bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of GABAC receptor ρ1 and ρ2 subunits during development of the mouse retina
Authors: Greka Anna , Lipton Stuart A. , Zhang Dongxian 
Published: March 2003

AbstractRetinal γ‐aminobutyric acid type C (GABAC) receptors consist of ρ subunits. Here we report our results from a competitive PCR and patch‐clamp electrophysiology study quantifying ρ subunit message and characterizing GABAC receptor‐mediated currents at different stages of mouse retinal development. Mouse ρ1 message is first detected at postnatal day 6 (P6), increases significantly until P9 and remains at this level through adulthood, whereas mouse ρ2 message does not appear until P9, peaks at P15 and remains at this level through adulthood. There is an approximate twofold excess of ρ1 compared to ρ2 message at most stages of development, which persists in adulthood. Functional GABAC receptors are detected in acutely dissociated bipolar cells of P9 or older mouse retina. Early in development (P9–10), GABAC receptors are composed solely of ρ1 subunits, but subsequently contain ρ1 and/or ρ2 subunits (by P11 and later). These findings are intriguing because the onset and rapid increase in ρ subunit transcription and functional expression match the initiation and active period of bipolar cell differentiation in retinal development as well as the stage of eye opening and initial visual experience in the rodent. The investigation of mouse ρ subunits here forms a basis for future studies on the role of GABAC receptors in retinal development.
Presynaptic inhibition by muscimol through GABAB receptors
Authors: Yamauchi Tatsuhito , Hori Tetsuya , Takahashi Tomoyuki 
Published: March 2003

AbstractThe γ‐aminobutyric acid type A (GABAA) receptor agonist muscimol is widely used as a tool for reducing neuronal activities particularly in experiments in vivo. At the synapse formed by the calyx of Held in the rat brainstem slice, the GABAA receptor agonist muscimol (> 10 μm) attenuated the amplitude of excitatory post synaptic currents (EPSCs) accompanied by an increase in the coefficient of variation of EPSCs, suggesting its presynaptic inhibitory effect. This muscimol effect was not affected by bicuculline but occluded the presynaptic inhibitory effect of the GABAB receptor agonist baclofen and was abolished by the type B GABA (GABAB) receptor‐specific antagonist (+)‐5,5‐dimethyl‐2‐morpholineacetic acid (SCH 50911; 20 μm). We conclude that muscimol activates presynaptic GABAB receptors thereby attenuating synaptic transmission.
Involvement of sst2 somatostatin receptor in locomotor, exploratory activity and emotional reactivity in mice
Authors: Viollet C. , Vaillend C. , Videau C. , Bluet‐Pajot M. T. , Ungerer A. , L'héritier A. , Kopp C. , Potier B. , Billard J. ‐M. , Schaeffer J. , Smith R. G. , Rohrer S. P. , Wilkinson H. , Zheng H. , Epelbaum J. 
Published: March 2003

AbstractSomatostatin (SRIF) controls many physiological and pathological processes in the central nervous system but the respective roles of the five receptor isotypes (sst1–5) that mediate its effects are yet to be defined. In the present study, we attempted to identify functions of the sst2 receptor using mice with no functional copy of this gene (sst2 KO mice). In contrast with control 129Sv/C57Bl6 mice, sst2 mRNA was no longer detectable in the brain of sst2 KO mice; 125I‐labeled Tyr0DTrp8‐SRIF14 binding was also greatly reduced in almost all brain structures except for the hippocampal CA1 area, demonstrating that sst2 accounts for most SRIF binding in mouse brain. Invalidation of this subtype generated an increased anxiety‐related behaviour in a number of behavioural paradigms, while locomotor and exploratory activity was decreased in stress‐inducing situations. No major motor defects could be detected. sst2 KO mice also displayed increased release of pituitary ACTH, a main regulator of the stress response. Thus, somatostatin, via sst2 receptor isotype pathways, appears involved in the modulation of locomotor, exploratory and emotional reactivity in mice.
Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area
Authors: Forster Gina L. , Blaha Charles D. 
Published: March 2003

