequency. This is due to finite size noise effects related to the spiking activity in the network, and the divisive feedback inhibition implemented through inhibitory interneurons. Thus the neurophysiological basis for a psychophysical effect, Weber's Law, can be related to statistical fluctuations and divisive inhibition in an attractor decision‐making network.
Multisensory integration in the basal ganglia
Authors: Nagy Attila , Eördegh Gabriella , Paróczy Zsuzsanna , Márkus Zita , Benedek György
Published: August 2006

Sensorimotor co‐ordination in mammals is achieved predominantly via the activity of the basal ganglia. To investigate the underlying multisensory information processing, we recorded the neuronal responses in the caudate nucleus (CN) and substantia nigra (SN) of anaesthetized cats to visual, auditory or somatosensory stimulation alone and also to their combinations, i.e. multisensory stimuli. The main goal of the study was to ascertain whether multisensory information provides more information to the neurons than do the individual sensory components. A majority of the investigated SN and CN multisensory units exhibited significant cross–modal interactions. The multisensory response enhancements were either additive or superadditive; multisensory response depressions were also detected. CN and SN cells with facilitatory and inhibitory interactions were found in each multisensory combination. The strengths of the multisensory interactions did not differ in the two structures. A significant inverse correlation was found between the strengths of the best unimodal responses and the magnitudes of the multisensory response enhancements, i.e. the neurons with the weakest net unimodal responses exhibited the strongest enhancement effects. The onset latencies of the responses of the integrative CN and SN neurons to the multisensory stimuli were significantly shorter than those to the unimodal stimuli. These results provide evidence that the multisensory CN and SN neurons, similarly to those in the superior colliculus and related structures, have the ability to integrate multisensory information. Multisensory integration may help in the effective processing of sensory events and the changes in the environment during motor actions controlled by the basal ganglia.
Selective dopaminergic lesions of the ventral tegmental area impair preference for sucrose but not for male sexual pheromones in female mice
Authors: Martínez‐Hernández José , Lanuza Enrique , Martínez‐García Fernando
Published: August 2006

The role of the meso‐accumbens dopaminergic pathway in reward‐related behaviours is the subject of intense investigation. In this regard, here we analyse the effects of specific lesions of dopaminergic cells of the ventral tegmental area (VTA) of female mice on two goal‐directed behaviours, namely sucrose preference (intake of sucrose solution vs. water) and preference for male sexual pheromones (exploration of male‐soiled vs. clean bedding). The results indicate that partial lesions of the VTA that impair neither locomotion nor general exploratory behaviour reduce the preference for sucrose (over a 48‐h period) but do not alter the innate attraction that females display for male sexual pheromones (in 5‐min tests). This differential effect of the lesions can be interpreted as demonstrating the existence of separate neural mechanisms and circuits for signalling the reward of different natural reinforcers (e.g. sweet taste of sucrose and sexual pheromones). Alternatively, VTA lesions may result in an impaired attribution of incentive salience (which depends on the dopaminergic tegmento‐striatal system) of sucrose‐predicting cues, thus leading to a long‐term decrease in sucrose consumption. By contrast, the same lesions do not affect the unconditioned attraction to male‐derived pheromones, which may depend on amygdalo‐striatal pathways.
Differential down‐regulation of voltage‐gated calcium channel currents by glutamate and BDNF in embryonic cortical neurons
Authors: Bouron Alexandre , Boisseau Sylvie , De Waard Michel , Peris Leticia
Published: August 2006

