bluuebunny/crossref_metadata_2025_split huggingface dataset:
BDNF up‐regulates evoked GABAergic transmission in developing hippocampus by potentiating presynaptic N‐ and P/Q‐type Ca2+ channels signalling
Authors: Baldelli P. , Novara M. , Carabelli V. , Hernández‐Guijo J. M. , Carbone E. 
Published: March 2003

AbstractChronic application of brain‐derived neurotrophic factor (BDNF) induces new selective synthesis of non‐L‐type Ca2+ channels (N, P/Q, R) at the soma of cultured hippocampal neurons. As N‐ and P/Q‐channels support neurotransmitter release in the hippocampus, this suggests that BDNF‐treatment may enhance synaptic transmission by increasing the expression of presynaptic Ca2+ channels as well. To address this issue we studied the long‐term effects of BDNF on miniature and stimulus‐evoked GABAergic transmission in rat embryo hippocampal neurons. We found that BDNF increased the frequency of miniature currents (mIPSCs) by ≈40%, with little effects on their amplitude. BDNF nearly doubled the size of evoked postsynaptic currents (eIPSCs) with a marked increase of paired‐pulse depression, which is indicative of a major increase in presynaptic activity. The potentiation of eIPSCs was more relevant during the first two weeks in culture, when GABAergic transmission is depolarizing. BDNF action was mediated by TrkB‐receptors and had no effects on: (i) the amplitude and dose–response of GABA‐evoked IPSCs and (ii) the number of GABAA receptor clusters and the total functioning synapses, suggesting that the neurotrophin unlikely acted postsynaptically. In line with this, BDNF affected the contribution of voltage‐gated Ca2+ channels mediating evoked GABAergic transmission. BDNF drastically increased the fraction of evoked IPSCs supported by N‐ and P/Q‐channels while it decreased the contribution associated with R‐ and L‐types. This selective action resembles the previously observed up‐regulatory effects of BDNF on somatic Ca2+ currents in developing hippocampus, suggesting that potentiation of presynaptic N‐ and P/Q‐channel signalling belongs to a manifold mechanism by which BDNF increases the efficiency of stimulus‐evoked GABAergic transmission.
Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin‐releasing hormone receptor‐dependent mechanism
Authors: Linthorst Astrid C. E. , Peñalva Rosana G. , Flachskamm Cornelia , Holsboer Florian , Reul Johannes M. H. M. 
Published: March 2003

SummarySerotonin is important for adequate coping with stress. Aberrant serotonin function is implicated in the aetiology of major depression and anxiety disorders. Dysregulation of the hypothalamic–pituitary–adrenocortical axis, involving elevated corticotropin‐releasing hormone (CRH) activity, also plays a role in these stress‐related illnesses. Here we studied the effects of stress on hippocampal serotonin and the role of the CRH system using in vivo microdialysis. First, rats were subjected to a forced swim stress, resulting in a dramatic increase in hippocampal serotonin (1500% of baseline), which was associated with the occurrence of diving behaviour. The diving‐associated increase in serotonin depended on activation of CRH receptors, as it was antagonized by intracerebroventricular pretreatment with D‐Phe‐CRH12−41. Secondly, the effects of intracerebroventricular administration of CRH and urocortin (0.03–1.0 µg) were studied. Both CRH and urocortin caused a dose‐dependent rise in hippocampal serotonin (maximally 350% of baseline) and 5‐hydroxyindoleacetic acid levels, suggesting the involvement of CRH receptor type 1. Because the effects of urocortin were prolonged, CRH receptor type 2 could play a role in a later phase of the neurotransmitter response. Experiments using adrenalectomized rats showed that CRH‐induced serotonin changes were adrenally independent. These data suggest that the raphe‐hippocampal serotonin system is able to mount, CRH receptor‐dependent, responses to specific stressful situations that surpass the usually observed maximal increases of about 300% of baseline during stress and enhanced vigilance.
Vasopressin and oxytocin reverse adenosine‐induced pituicyte stellation via calcium‐dependent activation of Cdc42
Authors: Rosso Lia , Peteri‐Brunbäck Brigitta , Vouret‐Craviari Valérie , Deroanne Christophe , Van Obberghen‐Schilling Ellen , Mienville Jean‐Marc 
Published: March 2003