AbstractCholinergic and glutamatergic neurons in the laterodorsal tegmentum (LDT) and neighbouring mesopontine nuclei are thought to influence mesolimbic dopaminergic neuronal activity involved in goal‐directed behaviours. We measured the changes in dopamine oxidation current (corresponding with dopamine efflux) in the nucleus accumbens (NAc) in response to electrical stimulation of the LDT using in vivo chronoamperometry in urethane‐anaesthetized rats. LDT stimulation (35 Hz pulse trains for 60 s, 1 s intertrain interval) evoked a three‐component change in dopamine efflux in the NAc: (i) an initial stimulation time‐locked increase in the dopamine signal above baseline, followed by (ii) an immediate decrease below baseline, and thereafter by (iii) a prolonged increase in the dopamine signal above baseline. Intra‐VTA infusion of the nicotinic receptor antagonist mecamylamine (5 μg/0.5 μL) or the ionotropic glutamate receptor antagonist kynurenate (10 μg/μL) attenuated the first LDT‐elicited component. The second suppressive component was abolished by intra‐LDT infusions of either the nonselective or the M2‐selective muscarinic receptor antagonists scopolamine (100 μg/μL) and methoctramine (50 μg/μL), respectively. In contrast, intra‐VTA infusions of scopolamine (200 μg/μL) resulted in a selective attenuation of the third facilitatory component, whereas both second and third components were abolished by systemic injections of scopolamine (5 mg/kg). These results suggest that the initial increase, subsequent decrease, and final prolonged increase in extracellular dopamine levels in the NAc are selectively mediated by LDT‐elicited activation of (i) nicotinic and glutamatergic receptors in the VTA, (ii) muscarinic M2 autoreceptors on LDT cell bodies, and (iii) muscarinic receptors in the VTA, respectively.
Graded expression of EphA3 in the retina and ephrin‐A2 in the superior colliculus during initial development of coarse topography in the wallaby retinocollicular projection
Authors: Stubbs Janine , Palmer Ann , Vidovic Maria , Marotte Lauren R. 
Published: March 2003

AbstractWe describe the expression of EphA3 and EphA7 receptors and ephrin‐A2 ligand in the retina and the superior colliculus during the development of the retinocollicular projection in the marsupial wallaby (Macropus eugenii), using immunoblotting and immunohistochemistry. EphA3 in the retina was in a striking, low central to high peripheral gradient, superimposed on which was a high temporal to low nasal level of expression. This distribution was evident from postnatal day 30, when axons are growing into the colliculus and forming a coarsely organized topographic projection, to postnatal day 65, when axons have arborized in their correct retinotopic positions. EphA7 showed a shallow centroperipheral gradient with no nasotemporal differences in expression. In the superior colliculus no rostrocaudal differences in distribution were detected for either of these receptors. Ephrin‐A2 was distributed in a gradient increasing from the rostral to the caudal pole in the superficial layers of the superior colliculus only up to postnatal day 30. Ephrin‐A2 was evenly distributed in the retina throughout development of the projection. Expression of EphA3 in the retina increased, while the expression of ephrin‐A2 in the colliculus was downregulated over time. The graded expression of EphA3 and ephrin‐A2 early in the development of the projection suggests that they play a role in establishment of coarse topography of retinal axons along the rostrocaudal axis of the superior colliculus. However, the gradients were not complementary, meaning that EphA3 alone cannot mediate the repulsive interactions with ephrin‐A2 that have been postulated to underlie formation of the topographic map.
Early and delayed induction of immediate early gene expression in a novel focal cerebral ischemia model in the rat
Authors: Johansson Inga‐Maj , Wester Per , Háková Michaela , Gu WeiGang , Seckl Jonathan R. , Olsson Tommy 
Published: March 2003

AbstractThis study aimed at evaluating changes in expression of immediate early genes in a new photothrombotic focal ischemia model that exhibits late spontaneous reperfusion and morphological restoration in the region‐at‐risk within the cerebral cortex. Gene expression was studied with Northern blots, in situ hybridization and immunohistochemistry. At early time points (1–4 h), nerve growth factor‐induced gene A and B, and c‐fos mRNAs, were quickly induced throughout the ipsilateral cortex, with no obvious differences between the region‐at‐risk and remote cortical areas. High concentrations of nerve growth factor‐induced gene A and c‐Fos proteins were present within the region‐at‐risk even when cortical cerebral blood flow was as low as 40% of control values. At 4 h the nerve growth factor‐induced gene A mRNA and protein expression was significantly decreased in the hippocampus vs. naive controls. However, a small decrease was also found in sham‐operated and anaesthetized controls. A late induction, at 5 days, of c‐fos and nerve growth factor‐induced gene B mRNAs was seen bilaterally in the hippocampus and also, in the case of nerve growth factor induced‐gene B, in the contralateral cortex. A complex pattern of changes in immediate early gene expression occurs after reversible focal cortical ischemia. This may be important for tissue recovery as well as neuropsychiatric symptoms after stroke.
Functional connections and epileptic spread between hippocampus, entorhinal cortex and amygdala in a modified horizontal slice preparation of the rat brain
Authors: Stoop Ron , Pralong Etienne 
Published: March 2003

