bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apomorphine induces trophic factors that support fetal rat mesencephalic dopaminergic neurons in cultures
Authors: Guo Hong , Tang Zhongshu , Yu Yi , Xu Lei , Jin Guozhang , Zhou Jiawei 
Published: March 2003

AbstractApomorphine, the catechol‐derived dopamine D1/D2 receptor agonist, is currently in use as an antiparkinsonian drug. It has previously been reported that apomorphine was able to elicit expression of the enzyme tyrosine hydroxylase, a marker for DA neurons, in the fetal rat cerebrocortical cultures whilst in the presence of brain‐derived neurotrophic factor. The present study demonstrated that treatment of fetal rat ventral mesencephalic cultures with apomorphine caused a marked increase in the number of dopaminergic neurons. The action of apomorphine can be mimicked by dopamine receptor (D1 and D2) agonists or blocked by preincubation with D1/D2 receptor antagonists. Incubation of recipient mesencephalic cultures with the conditioned medium derived from apomorphine‐stimulated donor mesencephalic cultures elicited a 3.72‐fold increase in the number of TH‐positive neurons. Increased mRNA expression levels of brain‐derived neurotrophic factor and glial cell line‐derived neurotrophic factor were also found in the apomorphine‐treated mesencephalic cells along with concomitant protein expression increases in the conditioned medium. Moreover, the trophic activity observed could be partially neutralized by antibodies against either brain‐derived neurotrophic factor or glial cell line‐derived neurotrophic factor. Cultured fetal striatal cells, but not hippocampal cells, also responded to apomorphine treatment. The membrane filtration studies revealed that both <30 kDa and >50 kDa fractions contained trophic activities. The latter characterization distinguishes them from most known neurotrophic factors. These results suggest that the apomorphine‐modulated development of dopaminergic neurons may be mediated by activation of the dopamine receptor subtypes D1and D2 thereby increasing the production of multiple growth factors.
The rat ponto‐medullary network responsible for paradoxical sleep onset and maintenance: a combined microinjection and functional neuroanatomical study
Authors: Boissard Romuald , Gervasoni Damien , Schmidt Markus H , Barbagli Bruno , Fort Patrice , Luppi Pierre‐Hervé 
Published: March 2003

AbstractThe neuronal network responsible for paradoxical sleep (PS) onset and maintenance has not previously been identified in the rat, unlike the cat. To fill this gap, this study has developed a new technique involving the recording of sleep–wake states in unanaesthetized head‐restrained rats whilst locally administering pharmacological agents by microiontophoresis from glass multibarrel micropipettes, into the dorsal pontine tegmentum and combining this with functional neuroanatomy. Pharmacological agents used for iontophoretic administration included carbachol, kainic acid, bicuculline and gabazine. The injection sites and their efferents were then identified by injections of anterograde (phaseolus vulgaris leucoagglutinin) or retrograde (cholera toxin B subunit) tracers through an adjacent barrel of the micropipette assembly and by C‐Fos immunostaining. Bicuculline, gabazine and kainic acid ejections specifically into the pontine sublaterodorsal nucleus (SLD) induced within a few minutes a PS‐like state characterized by a continuous muscle atonia, low voltage EEG and a lack of reaction to stimuli. In contrast, carbachol ejections into the SLD induced wakefulness. In PHA‐L, glycine and C‐Fos multiple double‐labelling experiments, anterogradely labelled fibres originating from the SLD were seen apposed on glycine and C‐Fos positive neurons (labelled after 90 min of pharmacologically induced PS‐like state) from the ventral gigantocellular and parvicellular reticular nuclei. Altogether, these data indicate that the SLD nuclei contain a population of neurons playing a crucial role in PS onset and maintenance. Furthermore, they suggest that GABAergic disinhibition and glutamate excitation of these neurons might also play a crucial role in the onset of PS.
Ionic currents determining the membrane characteristics of type I spiral ganglion neurons of the guinea pig
Authors: Szabó ZS. , Harasztosi CS. , Sziklai I. , Szûcs G. , Rusznák Z. 
Published: March 2003