AbstractIn view of the potential impact of pituicyte morphology on neurohypophysial hormone secretion, we have studied the mechanisms involved in the shape changes induced by vasopressin (AVP) and oxytocin (OXT) in cultured rat pituicytes. Pituicytes induced to become stellate in the presence of 10 µm adenosine revert to their nonstellate shape ∼20 min after application of AVP or OXT. The IC50 for this effect is 0.1 nm for AVP and 36 nm for OXT. Both agonists induce Ca2+ signals in pituicytes, comprised of a transient peak and a plateau phase that is dependent on the presence of extracellular Ca2+. The EC50 values of AVP for the transient and sustained responses are 4.5 and 0.1 nm, respectively; corresponding values for OXT are 180 and 107 nm. We determined pharmacologically that these hormone‐induced Ca2+ signals are mediated by the V1a subtype of vasopressin receptors, similar to what we previously observed for hormone‐induced reversal of stellation. Removal of extracellular Ca2+ or chelation of intracellular Ca2+ partially prevented AVP from reversing stellation, suggesting a role for Ca2+ in this event. We previously established that adenosine‐induced stellation of pituicytes occurs via RhoA inhibition. However, pharmacological experiments and pull‐down assays presented here show that AVP‐induced reversal of stellation does not involve RhoA activation. Rather, AVP was found to induce a time‐dependent activation of Cdc42, another small GTPase involved in cytoskeletal plasticity. Activation of Cdc42 by AVP is sensitive to intra‐ and extracellular Ca2+ depletion, similar to AVP‐induced reversal of stellation. Furthermore, AVP‐induced reversal of stellation is blocked by expression of an NWASP fragment known to inhibit endogenous Cdc42.
Characterization of the expression of PDZ‐RhoGEF, LARG and Gα12/Gα13 proteins in the murine nervous system
Authors: Kuner R. , Swiercz J. M. , Zywietz A. , Tappe A. , Offermanns S. 
Published: March 2003

AbstractSmall GTPases of the Rho‐family, like Rho, Rac and Cdc42, are involved in neuronal morphogenesis by regulating growth cone morphology or dendritic spine formation. G‐proteins of the G12‐family, G12 and G13, couple G‐protein‐coupled receptors (GPCRs) to the activation of RhoA. Recently, two novel Rho‐specific guanine nucleotide exchange factors (RhoGEFs), PDZ‐RhoGEF and LARG, have been identified to interact with the activated α‐subunits of G12/G13 and are thus believed to mediate GPCR‐induced Rho activation. Although studies in neuronal cell lines have shown that G12/G13 and PDZ‐RhoGEF mediate GPCR‐induced neurite retraction, the role, as well as the expression of this signalling pathway, in intact brain has not been adequately studied. In the present study, we have characterized systematically the expression of Gα12, Gα13, PDZ‐RhoGEF and LARG in various murine tissues as well as their subcellular localization in the central and peripheral nervous systems. By performing immunohistochemistry, using polyclonal antibodies raised against the above proteins, we observed that Gα12, Gα13 and their RhoGEF‐effectors are distributed widely in the mammalian nervous system. Moreover, these proteins localize to distinct morphological compartments within neurons. While LARG and Gα12 were mainly found in somata of the neurons, PDZ‐RhoGEF and Gα13 were predominantly localized in the neuropil of central neurons. Interestingly, PDZ‐RhoGEF is a neural‐specific protein, whereas LARG is nearly ubiqoutous. Our data provide evidence that the G12/13–RhoGEF‐mediated pathway is present throughout the adult brain and may be involved in regulation of neuronal morphogenesis and function via GPCRs.
Expression of functional NR1/NR2B‐type NMDA receptors in neuronally differentiated SK‐N‐SH human cell line
Authors: Pizzi Marina , Boroni Flora , Bianchetti Andrea , Moraitis Costantinos , Sarnico Ilenia , Benarese Marina , Goffi Francesca , Valerio Alessandra , Spano PierFranco 
Published: March 2003