AbstractThe hippocampus, the entorhinal cortex and the amygdala are interconnected structures of the limbic system that are implicated in memory and emotional behaviour. They demonstrate synaptic plasticity and are susceptible to development of temporal lobe epilepsy, which may lead to emotional and psychological disturbances. Their relative anatomical disposition has limited the study of neurotransmission and epileptic spread between these three regions in previous in vitro preparations. Here we describe a novel, modified‐horizontal slice preparation that includes in the same plane the hippocampus, entorhinal cortex and amygdala. We found that, following application of bicuculline, each region in our preparation could generate spontaneous bursts that resembled epileptic interictal spikes. This spontaneous activity initiated in the hippocampal CA3/2 region, from where it propagated and controlled the activity in the entorhinal cortex and the amygdala. We found that this spontaneous bursting activity could spread via two different pathways. The first pathway comprises the well‐known subiculum–entorhinal cortex–perirhinal cortex–amygdala route. The second pathway consists of a direct connection between the CA1 region and perirhinal cortex, through which the hippocampal bursting activity can spread to the amygdala while bypassing the entorhinal cortex. Thus, our experiments provide a new in vitro model of initiation and spread of epileptic‐like activity in the ventral part of the limbic system, which includes a novel, fast and functional connection between the CA1 region and perirhinal cortex.
Tone‐evoked oscillations in the rat auditory cortex result from interactions between the thalamus and reticular nucleus
Authors: Cotillon N. , Edeline J. ‐M. 
Published: March 2003

AbstractThis study investigates the origins of tone‐evoked oscillations (5–13 Hz) in the thalamo‐cortical auditory system of anaesthetized rats. In three separate experiments, the auditory sector of the reticular nucleus (RE), the auditory cortex and the auditory thalamus were inactivated by local applications of muscimol (1 mg/mL). To assess the efficacy of this procedure, recordings were performed in the inactivated structure in each experiment; and to determine the extent of the drug diffusion autoradiographic experiments were carried out. The evolution of the strength of the oscillations was followed using power spectra during the whole recording session. In the first experiment, muscimol injection in the auditory RE totally suppressed the tone‐evoked oscillations in the auditory thalamus and cortex. In the second experiment, inactivation of the auditory cortex did not interfere with the presence of tone‐evoked oscillations in the auditory RE. In the third experiment, inactivation of the auditory thalamus impaired the oscillations produced by cortical stimulation in the auditory RE. From these results, it appears that both the auditory thalamus and the auditory sector of the RE, but not the auditory cortex, are involved in the generation of stimulus‐evoked oscillations in the thalamo‐cortical auditory system.
Adenoviral gene transfer to the injured spinal cord of the adult rat
Authors: Huber Andrea B. , Ehrengruber Markus U. , Schwab Martin E. , Brösamle Christian 
Published: March 2003

AbstractWe have investigated gene transfer to the injured adult rat spinal cord by the use of a recombinant adenovirus. 105 or 5 × 106 plaque‐forming units (pfu) of a replication‐defective adenoviral vector carrying the green fluorescent protein (GFP) reporter gene were injected into a dorsal hemisection lesion at spinal level T8. Gene expression and inflammatory responses were studied 4, 8 and 21 days after surgery. Numerous cells within 3 mm on each side of the lesion were found to express high levels of GFP at 4 days after infection as shown by GFP fluorescence and immunohistochemistry. At 8 days, expression was still strong although weaker than at 4 days. After 21 days, transgene expression had almost ceased. Expression was neither higher nor more prolonged in animals that had received the higher vector dose. Delayed injection 1 week after spinal injury also did not increase transgene expression. Infected cell types were identified immunohistochemically. The most prominent transduced cells were spinal motoneurons. Additionally, we could identify other neurons, astrocytes, oligodendrocytes and peripheral cells infiltrating the lesion site. The glial and inflammatory reaction at and around the lesion was studied by cresyl violet histology, α‐GFAP, OX42 and α‐CD‐8 immunohistochemistry. No significant differences from controls were found in the low virus group; in the high virus group a strong invasion of CD‐8‐positive lymphocytes was found. Open‐field locomotion analysis showed virus‐infected animals performing as well as control animals. Adenoviral gene transfer may be an efficient way to introduce factors to the injured spinal cord in paradigms of research or therapy.
SAP97 concentrates at the postsynaptic density in cerebral cortex
Authors: Valtschanoff Juli G. , Burette Alain , Davare Monika A. , Leonard A. Soren , Hell Johannes W. , Weinberg Richard J. 
Published: March 2003

