bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous activity and recurrent inhibition in cultured hippocampal networks
Authors: Siebler Mario , Köller Hubertus , Stichel Christine C. , Müller Hans Werner , Freund Hans‐Joachim 
Published: December 2004

AbstractAs a model for an integrated neuronal network based on the concept of modular units, we have investigated the occurrence of spontaneous activity and the formation of synaptic circuits in primary cultures of dissociated hippocampal neurons from the embryonic rat. Sodium‐dependent action potentials (APs) could be elicited after 1 day in vitro (DIV), whereas spontaneous postsynaptic potentials (PSPs), “miniature” PSPs and APs appeared after 3‐6 DIV. The number of cells with spontaneous APs and the rate of APs increased during development of the neuritic network. In addition to a stochastic spike interval distribution, pyramid‐shaped neurons could be identified after 10‐12 DIV, which fired preferentially at interspike intervals between 20‐120 ms and 190‐400 ms. This distinctive bimodal interspike interval pattern was sensitive to GABA‐A antagonists. Simultaneous recordings of pairs of neurons demonstrated recurrent inhibitory, GABA‐ergic synaptic circuits. In addition, a subpopulation of GABAergic neurons could be visualized by immunocytochemistry. These results are discussed in relation to the hypothesis that spontaneous firing of connected neurons is networkdriven, based on synaptic “noise” and patterned by recurrent inhibition. © 1993 Wiley‐Liss, Inc.
Depression of glutamatergic and gabaergic synaptic responses in striatal spiny neurons by stimulation of presynaptic GABAB receptors
Authors: Nisenbaum Eric S. , Berger Theodore W. , Grace Anthony A. 
Published: December 2004

AbstractThe influence of γ‐aminobutyric acidB (GABAB) receptor stimulation on the excitatory and inhibitory synaptic potentials and membrane properties of identified striatal spiny neurons was examined in a corticostriatal slice preparation. Stimulation of the subcortical white matter evoked a monosynaptic, excitatory postsynaptic potential (EPSP) and a polysynaptic, inhibitory postsynaptic potential (IPSP) in spiny neurons. The EPSP had two components: a large amplitude response which could be blocked by the kainate/quisqualate receptor antagonist, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 10μM), and a small amplitue, long‐duration depolarization which could be blocked by the N‐methyl‐D‐aspartate receptor antagonist, d‐(‐)‐2‐amino‐5‐phosphonovaleric acid (APV, 100 μM). The IPSP was observed as a membrane depolarization when recorded from neurons at resting membrane potential. However, when neurons were injected with the Na+‐channel blocker, QX‐314, allowing cells to be depolarized above their spike thresholds, a prominent hyperpolarizing IPSP was readily observed which could be blocked by the GABAA antagonist, bicuculline (10‐50 μM). This bicuculline‐sensitive IPSP was responsible for the inhibition of EPSP amplitude and probability of spike discharge revealed using paired stimulation of the subcortical white matter. The amplitude of both the EPSP and the IPSP were depressed by the GABAB receptor agonist, p‐chlorophenyl‐GABA (baclofen, 0.5‐100 μM) in a concentration‐dependent manner. Baclofen also blocked paired stimulus inhibition of spike discharge. These effects of baclofen persisted in slices in which the cortex was removed and were reversed by the GABAB receptor antagonist, 3‐amino‐3‐hydroxy‐2‐(4‐chlorophenyl)‐propanesulphonic acid (saclofen, 100‐500 μM). In contrast to its profound influence on synaptic input, baclofen did not alter resting membrane potential, input resistance, membrane current‐voltage relationship, or spike threshold of the cells recorded, and therefore did not appear to exert direct postsynaptic effects on the striatal spiny neurons.Taken together, these data indicate that the depressant effects of baclofen on EPSPs are mediated through GABAB receptors located on the terminals of glutamatergic afferents within the striatum. Moreover, the results suggest that the actions of baclofen on IPSPs and paired stimulus inhibition are produced by activation of GABAB receptors within the striatum at a site presynaptic to spiny neurons, either on the terminals of GABAergic afferents or on an interposed non‐spiny GABAergic cell. Thus, GABAB hetero‐ and auto‐receptors have the capacity to provide a negative feedback mechanism through which the major excitatory and inhibitory inputs to striatal spiny neurons are regulated. © 1993 Wiley‐Liss, Inc.
Electrophysiological evidence for a large receptor reserve for inhibition of dorsal raphe neuronal firing by 5‐HT1A agonists
Authors: Cox Richard F. , Meller Emanuel , Waszczak Barbara L. 
Published: December 2004

