bluuebunny/crossref_metadata_2025_split huggingface dataset:
AMPA‐receptor involvement in c‐fos expression in the medial prefrontal cortex and amygdala dissociates neural substrates of conditioned activity and conditioned reward
Authors: Mead Andy N. , Vasilaki Anna , Spyraki Christina , Duka Theodora , Stephens David N. 
Published: March 2003

AbstractExposure to an environment, previously conditioned to amphetamine (1 mg/kg, i.p.), induced locomotor activity and c‐fos expression (a marker for neuronal activation) in the mouse medial prefrontal cortex (mPFC) and amygdala; acute or repeated amphetamine (1 mg/kg, i.p.) administration induced c‐fos expression additionally in the nucleus accumbens. An α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)‐receptor antagonist, 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo(f)quinoxaline (NBQX), blocked expression of conditioned activity, and prevented the increase in c‐fos expression in mPFC, implicating mPFC AMPAergic transmission in the conditioned component of behavioural sensitization to amphetamine. NBQX failed to block the expression of amphetamine‐conditioned place preference, a measure of conditioned reward, or conditioned c‐fos expression in the amygdala, an area implicated in the expression of conditioned place preference. These findings indicate that the conditioned components of behavioural sensitization depend on AMPA‐receptor‐mediated activation in mPFC, but that conditioned reward does not.
Role of the corpus callosum in the somatosensory activation of the ipsilateral cerebral cortex: an fMRI study of callosotomized patients
Authors: Fabri Mara , Polonara Gabriele , Quattrini Angelo , Salvolini Ugo , Del Pesce Maria , Manzoni Tullio 
Published: March 2003

AbstractTo verify whether the activation of the posterior parietal and parietal opercular cortices to tactile stimulation of the ipsilateral hand is mediated by the corpus callosum, a functional magnetic resonance imaging (fMRI, 1.0 tesla) study was performed in 12 control and 12 callosotomized subjects (three with total and nine with partial resection). Eleven patients were also submitted to the tactile naming test. In all subjects, unilateral tactile stimulation provoked a signal increase temporally correlated with the stimulus in three cortical regions of the contralateral hemisphere. One corresponded to the first somatosensory area, the second was in the posterior parietal cortex, and the third in the parietal opercular cortex. In controls, activation was also observed in the ipsilateral posterior parietal and parietal opercular cortices, in regions anatomically corresponding to those activated contralaterally. In callosotomized subjects, activation in the ipsilateral hemisphere was observed only in two patients with splenium and posterior body intact. These two patients and another four with the entire splenium and variable portions of the posterior body unsectioned named objects explored with the right and left hand without errors. This ability was impaired in the other patients. The present physiological and anatomical data indicate that in humans activation of the posterior parietal and parietal opercular cortices in the hemisphere ipsilateral to the stimulated hand is mediated by the corpus callosum, and that the commissural fibres involved probably cross the midline in the posterior third of its body.
Experience‐dependent increase in cAMP‐responsive element binding protein in synaptic and nonsynaptic mitochondria of the rat hippocampus
Authors: Bevilaqua Lia R. M. , Cammarota Martín , Paratcha Gustavo , De Stein Miguelina Levi , Izquierdo Iván , Medina Jorge H. 
Published: March 2003

AbstractCyclic AMP‐responsive element binding protein (CREB) plays a pivotal role in the formation of long‐term memory in Drosophila, Aplysia, mice and rats. Recently, we were able to demonstrate that CREB and its serine 133 phosphorylated form p‐CREB are localized in synaptic and nonsynaptic mitochondria of the rat brain. Here we report on the effect of a one‐trial inhibitory avoidance training procedure on mitochondrial CREB from the rat hippocampus. This aversively motivated training task is associated with a time‐dependent increase (34–35%) in both p‐CREB and CREB immunoreactivities detected in synaptic mitochondria of the hippocampus. In nonsynaptic mitochondria, p‐CREB levels increased in both trained and shocked animals. In addition to CREB, two CRE‐element binding repressors, CREB‐2 and CREM‐1, were also detected in purified brain mitochondria. No changes were observed in CREB‐2 and CREM‐1 immunoreactivities in hippocampal synaptic mitochondria after an inhibitory avoidance training. Taken together the present findings represent the first evidence showing that brain mitochondrial CREB may participate in plasticity‐dependent changes associated with a behavioural training procedure.
Late embryonic expression of AMPA receptor function in the CA1 region of the intact hippocampus in vitro
Authors: Diabira D. , Hennou S. , Chevassus‐au‐Louis N. , Ben‐Ari Y. , Gozlan H. 
Published: March 2003