AbstractSAP97, a PDZ‐containing protein, is reported to concentrate in axon terminals, where its function remains unknown. Using highly specific new antibodies, we show that SAP97 in rat cerebral cortex is associated with heteromeric AMPA receptors via a selective biochemical interaction between SAP97 and the GluR1 subunit. Using light and electron microscopic immunocytochemistry, we demonstrate cellular and synaptic colocalization of SAP97 and GluR1, and show that SAP97 concentrates at synapses that contain GluR1 but not necessarily GluR2 or GluR3. Using quantitative postembedding immunogold electron microscopy, we find that SAP97 is at highest concentration within the postsynaptic density of asymmetric synapses. These data suggest that SAP97 may help to anchor GluR1‐containing AMPA receptors at the synapse. As a multifunctional scaffolding protein, SAP97 may organize components of AMPA‐related intracellular signalling pathways, including those associated with calcium‐permeable homomeric GluR1 channels.
Differential learning‐stage dependent patterns of c‐Fos protein expression in brain regions during the acquisition and memory consolidation of an operant task in mice
Authors: Bertaina‐Anglade Valérie , Tramu Gérard , Destrade Claude 
Published: March 2003

AbstractThe present study analysed the effects of the stage of learning of an appetitive operant conditioning task on the spatial and temporal patterns of c‐Fos protein levels in the brain of BALB/c mice. c‐Fos levels were assessed by immunohistochemistry at either 60, 120 or 180 min after either the first, the second or the fifth daily training session and compared to sham animals. The results show an increase of c‐Fos‐positive nuclei in several subcortical and cortical brain regions, 60‐min post‐acquisition. Because these activations were a function of task mastery, the data indicate that they were specifically related to learning. Following the first acquisition session, significant increases in c‐Fos‐positive neurons were observed in the dorsal hippocampus (CA3), anterior cingulate, occipital and parietal cortices. Following the second daily training session, c‐Fos was highly expressed in some subcortical regions, the hippocampus, the subiculum, the entorhinal, and posterior cingulate areas. Moreover, a significant correlation was found between the progression of performance from day 1 to day 2 and c‐Fos expression on the hippocampal CA1 subfield. Following complete acquisition, no further task‐dependent increases in c‐Fos‐labelled nuclei was observed in any brain region sampled, suggesting that the intervention of c‐Fos‐induced mechanisms in the consolidation process were terminated. The training stage‐dependent changes in regional post‐training c‐Fos expression in the hippocampus and the connected limbic regions suggest that this neuronal network is actively engaged in memory consolidation processes.
Activation of nicotinic acetylcholine receptors induces long‐term potentiation in vivo in the intact mouse dentate gyrus
Authors: Matsuyama Shogo , Matsumoto Akira , Enomoto Taira , Nishizaki Tomoyuki 
Published: March 2003