AbstractPrevious studies [Meller et al. (1990) Mol. Pharmacol., 37:231‐237] have shown that a large receptor reserve exists for the inhibition of serotonin synthesis in rat cortex and hippocampus by the 5‐HT1A agonist 8‐hydroxy‐2(di‐n‐propylamino)tetralin (8‐OH‐DPAT), whereas little or no reserve exists for the lower efficacy agonists ipsapirone and BMY 7378. The current studies were undertaken to determine if the above drugs exhibit similar relative efficacies and receptor reserves in an electrophysiological model of 5‐HT1A receptor activation, i. e., the inhibition of dorsal raphe cell firing. Intravenous dose‐response curves were constructed in untreated control rats, or in rats which received an injection of the irreversible receptor inactivator N‐ethoxycarbonyl‐2‐ethoxy‐1, 2‐dihydroquinoline (EEDQ, 6 mg/kg, s. c.) 24 hours before recording. All three drugs fully inhibited dorsal raphe cell firing in control rats (ED50's: 1.5 μg/kg, 8‐OH‐DPAT; 30.0 μg/kg, ipsapirone; 17.5 μg/kg, BMY 7378). However, unlike effects on serotonin synthesis, EEDQ treatments caused no depression of the maximal inhibitory response for any of the agonists, although all dose‐response curves were shifted to the right (ED50's: 10.1 μg/kg, 6.7‐fold shift, 8‐OH‐DPAT; 139.9 μg/kg, 4.7‐fold shift, ipsapirone; 53.8 μg/kg, 3.1‐fold shift, BMY 7378). Although the order of agonist efficacies was similar for both inhibition of serotonin synthesis and dorsal raphe cell firing (8‐OH‐DPAT > ipsapirone > BMY 7378), a large (>50%) receptor reserve was estimated for all three drugs in this electrophysiological system. This suggests that 5‐HT1A receptor populations mediating the inhibition of transmitter synthesis and neuronal firing may be differently regulated or have different receptor‐effector coupling characteristics (G‐proteins, effectors, and/or transduction efficiencies). © 1993 Wiley‐Liss, Inc.
Chronic fluoxetine treatment upregulates 5‐HT uptake sites and 5‐HT2 receptors in rat brain: An autoradiographic study
Authors: Hrdina Pavel D. , Vu Thu B. 
Published: December 2004

AbstractThis study was undertaken to investigate the effect of chronic treatment with fluoxetine, a selective serotonin uptake inhibitor used widely in the treatment of depression, on the distribution and density of 5‐HT uptake sites, 5‐HT2 receptors, and vesicular amine uptake sites in rat brain. Fluoxetine (10 mg/kg i. p.) was administered daily for 21 days. The density of 5‐HT uptake sites labelled by [3H]paroxetine, 5‐HT2 receptors labelled by [3H]ketanserin in presence of tetrabenazine and vesicular amine uptake sites labelled by [3H]ketanserin in the presence of mianserin were measured by quantitative autoradiography in 22 areas of rat brain, using coronal tissue sections. Chronic administration of fluoxetine produced significant increases in the density of 5‐HT uptake sites in layers of frontoparietal cortex (by 32–43%), of striate cortex (by 55%), in CA1 field of hippocampus (by 111%) and in superior colliculus (by 20%). Fluoxetine treatment also resulted in upregulation of 5‐HT2 receptors in layers of frontparietal cortex (31–38%) and in CA2‐3 fields of hippocampus (by 39%). The density of tetrabenazine‐sensitive vesicular amine uptake sites in the caudate‐putamen was also significantly increased (by 66%). The observed alterations in 5‐HT uptake site and 5‐HT2 receptor densities are likely a part of adaptive neuronal changes that occur after chronic administration of fluoxetine and may be related to the antidepressant effect of the drug. © 1993 Wiley‐Liss, Inc.
Gender disparity in the academic pipeline: Women in neuroscience
Authors: Smith Dean O. 
Published: December 2004

