bluuebunny/crossref_metadata_2025_split huggingface dataset:
The postnatal reorganization of primary afferent input and dorsal horn cell receptive fields in the rat spinal cord is an activity‐dependent process
Authors: Beggs Simon , Torsney Carole , Drew Liam J. , Fitzgerald Maria 
Published: March 2003

AbstractThe dorsal horn of the spinal cord in the newborn rat is characterized by large cutaneous mechanoreceptive fields, a predominance of A‐fibre synaptic inputs and diffuse primary afferent A‐fibre projections, all of which are gradually reduced and refined over the first postnatal weeks. This may be partly responsible for the reduction in cutaneous flexion reflex sensitivity of rats over the postnatal period. Here we show that chronic, local exposure of the dorsal horn of the lumbar spinal cord to the NMDA antagonist MK801 from birth prevents the normal functional and structural reorganization of A‐fibre connections. Dorsal horn cells in spinal MK801‐treated animals, investigated at eight weeks of age by in vivo electrophysiological recording, had significantly larger cutaneous mechanoreceptive fields and greater A‐fibre evoked responses than vehicle controls. C‐fibre evoked responses were unaffected. Chronic MK801 also prevented the normal structural reorganization of A‐fibre terminals in the spinal cord. The postnatal withdrawal of superficially projecting A‐fibre primary afferents to deeper laminae did not occur in treated animals although C‐fibre afferent terminals and cell density in the dorsal horn were apparently unaffected. Spinal MK801‐treated animals also had significantly reduced behavioural reflex thresholds to mechanical stimulation of the hindpaw compared to naïve and vehicle‐treated animals, whereas noxious heat thresholds remained unaffected. The results indicate that the normal postnatal structural and functional development of A‐fibre sensory connectivity within the spinal cord is an activity‐dependent process requiring NMDA receptor activation.
Characterization of the mouse adenylyl cyclase type VIII gene promoter: regulation by cAMP and CREB
Authors: Chao Jennifer R. , Ni Yan G. , Bolaños Carlos A. , Rahman Zia , DiLeone Ralph J. , Nestler Eric J. 
Published: March 2003

AbstractAdenylyl cyclase (AC) type VIII has been implicated in several forms of neural plasticity, including drug addiction and learning and memory. In the present study, we directly examined the role for the transcription factor CREB (cAMP response element binding protein) in regulating ACVIII expression by cloning a 5.2 kilobase region upstream of the translation start site of the mouse ACVIII gene. Analysis of this fragment revealed consensus elements for several transcription factors, including a canonical cAMP response element (CRE) in close proximity to the transcription initiation region. Next, ACVIII promoter activity was studied in two neural‐derived cell lines and in primary cultures of rat striatal neurons. Activation of the cAMP pathway by forskolin treatment increased promoter activity, and a series of deletion and point mutants demonstrated that this activation is mediated specifically via the canonical CRE site. Gel shift assays confirmed that this site can bind CREB and several CREB family proteins. Further, activation of the ACVIII promoter by forskolin was potentiated by expression of a constitutively active form of CREB, CREB‐VP16, whereas it was inhibited by expression of a dominant‐negative form of CREB, A‐CREB. Finally, over‐expression of CREB in vivo, by viral‐mediated gene transfer, induced ACVIII promoter activity in the brains of ACVIII‐LacZ transgenic mice. These results suggest that the ACVIII gene is regulated by CREB in vitro and in vivo and that this regulation may contribute to CREB‐dependent neural plasticity.
Neural correlates of the motivational and somatic components of naloxone‐precipitated morphine withdrawal
Authors: Frenois François , Cador Martine , Caillé Stéphanie , Stinus Luis , Le Moine Catherine 
Published: March 2003