In the embryonic brain, post‐mitotic cortical neurons migrate from their place of origin to their final location. Various external factors such as hormones, neurotransmitters or peptides regulate their migration. To date, however, only a few studies have investigated the effects of these external factors on the electrical properties of the newly formed embryonic cortical neurons. The aim of the present study was to determine whether glutamate and brain‐derived neurotrophic factor (BDNF), known to regulate neuronal cell migration, could modulate currents through voltage‐gated calcium channels (ICa) in cortical neurons isolated from embryonic day 13 (E13) mouse foetuses. Whole cell recordings of ICa showed that E13 cortical cells kept 1 day in vitro expressed functional low‐ and high‐voltage activated (LVA and HVA) Ca2+ channels of T‐, L‐ and N‐types. A 1‐day glutamate treatment non‐specifically inhibited LVA and HVA ICa whereas BDNF down‐regulated HVA with N‐type ICa being more depressed than L‐type ICa. The glutamate‐induced ICa inhibition was mimicked by NMDA. BDNF exerted its action by recruiting trkB receptors and SKF‐96365‐sensitive channels. BAPTA prevented the glutamate‐ and the BDNF‐dependent inhibition of Ica, indicating a Ca2+‐dependent mechanism of action. It is proposed that an influx of Ca2+ through NMDA receptors depresses the expression of LVA and HVA Ca2+ channels whereas a Ca2+ influx through SKF‐96365‐sensitive TRPC (transient receptor potential protein of C subtype) channels preferentially inhibits the expression of HVA Ca2+ channels. Glutamate and BDNF appear as potent modulators of the electrical properties of early post‐mitotic neurons. By down‐regulating ICa they could exert a neuroprotective action on embryonic cortical neurons.
Role of the synprint site in presynaptic targeting of the calcium channel CaV2.2 in hippocampal neurons
Authors: Szabo Zsolt , Obermair Gerald J. , Cooper Conan B. , Zamponi Gerald W. , Flucher Bernhard E.
Published: August 2006

Sequences in the cytoplasmic II–III loop of CaV2 voltage‐gated calcium channels, termed the synaptic protein interaction (synprint) site, are considered important for the functional incorporation of presynaptic calcium channels into the synaptic vesicle fusion apparatus. Two novel CaV2.2 splice variants lack large parts of the cytoplasmic II‐III loop (Δ1 R756‐L1139, Δ2 K737‐A1001) including the synprint protein–protein interaction domain. Here we expressed green fluorescent protein (GFP)‐α1B subunit fusion constructs of CaV2.2 splice variants in mouse hippocampal neurons to study their distribution in distinct neuronal compartments and to address the question of whether and how the synprint site functions in the presynaptic targeting of N‐type calcium channels. Similar to full‐length GFP‐α1B but divergent from the somatodendritic α1C‐HA (CaV1.2) channel type, the splice variants GFP‐α1B‐Δ1 and GFP‐α1B‐Δ2 were targeted into the axons. Nevertheless, their ability to form bona fide presynaptic clusters was almost abolished for GFP‐α1B‐Δ1 and significantly reduced for GFP‐α1B‐Δ2. Thus, the synprint site is important for normal synaptic targeting of CaV2.2 but not essential. Conversely, insertion of the synprint site into the II–III loop of α1C‐HA did not restore axonal targeting or synaptic clustering. Together these results indicate that protein–protein interactions with the synprint site must cooperate with other targeting mechanisms in the incorporation of CaV2.2 into presynaptic specializations of hippocampal neurons but are neither necessary nor sufficient for axonal targeting. The unique targeting properties of the splice variants lacking the synprint site are suggestive of specific functions of these calcium channels apart from activating fast synaptic transmission.
5‐HT4 receptor activation induces long‐lasting EPSP‐spike potentiation in CA1 pyramidal neurons
Authors: Mlinar Boris , Mascalchi Simona , Mannaioni Guido , Morini Raffaella , Corradetti Renato
Published: August 2006

Recent studies implicated involvement of the 5‐hydroxytryptamine4(5‐HT4) receptor in cognitive and emotional processes. The highest 5‐HT4 receptor densities in the brain are found in the limbic system including the hippocampus. Here we used the selective 5‐HT4 receptor full agonist,N‐pentyl‐N′‐aminoguanidine carbazimidamide (SDZ‐216454) to characterize effects of 5‐HT4 receptor activation in whole‐cell and field recordings in the area CA1 in hippocampal slices prepared from 3 to 4‐ and 6 to 9‐week‐old rats, respectively. Extracellular recordings showed that transient 5‐HT4 receptor activation by 10–20 min application of SDZ‐216454 induces field excitatory postsynaptic potential (fEPSP)‐population spike potentiation (ESP5‐HT4), which persisted for as long as we held the recordings (> 2 h). ESP5‐HT4displayed characteristics different from EPSP‐spike potentiation that accompanies long‐term potentiation; it developed without an associated increase in synaptic transmission, was independent on afferent input, activity of postsynaptic neurons andN‐methyl‐d‐aspartate receptor activation; and was expressed in the presence of GABA receptor antagonists. ESP5‐HT4was also induced by transient application of the natural neurotransmitter, 5‐HT. The increase in the evoked population spike (PS) induced by SDZ‐216454 was not prevented by blockers of hyperpolarization‐activated cation current (Ih), Cs+and ZD‐7288, but was mimicked and occluded by 150 µmBa2+. Whole‐cell voltage‐clamp recordings from pyramidal neurons demonstrated that SDZ‐216454 application increases membrane resistance with a concomitant decrease in a Ba2+‐sensitive inwardly rectifying K+current and the Ba2+‐insensitive K+current underlying slow afterhyperpolarization (IsAHP). We conclude that 5‐HT4 receptor activation may cause a long‐lasting excitability increase in CA1 pyramidal neurons by inhibition of a Ba2+‐sensitive inwardly rectifying K+current.
Distinct expression of Cbln family mRNAs in developing and adult mouse brains
Authors: Miura Eriko , Iijima Takatoshi , Yuzaki Michisuke , Watanabe Masahiko
Published: August 2006

