bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoarchitecture of serotonin‐synthesizing neurons in the pontine tegmentum of the human brain
Authors: Baker K. G. , Halliday G. M. , Halasz P. , Hornung J‐P. , Geffen L. B. , Cotton R. G. H. , Törk I. 
Published: December 2004

AbstractWe have employed immunohistochemical and morphometric procedures to study serotonin‐synthesizing (PH8‐immunoreactive) neurons in the pontine reticular formation of the adult human. PH8‐immunoreactive neurons were found in three cytoarchitectural regions: the median rahpe nucleus (MnR), oral pontine reticular nucleus (PnO), and supralemniscal region (group B9). On the basis of cell size, morphology, and position, it was possible to distinguish distinct subgroups within the MnR (dorsal, midline, and paramedian cell clusters) and within the PnO (dorsal and central cell clusters), whereas within the B9 there were no distinct cell clusters. We have estimated that there are approximately 125,000 PH8‐immunoreactive neurons in the human pontine tegmentum; 64,400 in the MnR, 30,700 in PnO and 29,000 in B9. The large numbers of serotonin‐synthesizing neurons in the human pontine tegmentum contrasts with their relative paucity in nonprimate species such as rats and cats. Nonhuman primates also have large numbers of pontine serotonergic neurons but the morphology of these neurons and their spatial arrangement is significantly different in humans. These results are discussed with respect to the possible projections and functions of these neurons in humans.
Two dynamic modes of striatal function under dopaminergic‐cholinergic control: Simulation and analysis of a model
Authors: Wickens J. R. , Alexander M. E. , Miller R. 
Published: December 2004

AbstractA neural network model based on the anatomy and physiology of the matrix compartment of the striatum is described. The model consists of a network of neurons which are mutually inhibitory within a defined domain. A membrane potassium conductance (GK) under dopaminergic‐cholinergic control is included in the model. Computer simulation results show that changes in GmaxK, can modulate the behaviour of the network to produce either competition or coactivation among striatal output neurons. An analysis of a two‐neuron system based on the model shows that the maximum steepness of the threshold function plays a decisive role in the dynamics, in particular with regard to the competition that exists between the neurons. Competitive interations predominate at low GmaxK, while coactivation predominates at high GmaxK. We suggest that the former dynamic governs reciprocal inhibition of antagonistic muscles, while the latter governs cocontraction and rigidity. The model offers insights into the control of striatal neurodynamics by GmaxK which establish closer links between dopaminergic actions in the striatum and the mechanism of Parkinsonian rigidity. A prediction of the model is that acetylcholine should increase GmaxK in striatal output neurons.
GABAA receptors containing α1 and β2 subunits are mainly localized on neurons in the ventral pallidum
Authors: Churchill Lynn , Bourdelais Andrea , Austin Mark C. , Lolait Stephen J. , Mahan Lawrence C. , O'Carroll Anne‐Marie , Kalivas Peter W. 
Published: December 2004

AbstractThe γ‐aminobutyric acid (GABA) projection from the nucleus accumbens to the ventral pallidum (VP) is important in the regulation of locomotion. Thus, stimulation and inhibition of GABAA receptors in the VP can alter locomotor activity. To determine whether the GABAA receptors are located presynaptically on accumbens efferents to the VP or postysnaptically on neurons intrinsic to the VP two experiments were performed. In the first, quinolinic acid lesions of the nucleus accumbens did not alter [3H]muscimol binding in the VP, while lesions in the VP significantly reduced (60–80%) binding as measured by light microscopic receptor autoradiography. In the second experiment, in situ hybridization with oligonucleotide probes for mRNAs of the α1 and β2 subunits of the GABAA receptor was examined in the nucleus accumbens and VP. No mRNA for either subunit was observed in the nucleus accumbens, although many positively labeled neurons were present within the VP. By contrast, a moderate to high density of cells in both the nucleus accumbens and VP contained mRNA for glutamic acid decarboxylase. These data argue that the majority of GABAA receptors in the VP are not located presynaptically on axonal terminals originating from neurons in the nucleus accumbens.
ACTH and enkephalin axonal input to paraventricular neurons containing c‐fos‐like immunoreactivity
Authors: Pretel S. , Piekut D. T. 
Published: December 2004