AbstractIn morphine‐dependent rats, low naloxone doses have been shown to induce conditioned place aversion, which reflects the negative motivational component of opiate withdrawal. In contrast, higher naloxone doses are able to induce a ‘full’ withdrawal syndrome, including overt somatic signs. The c‐fos gene is commonly used as a marker of neuronal reactivity to map the neural substrates that are recruited by various stimuli. Using in situ hybridization, we have analysed in the brain of morphine‐dependent rats the effects of acute withdrawal syndrome precipitated by increasing naloxone doses on c‐fos mRNA expression. Morphine dependence was induced by subcutaneous implantation of slow‐release morphine pellets for 6 days and withdrawal was precipitated by increasing naloxone doses inducing the motivational (7.5 and 15 µg/kg) and somatic (30 and 120 µg/kg) components of withdrawal. Our mapping study revealed a dissociation between a set of brain structures (extended amygdala, lateral septal nucleus, basolateral amygdala and field CA1 of the hippocampus) which exhibited c‐fos mRNA dose‐dependent variations from the lowest naloxone doses, and many other structures (dopaminergic and noradrenergic nuclei, motor striatal areas, hypothalamic nuclei and periaqueductal grey) which were less sensitive and recruited only by the higher doses. In addition, we found opposite dose‐dependent variations of c‐fos gene expression within the central (increase) and the basolateral (decrease) amygdala after acute morphine withdrawal. Altogether, these results emphasize that limbic structures of the extended amygdala along with the lateral septal nucleus, the basolateral amygdala and CA1 could specifically mediate the negative motivational component of opiate withdrawal.
Amygdala norepinephrine levels after training predict inhibitory avoidance retention performance in rats
Authors: McIntyre Christa K. , Hatfield Tammy , McGaugh James L. 
Published: March 2003

AbstractPrevious findings indicate that footshock and several drugs that modulate memory consolidation alter norepinephrine (noradrenaline) release in the amygdala, as assessed byin vivomicrodialysis and high‐performance liquid chromatography. Such findings suggest that norepinephrine release in the amygdala may be critical for regulating memory consolidation. The present study was the first to examine the relationship between norepinephrine release in the amygdala assessed after inhibitory avoidance training and 24‐h retention performance within individual animals. Norepinephrine levels increased to > 300% of pretraining baseline 30 min after training and remained elevated for 2 h. In individual rats, the increase in norepinephrine levels after training correlated highly with 24‐h retention performance. These findings indicate that the degree of activation of the noradrenergic system within the amygdala in response to a novel, emotionally arousing experience predicts the extent of long‐term memory for that experience.
Cellular architecture of the nucleus reuniens thalami and its putative aspartatergic/glutamatergic projection to the hippocampus and medial septum in the rat
Authors: Bokor Hajnalka , Csáki Ágnes , Kocsis Katalin , Kiss József 
Published: March 2003

AbstractLittle is known about the neurochemical features of the nucleus reuniens thalami (RE). In the present study, immunocytochemical experiments were performed to characterize the expression pattern of certain neurochemical markers, e.g. the calcium‐binding proteins calbindin and calretinin and several neuropeptides. Colocalization studies revealed that half of the calbindin‐positive cells express calretinin, and numerous calretinin‐immunoreactive neurons contain calbindin. In contrast, immunolabelling for neuropeptides did not reveal cell bodies in the RE. The RE establishes widespread connections with several limbic structures. To correlate these projection patterns with the neurochemical characteristics of RE neurons, the retrograde tracer [3H]d‐aspartate, which is selectively taken up by high affinity uptake sites that use glutamate as neurotransmitter, and the nonselective retrograde tracer wheatgerm agglutinin‐conjugated colloidal gold was injected into the stratum lacunosum moleculare of the hippocampal CA1 subfield and into the medial septum. The results provide direct anatomical demonstration of aspartatergic/glutamatergic projection from the RE to the hippocampus and to the medial septum. Nearly all of the projecting neurons proved to be calbindin‐immunopositive and many of them expressed calretinin. Both retrograde labelling techniques revealed that neurons projecting to the hippocampus were located in clusters in the dorsolateral part of the RE, whereas neurons projecting to the medial septum were mainly distributed in the ventromedial portion of the nucleus, indicating that different cell populations project to these limbic areas. These results suggest that neurons in the RE are heterogeneous and contribute to the excitatory innervation of the septo‐hippocampal system.
Attentional demands reflect learning‐induced alterations of bimanual coordination dynamics
Authors: Temprado J. J. , Monno A. , Zanone P. G. , Kelso J. A. S. 
Published: March 2003