Cbln1 belongs to the C1q and tumour necrosis factor superfamily, and plays crucial roles as a cerebellar granule cell‐derived transneuronal regulator for synapse integrity and plasticity in Purkinje cells. Although Cbln2–Cbln4 are also expressed in the brain and could form heteromeric complexes with Cbln1, their precise expressions remain unclear. Here, we investigated gene expression of the Cbln family in developing and adult C57BL mouse brains by reverse transcriptase‐polymerase chain reaction (RT‐PCR), Northern blot, and high‐resolution in situ hybridization (ISH) analyses. In the adult brain, spatial patterns of mRNA expression were highly differential depending on Cbln subtypes. Notably, particularly high levels of Cbln mRNAs were expressed in some nuclei and neurons, whereas their postsynaptic targets often lacked or were low for any Cbln mRNAs, as seen for cerebellar granule cells/Purkinje cells, entorhinal cortex/hippocampus, intralaminar group of thalamic nuclei/caudate‐putamen, and dorsal nucleus of the lateral lemniscus/central nucleus of the inferior colliculus. In the developing brain, Cbln1, 2, and 4 mRNAs appeared as early as embryonic day 10–13, and exhibited transient up‐regulation during the late embryonic and neonatal periods. For example, Cbln2 mRNA was expressed in the cortical plate of the developing neocortex, displaying a high rostromedial to low caudolateral gradient. In contrast, Cbln3 mRNA was selective to cerebellar granule cells throughout development, and its onset was as late as postnatal day 7–10. These results will provide a molecular‐anatomical basis for future studies that characterize roles played by the Cbln family.
Impaired behavioural and molecular adaptations to dopamine denervation and repeated L‐DOPA treatment in Nur77‐knockout mice
Authors: St‐Hilaire Michel , Bourhis Emmanuelle , Lévesque Daniel , Rouillard Claude
Published: August 2006

We have previously shown that dopamine (DA) denervation and repeated L‐DOPA treatment modulate the pattern of Nur77 mRNA expression in the striatum. However, the exact role of this nuclear receptor in L‐DOPA‐induced molecular and behavioural adaptations observed in animal models of Parkinson's disease is still unknown. In the present study, we investigated the effects of Nur77 gene deletion on the development of behavioural sensitization and on changes in the regulation of neuropeptides and DA D3 receptor expression following DA denervation and repeated L‐DOPA treatment in Nur77+/+ and Nur77–/– hemiparkinsonian mice. One week postsurgery, hemiparkinsonian mice were treated with L‐DOPA (10 mg/kg) plus benserazide (3 mg/kg) once a day for 7 days. Despite similar extents of nigrostriatal denervation, L‐DOPA‐induced rotational response was exacerbated in Nur77–/– mice compared to Nur77+/+ ones. However, the rate of increase of the rotational behaviour after repeated L‐DOPA injections was similar in the two mouse strains. Lesioning the nigrostriatal pathway increased enkephalin (ENK) and neurotensin (NT) mRNA levels in both mouse strains. However, the up‐regulation of these neuropeptides was significantly reduced in Nur77–/– mice. There was no difference in the modulation of D3 receptor density and dynorphin (DYN) mRNA expression between the two mouse strains. The present results suggest that Nur77 is involved in setting the threshold level for L‐DOPA‐induced rotational behaviour, rather than controlling the development of behavioural sensitization. This specific behavioural change is associated with a selective regulation of neuropeptide expression specifically in the indirect striatal output pathway.
Lactosamine modulates the rate of migration of GnRH neurons during mouse development
Authors: Bless Elizabeth , Raitcheva Denitza , Henion Timothy R. , Tobet Stuart , Schwarting Gerald A.
Published: August 2006

