bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cav2.1/α1A (P/Q‐type) voltage‐dependent calcium channel mediates inhibitory neurotransmission onto mouse cerebellar Purkinje cells
Authors: Stephens Gary J. , Morris Neil P. , Fyffe Robert E.W. , Robertson Brian 
Published: March 2003

AbstractThe effects of voltage‐dependent calcium channel (VDCC) antagonists on spontaneous inhibitory postsynaptic currents (sIPSCs) in mouse Purkinje cells were examined using in vitro cerebellar slices. The inorganic ion Cd2+ reduced sIPSC amplitude and frequency. No additional block was seen with the Na+ channel antagonist tetrodotoxin (TTX) suggesting that all action potential‐evoked inhibitory GABA release was mediated by high‐voltage‐activated VDCCs. No evidence was found for involvement of Cav1/α1C and α1D (L‐type), Cav2.2/α1B (N‐type) or Cav2.3/α1E (R‐type) high‐voltage‐activated VDCCs or low‐voltage‐activated Cav3/α1G, α1H and α1I (T‐type) VDCCs in mediating presynaptic GABA release. Blockade of sIPSCs by 200 nmω‐agatoxin IVA implicated the Cav2.1/α1A (P/Q‐type) subtype of high‐voltage‐activated VDCCs in mediating inhibitory transmission. Inhibition by ω‐agatoxin IVA was similar to that seen with Cd2+ and TTX. Selective antibodies directed against the Cav2.1 subunit revealed staining in regions closely opposed to Purkinje cell somata. Cav2.1 staining was colocalized with staining for antibodies against glutamic acid decarboxylase and corresponded well with the pericellular network formed by GABAergic basket cell interneurons. Antibody labelling of Cav2.3 revealed a region‐specific expression. In the cerebellar cortex anterior lobe, Cav2.3 staining was predominantly somatodendritic; whilst in the posterior lobe, perisomatic staining was seen primarily. However, electrophysiological data was not consistent with a role for the Cav2.3 subunit in mediating presynaptic GABA release. No consistent staining was seen for other Cav (α1) subunits. Electrophysiological and immunostaining data support a predominant role for Cav2.1 subunits in mediating action potential‐evoked inhibitory GABA release onto mouse Purkinje cells.
Efferent axons in the avian auditory nerve
Authors: Köppl Christine 
Published: March 2003

AbstractThe sensory hair cells of the inner ear receive both afferent and efferent innervation. The efferent supply to the auditory organ has evolved in birds and mammals into a separate complex system, with several types of neurons of largely unknown function. In this study, the efferent axons in four different species of birds (chicken, starling, barn owl and emu) were examined anatomically. Total numbers of efferents supplying the cochlear duct (auditory basilar papilla and the vestibular lagenar macula) were determined; separate estimates of the efferents to the lagenar macula only were also derived and subtracted. The numbers for auditory efferents thus varied between 120 (chicken) and 1068 (barn owl). Considering the much larger numbers of hair cells in the basilar papilla, each efferent is predicted to branch extensively. However, pronounced species‐specific differences as well as regional differences along the tonotopic gradient of the basilar papilla were documented. Myelinated and unmyelinated axons were found, with mean diameters of about 1 µm and about 0.5 µm, respectively. This suggests two basic populations of efferents, however, they did not appear to be distinguished sharply. Evidence is presented that some efferents lose their myelination at the transition from central oligodendrocyte to peripheral Schwann cell myelin. Finally, a comparison of the four bird species evaluated suggests that the efferent population with smaller, unmyelinated axons is the phylogenetically more primitive one. A new population probably arose in parallel with the evolution and differentiation of the specialized hair‐cell type it innervates, the short hair cell.
Daily variation and appetitive conditioning‐induced plasticity of auditory cortex receptive fields
Authors: Kisley Michael A. , Gerstein George L. 
Published: March 2003