AbstractStudies in slices suggest that α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor‐mediated synaptic currents are not present in CA1 (Cornu ammonis) pyramidal neurons at birth (P0). We have re‐examined this issue in the rat intact hippocampal formation (IHF) in vitro. Injections of biocytin or carbocyanine show that the temporo‐ammonic, commissural and Schaffer collateral pathways are present at birth in the marginal zone of CA1. Electrical stimulation of these pathways evoked field excitatory postsynaptic potentials (fEPSPs) in the marginal zone of CA1 from embryonic day 19 (E19) to postnatal day 9 (P9). These fEPSPs are mediated by synaptic AMPA receptors as they are reduced or completely blocked by: (i) tetrodotoxin; (ii) high divalent cation concentrations; (iii) the adenosine A1 receptor agonist CPA; (iv) anoxic episodes; (v) the selective AMPA receptor antagonist 1‐(4‐aminophenyl)‐3‐methylcarbamyl‐4‐methyl‐7,8‐methylenedioxy‐3,4‐dihydro‐5H‐2,3‐benzodiazepine (GYKI‐53655) or the mixed AMPA‐kainate receptor antagonists 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and 6‐nitro‐7‐sulphamoylbenzo[f]quinoxaline‐2,3‐dione (NBQX). The amplitude of the fEPSPs is also reduced by d(–)‐2‐amino‐5‐phosphonopentanoic acid (D‐APV) and its duration is increased by bicuculline suggesting the participation of N‐methyl‐d‐aspartate (NMDA) and GABAA (γ‐aminobutyric acid) receptors. Finally, AMPA receptor‐mediated fEPSPs are also recorded in P0 slices, but they are smaller and more labile than in the IHF. Our results suggest that in embryonic CA1 neurons, glutamate acting on AMPA receptors already provides a substantial part of the excitatory drive and may play an important role in the activity‐dependent development of the hippocampus. Furthermore, the IHF may be a convenient preparation to investigate the properties of the developing hippocampus.
Analysis of neurotrophic effects of hepatocyte growth factor in the adult hypoglossal nerve axotomy model
Authors: Okura Yoshio , Arimoto Hirohiko , Tanuma Naoyuki , Matsumoto Kunio , Nakamura Toshikazu , Yamashima Tetsumori , Miyazawa Takahito , Matsumoto Yoh 
Published: March 2003

AbstractRecent studies have shown that hepatocyte growth factor (HGF) promotes the survival of embryonic motor neurons. However, it remains unclear whether HGF has trophic effects on mature motor neurons. In the present study, we examined the effects of HGF on adult motoneurons using the hypoglossal nerve transection model. In adult rats, neurons in the hypoglossal nucleus show a dramatic loss of choline acetyltransferase (ChAT) protein and mRNA after the axotomy. This reduction of ChAT was markedly prevented when HGF was administered continuously at the cut end of the nerve using an osmotic pump. The HGF receptor, c‐met, protein and mRNA, which were faintly expressed in hypoglossal neurons under normal conditions, gradually increased and reached maximal levels 2 weeks after the axotomy. Administration of HGF reduced this c‐met upregulation almost to normal levels. We also quantified HGF mRNA in the tongue and hypoglossal nucleus. The tongue contained abundant HGF mRNA, whereas the nucleus contained only low levels. Interestingly, the HGF mRNA level in the nucleus did not increase after the axotomy. These findings suggest that HGF is principally produced in the tongue and contributes to maintain ChAT expression in the nucleus. HGF produced in the hypoglossal nucleus alone after disconnection from the tongue may not be sufficient for the maintenance of the motor neuron function. Thus, exogenously applied HGF was effective to prevent the downregulation of ChAT activities. These findings provide a strong rationale for the potential clinical use of HGF for the treatment of motor neuron degenerative disease.
Behavioural trait of reactivity to novelty is related to hippocampal neurogenesis
Authors: Lemaire V. , Aurousseau C. , Le Moal M. , Abrous D. N. 
Published: March 2003