Gonadotropin‐releasing hormone (GnRH) neurons are derived from progenitor cells in the olfactory placodes and migrate from the vomeronasal organ (VNO) across the cribriform plate into the forebrain. At embryonic day (E)12 in the mouse most of these neurons are still in the nasal compartment but by E15 most GnRH neurons have migrated into the forebrain. Glycoconjugates with carbohydrate chains containing terminal lactosamine are expressed by neurons in the main olfactory epithelium and in the VNO. One of the key enzymes required to regulate the synthesis and expression of lactosamine, β1,3‐N‐acetylglucosaminyltransferase‐1 (β3GnT1), is strongly expressed by neurons in the olfactory epithelium and VNO, and on neurons migrating out of the VNO along the GnRH migratory pathway. Immunocytochemical analysis of lactosamine and GnRH in embryonic mice reveals that the percentage of lactosamine+–GnRH+ double‐labeled neurons decreases from > 80% at E13, when migration is near its peak, to ∼ 30% at E18.5, when most neurons have stopped migrating. In β3GnT1–/– mice, there is a partial loss of lactosamine expression on GnRH neurons. Additionally, a greater number of GnRH neurons were retained in the nasal compartment of null mice at E15 while fewer GnRH neurons were detected later in embryonic development in the ventral forebrain. These results suggest that the loss of lactosamine on a subset of GnRH neurons impeded the rate of migration from the nose to the brain.
Effects of expectation on amygdala‐kindled convulsions and interictal behaviour in rats: confirmation of a Pavlovian mechanism
Authors: Barnes Steven J. , Pinel John P. J. , Wee Ellisa , Archambault Jason , Ailon Tamir
Published: August 2006

We found evidence that the effects of exposure to the stimulation environment on the convulsions and interictal behaviour of basolateral amygdala (BA)‐kindled rats are the result of Pavlovian conditioning. In Experiment 1, the rats first received 45 BA stimuli in one environment (CS+) and 45 sham stimuli in another environment (CS–). During this first phase of the experiment, the CS+ and CS– began to exert differential effects on interictal behaviour and convulsions. Then, during the second phase, rats received 45 stimuli and 45 sham stimuli, either as before in their original CS+ and CS– (nonreversal rats) or with their original CS+ and CS– interchanged (reversal rats). During the second phase, the CS+ and CS– continued to exert the same pattern of differential effects on the interictal behaviour and convulsions of the nonreversal rats, whereas the reversal rats began to display the reverse pattern. In Experiment 2, rats received 60 sham stimuli in one environment (CS1). Then, half of the rats received 30 stimuli in a second environment (CS2) and 30 sham stimuli in CS1 (no‐pre‐exposure rats), whereas the other half (pre‐exposure rats) received 30 stimuli and 30 sham stimuli in CS1. Pre‐exposure to the stimulation environment attenuated the kindled convulsions. These findings confirm that the conditioned effects of kindling are mediated by a Pavlovian mechanism.
Electroconvulsive seizure increases adult hippocampal angiogenesis in rats
Authors: Newton Samuel S. , Girgenti Matthew J. , Collier Emily F. , Duman Ronald S.
Published: August 2006

Electroconvulsive seizure has a proven therapeutic application in the treatment of severe depression and treatment‐resistant depression. Despite the efficacy of electroconvulsive seizure as a non‐chemical antidepressant treatment, the mechanism of action is unclear. Elevation in hippocampal trophic factor expression and concomitant cellular proliferation are thought to play a role in its action. We examined whether the reported induction of angiogenic factors and endothelial cell proliferation leads to an increase in vascular density. Two hippocampal regions, the dentate gyrus and the stratum lacunosum moleculare (SLM), were examined employing a combination of vascular density quantification, angiogenic gene expression analysis and immunohistochemistry. A 6% increase in vascular density was observed in the dentate gyrus but this did not achieve statistical significance. The SLM of the hippocampus exhibited a robust 20–30% increase in vascular density and was accompanied by an increase in expression of inhibitor of differentiation‐3. There was also an induction of the angiogenesis markers αVβ3 integrin and Del1. Increases in the vascular density of the SLM could be in response to enhanced metabolic activity in this region. This is supported by the induction of glutamine synthetase and the glutamate transporter GLT1.
Cross‐modal plasticity of the motor cortex while listening to a rehearsed musical piece
Authors: D'Ausilio A. , Altenmüller E. , Olivetti Belardinelli M. , Lotze M.
Published: August 2006

