bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of cation‐chloride cotransporter expression during embryonic rodent CNS development
Authors: Li Hong , Tornberg Janne , Kaila Kai , Airaksinen Matti S. , Rivera Claudio 
Published: March 2003

AbstractIntracellular Cl– plays a key role in cellular volume regulation, cell cycle control and shaping the polarity of inhibitory postsynaptic responses mediated by anion‐permeable GABA and glycine receptors. In this study, we have investigated the expression patterns of members of the cation‐chloride cotransporters (CCCs), including the K‐Cl cotransporters KCC1‐4 and the Na‐K‐2 Cl cotranporter NKCC1 during rodent embryonic brain development. At the time of neurogenesis (embryonic days; E12.5–14.5), KCC1 was only detectable in the developing choroid plexus. KCC2 mRNA was detectable as early as E12.5 in the ventral part of the (cervical) spinal cord, and by E14.5, the expression had spread to TUJ1‐positive differentiating regions of the rhombencephalon, diencephalon and olfactory bulb, in parallel with neuronal maturation. KCC3 mRNA was scarce in the cortical plate at E14.5, and slightly up‐regulated at birth. In contrast, KCC4 mRNA was abundantly expressed in the ventricular zone and was down‐regulated perinatally. At E14.5, NKCC1 was highly expressed in the vimentin‐positive radial glia of the proliferative zone of the subcortical region. At later embryonic stages, during gliogenesis (E17‐P0), there was a shift in NKCC1 expression to the neuron specific Class III β‐tubulin (βIII) positive region of the cortical plate. These unique spatiotemporal expression patterns of distinct CCCs during embryonic development suggests that Cl– regulatory mechanisms are critically involved in the control of neuronal development.
Altering electrical connections in the nervous system of the pteropod mollusc Clione limacina by neuronal injections of gap junction mRNA
Authors: Kelmanson Ilya V. , Shagin Dmitry A. , Usman Natalia , Matz Mikhail V. , Lukyanov Sergey A. , Panchin Yury V. 
Published: March 2003

AbstractNeurons can communicate with each other either via exchange of specific molecules at synapses or by direct electrical connections between the cytoplasm of either cell [for review see Bruzzone et al. (1996) Eur. J. Biochem., 238, 1–27]. Although electrical connections are abundant in many nervous systems, little is known about the mechanisms which govern the specificity of their formation. Recent cloning of the innexins – gap junction proteins responsible for electrical coupling in invertebrates (Phelan et al. (1998) Trends Genet., 14, 348–349], has made it possible to study the molecular mechanisms of patterning of the electrical connections between individual neurons in model systems. Here we demonstrate that intracellular injection of mRNA encoding the molluscan innexin Panx1 (Panchin et al. 2000 Curr. Biol., 10, R473‐R474) drastically alters the specificity of electrical coupling between identified neurons of the pteropod mollusc Clione limacina.
The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn
Authors: Todd A. J. , Hughes D. I. , Polgár E. , Nagy G. G. , Mackie M. , Ottersen O. P. , Maxwell D. J. 
Published: March 2003

AbstractTwo vesicular glutamate transporters, VGLUT1 and VGLUT2, have recently been identified, and it has been reported that they are expressed by largely nonoverlapping populations of glutamatergic neurons in the brain. We have used immunocytochemistry with antibodies against both transporters, together with markers for various populations of spinal neurons, in an attempt to identify glutamatergic interneurons in the dorsal horn of the mid‐lumbar spinal cord of the rat. The great majority (94–100%) of nonprimary axonal boutons that contained somatostatin, substance P or neurotensin, as well as 85% of those that contained enkephalin, were VGLUT2‐immunoreactive, which suggests that most dorsal horn neurons that synthesize these peptides are glutamatergic. In support of this, we found that most somatostatin‐ and enkephalin‐containing boutons (including somatostatin‐immunoreactive boutons that lacked calcitonin gene‐related peptide and were therefore probably derived from local interneurons) formed synapses at which AMPA receptors were present.We also investigated VGLUT expression in central terminals of primary afferents. Myelinated afferents were identified with cholera toxin B subunit; most of those in lamina I were VGLUT2‐immunoreactive, whereas all those in deeper laminae were VGLUT1‐immunoreactive, and some (in laminae III–VI) appeared to contain both transporters. However, peptidergic primary afferents that contained substance P or somatostatin (most of which are unmyelinated), as well as nonpeptidergic C fibres (identified with Bandeiraea simplicifolia isolectin B4) showed low levels of VGLUT2‐immunoreactivity, or were not immunoreactive with either VGLUT antibody. As all primary afferents are thought to be glutamatergic, this raises the possibility that unmyelinated afferents, most of which are nociceptors, express a different vesicular glutamate transporter.
The mouse MPTP model: gene expression changes in dopaminergic neurons
Authors: Kühn Kati , Wellen Jennifer , Link Nina , Maskri Lyutha , Lübbert Hermann , Stichel Christine C. 
Published: March 2003