AbstractThe hippocampal formation is one of the brain areas where neurogenesis persists during adulthood, with new neurons being continuously added to the population of dentate granule cells. However, the functional implications of this neurogenesis are unknown. On the other hand, the hippocampal formation is particularly concerned with the detection of novelty, and there are indications that dentate granule cells play a significant role in this function. Recently, the existence of inter‐individual differences in behavioural reactivity to novelty has been evidenced, related to differences in the reactivity of the hypothalamic–pituitary–adrenal axis (HPA). Rats that are highly reactive to novelty (HR) exhibit a prolonged corticosterone secretion in response to novelty and to stress when compared with low reactive rats (LR). Taking advantage of the existence of these inter‐individual differences, we investigated whether neurogenesis in the dentate gyrus is correlated with the behavioural trait of reactivity to novelty. Rats were first selected according to their locomotor reactivity to a novel environment. Two weeks later, cell proliferation, evaluated by the incorporation of 5‐bromo‐2′‐deoxyuridine (BrdU) in progenitors, was studied by immunohistochemistry. We found that cell proliferation in the dentate gyrus was negatively correlated with locomotor reactivity to novelty. Indeed, cell proliferation in LR rats was twice that observed in HR rats. In contrast, survival of nascent neurons was not influenced by the behavioural trait of reactivity to novelty. Using an unbiased stereology, we show that LR rats had more cells within the granule cell layer of the dentate gyrus than did HR rats. These results demonstrate the existence of inter‐individual differences in neurogenesis and total granule cell number within the dentate gyrus. These differences in hippocampal plasticity can be predicted by the behavioural trait of reactivity to novelty.
Functional heterogeneity of the rat medial prefrontal cortex: effects of discrete subarea‐specific lesions on drug‐induced conditioned place preference and behavioural sensitization
Authors: Tzschentke Thomas M. , Schmidt Werner J. 
Published: March 2003

AbstractWhile the principal components of the brain reward system, the nucleus accumbens septi and the ventral tegmental area have received much attention, their efferent and afferent structures have not been investigated to the same degree. One major input to this system originates from the medial prefrontal cortex (mPFC) which is not a homogenous structure but can be divided into different subareas that can be distinguished on anatomical and possibly functional grounds. We examined the effects of discrete bilateral quinolinic acid lesions (45 nmol/0.5 μL) of each of the mPFC subareas, the infralimbic (il), prelimbic (pl) and the anterior cingulate (cg) mPFC, on the conditioned place preference (CPP) and psychomotor activation induced by several drugs. Lesions of the il mPFC blocked CPP induced by morphine (10 mg/kg) and CGP37849 [dl‐(E)‐2‐amino‐4‐methyl‐5‐phosphono‐3‐pentic acid, a competitive N‐methyl‐d‐aspartate receptor antagonist; 10 mg/kg]. Lesions of the pl mPFC blocked CPP induced by cocaine (15 mg/kg) and CGP37849, and lesions of the cg mPFC only blocked CGP37849‐induced CPP. Lesions of the whole mPFC blocked morphine‐, cocaine‐ and CGP37849‐induced CPP. None of the lesions affected dl‐amphetamine (4 mg/kg)‐induced CPP. During the conditioning period, none of the lesions affected amphetamine‐induced psychomotor activation and sensitization, whereas both phenomena were attenuated by pl and whole mPFC lesions in the case of cocaine, and by il and whole mPFC lesions in the case of morphine. These results show that the different mPFC subregions have distinct functional roles in the generation of behavioural effects produced by different classes of drugs. This heterogeneity should be taken into account in future studies addressing the role of the mPFC in drug reward and sensitization.
Perirhinal cortex input to the hippocampus in the rat: evidence for parallel pathways, both direct and indirect. A combined physiological and anatomical study
Authors: Naber P. A. , Witter M. P. , Da Silva F. H. Lopes 
Published: March 2003