Learning a musical piece requires the development of a strong linkage between sensory and motor representations. Audition plays a central role and a tight cortical auditory–motor corepresentation is a characteristic feature of music processing. Recent works have indicated the establishment of a functional connection between auditory and motor cortices during the learning of a novel piece, although no causal relation has yet been demonstrated. Here transcranial magnetic stimulation of the cortical motor representation involved in musical performance was used to test excitability changes in piano players during auditory presentation of a rehearsed and a non‐rehearsed piece. Results showed an increased motor excitability for the rehearsed but not for the non‐rehearsed piece. Moreover, we observed an increase of excitability over time as intracortical facilitation was already present after 30 min of training whereas cortico‐spinal facilitation increased after a longer training period (5 days).
Healthy‐side dominance of middle‐ and long‐latency neuromagnetic fields in idiopathic sudden sensorineural hearing loss
Authors: Li L. P. H. , Shiao A. S. , Chen L. F. , Niddam D. M. , Chang S. Y. , Lien C. F. , Lee S. K. , Hsieh J. C.
Published: August 2006

Any lesion along the neural axis may induce a subsequent functional reorganization at the level above. The present study used magnetoencephalography to investigate auditory‐evoked magnetic fields [a component of the middle‐latency auditory evoked fields peaking at ~50 ms (P50m) and a component of the long‐latency auditory evoked fields peaking at ~100 ms (N100m)] on stimulation of both healthy and affected ears in patients with acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) of moderate degree in order to elucidate the functional plasticity of the auditory system. Sixteen right‐handed, previously untreated adult patients with acute unilateral left (n = 8) or right (n = 8) ISSNHL of moderate degree were studied. Sixteen right‐handed healthy volunteers with normal hearing served as control. Auditory neuromagnetic responses, measured by a whole‐head 306‐channel neuromagnetometer, were detected by monaural tone stimulation applied to affected and healthy ears, respectively, in different sessions. Intragroup and intergroup interhemispheric differences of peak dipole strengths and latencies of P50m and N100m, respectively, to monaural tones were evaluated. Healthy‐side amplitude dominance of both P50m and N100m was found in ISSNHL, i.e. contralateral dominance was preserved on affected‐ear stimulation but ipsilateral dominance was seen on healthy‐ear stimulation. The phenomena could be attributed to the combined contralateral attenuation and ipsilateral enhancement of P50m and N100m activity in response to healthy‐ear stimulation. Our findings confirmed that functional modulation can occur within the first few tens of milliseconds of evoked response at the auditory cortex in ISSNHL. The mechanisms of healthy‐side dominance might be ascribed to a functional retune of auditory pathways, i.e. conjoined contralateral inhibition and ipsilateral excitation of the auditory pathway in response to healthy‐ear stimulation. The effect could be registered in cortical responses.
Associative Pavlovian conditioning leads to an increase in spinophilin‐immunoreactive dendritic spines in the lateral amygdala
Authors: Radley Jason J. , Johnson Luke R. , Janssen William G. M. , Martino Jeremiah , Lamprecht Raphael , Hof Patrick R. , LeDoux Joseph E. , Morrison John H.
Published: August 2006

Changes in dendritic spine number and shape are believed to reflect structural plasticity consequent to learning. Previous studies have strongly suggested that the dorsal subnucleus of the lateral amygdala is an important site of physiological plasticity in Pavlovian fear conditioning. In the present study, we examined the effect of auditory fear conditioning on dendritic spine numbers in the dorsal subnucleus of the lateral amygdala using an immunolabelling procedure to visualize the spine‐associated protein spinophilin. Associatively conditioned rats that received paired tone and shock presentations had 35% more total spinophilin‐immunoreactive spines than animals that had unpaired stimulation, consistent with the idea that changes in the number of dendritic spines occur during learning and account in part for memory.
Laminin and growth factor receptor activation stimulates differential growth responses in subpopulations of adult DRG neurons
Authors: Tucker Budd A. , Rahimtula Masuma , Mearow Karen M.
Published: August 2006