AbstractEnzymatically isolated type I spiral ganglion neurons of the guinea pig have been investigated in the present study. The identity of the cells was confirmed by using anti‐neuron‐specific enolase immunostaining. The presence and shredding of the myelin sheath was also documented by employing anti‐S100 immunoreaction. The membrane characteristics of the cells were studied by using the whole‐cell patch‐clamp technique. The whole‐cell capacitance of the cells was 9 ± 2 pF (n = 51), while the resting membrane potential of the cells was −62 ± 9 mV (n = 19). When suprathreshold depolarizing stimuli were applied, the neurons fired a single action potential at the beginning of the stimulation. It was confirmed in this study that type I spiral ganglion cells possess a hyperpolarization‐activated nonspecific cationic current (Ih). The major characteristics of this current component were unaffected by the enzyme treatment. Type I spiral ganglion cells also expressed various depolarization‐activated K+ current components. A high‐threshold outward current was sensitive to 1–10 mm TEA+ application. The ganglion cells also expressed a relatively small, but nevertheless present, transient outward current component which was less sensitive to TEA+ but could be inhibited by 100 µm 4‐aminopyridine. A DTX‐I‐sensitive current was responsible for some 30% of the total outward current (at 0 mV), showed rapid activation at membrane potentials positive to −50 mV and demonstrated very little inactivation. However, inhibition of the highly 4‐AP‐ or DTX‐I‐sensitive component did not alter the rapidly inactivating nature of the firing pattern of the cells.
Physiological and morphological plasticity induced by chronic treatment with NT‐3 or NT‐4/5 in hippocampal slice cultures
Authors: Schwyzer Lucia , Mateos José María , Abegg Mathias , Rietschin Lotty , Heeb Lucette , Thompson Scott M. , Lüthi Andreas , Gähwiler Beat H. , McKinney R. Anne 
Published: March 2003

AbstractExpression of neurotrophins (NTs) and their receptors is elevated in the adult CNS under several neuropathological conditions. We have investigated the anatomical and electrophysiological consequences of chronic NT‐3 or NT‐4/5 treatment on established organotypic hippocampal slice cultures maintained in vitro for > 14 days. Both NT‐3 and NT‐4/5 increased spontaneous, action potential‐dependent excitatory synaptic activity (sEPSCs), but only NT‐3 increased inhibitory synaptic activity (sIPSCs) in CA3 pyramidal cells. Both NTs strongly promoted spontaneous synaptic bursting activity. Spontaneous bursts of EPSCs were observed after either NT treatment but only NT‐3‐treated cultures exhibited an increase in spontaneous bursts of IPSCs. In addition, sIPSC bursts were eliminated by blocking glutamatergic excitation. The frequency of miniature inhibitory postsynaptic currents, but not miniature excitatory postsynaptic currents, was also increased by both NT‐3 and NT‐4/5. Furthermore, NT‐3 and NT‐4/5 induced an up‐regulation of the growth‐associated protein GAP‐43, suggesting that neurotrophins may be able to induce axonal reorganization in established neuronal networks. CA1 pyramidal cells exhibited slight alterations in dendritic branching after NT‐4/5, but not NT‐3 treatment. We conclude that chronic treatment with NT‐3 or NT‐4/5 can affect an established hippocampal network by elevating spontaneous inhibitory and excitatory synaptic activity and inducing coordinated pre‐ and postsynaptic structural changes.
Genetic and pharmacological demonstration of a role for cyclic AMP‐dependent protein kinase‐mediated suppression of protein phosphatases in gating the expression of late LTP
Authors: Woo Newton H. , Abel Ted , Nguyen Peter V. 
Published: March 2003

AbstractProtein kinases and phosphatases play antagonistic roles in regulating hippocampal long‐term potentiation (LTP), with kinase inhibition and phosphatase activation both impairing LTP. The late phase of LTP (L‐LTP) requires activation of cAMP‐dependent protein kinase (PKA) for its full expression. One way in which PKA may critically modulate L‐LTP is by relieving an inhibitory constraint imposed by protein phosphatases. Using mutant PKA mice [R(AB) transgenic mice] that have genetically reduced hippocampal PKA activity, we show that deficient L‐LTP in area CA1 of mutant hippocampal slices is rescued by acute application of two inhibitors of protein phosphatase‐1 and protein phosphatase‐2A (PP1/2A) (okadaic acid and calyculin A). Furthermore, synaptic facilitation induced by forskolin, an adenylyl cyclase activator, was impaired in R(AB) transgenics and was also rescued by a PP1/2A inhibitor in mutant slices. Inhibition of PP1/2A did not affect early LTP (E‐LTP) or basal synaptic transmission in mutant and wildtype slices. Our data show that genetic inhibition of PKA impairs L‐LTP by reducing PKA‐mediated suppression of PP1/2A.
Periaqueductal gray and the region of the paralemniscal area have different functions in the control of vocalization in the neotropical bat, Phyllostomus discolor
Authors: Fenzl T. , Schuller G. 
Published: March 2003