AbstractLong‐term modification of cortical receptive field maps follows learning of sensory discriminations and conditioned associations. In the process of determining whether appetitive – as opposed to aversive – conditioning is effective in causing such plastic changes, it was discovered that multineuron receptive fields, when measured in rats under ketamine‐sedation, vary substantially over the course of a week, even in the absence of classical conditioning and electrode movement. Specifically, a simple correlation analysis showed that iso‐intensity frequency response curves of multiunit clusters and local field potentials recorded from auditory cortex are nonstationary over 7 days. Nevertheless, significant plastic changes in receptive fields, due to conditioned pairing of a pure tone and electrical stimulation of brain reward centres, are detectable above and beyond these spontaneous daily variations. This finding is based on a novel statistical plasticity criterion which compares receptive fields recorded for three days before and three days after conditioning. Based on a more traditional criterion (i.e. one day before and after conditioning), the prevalence of learning‐induced changes caused by appetitive conditioning appears to be comparable to that described in previous studies involving aversive conditioning.
A single administration of interleukin‐1 or amphetamine induces long‐lasting increases in evoked noradrenaline release in the hypothalamus and sensitization of ACTH and corticosterone responses in rats
Authors: Schmidt E. D. , Schoffelmeer A. N. M. , De Vries T. J. , Wardeh G. , Dogterom G. , Bol J. G. J. M. , Binnekade R. , Tilders F. J. H. 
Published: March 2003

AbstractSingle administration of the cytokine interleukin‐1β (IL‐1) or the psychostimulant amphetamine causes long‐term sensitization of the hypothalamus pituitary adrenal (HPA) axis, i.e. enhanced adrenocorticotropine hormone (ACTH) and corticosterone responses weeks later. HPA responses to these stimuli involve activation of hypothalamic corticotropin‐releasing hormone (CRH) neurons by noradrenergic projections to the paraventricular nucleus (PVN). In search of the underlying mechanisms, we studied the temporal pattern of HPA sensitization in relation to (1) the reactivity of noradrenergic projections to the PVN and (2) altered secretagogue production in hypothalamic CRH neurons. Single exposure to IL‐1 or amphetamine induced cross‐sensitization of ACTH and corticosterone responses 11 and 22 days later, but not after 42 days. Amphetamine‐induced HPA sensitization was not accompanied by increased costorage of arginine vasopressin (AVP) in CRH terminals, as found previously after IL‐1 pretreatment. The reactivity of noradrenergic terminals was assessed by measuring the electrically evoked release of [3H]‐noradrenaline from superfused PVN slices. Single administration of amphetamine and IL‐1 induced a long‐lasting (up to 22 days) increase (up to 165%) of evoked noradrenaline release. This indicates that single exposure to psychostimulants or to cytokines can induce a long‐lasting increase in stimulus–secretion coupling in brainstem noradrenergic neurons that innervate the PVN. This common, long‐lasting functional change may underlie, at least in part, IL‐1‐ and amphetamine‐induced HPA cross‐sensitization. In addition, increased AVP signalling by hypothalamic CRH neurons appears to play a role in IL‐1‐induced, but not in amphetamine‐induced, HPA sensitization.
Deficient long‐term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C β4 mutant mice
Authors: Miyata Mariko , Kim Hyun‐Taek , Hashimoto Kouichi , Lee Tae‐Kwan , Cho Sun‐Young , Jiang Huiping , Wu Yanping , Jun Kisun , Wu Dianqing , Kano Masanobu , Shin Hee‐Sup 
Published: March 2003