AbstractThis study aimed to investigate the effects of practice on bimanual coordination dynamics and attentional demands. Participants were asked to perform a dual‐task associating a cyclic antiphase bimanual pattern and a discrete reaction time task. A pretest determined each individual critical transition frequency. In the training session, participants practised 120 trials. They were instructed to maintain the antiphase coordination pattern at the critical transition frequency. The training session was interrupted and followed by an intermediate test (after 60 trials) and a post‐test (30 min after 120 trials), respectively. A retention test was performed 7 days after the end of the training session. Results showed that: (i) the number of transitions decreased as a consequence of practice; and (ii), subjects were able to maintain the antiphase pattern at a higher frequency than in the pretest. Analysis of the trade‐off between relative phase variability and reaction time showed that participants were able to maintain a higher level of stability at the same (intermediate and post‐test) or a lower attentional cost (retention test). These findings show that phase transition dynamics and pattern stability can be significantly modified as a result of practice. Changes in the trade‐off between pattern stability and cost with learning confirm that the attentional cost incurred by the central nervous system to maintain pattern stability decreased with practice. In line with recent neurobiological studies, the present study provides new insights regarding relationships between brain processes, attentional demands and coordinated behaviour in learning bimanual patterns.
Decreased glucocorticoid receptor mRNA and dysfunction of HPA axis in rats after removal of the cholinergic innervation to hippocampus.
Authors: Han Jung‐Soo , Bizon Jennifer L. , Chun Hyun‐Ja , Maus Courtney E. , Gallagher Michela 
Published: March 2003

AbstractExcess exposure to glucocorticoids can have deleterious effects on physiology and cognition. Glucocorticoids acting via receptors located in hippocampal neurons contribute to negative feedback after stress by terminating the further release of glucocorticoids. The current study investigated the effects of selective immunolesions of septo‐hippocampal cholinergic neurons on hippocampal corticosterone receptor mRNA and on hypothalamic‐pituitary‐adrenal (HPA) activity. As evaluated by in situ hybridization, hippocampal glucocorticoid receptor (GR) mRNA, but not mineralocorticoid receptor (MR) mRNA, was significantly decreased in lesioned rats compared to controls. In a companion study, the peak corticosterone response to one hour of restraint stress did not differ between lesion and control groups but the post‐stress decline of corticosterone was more protracted in the lesioned rats. These findings are discussed in terms of their possible relevance to ageing as age‐related degeneration of the basal forebrain cholinergic system may contribute to the commonly observed dysfunction of the HPA axis in older animals.
The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety
Authors: Haller J. , Bakos N. , Szirmay M. , Ledent C. , Freund T. F. 
Published: March 2003

AbstractThe aim of this study was to compare the effects of the genetic and pharmacological disruption of CB1 cannabinoid receptors on the elevated plus‐maze test of anxiety. In the first experiment, the behaviour of CB1‐knockout mice and wild‐type mice was compared. In the second experiment, the cannabinoid antagonist SR141716A (0, 1, and 3 mg/kg) was administered to both CB1‐knockout and wild type mice. Untreated CB1‐knockout mice showed a reduced exploration of the open arms of the plus‐maze apparatus, thus appearing more anxious than the wild‐type animals, however no changes in locomotion were noticed. The vehicle‐injected CB1‐knockout mice from the second experiment also showed increased anxiety as compared with wild types. Surprisingly, the cannabinoid antagonist SR141716A reduced anxiety in both wild type and CB1 knockout mice. Locomotor behaviour was only marginally affected. Recent evidence suggests the existence of a novel cannabinoid receptor in the brain. It has also been shown that SR141716A binds to both the CB1 and the putative novel receptor. The data presented here supports these findings, as the cannabinoid receptor antagonist affected anxiety in both wild type and CB1‐knockout mice. Tentatively, it may be suggested that the discrepancy between the effects of the genetic and pharmacological blockade of the CB1 receptor suggests that the novel receptor plays a role in anxiety.
Fibroblast growth factor‐2 increases functional excitatory synapses on hippocampal neurons
Authors: Li Ai‐Jun , Suzuki Seigo , Suzuki Masashi , Mizukoshi Eiichi , Imamura Toru 
Published: March 2003