AbstractThe percentages of females at critical steps in the academic career ladder were examined for one specific field, neuroscience. There was a slight attrition among females completing the Ph. D. However, the major drop‐off occurred when qualified post‐doctorates did not apply for faculty positions. Remedial actions should focus on not only the graduate school environment but also on the more critical postdoctoral experience. © 1993 Wiley‐Liss, Inc.
Evidence for the cholinergic nature of C‐terminals associated with subsurface cisterns in α‐Motoneurons of rat
Authors: Nagy J. I. , Yamamoto T. , Jordan L. M. 
Published: December 2004

AbstractC‐terminals can be distinguished at the ultrastructural level from other types of nerve endings on motoneurons by their prominent and regularly occurring postsynaptic specializations termed subsurface cisterns (SSC). We have previously shown (Yamamoto et al., 1991) that an antibody directed against a sequence within the gap junction protein connexin 32 immunolabels these motoneuronal SSCs and can therefore serve as a immunohistochemical tool to visualize indirectly the location of C‐terminals on motoneurons at the light microscope level. Here we have used this anti‐SSC antibody in combination with antibodies against choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) to determine whether C‐terminals on motoneurons contain these cholinergic enzyme; markers. In sections at all major spinal cord levels and in several cranial motor nuclei examined, motoneuronal cell bodies and their proximal dendrites were studded with large ChAT‐immunoreactive (ChAT‐IR) boutons. Boutons having a similar distribution and appearance on motoneurons were also immunolabelled for AChE. In addition, motoneurons were surrounded by a dense plexus of AChE‐immunoreactive (AChE‐IR) varicose fibers and fine preterminal axons. In double‐labeled sections, AChE‐IR boutons corresponded to those immunolabeled for ChAT. In sections processed for simultaneous immunofluorescence detection of ChAT and SSCs, ChAT‐IR boutons were very often found in apposition to immunolabeled SSCs. In sections processed for simultaneous labeling of AChE and SSCs, AChE‐IR boutons were again frequently seen abutting labeled SSCs. These results provide the first strong evidence at the LM level that a large proportion, if not the entirety, of C‐terminals are cholinergic and show that these terminals consist in part of relatively large varicosities along highly varicose axons that form en passant type contacts on motoneurons. At the same time, our results substantially narrow possibilities regarding the as yet undetermined source of C‐terminals, which can now be considered to originate from cholinergic neurons, such as those located in the brainstem and/or the spinal cord. © 1993 Wiley‐Liss, Inc.
Chronic repeated cocaine administration alters basal and opioid‐regulated adenylyl cyclase activity
Authors: Unterwald Ellen M. , Cox Brian M. , Kreek Mary Jeanne , Cote Thomas E. , Izenwasser Sari 
Published: December 2004

AbstractRepeated daily cocaine injections have been shown to alter μ‐opioid receptor densities in the caudate putamen and nucleus accumbens of rat brain (Unterwald et al., 1991, 1992). Addenylyl cyclase activity was measured in rat rostral caudate putamen and nucleus accumbens following repeated cocaine administration to determine the functional consequences of cocaine‐induced opioid receptor changes. Male Fischer rats were injected daily for 14 days with saline or cocaine HC1 (30 or 45 mg/kg/day, i.p.) in three equal doses at 1‐hr intervals. Basal adenylyl cyclase activity and the effects of the selective μ‐ and δ‐opioid agonists [D‐Ala2, N‐Me‐Phe4, Gly‐ol5]enkephalin (DAMGO) and [D‐penicillamine2, D‐Penicillamine5]enkephalin (DPDPE), respectively, on arenylyl cy‐clase activity were examined 30 min after the last injection using a cAMP radioligand binding assay in crude membrane preparations. Basal adenylyl cyclase activity was 49% and 34% lower in the caudate putamen of animals treated with 30 and 45 mg/kg/day of cocaine, respectively, as compared to those receiving saline injections. Basal adenylyl cyclase activity was unchanged in the nucleus accumbens following cocaine treatment. DAMGO and DPDPE each maximally inhibited approximately 25% and 30%, respectively, of basal adenylyl cyclase in the caudate putamen and nucleus accumbens of saline‐injected animals. Administration of cocaine attenuated the ability of DPDPE to inhibit adenylyl cyclase in both brain regions, but had no effect on the efficacy or potency of DAMGO for inhibiting adenylyl cyclase activity. These results suggest that chronic, repeated cocaine administration results in a selective impairment of δ‐opioid receptor‐mediated effector function in the caudate putamen and nucleus accumbens. © 1993 Wiley‐Liss, Inc.
Failure of the three compartment model to describe the pharmacokinetics in brain of a high affinity substituted benzamide
Authors: Votaw John R. , Kessler Robert M. , de Paulis Tomas 
Published: December 2004