Neurons in the adult rat dorsal root ganglion (DRG) can be classified into at least three separate subpopulations based on morphologic and phenotypic differences. In this study we have focused on the growth response of these specific subpopulations in vitro with respect to laminin (LN) and growth factor receptor activation. Using a cell selection approach we show that LN‐induced neurite growth occurs in the absence of added trophic factors only in heavy‐chain neurofilament‐positive and calcitonin gene‐related peptide‐positive DRG neurons [nerve growth factor (NGF)‐responsive population]. In contrast, LN alone is not sufficient to stimulate significant neurite growth from lectin Griffonia simplicifolia IB4‐positive neurons (IB4+ve), although it is still required to elicit a growth response from these cells in the presence of glial‐derived neurotrophic factor (GDNF, e.g. neurite growth occurred only when cells were plated on LN in the presence of GDNF). By using chemical inhibitors we demonstrate that only the phosphatidylinositol 3 kinase (PI 3‐K)/Akt pathway is required for neurite growth from the NGF‐responsive cell population. However, both the PI 3‐K/Akt and MEK/mitogen‐activated protein kinase signaling pathways are required for neurite growth from the IB4+ve cell population. Thus, we have identified specific signaling events and environmental requirements associated with neurite growth for different subpopulations of adult DRG neurons, pointing to potential therapeutic targets while identifying an inability for any one treatment alone to repair peripheral nerve damage.
Neural correlates of memory retrieval in the prefrontal cortex
Authors: Nácher Verónica , Ojeda Sabiela , Cadarso‐Suárez Carmen , Roca‐Pardiñas Javier , Acuña Carlos
Published: August 2006

Working memory includes short‐term representations of information that were recently experienced or retrieved from long‐term representations of sensory stimuli. Evidence is presented here that working memory activates the same dorsolateral prefrontal cortex neurons that: (a) maintained recently perceived visual stimuli; and (b) retrieved visual stimuli from long‐term memory (LTM). Single neuron activity was recorded in the dorsolateral prefrontal cortex while trained monkeys discriminated between two orientated lines shown sequentially, separated by a fixed interstimulus interval. This visual task required the monkey to compare the orientation of the second line with the memory trace of the first and to decide the relative orientation of the second. When the behavioural task required the monkey to maintain in working memory a first stimulus that continually changed from trial to trial, the discharge in these cells was related to the parameters − the orientation − of the memorized item. Then, what the monkey had to recall from memory was manipulated by switching to another task in which the first stimulus was not shown, and had to be retrieved from LTM. The discharge rates of the same neurons also varied depending on the parameters of the memorized stimuli, and their response was progressively delayed as the monkey performed the task. These results suggest that working memory activates dorsolateral prefrontal cortex neurons that maintain parametrical visual information in short‐term and LTM, and that the contents of working memory cannot be limited to what has recently happened in the sensory environment.
A thalamo‐cortico‐amygdala pathway mediates auditory fear conditioning in the intact brain
Authors: Boatman Jeffrey A. , Kim Jeansok J.
Published: August 2006

The neural substrates of fear conditioning in rats have been well characterized, with converging lines of evidence indicating that conditioned stimulus (CS) and unconditioned stimulus (US) information form a CS–US association in the amygdala. Auditory CS information can reach the amygdala via two routes: a direct thalamo‐amygdala pathway, and an indirect thalamo‐cortico‐amygdala pathway. Although either pathway can fully support learning when the alternate pathway is disrupted, many studies to date have argued that the thalamo‐amygdala pathway is the principal auditory CS pathway in intact brains. To test this hypothesis, we trained rats in auditory fear conditioning, and 24 h later lesioned either pathway, leaving the alternate pathway intact. Later, animals were tested for conditioned freezing to the auditory CS. We report that lesions of the thalamo‐amygdala pathway produced severe but incomplete deficits in freezing during the tone retention test, while lesions of the thalamo‐cortico‐amygdala pathway completely abolished freezing during tone presentation. These results suggest that the thalamo‐cortico‐amygdala pathway is the principal auditory CS pathway when the brain is intact.
Local and descending circuits regulate long‐term potentiation and zif268 expression in spinal neurons
Authors: Rygh Lars Jørgen , Suzuki Rie , Rahman Wahida , Wong Yuk , Vonsy Jean Laurent , Sandhu Hardip , Webber Mark , Hunt Stephen , Dickenson Anthony H.
Published: August 2006