AbstractThe periaqueductal gray matter and the region of the paralemniscal area were neuroanatomically delineated in the brain of the neotropical bat Phyllostomus discolor[Wagner (1843) Arch. Naturgesch., 9, 365–368] and were probed with electrical microstimulation for eliciting vocalizations. In a well‐delimited rostral portion of the periaqueductal gray exclusively, communication calls could be triggered at low stimulation currents. Communication calls as well as echolocation calls could be elicited at the dorsal and ventral edges of this area. Pharmacological stimulation with microdialysed kainic acid in this particular periaqueductal gray area demonstrated that neurons and not fibres of passage are activated for triggering vocalization. Solely echolocation calls were emitted upon electrical microstimulation or with microdialysed kainic acid in the region of the paralemniscal area. The periaqueductal gray appears to be involved in vocal pathways that control both communication calls and echolocation calls, while the region of the paralemniscal area seems to be specialized for control of echolocation calls only. Respiration is similarly influenced by stimulation in the periaqueductal gray and the region of the paralemniscal area. Periaqueductal gray and paralemniscal area interact differently with the final common pathway for vocalization, and may represent different functional organization in the vocal controlling pathways for communication calls and echolocation calls.
Tonically active neurons in the primate striatum and their role in the processing of information about motivationally relevant events
Authors: Apicella Paul 
Published: March 2003

AbstractAnalysis of recordings of single neuronal activity in the striatum of monkeys engaged in behavioural tasks has shown that tonically active neurons (TANs) can be distinguished by their distinct spontaneous firing and functional properties. As TANs are assumed to be cholinergic interneurons, the study of their physiological characteristics allows us to gain an insight into the role of a particular type of local‐circuit neuron in the processing of information at the striatal level. In monkeys performing various behavioural tasks, the change in the activity of TANs, unlike the diversity of task‐related activations exhibited by the phasically active population of striatal neurons, involves a transient depression of the tonic firing related to environmental events of motivational significance. Such events include primary rewards and stimuli that have acquired a reward value during associative learning. These neurons also respond to an aversive air puff, indicating that their responsiveness is not restricted to appetitive conditions. Another striking feature of the TANs is that their responses can be modulated by predictions about stimulus timing. Temporal variations in event occurrence have been found to favour the responses of TANs, whereas the responses are diminished or abolished in the presence of external cues that predict the time at which events will occur. These data suggest that the TANs respond as do detectors of motivationally relevant events, but they also demonstrate that these neurons are influenced by predictive information based on past experience with a given temporal context. TANs represent a unique subset of striatal neurons that might serve a modulatory function, monitoring for temporal relationships between environmental events.
The rostral migratory stream in adult squirrel monkeys: contribution of new neurons to the olfactory tubercle and involvement of the antiapoptotic protein Bcl‐2
Authors: Bédard Andréanne , Lévesque Martin , Bernier Patrick J. , Parent André 
Published: March 2003

AbstractThe subventricular zone (SVZ) lying along the ependymal layer of lateral ventricle is known to generate neural progenitor cells throughout adulthood in specific areas of the mammalian brain. In rodents, the anterior region of the SVZ produces neuroblasts that migrate in chain toward the olfactory bulb along the so‐called rostral migratory stream (RMS). In the present study, the organization of the RMS in a representative of New World primates – the squirrel monkey (Saimiri sciureus) – was studied by using bromodeoxyuridine (BrdU), a thymidine analogue that incorporates itself into the DNA of cells undergoing mitotic division. Double and triple immunofluorescence labelling with a confocal microscope served to visualize cells that expressed BrdU as well as molecular markers of neurogenesis. Numerous newborn (BrdU+) cells, many ensheated in glial (GFAP+) tubes, were scattered along the entire RMS in squirrel monkeys. Some of these BrdU+ cells expressed molecular markers for early committed neurons (TuJ1), postmitotic granular neuroblasts (TUC‐4) or mature neurons (MAP‐2, NeuN), and virtually all of them expressed the antiapoptotic protein Bcl‐2. A significant number of BrdU+ cells were found to deviate from the main stream of the RMS. Instead of reaching the olfactory bulb, these cells migrated ventrally into the olfactory tubercle, where they expressed a mature neuronal phenotype (MAP‐2). These findings reveal that the RMS in New World monkeys is mitotically robust and markedly extended and suggest that Bcl‐2 might play a role in the survival and/or differentiation of newborn neurons destined to olfactory bulb and olfactory tubercle in primates.
In vivo blockade of neural activity alters dendritic development of neonatal CA1 pyramidal cells
Authors: Groc Laurent , Petanjek Zdravko , Gustafsson Bengt , Ben‐Ari Yehezkel , Hanse Eric , Khazipov Roustem 
Published: March 2003