AbstractThe present study demonstrates that human SK‐N‐SH neuroblastoma cells, differentiated by retinoic acid (RA), express functional NMDA receptors and become vulnerable to glutamate toxicity. During exposure to RA, SK‐N‐SH cells switched from non‐neuronal to neuronal phenotype by showing antigenic changes typical of postmitotic neurons together with markers specific for cholinergic cells. Neuronally differentiated cells displayed positive immunoreactivity to the vesicular acetylcholine transporter and active acetylcholine release in response to depolarizing stimuli. The differentiation correlated with the expression of NMDA receptors. RT‐PCR and immunoblotting analysis identified NMDA receptor subunits NR1 and NR2B, in RA‐differentiated cultures. The NR1 protein immunolocalized to the neuronal cell population and assembled with the NR2B subunit to form functional N‐methyl‐d‐aspartate (NMDA) receptors. Glutamate or NMDA application, concentration‐dependently increased the intracellular Ca2+ levels and acetylcholine release in differentiated cultures, but not in undifferentiated SK‐N‐SH cells. Moreover, differentiated cultures became vulnerable to NMDA receptor‐mediated excitotoxicity. The glutamate effects were enhanced by glycine application and were prevented by the NMDA receptor blocker MK 801, as well as by the NR2B selective antagonist ifenprodil. These data suggest that SK‐N‐SH cells differentiated by brief treatment with RA may represent an unlimited source of neuron‐like cells suitable for studying molecular events associated with activation of human NR1/NR2B receptors.
Lateral hypothalamic lesions impair flavour‐nutrient and flavour‐toxin trace learning in rats
Authors: Touzani Khalid , Sclafani Anthony 
Published: March 2003

AbstractFood‐restricted rats with ibotenic acid lesions of the lateral hypothalamus (LHx) learned to prefer a flavour paired with concurrent intragastric (i.g.) infusions of maltodextrin, although their preference was weaker than that displayed by sham controls. Unlike controls, the LHx rats failed to acquire a flavour preference when the i.g. maltodextrin infusion was delayed by 15 min. The same rats learned to avoid flavours paired with i.g. lactose or lithium chloride over short delays (15–30 min), but were impaired, relative to controls, at a long conditioned–unconditioned stimuli delay (2 h). These data indicate that the LH is critical for the formation of flavour‐postingestive consequence learning over a delay, particularly with nutrient reinforcement. Lateral hypothalamus lesions might specifically impair the processing of nutrient‐generated unconditioned stimuli and, more generally, could interfere with the maintenance of flavour memories.
Morphological alterations in the amygdala and hippocampus of mice during ageing
Authors: Von Bohlen und Halbach Oliver , Unsicker Klaus 
Published: March 2003

AbstractDeclines in memory function and behavioural dysfunction accompany normal ageing in mammals. However, the cellular and morphological basis of this decline remains largely unknown. It was assumed for a long time that cell losses in the hippocampus accompany ageing. However, recent stereological studies have questioned this finding. In addition, the effect of ageing is largely unknown in another key structure of the memory system, the amygdala. In the present study, we have estimated neuronal density and total neuronal numbers as well as density of fragments of degenerated axons in different hippocampal subfields and amygdaloid nuclei. Comparisons were made among aged (21–26 months old) mice and normal adult littermates (8 months old). No significant volume loss occurs in the hippocampus of aged mice. Small but insignificant reductions in total neuronal numbers were found in the hippocampus and in the amygdaloid nuclei. In contrast to the mild effects of ageing upon neuronal numbers, fragments of degenerated axons were increased in both hippocampus and amygdala of aged mice. These data suggest that ageing does not induce prominent cell loss in the hippocampus or amygdala, but leads to degeneration of axons that innervate these forebrain structures. Thus, mechanisms underlying age‐related dysfunction depend on parameters other than neuronal numbers, at least in the hippocampal formation and the amygdala.
mGluR1 in cerebellar Purkinje cells is required for normal association of temporally contiguous stimuli in classical conditioning
Authors: Kishimoto Yasushi , Fujimichi Ryoko , Araishi Kenji , Kawahara Shigenori , Kano Masanobu , Aiba Atsu , Kirino Yutaka 
Published: March 2003