AbstractThe possibility of a direct projection from the perirhinal cortex (PER) to areas CA1 and subiculum (SUB) in the hippocampus has been suggested on the basis of tracer studies, but this projection has not unequivocally been supported by physiological studies. The demonstration of such a functional pathway might be important to understand the functioning of the hippocampal memory system. Here we present physiological and further anatomical evidence for such a connection between PER and the hippocampus. Electrical stimulation of PER in vivo evoked field potentials (EFPs) at the border area of CA1/SUB, consisting of a short latency and a longer latency component. Current source density analysis revealed that the sink of the short latency component was situated in the molecular layer of area CA1/SUB, while the longer latency component had its sink in the outer molecular layer of the dentate gyrus (DG). Anterograde tracer injections in PER showed labelled fibres in the border area of CA1/SUB, but anatomical evidence for a projection of PER to DG was not found. When synaptic transmission in the entorhinal cortex was partly blocked, the amplitude of the longer latency component of the recorded EFPs in the hippocampus was decreased while the short latency component was not affected, which suggests that the indirect pathway originating in PER is mediated through a synaptic relay in the entorhinal cortex. From the present results we conclude that information originating in PER reaches area CA1/SUB by parallel, direct and indirect, routes. The existence of this parallel organization appears to form an essential feature for the proper function of the medial temporal lobe memory system.
The modulation of calcium current by GABA metabotropic receptors in a sub‐population of pallidal neurons
Authors: Stefani Alessandro , Spadoni Francesca , Giacomini Patrizia , Lavaroni Franco , Bernardi Giorgio 
Published: March 2003

AbstractGlobus pallidus (GP) receives an abundant GABAergic (γ‐aminobutyric acid) pathway from the corpus striatum. Several evidences suggested that alterations of this pathway might underlie the development of movement disorders. Classical models on Parkinsonism are centred on the increased excitability of GABAergic striatofugal neurons impinging GP and, therefore, on the presumed hypoactivity of GP neurons, but very few electrophysiological studies have addressed the activation of GABA receptors in mammalian GP. We have isolated calcium currents in GP neurons dissociated from the adult rat brain and analysed GABA‐mediated responses. In the presence of bicuculline, the fast, chloride‐mediated, ionotropic responses were obscured and GABA produced a large (≥ 35%) inhibition of calcium currents. The GABA‐induced inhibition of calcium currents strongly desensitized was mimicked by baclofen and prevented by hydroxy‐saclofen, supporting the involvement of GABAB receptors. The baclofen‐mediated modulation was: (i) associated with slowing of activation kinetics; (ii) relieved by prepulse facilitation; and (iii) G‐protein‐mediated. The response was slow in onset, requiring the mobilization of intracellular cAMP, and was abolished by the combination of N‐type and P‐type calcium channel blockers. The GABAB‐mediated effect, however, was confined to a particular subtype of GP neurons, identified by relatively small to medium soma. Differently, in cells characterized by larger somata and capacitance, the baclofen response was negligible. Intriguingly, these baclofen‐resistant, larger neurons manifested a consistent low‐voltage‐activated (LVA) calcium current, not detected in baclofen‐sensitive cells, at least when recorded in whole‐cell mode. This study demonstrates that GP neurons express functional GABAA and GABAB receptors. In a subset of GP neurons, the activation of GABAB receptors induces a large modulation of high‐voltage‐activated (HVA) calcium currents, which may strongly influence basal ganglia circuitry and partially explain some discrepancies of classical models of extrapyramidal disorders.
Synchronization of GABAergic interneuronal networks during seizure‐like activity in the rat horizontal hippocampal slice
Authors: Velazquez Jose L. Perez , Carlen Peter L. 
Published: March 2003