AbstractDuring development, neural activity has been proposed to promote neuronal growth. During the first postnatal week, the hippocampus is characterized by an oscillating neural network activity and a rapid neuronal growth. In the present study we tested in vivo, by injecting tetanus toxin into the hippocampus of P1 rats, whether this neural activity indeed promotes growth of pyramidal cells. We have previously shown that tetanus toxin injection leads to a strong reduction in the frequency of spontaneous GABA and glutamatergic synaptic currents, and to a complete blockade of the early neural network activity during the first postnatal week. Morphology of neurobiotin‐filled CA1 pyramidal cells was analyzed at the end of the first postnatal week (P6–10). In activity‐reduced neurons, the total length of basal dendritic tree was three times less than control. The number, but not the length, of basal dendritic branches was affected. The growth impairment was restricted to the basal dendrites. The apical dendrite, the axons, or the soma grew normally during activity deprivation. Thus, the in vivo neural activity in the neonate hippocampus seems to promote neuronal growth by initiating novel branches.
Kindling‐induced overexpression of Homer 1A and its functional implications for epileptogenesis
Authors: Potschka H. , Krupp E. , Ebert U. , Gümbel C. , Leichtlein C. , Lorch B. , Pickert A. , Kramps S. , Young K. , Grüne U. , Keller A. , Welschof M. , Vogt G. , Xiao B. , Worley P. F. , Löscher W. , Hiemisch H. 
Published: March 2003

AbstractDespite an extensive research on the molecular basis of epilepsy, the essential players in the epileptogenic process leading to epilepsy are not known. Gene expression analysis is one strategy to enhance our understanding of the genes contributing to the functional neuronal changes underlying epileptogenesis. In the present study, we used the novel MPSS (massively parallel signature sequencing) method for analysis of gene expression in the rat kindling model of temporal lobe epilepsy. Kindling by repeated electrical stimulation of the amygdala resulted in the differential expression of 264 genes in the hippocampus compared to sham controls. The most strongly induced gene was Homer 1A, an immediate early gene involved in the modulation of glutamate receptor function. The overexpression of Homer 1A in the hippocampus of kindled rats was confirmed by RT‐PCR. In order to evaluate the functional implications of Homer 1A overexpression for kindling, we used transgenic mice that permanently overexpress Homer 1A. Immunohistochemical characterization of these mice showed a marked Homer 1A overexpression in glutamatergic neurons of the hippocampus. Kindling of Homer 1A overexpressing mice resulted in a retardation of seizure generalization compared to wild‐type controls. The data demonstrate that kindling‐induced epileptogenesis leads to a striking overexpression of Homer 1A in the hippocampus, which may represent an intrinsic antiepileptogenic and anticonvulsant mechanism in the course of epileptogenesis that counteracts progression of the disease.
Neurokinin‐receptor‐mediated depolarization of cortical neurons elicits an increase in glutamate release at excitatory synapses
Authors: Stacey Anne E. , Woodhall Gavin L. , Jones Roland S. G. 
Published: March 2003