AbstractParkinson's disease (PD) is a common neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although valuable animal models have been developed, our knowledge of the aetiology and pathogenic factors implicated in PD is still insufficient to develop causal therapeutic strategies aimed at halting its progression. The neurotoxicity induced by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is one of the most valuable models for analysing pathological aspects of PD. In this paper we studied the gene expression patterns underlying the pathogenesis of MPTP‐induced neurodegeneration. We treated young and old C57BL/6 mice with different schedules of MPTP to induce degenerative processes that vary in intensity and time‐course. During the first week after intoxication we used nonradioactive in situ‐hybridization to investigate the expression patterns of genes associated with (i) dopamine metabolism and signalling; (ii) familial forms of PD; (iii) protein folding and (iv) energy metabolism. MPTP injections induced different severities of neuronal injury depending on the age of the animals and the schedule of administration as well as a significant degeneration in the striatum. In situ hybridization showed that MPTP intoxication initiated a number of gene expression changes that (i) were restricted to the neurons of the substantia nigra pars compacta; (ii) were correlated in intensity and number of changes with the age of the animals and the severity of histopathological disturbances; (iii) displayed in each a significant down‐regulation by the end of one week after the last MPTP injection, but (iv) varied within one MPTP regimen in expression levels during the observation period. The subacute injection of MPTP into one‐year‐old mice induced the most severe changes in gene expression. All genes investigated were affected. However, α‐synuclein was the only gene that was exclusively up‐regulated in MPTP‐treated animals displaying cell death.
Cannabinoid withdrawal syndrome is reduced in double mu and delta opioid receptor knockout mice
Authors: Castañé Anna , Robledo Patricia , Matifas Audrey , Kieffer Brigitte L. , Maldonado Rafael 
Published: March 2003

AbstractSeveral studies have shown a functional relationship between the endogenous cannabinoid and opioid systems. However, acute effects of Δ9‐tetrahydrocannabinol (THC) and physical dependence were not modified in knockout mice with single deletion of mu (MOR), delta (DOR) or kappa (KOR) opioid receptors. To further investigate the neurobiological basis of cannabinoid dependence, we have evaluated acute pharmacological responses, rewarding effects, tolerance and dependence to THC in double MOR/DOR knockout mice. Antinociception and hypolocomotion induced by acute THC administration remained unaffected, whereas the hypothermic effect was slightly attenuated in these double knockout mice. During chronic THC treatment, knockout mice developed slower tolerance to the hypothermic effect, but the development of tolerance to antinociceptive and hypolocomotor effects was unchanged. The rewarding properties of THC, measured in the conditioned place preference paradigm, were reduced in knockout mice. Interestingly, the somatic manifestations of THC withdrawal were also significantly attenuated in mutant mice, suggesting that a cooperative action of MOR and DOR is required for the entire expression of THC dependence.
Behavioural learning‐induced increase in spontaneous GABAA‐dependent synaptic activity in rat striatal cholinergic interneurons
Authors: Bonsi Paola , Florio Tiziana , Capozzo Annamaria , Pisani Antonio , Calabresi Paolo , Siracusano Alberto , Scarnati Eugenio 
Published: March 2003