AbstractWe studied the contribution of GABAergic (γ‐aminobutyric acid) neurotransmission to epileptiform activity using the horizontal hippocampal rat brain slice. Seizure‐like (ictal) activity was evoked in the CA1 area by applying high‐frequency trains (80 Hz for 2 s) to the Schaffer collaterals. Whole‐cell recordings from stratum oriens‐alveus interneurons revealed burst firing with superimposed high‐frequency spiking which was synchronous with field events and pyramidal cell firing during ictal activity. On the other hand, interictal interneuronal bursts were synchronous with large‐amplitude inhibitory postsynaptic potentials (IPSPs) in pyramidal cells. Excitatory and inhibitory postsynaptic potentials were simultaneously received by pyramidal neurons during the ictal afterdischarge, and were synchronous with interneuronal bursting and field potential ictal events. The GABAA receptor antagonist bicuculline greatly reduced the duration of the ictal activity in the CA1 layer, and evoked rhythmic interictal synchronous bursting of interneurons and pyramidal cells. With intact GABAergic transmission, interictal field potential events were synchronous with large amplitude IPSPs (9.8 ± 2.4 mV) in CA1 pyramidal cells, and with interneuronal bursting. Simultaneous dual recordings revealed synchronous IPSPs received by widely separated pyramidal neurons during ictal and interictal periods, indicative of widespread interneuronal firing synchrony throughout the hippocampus. CA3 pyramidal neurons fired in synchrony with interictal field potential events recorded in the CA1 layer, and glutamate receptor antagonists abolished interictal interneuronal firing and synchronous large amplitude IPSPs received by CA1 pyramidal cells. These observations provide evidence that the interneuronal network may be entrained in hyperexcitable states by GABAergic and glutamatergic mechanisms.
Brain somatostatin: a candidate inhibitory role in seizures and epileptogenesis
Authors: Vezzani Annamaria , Hoyer Daniel 
Published: March 2003

AbstractRecent evidence shows that neuropeptide expression in the CNS is markedly affected by seizure activity, particularly in the limbic system. Changes in neuropeptides in specific neuronal populations depend on the type and intensity of seizures and on their chronic sequelae (i.e. neurodegeneration and spontaneous convulsions). This paper reviews the effects of seizures on somatostatin‐containing neurons, somatostatin mRNA and immunoreactivity, the release of this peptide and its receptor subtypes in the CNS. Differences between kindling and status epilepticus in rats are emphasized and discussed in the light of an inhibitory role of somatostatin on hippocampal excitability. Pharmacological studies show that somatostatin affects electrophysiological properties of neurons, modulates classical neurotransmission and has anticonvulsant properties in experimental models of seizures. This peptidergic system may be an interesting target for pharmacological attempts to control pathological hyperactivity in neurons, thus providing new directions for the development of novel anticonvulsant treatments.
Hippocampal neuronal position selectivity remains fixed to room cues only in rats alternating between place navigation and beacon approach tasks
Authors: Trullier O. , Shibata R. , Mulder A. B. , Wiener S. I. 
Published: March 2003

AbstractTo study the relationship between brain representations and behaviour, we recorded hippocampal neuronal activity in rats repeatedly alternating between two different tasks on a circular platform with four reward boxes along the edge. In the beacon approach task, rewards were provided only at the pair of diametrically opposite boxes that was illuminated. In the place navigation task, rewards were available only at the boxes positioned near the north‐east and south‐west corners of the room. Performance levels were high and rats rapidly reoriented to changes in lamp cues in the beacon approach task. Neuropsychological studies show that rats with hippocampal lesions readily employ beacon approach strategies, while place navigation is severely impaired. Previous studies suggested that the neurons might change their behavioural correlates as the rat performed the respective tasks. However, of 34 hippocampal ‘place cells’ recorded, all showed position selectivity fixed with respect to room cues, even in the beacon approach task where coding the position of the rat in the room was of no use for locating rewards. Whether or not hippocampal signals are actually employed for ongoing behaviour would then be decided by structures downstream from the hippocampus. If this is the case, then the ‘counterproductive’ room referred place‐related discharges in the beacon approach task would be a background representation. This would provide support for proposals of multiple memory systems underlying different types of information processing and contrasts with the popular notion that local neuronal activity levels are selectively increased to the degree that the brain region is required for the ongoing function.