AbstractThe effect of fibroblast growth factor‐2 (FGF‐2) on synapse formation was investigated using rat cultured hippocampal neurons. Treatment with FGF‐2 (0.4–10 ng/mL) for 6 days enhanced synaptogenesis on these neurons by ∼50%, as determined by counting puncta immunostained for presynaptic‐ or postsynaptic‐specific proteins. This enhancement was statistically significant, and was abolished by a specific inhibitor of mitogen‐activated protein kinase (MAPK). The majority of neurons expressed FGF receptors (types 1–3) abundantly on the membrane of somata, dendrites, and growth cones, and in these regions phosphorylation of MAPK was enhanced after FGF‐2 application. Furthermore, our experiments showed that the majority of synapses formed in cultures containing FGF‐2 were positive both for presynaptic proteins and postsynaptic excitatory synapse‐specific proteins, and that these synapses had a similar capacity to recycle the fluorescent styryl dye FM4‐64 as those in the control culture. These results indicate that: (i) FGF‐2 increases excitatory synapses on hippocampal neurons by activating MAPK activity through FGF receptors; and (ii) synapses formed in FGF‐2‐treated culture are capable of cycling vesicles.
Synaptic plasticity in the acoustic startle pathway: the neuronal basis for short‐term habituation?
Authors: Weber Maruschka , Schnitzler Hans‐Ulrich , Schmid Susanne 
Published: March 2003

AbstractThe aim of the present study was to analyse the cellular mechanism underlying short‐term habituation of the acoustic startle response (ASR). We explored distinct synapses of the neuronal startle pathway in rat brain slices by patch‐clamp recordings of giant neurons in the caudal pontine reticular formation. Presynaptic stimulation of auditory afferents by repeated bursts at 0.1 and 1 Hz led to an exponential decay of EPSC magnitudes. This homosynaptic depression (HSD) was reversible and repeatedly inducible after recovery. Many parameters of HSD in vitro match those of ASR habituation in vivo. The mechanisms underlying HSD are distinct from classical short‐term plasticity: paired‐pulse as well as paired‐burst stimulation revealed a facilitation of the second EPSC, occurring in a much smaller time window up to interstimulus intervals of 200 ms. Pharmacological experiments demonstrated that HSD could be completely blocked by the group II and III metabotropic glutamate receptor antagonist MPPG. Similar results were obtained by CPPG, another group II and III antagonist. In contrast, HSD was not affected by the group I and II antagonist MCPG. We conclude that we found a form of synaptic depression in synapses within the primary startle pathway which correlates in many respects with short‐term habituation of the ASR and which is presumably mediated by group III metabotropic glutamate receptors.
Time course of motor cortex reorganization following botulinum toxin injection into the vibrissal pad of the adult rat
Authors: Franchi G. 
Published: March 2003

AbstractThe present experiment studies representation patterns in the motor cortex (M1) of adult rats, 1, 3, 6, and 12 days after unilateral injection of Botulinum Toxin (BTX) into the vibrissa pad. Intracortical microstimulation (ICMS) was used to evidence changes in the representation over time and in the current thresholds required to evoke movements inside the disconnected vibrissa region. After 1 day, isolated as well as contiguous negative sites were observed within the motor cortex corresponding to the disconnected vibrissa region. Thereafter the percentage of unresponsive sites decreased so that after 6 days, the number of unresponsive sites was not significantly higher than those in the control hemispheres. Within the disconnected vibrissa region, electrical stimulation elicited forelimb, eye, ipsilateral vibrissa and neck movements. Following BTX injection, the enlargement of the forelimb representation into the disconnected vibrissa representation began during the first day and stabilized during the second week after injection. In the first days, stimulation thresholds in expanded forelimb sites were higher than those required for similar movement in normal M1 forelimb representation. These thresholds then declined so that in ∼6 days they were similar to normal. There was no clear evidence that stimulation of sites in the medial part of disconnected vibrissa‐cortex evoked eye movements during the first 6 days after BTX injection. After this time, thresholds required to evoke eye movement in expanded sites were generally similar to, and never higher than, those needed to evoke this movement in control sites. Intermingled ipsilateral vibrissa and neck movement occupies part of the medial vibrissa region. Over the 12 days, extension of the ipsilateral vibrissa representation shrank while the representation of neck movement remained unchanged. Throughout the entire time there was no change in the excitability of these sites and the thresholds remained higher than that needed to elicit the vibrissa movement normally represented in this cortical region. No significant differences in threshold were found over time for any of the other movement categories represented in M1. These results indicate that, over time, the new movements inside the disconnected vibrissa region develop differently in M1 following peripheral motor disconnection. The implications for mechanisms involved in cortical plasticity are discussed.
Indirect projections from the suprachiasmatic nucleus to the ventrolateral preoptic nucleus: a dual tract‐tracing study in rat
Authors: Deurveilher Samuel , Burns Joan , Semba Kazue 
Published: March 2003