AbstractUsing whole‐cell patch‐clamp recordings of spontaneous synaptic activity, we have previously shown that activation of neurokinin‐1 (NK1) but not NK3 receptors leads to increased GABA release onto principal cells in the rat entorhinal cortex. In the present study, we examine the effect of activation of these receptors on spontaneous excitatory synaptic responses mediated by glutamate. Both neurokinin B (NKB) and the specific NK3 receptor agonist, senktide, increased the spontaneous release of glutamate, and a similar effect was also seen with substance P (SP) and other NK1 receptor agonists. The increased release induced by either SP or senktide was absent in the presence of tetrodotoxin, demonstrating that it was likely to occur via activation of presynaptic excitatory neurons. Current‐clamp recordings confirmed that principal neurons were depolarized by both NK3 and NK1 agonists. However, the response to the former but not the latter persisted in tetrodotoxin, allowing us to conclude that NK3 receptor activation provoked glutamate release via recurrent collaterals between principal neurons, whereas the NK1 receptors may be localized to excitatory interneurons. Finally, the increased release induced by senktide, but not SP, was reduced by an antagonist of group III metabotropic glutamate receptors. Thus, glutamate release from recurrent collaterals is facilitated by a presynaptic group III autoreceptor [Evans, D.I.P., Jones, R.S.G. & Woodhall, G.L. (2000) J. Neurophysiol.,83, 2519–2525], whereas the terminals of neurons responsible for the NK1‐receptor induced glutamate release may not bear these receptors. These results have implications for control of activity and epileptogenesis in cortical networks.
The role of the medial supramammillary nucleus in the control of hippocampal theta activity and behaviour in rats
Authors: Pan Wei‐Xing , McNaughton Neil 
Published: March 2003

AbstractThe medial supramammillary nucleus (mSUM) controls the frequency of hippocampal theta activity, completely in anaethsetized rats and partially in free‐moving rats. mSUM could therefore influence hippocampal contributions to cognition and emotion. Using chemical lesions of mSUM in rats, we tested whether mSUM is involved in controlling several hippocampal‐dependent functions: (i) defensive behaviour (open field, fear conditioning); (ii) behavioural inhibition (fixed interval schedule, differential reinforcement of low rates schedule); and (iii) spatial learning (water maze). Theta frequency was measured in all these tasks. mSUM lesions produced a pattern of changes in motivated/emotional behaviours (hyperactivity in defensive and operant tasks) similar to the pattern produced by hippocampal lesions, but had no significant effect on spatial learning. mSUM lesion decreased theta frequency modestly (by ≈ 0.4 Hz) in behaving rats if the amount of movement was unchanged. There was not always a parallel between changes in theta frequency and behaviour; behaviours changed despite unchanged theta in defensive tasks and learning changed little despite a lower frequency of theta in the water maze task. This suggests that mSUM function impacts on emotional behaviour more than cognition, and can modulate theta and behaviour independently.
Depletion of norepinephrine decreases the proliferation, but does not influence the survival and differentiation, of granule cell progenitors in the adult rat hippocampus
Authors: Kulkarni Vaishali A. , Jha Shanker , Vaidya Vidita A. 
Published: March 2003

AbstractThe dentate gyrus region retains the ability to generate neurons throughout adulthood. A few studies have examined the neurotransmitter regulation of adult hippocampal neurogenesis and have shown that this process is regulated by serotonin and glutamate. Given the strong noradrenergic innervation of the adult hippocampus and the ability of norepinephrine to influence proliferation during development, we examined the influence of norepinephrine on adult hippocampal neurogenesis. Our study indicates that depletion of norepinephrine by the selective noradrenergic neurotoxin, N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromo benzylamine hydrochloride (DSP‐4), results in a 63% reduction in the proliferation of dentate gyrus progenitor cells identified through 5‐bromo‐2′‐deoxyuridine (BrdU) labelling. In contrast, the survival of BrdU‐positive cells labelled prior to treatment with DSP‐4 is not influenced by norepinephrine depletion. The differentiation of BrdU labelled progenitors into neurons or glia was also not sensitive to noradrenergic depletion. These results indicate that the proliferation, but not the survival or differentiation, of adult hippocampal granule cell progenitors is affected by norepinephrine depletion.
Translocation of apoptosis‐inducing factor in cerebellar granule cells exposed to neurotoxic agents inducing oxidative stress
Authors: Fonfría E. , Daré E. , Benelli M. , Suñol C. , Ceccatelli S. 
Published: March 2003

AbstractWe have previously shown that the neurotoxic compounds colchicine, methylmercury (MeHg) and hydrogen peroxide (H2O2) cause apoptosis in primary cultures of cerebellar granule cells (CGC), characterized by nuclear condensation and high‐molecular weight DNA fragmentation. However, only colchicine triggers the activation of caspases, suggesting that factors other than caspase‐activated DNase (CAD) are responsible for DNA cleavage in the other two models. Here we report that the two agents that cause oxidative stress, MeHg (1 µm) and H2O2 (50 µm), induce translocation of apoptosis‐inducing factor (AIF) from the mitochondria to the nucleus in CGC. Our data suggest that, in absence of caspase activity, AIF translocation could be a key event leading to chromatin condensation and DNA degradation in CGC exposed to MeHg and H2O2.