AbstractThe presence of c‐fos like protein in neuronal nuclei has been observed in several areas of the central nervous system. It is associated with activation of these neurons by specific stimuli, in particular stressful stimuli. The present study investigated the expression of c‐fos‐like immunoreactivity in the paraventicular nucleus (PVN) of the hypothalamus following stimulation of small diameter, nociceptive afferents in the hindfoot of the rat. The afferent innervation to these c‐fos containing PVN neurons was examined in order to identify putative neurotransmitters which might modulate the activity of stress responsive, i.e. c‐fos containing neurons in the PVN. Adrenocorticotropic releasing hormone (ACTH), enkephalin (ENK) and corticotropin releasing factor (CRF), peptides whose functions have been related to the regulation of stress behavior, were selected to investigate their potential innervation of c‐fos immunolabeled neurons. Analysis of immunocytochemically double‐labeled vibratome and semi‐thin plastic embedded sections revealed that ACTH and ENK immunoreactive axonal varicosities were present in close anatomical proximity to a substantial number of parvocellular PVN neurons that contained c‐fos in response to noxious stimulation. Few c‐fos containing PVN neurons were apposed by CRF axonal varicosities. The resulting data show that a large number of c‐fos immunoreactive PVN neurons, though not the majority, is innervted by ACTH and ENK. This suggests that the activity of stress responsive, c‐fos expressing neurons can substantially be modulated and regulated by ACTH and ENK and to a lesser degree by CRF.
Subsurface cisterns in α‐motoneurons of the rat and cat: Immunohistochemical detection with antibodies against connexin32
Authors: Yamamoto T. , Hertzberg E. L. , Nagy J. I. 
Published: December 2004

AbstractA monoclonal antibody against amino acids 224–234 of the gap junction protein connexin32 was found by immunohistochemistry to label subsurface cisterns (SSCs) in alpha‐motoneurons of the rat (Yamamoto et al., 1990) and was used here to document by light (LM) and electron microscopy (EM) the appearance of immunoreactive SSCs in motoneurons of the rat and cat. This antibody and a polyclonal antibody against connexin32 labelled gap junctions in rat liver as well as SSCs in facial motoneurons. By LM, SSCs were seen as labelled puncta on motoneuronal perikarya and proximal dendrites. In the rat, they appeared to be present on all motoneurons at cranial and spinal levels, but varied considerably in size and number among motor nuclei. Labelled SSCs were the smallest and most sparse in motoneurons of the dorsal vagal motor nucleus, moderate in size and most numerous in the trochlear, oculomotor, and trigeminal motor nuclei, and largest though less densely distributed in spinal motoneurons. Dendrites were seen to contain SSCs for distances of up to 230 μm from their somal origin. Labelling within individual SSCs seen en face consisted of either numerous small puncta or linear arrays of immunoreactivity. By EM, labelled SSCs in the rat facial nucleus were always seen beneath a cluster of C‐terminals. Immunolabelling was most dense in the space between the plasma membrane and SSC, which we define as the subsurface cisternal cleft. The SSCs were usually intermittently labelled along their length and exhibited a narrow luminal space ranging from 2 to 5 nm. On the basis of structural analogies between SSCs in neurons and the sacroplasmic reticulum terminal cistern/T‐tubule complex in muscle, SSCs have previously been suggested to be important sites of calcium mobilization. The constant association of C‐terminal with SSCs in motoneurons may represent a useful model in which to study SSC function as well as to investigate the possible presence of a connexinlike protein at regions of SSCs that form a narrow lumen similar to that at gap junctions.
Differential agonist profile of the enantiomers of 3‐PPP at striatal dopamine autoreceptors: Dependence on extracellular dopamine
Authors: Clark David , Salah Raymond S. , Galloway Matthew P. 
Published: December 2004