Long‐term potentiation (LTP), a use dependent long‐lasting modification of synaptic strength, was first discovered in the hippocampus and later shown to occur in sensory areas of the spinal cord. Here we demonstrate that spinal LTP requires the activation of a subset of superficial spinal dorsal horn neurons expressing the neurokinin‐1 receptor (NK1‐R) that have previously been shown to mediate certain forms of hyperalgesia. These neurons participate in local spinal sensory processing, but are also the origin of a spino‐bulbo‐spinal loop driving a 5‐hydroxytryptamine 3 receptor (5HT3‐R)‐ mediated descending facilitation of spinal pain processing. Using a saporin‐substance P conjugate to produce site‐specific neuronal ablation, we demonstrate that NK1‐R expressing cells in the superficial dorsal horn are crucial for the generation of LTP‐like changes in neuronal excitability in deep dorsal horn neurons and this is modulated by descending 5HT3‐R‐mediated facilitatory controls. Hippocampal LTP is associated with early expression of the immediate‐early gene zif268 and knockout of the gene leads to deficits in long‐term LTP and learning and memory. We found that spinal LTP is also correlated with increased neuronal expression of zif268 in the superficial dorsal horn and that zif268 antisense treatment resulted in deficits in the long‐term maintenance of inflammatory hyperalgesia. Our results support the suggestion that the generation of LTP in dorsal horn neurons following peripheral injury may be one mechanism whereby acute pain can be transformed into a long‐term pain state.
Cocaine‐induced locomotor activity and Fos expression in nucleus accumbens are sensitized for 6 months after repeated cocaine administration outside the home cage
Authors: Hope Bruce T. , Simmons Danielle E. , Mitchell Tim B. , Kreuter Justin D. , Mattson Brandi J.
Published: August 2006

Induction of the immediate early gene protein product Fos has been used extensively to assess neural activation in the striatum after repeated cocaine administration to rats in their home cages but rarely after repeated administration outside the home cage, which produces more robust locomotor sensitization. In the present study, we found cocaine‐induced Fos expression in nucleus accumbens, but not caudate‐putamen, was enhanced 1 and 6 months after repeated drug administration in locomotor activity chambers. Double‐labelling of Fos protein and enkephalin mRNA indicated that Fos expression in nucleus accumbens was enhanced in enkephalin‐positive, but not enkephalin‐negative, medium spiny neurons. In contrast, cocaine‐induced Fos expression was absent altogether in nucleus accumbens and unaltered in caudate‐putamen 1 month after repeated cocaine administration in the home cage. As cocaine‐induced locomotor activity was also enhanced 1 and 6 months after repeated cocaine administration in locomotor activity chambers, we wanted to confirm that neuronal activity in nucleus accumbens mediates cocaine‐induced locomotor activity using our particular treatment regimen. Bilateral infusions of the GABA agonists baclofen and muscimol (1 µg/side) into nucleus accumbens of sensitized rats blocked cocaine‐induced Fos expression and locomotor activity. Thus, while neuronal activity in both D1‐ and D2‐type neurons in nucleus accumbens can mediate acute cocaine‐induced locomotor activity, the enhanced activation of enkephalinergic D2‐type neurons suggests that these latter neurons mediate the enhancement of cocaine‐induced locomotor activity for up to 6 months after repeated drug administration outside the home cage.
Genetic or pharmacological inactivation of the dopamine D1 receptor differentially alters the expression of regulator of G‐protein signalling (Rgs) transcripts
Authors: Stanwood Gregg D. , Parlaman Joshua P. , Levitt Pat
Published: August 2006

Dysregulation of dopamine (DA) receptor signalling induces specific changes in behaviour, neuronal circuitry and gene expression in the mammalian forebrain. In order to better understand signalling adaptations at the molecular level, we used high‐density oligonucleotide microarrays (Codelink Mouse 20K) to define alterations in the expression of transcripts encoding regulator of G‐protein coupled receptor signalling in dopamine D1 receptor knockout mice (Drd1a‐KO). Regulator of G‐protein signalling (Rgs) 2, Rgs4, and Rgs9 were significantly decreased in the striatum (STR) of Drd1a‐KO mice. These changes were confirmed by in situ hybridization, and were also observed in the nucleus accumbens (NAc). In contrast, analysis of the medial frontal cortex (MFC) revealed a significant decrease in Rgs17 expression exclusively, and a modest up‐regulation of Rgs5 transcript. The expression of these gene products were not significantly altered in the dopamine‐poor visual cortex (VC). The Drd1a‐KO mouse, and a rabbit model of in utero cocaine exposure, in which D1R signalling is permanently reduced, possess analogous morphological and functional alterations in dopamine‐modulated brain circuits; thus we also examined long‐lasting changes in RGS transcript expression following prenatal exposure to cocaine. In sharp contrast to the Drd1a‐KO, Rgs2 and Rgs4 were unchanged, and Rgs9 and Rgs17 transcripts were increased in prenatal cocaine‐exposed progeny. These data suggest that an absolute absence of D1R signalling (Drd1a‐KO) and hypomorphic D1R signalling (prenatal cocaine) produce common alterations in neuronal morphology, but distinct outcomes in molecular neuroadaptations.
Receptive field structure–function correlates in developing turtle retinal ganglion cells
Authors: Mehta Vandana , Sernagor Evelyne
Published: August 2006