AbstractIn metabotropic glutamate receptor‐subtype 1 (mGluR1)‐null (mGluR1–/–) mice, cerebellar long‐term depression (LTD) and several forms of memory are impaired. However, because mGluR1 is expressed in various brain regions in wild‐type mice, it has been difficult to identify which type of memory depends on mGluR1 expressed in a given brain region. Furthermore, severe ataxia in mGluR1–/– mice complicated interpretation of the data from non‐cerebellum‐dependent tasks. We have generated mGluR1‐rescue mice, which express mGluR1 only in Purkinje cells (PCs) of their cerebellum, by introducing the mGluR1α transgene into mGluR1–/– mice under the control of a PC‐specific promoter. The mGluR1‐rescue mouse has normal LTD and displays no apparent ataxia. Therefore, this mouse is the first animal model in which effects of mGluR1 deficiency outside PCs can be studied without cerebellar dysfunction. We used three eyeblink conditioning paradigms with different temporal specificities between conditioned stimulus (CS) and unconditioned stimulus (US). Delay conditioning, in which CS and US coterminate, was impaired in mGluR1–/– mice but normal in mGluR1‐rescue mice. However, both strains of mice displayed severe impairment in trace conditionings, in which a stimulus‐free interval of 250 or 500 ms intervened between CS and US. We also examined social transmission of food‐preference and novel‐object‐recognition memory tests. In these tasks, mGluR1‐rescue mice showed normal short‐term but impaired long‐term memory. We conclude that mGluR1 in PCs is indispensable for normal learning of association of temporally contiguous stimuli in associative conditioning. In contrast, mGluR1 in other cell types is required for associating discontiguous stimuli and long‐term memory formation in nonspatial hippocampus‐dependent learning.
Thalamocortical oscillations in a genetic model of absence seizures
Authors: D'Arcangelo Giovanna , D'Antuono Margherita , Biagini Giuseppe , Warren Richard , Tancredi Virginia , Avoli Massimo 
Published: March 2003

AbstractWe used field potential recordings in an in vitro thalamocortical slice preparation to compare the rhythmic oscillations generated by reciprocally connected networks of the thalamus and cerebral cortex obtained from epileptic (> 160 days old) WAG/Rij and age‐matched, nonepileptic control (NEC) rats. To increase neuronal excitability, and thus to elicit spontaneous field potential activity in vitro, we applied medium containing: (i) zero [Mg2+]; (ii) high [K+] (8.25 mm); or (iii) low concentrations of the K+ channel blocker 4‐aminopyridine (4AP, 0.5–1 µm). Of these procedures, only the last was effective in triggering oscillatory activity that depended on the type of tissue. Thus, during 4AP application: (i) sequences of fast (intraburst frequency 9.5–16.1 Hz) and slower (5–8.9 Hz) field potential oscillations (FPOs) were recorded in WAG/Rij slices (n = 23), but (ii) only fast FPOs were seen in NEC slices (n = 7). Slower FPOs in WAG/Rij slices reflected a larger degree of thalamocortical synchronization than fast FPOs, and disappeared after surgical separation of cortex and thalamus (n = 5); under these conditions fast FPOs continued to occur in thalamus only. In addition, fast and slower FPOs disappeared in all areas of the WAG/Rij slice during thalamic application of the excitatory amino acid receptor antagonist kynurenic acid (n = 3), while fast FPOs continued to occur in thalamus when kynurenic acid was applied to the cortex (n = 4). Bath application of the N‐methyl‐d‐aspartic acid (NMDA) receptor antagonist 3,3‐(2‐carboxypiperazine‐4‐yl)‐propyl‐1‐phosphonate (CPP) abolished slower FPOs in WAG/Rij cortex and thalamus (n = 6) without infuencing fast FPOs recorded in WAG/Rij (n = 6) or NEC slices (n = 4). Moreover, cortical application of CPP (n = 6) abated slower FPOs although they persisted following CPP application to the thalamus (n = 7). Our data demonstrate that highly synchronized, slower FPOs can occur during 4AP application in WAG/Rij but not in NEC slices. This activity, which may represent an in vitro hallmark of thalamocortical epileptogenicity, requires the function of reciprocally connected thalamic and cortical networks and depends on cortical NMDA receptor‐mediated mechanisms.
Intrastriatal sonic hedgehog injection increases Patched transcript levels in the adult rat subventricular zone
Authors: Charytoniuk D. , Traiffort E. , Hantraye P. , Hermel J. M. , Galdes A. , Ruat M. 
Published: March 2003