AbstractThe effects of the enantiomers of 3‐hydroxyphenol‐N‐n‐propylpiperidine (3‐PPP) at dopamine (DA) synthesis modulating autoreceptors, measured as DOPA accumulation after decarboxylase inhibition, were assessed in vivo and in rat striatal slices. In vivo, (+)‐3‐PPP inhibited DOPA accumulation in the striatum, nucleus accumbens, and medial prefrontal cortex, whereas (−)‐3‐PPP either increased (striatal) or had no effect (accumbens, prefrontal cortex), on DOPA accumulation. In vitro, both (+)‐ and (−)‐3‐PPP reduced basal DOPA accumulation with a similar order of potency (apparent EC50 = 2.1 and 1.0 μm, respectively) and maximal effect, although they were less potent than the D2 DA receptor agonist quinpirole (EC50 = 0.15 μM). The inhibition of tyrosine hydroxylation was also observed in slices obtained from reserpine‐pretreated rats and was blocked by the selective D2 DA antagonist (−)‐sulpiride. This suggests that 3‐PPP inhibition of DOPA accumulation was mediated directly by stimulation of DA D2 receptors. Increasing the amount of extracellular DA by depolarizing slices with 30 mM K+ did not alter the qualitative effects of either quinpirole or (+)‐3‐PPP. However, the stimulation of DA autoreceptors by (−)‐3‐PPP was no longer apparent under conditions of elevated extracellular DA. Under these depolarizing conditions, (−)‐3‐PPP actually antagonized the inhibitory effect afforded by either quinpirole or pergolide. A similar switch in profile was observed with transdihydrolisuride (TDHL). The data support the notion that (−)‐3‐PPP and TDHL are partial agonists at synthesis modulating DA autoreceptors. The change in profile of (−)‐3‐PPP and TDHL is discussed in relation to their low intrinsic efficacy at synthesis modulating DA autoreceptors and to the variations in extracellular DA levels under different experimental conditions.
Differential effects of mu‐ and delta‐receptor selective opioid agonists on feedforward and feedback GABAergic inhibition in hippocampal brain slices
Authors: Lupica Carl R. , Dunwiddie Thomas V. 
Published: December 2004

AbstractPrevious studies have suggested that opioid receptor activation in the hippocampus increases pyramidal neuron excitability by reducing GABAergic inhibition. This hypothesis has received support with regard to μreceptor agonists but has not been adequately tested with selective δ‐receptor agonists. In the present investigation we compared the effects of the selective μ‐opioid receptor agonist [Tyr‐(D‐Ala)‐Gly‐(N‐Me‐Phe)‐Gly‐ol]‐enkephalin (DAGO) and the δ‐receptor agonist [D‐Pen2, D‐Pen5]‐enkephalin (DEDPE) to those of bicuculline methiodide (BMI) on extracellularly recorded feedforward (FFW) and recurrent (feedback; FB) inhibition. It was discovered that the control population spike response, evoked by Schaffer collateral/commissural axon stimulation, increased in response to DAGO, DPDPE, and BMI, while the secondary or test response incrased only in the presence of DAGO and BMI. The resulting hypothesis that δ‐opioid receptor activation facilitates synaptically evoked responses independently of a reduction of inhibition was investigated by examining the effect of DPDPE on the field EPSP response recorded in stratum radiatum of CA1, or postsynaptically on a burst response activated through antidromic stimulation of pyramidal neurons in low calcium medium. δ‐Opioid receptor activation had no effect on either the field EPSP response or the burst response, suggesting that neither synaptic transmission nor postsynaptic excitability were augmented. Finally, the possibility that DPDPE acts to enhance pyramidal cell excitability independently of GABAergic transmission was further investigated by examining responses to both μ‐and δ‐opioid agonists following treatment with BMI (30 μM). Responses to DPDPE and DAGO were completely blocked by this treatment, supporting the involvement of a GABAergic circuit in the actions of these enkephalins. These results suggest that the δ‐opioid receptor agonists DPDPE may mediate a reduction in GABAergic inhibition which is not detectable using paired stimulation techniques designed to examine FFW and FB inhibition in the hippocampal slice.
Dopaminergic modulation of excitotoxicity in rat striatum: Evidence from nigrostriatal lesions
Authors: Filloux F. , Wamsley James K. 
Published: December 2004

AbstractConsiderable evidence indicates that dopamine may, under certain circumstances, play a role in the mediation of central nervous system tissue damage. Furthermore, recent studies suggest a synergistic role between the neurotoxic effects of excitatory amino acids and dopamine. To address this issue, rats received a unilateral injection of 6‐hydroxydopamine or vehicle into the medial forebrain bundle. After recovery (18 days), both groups of animals received an ibotenic acid injection of the ipsilateral striatum. Seven days later the brains were removed and the size of the striatal lesion was assessed histologically and by means of receptor autoradiography. Regional analysis of profound D1 receptor loss was determined using [3H]SCH 23390, and extent of astrocytic proliferation was examined using autoradiography with the peripheral benzodiazepine receptor ligand [3H]R05‐4864. Prior interruption of the nigrostriatal pathway (resulting in dopaminergic denervation of the ipsilateral striatum) partially protected this latter structure from subsequent injection of ibotenic acid (the extent of the lesion was reduced by 28%, P < .05). The findings indicate that endogenous dopamine release may modulate (and intensify) the excitotoxic effects of ibotenic acid.
An arthropod NMDA receptor
Authors: Pfeiffer‐Linn Cindy , Glantz Raymon M. 
Published: December 2004