AbstractCholinergic striatal interneurons play a crucial role in cognitive aspects of context‐dependent motor behaviours. They are considered to correspond to the tonically active neurons (TANs) of the primate striatum, which phasically decrease their discharge at the presentation of reward‐related sensory stimuli. The origin of this response is still poorly understood. Therefore, in the present paper, we have investigated whether synaptic changes establish in cholinergic interneurons from young rats that have learned a rewarded, externally cued sensorimotor task. Corticostriatal slices were prepared from both control and trained rats. No significant change in intrinsic membrane properties and evoked synaptic activity was observed in cholinergic interneurons, nor the responsiveness to exogenously applied dopaminergic and glutamatergic agonists was modified. Conversely, an increased occurrence of spontaneous bicuculline‐sensitive depolarizing postsynaptic potentials (sDPSP) was recorded. The frequency of the GABAA‐mediated sDPSP was increased in comparison to not‐conditioned rats. Overall, these results suggest that after learning a rewarded sensorimotor paradigm an increased GABA influence develops on cholinergic interneurons. The origin of this effect might be searched in collaterals of GABAergic output spiny neurons as well as in GABAergic striatal interneurons impinging onto cholinergic interneurons. This intrastriatal mechanism might be involved in the phasic suppression of discharge of TANs at the presentation of reward‐related sensory stimuli.
Neuronal activation in female budgerigars is localized and related to male song complexity
Authors: Eda‐Fujiwara Hiroko , Satoh Ryohei , Bolhuis Johan J. , Kimura Takeji 
Published: March 2003

AbstractFemales of several songbird species have been shown to respond preferentially to a more complex song. The male budgerigar (Melopsittacus undulatus) sings complex songs consisting of discrete components, known as syllables. We exposed female budgerigars to either standard male song, complex song, or simple song, the iteration of only one syllable (either frequency‐modulated or unmodulated). Using immunocytochemistry, we analysed the expression of the protein product of the immediate early gene ZENK in a number of forebrain regions. The level of Zenk protein expression caused by song stimuli varied among each of the brain regions. Expression was highest in the caudomedial neostriatum (NCM), lower in the caudomedial hyperstriatum ventrale (CMHV), and lowest in the hippocampus. There was a significant effect of song complexity on the number of Zenk‐immunoreactive cells in the NCM, but not in the hippocampus. Zenk protein expression correlated significantly and positively with the number of different syllables to which the females were exposed in the NCM and to a lesser extent in the CMHV, but not in the hippocampus. For the NCM this correlation was also significant within the group exposed to natural song. These results suggest that the NCM is involved in the perception of song complexity in female budgerigars.
Phasic activation of substantia nigra and the ventral tegmental area by chemical stimulation of the superior colliculus: an electrophysiological investigation in the rat
Authors: Coizet Véronique , Comoli Eliane , Westby G. W. Max , Redgrave Peter 
Published: March 2003

AbstractThe source of short‐latency visual input to midbrain dopaminergic (DA) neurons is not currently known; however, the superior colliculus (SC) is a subcortical visual structure which has response latencies consistently shorter than those recorded for DA neurons in substantia nigra and the ventral tegmental area. To test whether the SC represents a plausible route by which visual information may gain short latency access to the ventral midbrain, the present study examined whether experimental stimulation of the SC can influence the activity of midbrain DA neurons. In urethane‐anaesthetized rats, 63 pairs of extracellular recordings were obtained from neurons in the SC and ipsilateral ventral midbrain, before and after local disinhibitory injections of the GABA antagonist bicuculline (20–40 ng/200–400 nL saline) into the SC. Neurons recorded from substantia nigra and the ventral tegmental area were classified as putative DA (25/63, 39.7%) or putative non‐DA (38/63, 60.3%). In nearly half the cases (27/63, 42.8%), chemical stimulation of the SC evoked a corresponding increase in neural activity in the ventral midbrain. This excitatory effect did not distinguish between DA and non‐DA neurons. In 6/63 cases (9.5%), SC activation elicited a reliable suppression of activity, while the remaining 30/63 cases (47.6%) were unaffected. In almost a third of cases (16/57, 28.1%) intense phasic activation of the SC was associated with correlated phasic activation of neurons in substantia nigra and the ventral tegmental area. These data suggest that the SC is in a position to play an important role in discriminating the appropriate stimulus qualities required to activate DA cells at short latency.
Nicotinic activation of reticulospinal cells involved in the control of swimming in lampreys
Authors: Le Ray Didier , Brocard Frédéric , Bourcier‐Lucas Céline , Auclair François , Lafaille Philippe , Dubuc Réjean 
Published: March 2003