Mature retinal ganglion cells (RGCs) have distinct morphologies that often reflect specialized functional properties such as On and Off responses. But the structural correlates of many complex receptive field (RF) properties (e.g. responses to motion) remain to be deciphered. In this study, we have investigated whether motion anisotropies (non‐homogeneities) characteristic of embryonic turtle RGCs arise from immature dendritic arborization in these cells. To test this hypothesis, we have looked at structure–function correlates of developing turtle RGCs from Stage 23 (S23) when light responses emerge, until 15 weeks post‐hatching (PH). Using whole cell patch clamp recordings, RGCs were labelled with Lucifer Yellow (LY) while recording their responses to moving edges of light. Comparison of RF and dendritic arbor layouts revealed a weak correlation. To obtain a larger structural sample of developing RGCs, we have looked at dendritic morphology in RGCs retrogradely filled with the tracer horseradish peroxidase (HRP) from S22 (when RGCs become spontaneously active, shortly before they become sensitive to light) until two weeks PH. We found that there was intense dendritic growth from S22 onwards, reaching peak proliferation at S25 (a week before hatching), while RGCs are still exhibiting significant motion anisotropies. Based on these observations, we suggest that immature anisotropic RGC RFs must originate from sparse synaptic inputs onto RGCs rather than from the immaturity of their growing dendritic trees.
Pain management in fulminating ulcerative colitis
Authors: WHITE MICHELLE , SHAH NEIL , LINDLEY KEITH , LLOYD‐THOMAS ADRIAN , THOMAS MARK
Published: August 2006

Background:  Toxic megacolon is a life‐threatening complication of ulcerative colitis (UC) characterized by systemic toxicity, loss of blood per rectum and severe pain. Pain management is challenging in these patients because nonsteroidal anti‐inflammatory drugs may exacerbate bleeding and opioids are contraindicated because they adversely affect bowel peristalsis causing an increased risk of colonic perforation.

Methods:  We describe three episodes of fulminating UC in two children in whom ketamine analgesia was used. Our protocol for a low‐dose continuous ketamine infusion with either nurse‐controlled analgesia (NCA) or patient‐controlled analgesia (PCA) bolus administration is presented and a review of the literature regarding the use of ketamine analgesia in children is discussed.

Results:  Low‐dose ketamine N/PCA with a continuous background infusion provided satisfactory analgesia and none of our children reported adverse effects.

Conclusions:  We have demonstrated the safe and effective use of ketamine analgesia in children with toxic megacolon, a condition in which the child is in severe pain and morphine is contraindicated.
Prolonged use of dexmedetomidine in an infant with respiratory failure following living donor liver transplantation
Authors: ENOMOTO YUKI , KUDO TOYOICHIRO , SAITO TAKASHI , HORI TETSUO , KANEKO MICHIO , MATSUI AKIRA , MIZUTANI TARO
Published: August 2006

We used dexmedetomidine for more than 2 months in a mechanically ventilated infant without serious adverse effects. An infant with liver cirrhosis of unknown cause underwent living donor liver transplantation at the age of 9 months. Long‐term mechanical ventilation was required postoperatively, and midazolam with fentanyl had been used to sedate the patient. They required increase to 1.7 mg·kg−1·h−1 and 3.5 μg·kg−1·h−1, respectively, which were still inadequate. On postoperative day 29, dexmedetomidine was added. The rate of dexmedetomidine infusion was increased gradually to 1.4 μg·kg−1·h−1. It was discontinued temporarily to exclude drug‐induced liver dysfunction. However, without dexmedetomidine, adequate sedation level was unattainable. Liver dysfunction was likely to be attributed to cytomegalovirus infection and after restarting dexmedetomidine, the respiratory condition improved. He was extubated 10 weeks after the operation. Dexmedetomidine was successfully tapered off over the following 2 weeks with no signs of withdrawal. Dexmedetomidine was a useful sedative for an infant who required mechanical ventilation for a prolonged period of time.