AbstractThe applicability of using the standard 3‐compartment model to describe the neuropharmacokinetics of a high affinity substituted benzamide was investigated. We performed the following experiments using the [18F]‐5‐(3‐fluoropropyl) analog of epidepride ([18F]5‐FPrEpid), a potent dopamine D2 receptor antagonist: constant left ventricular infusion, first‐pass clearance, varying ligand specific activity, and displacing bound ligand with varying amounts of unlabelled ligand. Taken together, the information from these experiments rigorously tests the standard 3‐compartment model. The obtained data and predictions from the model of the kinetic behavior of the ligand are inconsistent. The measured and model predicted dissociation rate (measured Koff = 0.065 min−1, model prediction Koff = 0.007 min−1) and the equilibrium dissociation constant (measured KD = 0.14 nM, model prediction KD = 2.2 nM) differ by an order of magnitude. Furthermore, the model cannot be used to accurately estimate the receptor density. We postulate that the synapse geometry and physical relationship between receptors are necessary components of a model that describes the pharmacokinetics of [18F]5‐FPrEpid. © 1993 Wiley‐Liss, Inc.
Prenatal methamphetamine attenuates serotonin mediated renin secretion in male and female rat progeny: Evidence for selective long‐term dysfunction of serotonin pathways in brain
Authors: Cabrera Theresa M. , Levy Andrew D. , Li Qian , Van De Kar Louis D. , Battaglia George 
Published: December 2004

AbstractIn adult rats, methamphetamine produces biochemical alterations in brain serotonin (5‐HT) neurons. Since 5‐HT is critical to the development of fetal 5‐HT neurons and target tissues, we hypothesized that in utero exposure to methamphetamine could result in long‐term alterations in postnatal 5‐HT systems. Pregnant Sprague‐Dawley rats, administred either saline or (±)methamphetamine (5 mg/kg, s.c., b.i.d.) from gestational day 13 to 20, were divided into three treatment groups: Saline‐injected/Ad Lib Fed (VEH); Saline‐injected/Pair Fed (PF); and methamphetamine injected (METH). Prenatal methamphetamine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny and in PD 30 female progeny by measuring changes in 5‐HT mediated increases in plasma hormones following a single injection of the 5‐HT releaser p‐chloroamphetamine (PCA; 8 mg/kg). Prenatal metham‐phetamine produced long‐term marked (−30 to −62%) attenuation of plasma renin responses to PCA in male and female progeny. In contrast, no alterations were observed in the ACTH, corticosterone, or prolactin responses to PCA in male and female progeny. Prenatal methamphetamine did not alter basal levels of any hormones measured regardless of gender. No significant differences were observed in the density of cortical or hypothalamic 5‐HT uptake sites, or in the density of cortical 5‐HT1 or 5‐HT2 receptors in male progeny. The lack of significant differences in cortical 5‐HT uptake sites observed between PF and METH treated dams 2 days post‐parturition indicates that methamphet‐amine was not neurotoxic to the pregnant dams. These data, which demonstrate long‐term postnatal deficits in 5‐HT mediated renin secretion, suggest selective functional alterations of brain 5‐HT systems in male and female progeny exposed in utero to methamphetamine. © 1993 Wiley‐Liss, Inc.
Kainic acid seizures cause enhanced expression of cholecystokinin‐octapeptide in the cortex and hippocampus of the rat
Authors: Gruber Bernhard , Greber Susanne , Sperk Günther 
Published: December 2004