AbstractThe morphogen sonic hedgehog (Shh) is implicated in neural tissue patterning and the growth of brain structures during embryogenesis and postnatal development and is also present in the adult brain. Shh signals through interaction with the tumour suppressor Patched (Ptc). This receptor for Shh is associated with Smoothened (Smo), a protein with high homology to the G‐protein coupled receptors. However, little is known about the transduction mechanisms implicated in Shh signalling in the adult brain. The study described here shows that injection of aminoterminal myristoylated Shh (myrShhN) into the adult rat striatum robustly increases the levels of Ptc transcripts in selective brain areas including the subventricular zone (SVZ). The adult SVZ contains cell progenitors, which can proliferate and differentiate into new neurons and glia. In the myrShhN injected animals, proliferation and differentiation of these SVZ precursor cells were not affected as demonstrated by BrdU incorporation and immunohistochemistry performed with specific antibodies for nestin (uncommitted neural progenitors), PSA‐NCAM (migrating neuroblasts) or GFAP (astrocytes). Together with the presence of Smo expressing cells and amino‐terminal Shh (ShhN) protein in SVZ area of untreated animals, the data presented here supports the hypothesis that the Shh pathway may be activated in the adult brain, and that a niche for Shh signalling exists within the adult SVZ.
Locus coeruleus activation modulates firing rate and temporal organization of odour‐induced single‐cell responses in rat piriform cortex
Authors: Bouret Sebastien , Sara Susan J. 
Published: March 2003

AbstractPiriform cortex (PCx) is the primary cortical projection region for olfactory information and has bidirectional monosynaptic connections with olfactory bulb and association cortices. PCx neurons display a complex receptive field, responding to odours rather than their molecular components, suggesting that these neurons are involved in higher order olfactory processing. Neuromodulators, especially noradrenaline (NA), have important influences on sensory processing in other cortical regions and might be responsible for the plasticity observed in PCx during learning. The present study is the first attempt to examine in vivo the actions of NA on sensory responses in the PCx. Stimulation of the noradrenergic nucleus locus coeruleus (LC) was used to induce release of NA in the forebrain in urethane‐anaesthetized rats. Extracellular recording of single units was made simultaneously in anterior and posterior PCx. The responses to an odour stimulus were measured over 25 trials. Twenty‐five subsequent odour presentations were preceded by stimulation of the ipsilateral LC through a bipolar electrode, previously placed in the LC under electrophysiological control. This priming stimulation modified the activity of 77 of the 135 recorded neurons. For most cells, LC stimulation enhanced cortical responses to odour in terms of both spike count and temporal organization, with some differential effects in anterior and posterior regions. These results are the first to show enhancement of sensory responses in the olfactory cortex by LC activation. Spontaneous activation of LC neurons such as occurs during learning could serve to enhance olfactory perception and promote learning.
Environmental conditions influence hippocampus‐dependent behaviours and brain levels of amyloid precursor protein in rats
Authors: Teather Lisa A. , Magnusson Jane E. , Chow Christina M. , Wurtman Richard J. 
Published: March 2003

AbstractSprague‐Dawley rats were reared in enriched (EC; group housing, exposure to stimulating objects, frequent handling) or restricted (RC; individual housing, no exposure to stimulating objects, minimal handling) environments starting on day 23 of life. At six months of age, they underwent behavioural tests to assess ‘cognitive’ and ‘stimulus‐response’ memory, selective attention, and inflammatory pain processing. Alterations in synapses and cell survival may occur as a result of environment differences; therefore we assessed the brain levels of several proteins implicated in neurite outgrowth, synaptogenesis, and cell survival. Brains were dissected and analysed for amyloid precursor protein (APP) and other synaptic and cytoskeletal proteins using Western blotting. The performance of EC animals in a hidden platform water maze task, and in a test of selective attention (both of which are thought to involve the hippocampus) was superior to that of RC animals. In contrast, performance of RC animals on two stimulus‐response tasks, the visible platform water maze test and simple visual discrimination (both of which are thought to be hippocampal independent) was indistinguishable from that of EC animals. Male EC rats displayed a different behavioural response to formalin during the inflammatory phase of nociception – the phase affected by hippocampal processing; a similar trend was observed in females. Female but not male RC rats exhibited elevated plasma corticosterone levels; adrenal weights were unaffected by environmental conditions. Region‐specific increases in brain levels of APP, neurofilament‐70 (NF‐70), and platelet‐activating factor receptor (PAF‐R) were found in EC rats. These data suggest that enriched animals manifest enhanced functioning of certain hippocampus‐mediated behaviours when compared with that of their restricted counterparts; and that brain levels of various synaptic and structural proteins involved in neurite outgrowth, cell survival, and synaptogenesis, are affected by environmental factors.