AbstractThe present study was conducted to clarify the role of nicotinic ACh receptors (nAChRs) on long‐term potentiation (LTP) in vivo in the intact mouse dentate gyrus using extracellular recording techniques. Intraperitoneal application of nicotine at a dose of 3.0 mg/kg but not 0.03 or 0.3 mg/kg produced a gradually developing, long‐lasting increase for 120 min similar to tetanic LTP. Nicotine at a dose of 9.0 mg/kg caused a temporary increase followed by depression. The long‐lasting potentiation induced by nicotine at 3.0 mg/kg, which was named nicotinic long‐term potentiation (LTPn), and tetanic LTP were significantly suppressed by pretreatment with mecamylamine (0.5 mg/kg i.p.), a nonselective nicotinic antagonist, but not affected by postapplication of mecamylamine. Interestingly, choline, a selective α7 nAChR agonist, at 3.0–90 mg/kg, induced the long‐lasting potentiation similar to LTPn in a dose‐dependent manner in vivo in the intact mouse dentate gyrus. The long‐lasting potentiation induced by choline (30 mg/kg i.p.) was additionally increased by postapplication of nicotine (3.0 mg/kg i.p.) or tetanic stimulation. The present study revealed that systemic application of nicotine or choline induced the long‐lasting potentiation in vivo in the intact mouse dentate gyrus, suggesting that α7 nAChRs may contribute to the induction of LTP by nicotine, and supporting in vivo animal studies that nicotine improves learning and memory performance.
Expression of c‐Met in developing rat hippocampus: evidence for HGF as a neurotrophic factor for calbindin D‐expressing neurons
Authors: Korhonen Laura , Sjöholm Ulrika , Takei Nobuyuki , Kern Michael A. , Schirmacher Peter , Castrén Eero , Lindholm Dan 
Published: March 2003

AbstractHepatocyte growth factor‐scatter factor (HGF) is expressed in different parts of the nervous system, and has been shown to exhibit neurotrophic activity. Here we show that c‐Met, the receptor for HGF, is expressed in developing rat hippocampus, with the highest levels during the first postnatal weeks. To study the function of HGF, hippocampal neurons were prepared from embryonic rats and treated with different HGF concentrations. In these cultures, HGF increased the number of neurons expressing the 28‐kDa calcium‐binding protein (calbindin D) in a dose‐dependent manner. The effect of HGF was larger than that observed with either brain‐derived neurotrophic factor (BDNF) or neurotrophin‐3 (NT‐3), and cotreatment of the cultures with HGF and the neurotrophins was additive with respect to calbindin D neurons. Besides affecting the number of neurons, HGF significantly increased the degree of sprouting of calbindin D‐positive neurons, suggesting an influence on neuronal maturation. BDNF and NT‐3 stimulated neurite outgrowth of calbindin D neurons to a much smaller degree. In contrast to calbindin D neurons, HGF did not significantly increase the number of neurons immunoreactive with the neurotransmitter γ‐aminobutyric acid (GABA) in the hippocampal cultures. Immunohistochemical studies showed that c‐Met‐, calbindin D‐ and HGF‐immunoreactive cells are all present in the dentate gyrus and partly colocalize within neurons. These results show that HGF acts on calbindin D‐containing hippocampal neurons and increases their neurite outgrowth, suggesting that HGF plays an important role for the maturation and function of these neurons in the hippocampus.
Late postnatal reorganization of GABAA receptor signalling in native GnRH neurons
Authors: Sim Joan A. , Skynner Michael J. , Pape Jean‐Rémi , Herbison Allan E. 
Published: March 2003

AbstractThe molecular and cellular characteristics of the gonadotropin‐releasing hormone (GnRH) neurons have been difficult to ascertain due to their scattered distribution within the basal forebrain. Using morphological criteria coupled with single cell RT‐PCR postidentification, we have developed a method for investigating native GnRH neurons in the mouse brain and used it to examine the development of GABAA receptor signalling in this phenotype. Following the harvesting of the cytoplasmic contents of individual GnRH neurons, single cell multiplex RT‐PCR experiments demonstrated that GABAA receptor α1–5, β1–3 and γ2 & 3 subunit transcripts were expressed by both neonatal (postnatal day 5) and juvenile (day 15–20) GnRH neurons in a heterogeneous manner. Following puberty, this profile was reduced to a predominant α1, α5, β1, γ2 subunit complement in rostral preoptic area GnRH neurons of the adult female. Whole‐cell patch‐clamp recordings revealed little difference between juvenile and adult GnRH neurons in their resting membrane potential and spontaneous firing rates. All GnRH neurons were found to be subjected to a tetrodotoxin‐insensitive, tonic GABAergic barrage signalling through the GABAA receptor. However, marked heterogeneity in the sensitivity of individual juvenile GnRH neurons to GABA was revealed and, in parallel with the change in subunit mRNA profile, this was dramatically reduced in the reproductively competent adult GnRH neurons. These findings provide the first electrical and molecular characterization of the GnRH phenotype and demonstrate a novel pattern of late postnatal reorganization of native GABAA receptor gene expression and signalling in the GnRH neuronal population.