AbstractImmunocytochemistry and in situ hybridization techniques were used for investigating changes in cholecystokinin immunoreactivity and mRNA in the cerebral cortex and hippocampus after kainic acid‐induced limbic seizures in the rat. Marked increases in cholecystokinin mRNA concentrations were observed in layers II/III and V/VI of the cerebral cortex, in CA1 pyramidal neurons of the hippocampus, and in presumptive basket cells of the dentate gyrus 1 and 2 days after the acute seizures. Whereas cholecystokinin mRNA contents returned to normal in the cerebral cortex and the CA1 sector at later intervals, high concentrations were observed in basket cells even 2 months after the initial seizures. Accordingly, cholecystokinin‐like immunoreactivity was intensified in the cerebral cortex, CA1 sector and in presumed basket cells of the hippocampus 30 days after kainic acid. Besides its high content in basket cells, cholecystokinin‐like immunoreactivity was primarily present in neuronal fibers or diffusely distributed in the respective brain area. In the hippocampus, strongly enhanced staining for cholecystokinin was also observed in the alveus, the stratum lacunosum moleculare, and in the inner molecular layer, suggesting increased concentrations of the peptide in afferent and efferent fibers of the hippocampus.The present experiments suggest a strong activation of cholecystokinin systems in the brain after kainic acid‐induced limbic seizures in the rat. This is indicated by pronounced increases in cholecystokinin mRNA in the cortex and individual cell types of the hippocampus (basket cells, granule cells, and CA1 pyramidal neurons). The subsequent increases in cholecystokin immunoreactivity even surpass those in mRNA. The observed changes may be part of the self‐defense mechanisms that protect the animals during subsequent epileptic episodes. © 1993 Wiley‐Liss, Inc.
Long‐term action of lithium: A role for transcriptional and posttranscriptional factors regulated by protein kinase C
Authors: Manji Husseini K. , Lenox Robert H. 
Published: December 2004

AbstractLithium, a simple monovalent cation, represents one of psychiatry's most important treatments and is the most effective treatment for reducing both the frequency and severity of recurrent affective episodes. Despite extensive research, the underlying biologic basis for the therapeutic efficacy this drug remains unknown, and in recent years, research has focused on signal transduction pathways to explain lithium's efficacy in treating both poles of manic‐depressive illness. Critical to attributions of therapeutic relevance to any observed biochemical effect, however, is the observation that the characteristic prophylactic action of lithium in stabilizing the profound mood cycling of bipolar disorder requires a lag period for onset and is not immediately reversed upon discontinuation of treatment. Biochemical changes requiring such prolonged administration of a drug suggest alterations at the genomic level but, until recently, little has been known about the transcriptional and posttranscriptional factors regulated by chronic drug treatment, although long‐term changes in neuronal synaptic function are known to be dependent upon the selective regulation of gene expression. In this paper, we will present evidence to show that chronic lithium exerts significant transcriptional and posttranscriptional effects, and that these actions of lithium may be mediated via protein kinase C (PKC)‐induced alterations in nuclear transcription regulatory factors responsible for modulating the expression of proteins involved in long‐term neural plasticity and cellular response. Such target sites for chronic lithium may help unravel the processes by which a, simple monovalent cation can produce a long‐term stabilization of mood in individuals vulnerable to bipolar illness. © 1994 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Systemic nicotine‐induced dopamine release in the rat nucleus accumbens is regulated by nicotinic receptors in the ventral tegmental area
Authors: Nisell Magnus , Nomikos George G. , Svensson Torgny H. 
Published: December 2004

AbstractStimulation of the mesolimbic dopamine (DA) system is considered of major importance for the rewarding and dependence producing properties of nicotine (NIC). To identify the site of this stimulatory action, simultaneous microdialysis was performed in the ventral tegmental area (VTA) and the ipsilateral nucleus accumbens (NAC) of awake rats. Extracellular concentrations of DA and its metabolites were measured in the NAC. NIC (0.5 mg/kg, s.c.) increased DA and its metabolites by ∼50%.Concomitant infusion of the nicotinic receptor antagonist mecamylamine (MEC, 100 μ) through the VTA probe, starting 40 min before NIC injection, antagonized the NIC induced increases of DA and its metabolites. In contrast, similar MEC pretreatment (40 or 140 min) in the NAC did not affect DA or metabolite responses to systemic NIC. Infusion of NIC (1,000 μ) in the NAC or the VTA increased DA release by 49% and 48%, respectively, whereas only the VTA infusion increased metabolite concentrations by ‐25%. MEC infusion (1–1,000 μ) in the VTA did not affect DA or its metabolites, whereas the 1,000 μ concentration infused in the NAC increased DA by 77%. These results suggest that nicotinic receptors in the somatodendritic region may be of greater importance than those located in the terminal area for the stimulatory action of systemic NIC on the mesolimbic DA system. Furthermore, our findings support the notion that the mesolimbic dopaminergic system is phasically rather than tonically regulated by nicotinic receptor activation within the VTA. © 1994 Wiley‐Liss, Inc.