AbstractIn lampreys as in other vertebrates, brainstem centres play a key role in the initiation and control of locomotion. One such centre, the mesencephalic locomotor region (MLR), was identified physiologically at the mesopontine border. Descending inputs from the MLR are relayed by reticulospinal neurons in the pons and medulla, but the mechanisms by which this is carried out remain unknown. Because previous studies in higher vertebrates and lampreys described cholinergic cells within the MLR region, we investigated the putative role of cholinergic agonists in the MLR‐controlled locomotion. The local application of either acetylcholine or nicotine exerted a direct dose‐dependent excitation on reticulospinal neurons as well as induced active or fictive locomotion. It also accelerated ongoing fictive locomotion. Choline acetyltransferase‐immunoreactive cells were found in the region identified as the MLR of lampreys and nicotinic antagonists depressed, whereas physostigmine enhanced the compound EPSP evoked in reticulospinal neurons by electrical stimulation of this region. In addition, cholinergic inputs from the MLR to reticulospinal neurons were found to be monosynaptic. When the brainstem was perfused with d‐tubocurarine, the induction of swimming by MLR stimulation was depressed, but not prevented, in a semi‐intact preparation. Altogether, the results support the hypothesis that cholinergic inputs from the MLR to reticulospinal cells play a substantial role in the initiation and the control of locomotion.
Relationship between two types of vesicular glutamate transporters and neurokinin‐1 receptor‐immunoreactive neurons in the pre‐Bötzinger complex of rats: light and electron microscopic studies
Authors: Liu Ying‐Ying , Wong‐Riley Margaret T. T. , Liu Jin‐Ping , Jia Yi , Liu Hui‐Ling , Fujiyama Fumino , Ju Gong 
Published: March 2003

AbstractOur previous study demonstrated GABAergic and glycinergic synapses onto neurokinin‐1 receptor (NK1R)‐immunoreactive (ir) neurons in the pre‐Bötzinger complex (pre‐BötC), the hypothesized kernel of normal respiratory rhythmogenesis. In the present study, we aimed to identify glutamatergic synapses onto NK1R‐ir pre‐BötC neurons, as excitatory synaptic transmission is a prerequisite to normal respiratory rhythmogenesis. Two types of vesicular glutamate transporters (VGLUT), VGLUT1 and VGLUT2, have been recently implicated in glutamate‐mediated transmission. The present study used immunofluorescence and immunogold‐silver staining to determine the relationship between the transporters and NK1R‐ir neurons in the pre‐BötC of adult rats. Under the confocal laser‐scanning microscope, VGLUT2‐ir boutons were found to be widely distributed in the pre‐BötC, some of which were in close apposition to NK1R‐ir somas and dendrites. VGLUT1‐ir boutons were relatively rare and only a few were found to be in close apposition to NK1R‐ir somas and dendrites. Electron microscopic observation revealed that approximately 41% of VGLUT2‐ir terminals were in close apposition to, or made asymmetric synapses with NK1R‐ir somas and dendrites in the pre‐BötC. On the other hand, 50.5% of NK1R‐ir dendrites were closely apposed to, or synapsed with VGLUT2‐ir terminals. Occasionally, VGLUT1‐ir terminals were found in close apposition to NK1R‐ir somas or dendrites, but we were unable to identify synapses between them. The present findings provide the morphological basis for excitatory synaptic inputs onto NK1R‐ir neurons in the pre‐BötC. VGLUT2 may be involved in a dominant excitatory synaptic pathway for normal respiratory rhythmogenesis.
Developmental plasticity of mouse visual acuity
Authors: Prusky Glen T. , Douglas Robert M. 
Published: March 2003