AbstractIdentified crayfish visual interneurons respond to illumination with a compound EPSP of up to 40 mV. L‐gultamate, quisqualate, and kainate mimic the depolarizing action of the natural transmitter. In reduced Mg2+, N‐methyl‐D‐aspartate (NMDA) elicits a depolarization with a reversal potential (Erev) = −60 mV. Erev is independent of extracellular calcium but shifts to +4 mV if potassium conductances are blocked by intracellular CS+. The results suggest that NMDA may gate more than one class of ionic channel. The NMDA‐elicited response is enhanced and prolonged by glycine, and kynurenate competitively blocks the action of glycine. The NMDA antagonist, D‐AP7, selectively blocks the NMDA response while enhancing the EPSP. The actions of NMDA are consistent with a role in the neural mechanisms of visual adaptation. This is the first description of an NMDA receptor in an invertebrate.
Aminooxyacetic acid produces excitotoxic lesions in the rat striatum
Authors: Urbańska Ewa , Ikonomidou Chrysanthy , Sieklucka Maria , Turski Waldemar A. 
Published: December 2004

AbstractThe neuropathological, biochemical, and behavioral effects of intrastriatal injection of aminooxyacetic acid (AOAA), a non‐specific transaminase inhibitor, were examined in rats. AOAA, 0.1–1 μmol, produced neuronal damage when injected into the striatum of adult rats but failed to damage the striatum of 6‐d‐old or decorticated rats. AOAA‐induced (0.25 μmol‐1 μmol) striatal lesions in adult rats displayed excitotoxic characteristics and could be prevented by the N‐methyl‐D‐aspartate (NMDA) receptor antagonists (–)‐2‐amino‐7‐phosphono‐heptanoate (AP7; 0.25 μmol) or kynurenate (KYNA; 0.5 μmol), but not by the non‐NMDA antagonist 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo(F)quinoxaline (NBQX; 0.25 μmol). AOAA produced a dose‐dependent reduction in striatal L‐glutamate decarboxylase activity, as measured 14 d following intrastriatal injection, which could also be prevented by AP7 or KYNA, but not by NBQX. These findings suggest that AOAA‐induced lesions are preferentially mediated by activation of the NMDA subtype of excitatory amino acid receptors. Behavioral studies revealed that the cataleptic response to haloperidol, 2 mg/kg, was decreased whereas the cataleptic response to arecoline, 15 mg/kg, and morphine, 15 mg/kg, was potentiated in AOAA lesioned animals 14 d following bilateral intrastriatal injections of AOAA, 0.25 and 1 μmol. In rats which received unilateral intrastriatal injection of AOAA, 0.1–1 μmol, apomorphine, 0.5 mg/kg, induced circling towards the lesioned side. Rats which received AP7, 0.25 μmol, or KYNA, 0.5 μmol, coadministered with AOAA, 0.25 μmol, behaved as vehicle‐treated controls, while those which received NBQX, 0.25 μmol, and AOAA, 0.25 μmol, had behavioral patterns similar to those subjected to AOAA alone. γ‐Vinyl‐GABA (4‐amino‐5‐hexenoate; 1 μmol), an inhibitor of the γ‐aminobutyrate (GABA) transaminase, and 3‐mercaptoproprionate (1 μmol), a preferential inhibitor of L‐aspartate transaminase, caused no damage when injected into the striatum of adult rats. Therefore we propose that inhibition of endogenous KYNA synthesis might be responsible for the neurotoxic properties of AOAA. Our findings are consistent with the hypothesis on the existence of a sensitive balance between endogenous excitotoxins and endogenous antagonists in the adult rat brain and suggest that blockede of the synthesis of the latter may result in excitotoxic cell death.
Partial dopamine depletions result in an enhanced sensitivity of residual dopamine neurons to apomorphine
Authors: Pucak M. L. , Grace A. A. 
Published: December 2004