AbstractThe suprachiasmatic nucleus (SCN) contains a master clock for most circadian rhythms in mammals, including daily sleep–wake cycles. The ventrolateral preoptic nucleus (VLPO) plays a key role in sleep generation and, as such, might be an important target of the SCN circadian signal. However, direct SCN projections to the VLPO are limited, suggesting that most of the SCN output to the VLPO might be conveyed indirectly. We examined this possibility by microinjecting selected known major targets of SCN efferents with biotinylated dextran‐amine and/or cholera toxin B subunit, followed by analyses of retrograde labelling in the SCN and anterograde labelling in the VLPO. Retrograde labelling results confirmed that the medial preoptic area, subparaventricular zone, dorsomedial hypothalamic nucleus and posterior hypothalamic area all received projections from the SCN; these projections arose predominantly from the shell, as opposed to the core, of the SCN. Anterograde labelling results indicated that these same nuclei also projected to the VLPO, mainly its medial and ventral aspects. Comparison of the results of injections of similar sizes across different target groups indicated that the rostral part of the medial preoptic area and the caudal part of the dorsomedial hypothalamic nucleus were particularly noteworthy for the abundance of both SCN source neurons and efferent fibres and terminals in the VLPO. These results suggest that the SCN might provide indirect input to the VLPO via the medial preoptic area and the dorsomedial hypothalamic nucleus, and that these indirect neuronal pathways might play a major role in circadian control of sleep–wake cycles.
Differential excitability and voltage‐dependent Ca2+ signalling in two types of medial entorhinal cortex layer V neurons
Authors: Egorov Alexei V. , Heinemann Uwe , Müller Wolfgang 
Published: March 2003

AbstractThe entorhinal cortex (EC) is a key structure in memory formation, relaying sensory information to the hippocampal formation and processed information to the neocortex. EC neurons in the deep layers modulate the transfer of sensory information by the superficial layers and the dentate gyrus, and form the output to the neocortex. Here we characterize two types of EC layer V neurons by their fluorescence morphology, electrophysiology and intracellular Ca2+ signalling using intracellular recording and Ca2+ imaging. Pyramidal neurons show, in response to depolarizing current pulses, regular firing with strong adaptation and a fast and medium afterhyperpolarization (AHP) which are separated by a depolarizing notch and, with hyperpolarizing current injection, a transient sag. Multipolar cells respond to depolarization with delayed firing with very weak adaptation and have no depolarizing notch between fast and medium AHP and no sag with hyperpolarization. The delayed firing was blocked by 30 µm 4‐aminopyridine, indicating mediation by the D‐type potassium current. Subthreshold depolarization evoked membrane potential oscillations of 2–5 Hz in both cell types and an increase in [Ca2+]i of 37 nm in pyramidal and 59 nm in multipolar neurons. Repetitive firing at 10 Hz for 30 s increased [Ca2+]i in pyramidal and multipolar neurons by 194 and 295 nm, respectively. Differential temporal firing and Ca2+ signalling suggest specific information processing and synaptic memory storage possibilities in these two layer V cell types of the EC.