AbstractMonocular deprivation in mice between postnatal days 19 and 32 has been reported to significantly shift ocular dominance within the binocular region of primary visual cortex; however, it is not known whether visual deprivation in mice during this physiologically defined critical period also results in amblyopia, as it does in other mammals. We addressed this uncertainty by psychophysically assessing in adulthood (postnatal day 70 or older) the grating acuity of normal and monocularly deprived mice, using the Visual Water Task. The visual acuity of mice tested with their nondeprived eyes was equivalent to that of normal mice (≈ 0.5 cycles/degree); however, acuity measured with eyes monocularly deprived of vision transiently between postnatal days 19 and 32 was reduced by over 30% (≈ 0.31 cycles/degree). Identical binocular deprivation produced a significant, but smaller, decrease in acuity (≈ 0.38 cycles/degree). The effects of monocular and binocular deprivation were long lasting and occurred only if visual deprivation occurred between postnatal days 19 and 32. These data indicate that the deleterious effects of early visual deprivation on visual acuity in mice are similar to those reported in other mammals, and together with electrophysiological evidence of ocular dominance plasticity, suggest that the mechanisms of mouse visual plasticity are fundamentally the same as that in other mammals. Therefore, the mouse is probably a good model for investigating the basic cellular and molecular mechanisms underlying visual developmental plasticity and amblyopia.
Lesions of basolateral amygdala impair extinction of CS motivational value, but not of explicit conditioned responses, in Pavlovian appetitive second‐order conditioning
Authors: Lindgren John L. , Gallagher Michela , Holland Peter C. 
Published: March 2003

AbstractThe basolateral amygdala (BLA) is important for the modification of the motivational significance of events through associative learning. In previous work, we found that BLA was critical for the acquisition of conditioned reinforcement value to a visual conditioned stimulus (CS) paired with food. Unlike normal rats, rats with neurotoxic lesions of the BLA failed to acquire Pavlovian second‐order conditioning to an auditory stimulus paired with the first‐order visual CS in the absence of food. In this experiment, we examined the role of BLA in the extinction of the previously acquired conditioned reinforcement value of a Pavlovian CS. Rats received first‐order visual CS‐food pairings prior to either BLA‐ or sham‐lesions. Subsequent CS‐alone extinction training reduced the ability of the visual CS to reinforce second‐order conditioning of an auditory stimulus in the sham‐lesioned rats, but not in the BLA‐lesioned rats. Despite this persistence of the conditioned reinforcement value of the visual first‐order CS in the BLA‐lesioned rats, no effects of the lesions were observed on extinction of the explicit behavioural conditioned responses elicited by that CS.
Ciproxifan, a histamine H3‐receptor antagonist/inverse agonist, modulates the effects of methamphetamine on neuropeptide mRNA expression in rat striatum
Authors: Pillot Catherine , Héron Anne , Schwartz Jean‐Charles , Arrang Jean‐Michel 
Published: March 2003

AbstractWe have explored the effect of histamine H3‐receptor ligands on the regulation of neuropeptide mRNA expression in the striatum by using in situ hybridization performed with proenkephalin, prodynorphin, substance P and proneurotensin riboprobes. Acute administration of ciproxifan, an H3‐receptor antagonist/inverse agonist, or (R)‐α‐methylhistamine, an H3‐receptor agonist, did not modify the striatal expression of the neuropeptides by itself. However, ciproxifan strongly and differentially modulated the effect of a single administration of 3 mg/kg methamphetamine on neuropeptide mRNA expression. This modulation was suppressed by the administration of (R)‐α‐methylhistamine and occurred in both the caudate–putamen and nucleus accumbens. Ciproxifan strongly potentiated the decrease of proenkephalin mRNA expression induced by methamphetamine. In contrast, it suppressed the increase in prodynorphin and substance P mRNA expression induced by methamphetamine. Methamphetamine alone or with ciproxifan did not modify proneurotensin mRNA expression. These neurochemical findings indicate that ciproxifan differentially regulates the effect of methamphetamine on the neuropeptides contained in striatonigral and striatopallidal neurons. They suggest that endogenous histamine and dopamine cooperate to modulate the activity of striatal projection neurons and strengthen the interest of H3‐receptors as new targets for the treatment of psychotic disorders and drug abuse.