AbstractExtracellular recordings from identified dopamine neurons were used to assess the effect of 6‐hydroxydopamine‐induced partial lesions of the nigrostriatal dopamine system on the sensitivity of the residual dopamine neurons to the dopamine agonist apomorphine. This was done by testing the response of identified nigral dopamine neurons in control and lesioned rats to systemic apomorphine administration at two time points: (1) 6–10 days post‐lesion, when the loss of dopamine cells is nearly complete, and (2) 4–8 weeks post‐lesion, which should be sufficient time for changes in dopamine receptor density to occur. As reported previously, dopamine neurons in control rats were inhibited by systemic administration of apomorphine, with their sensitivity being inversely related to their initial firing rate. The sensitivity of the residual dopamine neurons to apomorphine was unaltered in rats tested 6–10 days after depletions of at least 60% of striatal dopamine. However, by 4–8 weeks post‐lesion, there was a significant increase in the sensitivity to apomorphine; furthermore, sensitivity was no longer related to baseline firing rate, but instead was uniformly high in all dopamine neurons tested at this time. This enhanced sensitivity was not altered by hemisection of the striatonigral projection, suggesting that the increased sensitivity to apomorphine was most likely a result of a time‐dependent up‐regulation of somatodendritic autoreceptors on the residual dopamine neurons.
Effects of CI‐943, a potential antipsychotic drug, and haloperidol on regional brain neurotensin concentrations
Authors: Levant Beth , Bissette Garth , Davis M. Duff , Heffner Thomas G. , Nemeroff Charles B. 
Published: December 2004

AbstractTreatment with efficacious antipsychotic drugs such as haloperidol increases the concentrations of neurotensin (NT) in the nucleus accumbens and caudate nucleus of the rat. These increases in NT concentrations may be associated with the therapeutic and/or side effects of these drugs. CI‐943, a novel compound without appreciable affinity for dopamine‐binding sites, produces behavioral effects in animals, which suggest that it may possess antipsychotic activity. This study evaluated the effects of subchronic treatment (3 weeks) with CI‐943 or haloperidol on regional brain NT concentrations in rats. Haloperidol treatment (1 mg/kg) produced significant increases in the concentrations of NT in the nucleus accumbens and caudate nucleus but not in the other brain regions studied. Like haloperidol, CI‐943 (40 mg/kg) increased NT concentrations in the nucleus accumbens and caudate but differed in that CI‐943 produced significantly greater increases in NT concentration in the caudate than haloperidol and also increased NT content in the substantia nigra/ventral tegmental area and hypothalamus. The regional specificity of the NT alterations produced by chronic treatment with CI‐943, a nondopamine receptor ligand, was similar to that previously reported after treatment with multiple doses of methamphetamine.
Immunocytochemical evidence for methamphetamine‐induced serotonergic axon loss in the rat brain
Authors: Axt Karen J. , Molliver Mark E. 
Published: December 2004

AbstractCentral serotonin (5‐HT) axons were visualized by immunocytochemistry to assess both acute and long‐lasting changes in innervation density following methamphetamine administration to rats. Two morphologically distinct subtypes of 5‐HT axons (fine and beaded) were differentially affected by d‐methamphetamine (d‐MA); the density of fine serotonergic axons was selectively decreased both 4 hours and 2 weeks after administration of d‐MA. Acute depletion of 5‐HT from fine axons, but not from beaded axons, was observed in the brains of all rats treated 4 hours previously with either a 100 mg/kg or 15 mg/kg dose of d‐MA. Persistent loss of 5‐HT axons was observed in 30% of rats treated 1 or 2 weeks previously with doses of d‐MA which produce long‐term deficits in biochemical markers for 5‐HT. In the fraction of animals that exhibited denervation, fine serotonergic fibers were selectively ablated by d‐MA, but beaded serotonergic fibers were spared. Thus, d‐MA is similar to other amphetamine derivatives (e.g., p‐chloroamphetamine, 3,4‐methylenedioxyamphetamine) in that it acts selectively upon a morphologically distinct class of 5‐HT axons but differs in that it produces long‐lasting axon loss in only a fraction of animals.These data provide morphologic evidence of 5‐HT axon loss following methamphetamine administration and further confirm the differential vulnerability of a particular morphological subtype of serotonergic axons to the neurotoxic effects of substituted amphetamines.