AbstractLong‐term depression (LTD) at parallel fibre–Purkinje cell synapse of the cerebellum is thought to be a cellular substrate for motor learning. LTD requires activation of metabotropic glutamate receptor subtype 1 (mGluR1) and its downstream signalling pathways, which invariably involves phospholipase Cβs (PLCβs). PLCβs consist of four isoforms (PLCβ1–4) among which PLCβ4 is the major isoform in most Purkinje cells in the rostral cerebellum (lobule 1 to the rostral half of lobule 6). We studied mutant mice deficient in PLCβ4, and found that LTD was deficient in the rostral but not in the caudal cerebellum of the mutant. Basic properties of parallel fibre–Purkinje cell synapses and voltage‐gated Ca2+ channel currents appeared normal. The mGluR1‐mediated Ca2+ release induced by repetitive parallel fibre stimulation was absent in the rostral cerebellum of the mutant, suggesting that their LTD lesion was due to the defect in the mGluR1‐mediated signalling in Purkinje cells. Importantly, the eyeblink conditioning, a simple form of discrete motor learning, was severely impaired in PLCβ4 mutant mice. Wild‐type mice developed the conditioned eyeblink response, when pairs of the conditioned stimulus (tone) and the unconditioned stimulus (periorbital shock) were repeatedly applied. In contrast, PLCβ4 mutant mice could not learn the association between the conditioned and unconditioned stimuli, although their behavioural responses to the tone or to the periorbital shock appeared normal. These results strongly suggest that PLCβ4 is essential for LTD in the rostral cerebellum, which may be required for the acuisition of the conditioned eyeblink response.
Differentiation‐dependent sensitivity to cell death induced in the developing retina by inhibitors of the ubiquitin‐proteasome proteolytic pathway
Authors: Neves D. D. C. , Rehen S. K. , Linden R. 
Published: March 2003

AbstractThe effects of inhibitors of proteasome function were studied in the retina of developing rats. Explants from the retina of neonatal rats at postnatal day (P) 3 or P6 were incubated with various combinations of the proteasome inhibitor carbobenzoxyl‐leucinyl‐leucinyl‐leucinal (MG132), the protein synthesis inhibitor anisomycin, or the adenylyl cyclase activator forskolin. MG132 induced cell death in a subset of cells within the neuroblastic (proliferative) layer of the retinal tissue. The cells sensitive to degeneration induced by either MG132 or anisomycin, were birthdated by bromodeoxyuridine injections. This showed that the MG132‐sensitive population includes both proliferating cells most likely in their last round of cell division, and postmitotic undifferentiated cells, at a slightly earlier stage than the population, sensitive to anisomycin‐induced cell death. The results show that sensitivity to cell death induced by proteasome inhibitors defines a window of development in the transition from the cell cycle to the differentiated state in retinal cells.
Activation of glycogen synthase kinase 3 beta (GSK‐3β) by platelet activating factor mediates migration and cell death in cerebellar granule neurons
Authors: Tong Ning , Sanchez Joseph F. , Maggirwar Sanjay B. , Ramirez Servio H. , Guo Huang , Dewhurst Stephen , Gelbard Harris A. 
Published: March 2003

AbstractChildren with vertically acquired HIV‐1 can present with a rapidly progressive encephalopathy and neuronal apoptosis in the first 12–18 months of life. Furthermore, abnormal prenatal platelet activating factor (PAF) signalling may result in lissencephaly, a disorder of neuronal migration. PAF, produced from human immunodeficiency virus type 1 (HIV‐1) ‐infected brain‐resident macrophages, induces neuronal apoptosis in cultured cerebellar granule neurons (CGNs) in part by activating glycogen synthase kinase 3 beta (GSK‐3β). However, PAF can also inhibit migration of CGNs that are dispersed and allowed to reaggregate. Therefore, we investigated the biological effects following activation of GSK‐3β by PAF, and whether these effects were dependent on the culture conditions of the CGNs. We show here that activation of neuronal GSK‐3β by PAF is receptor‐specific, with similar kinetics of activation in both monolayer cultures of CGNs that have ceased to migrate and reaggregate cultures of CGNs that are actively migrating. However, PAF receptor activation in reaggregated CGNs inhibits neuronal migration and induces approximately half the level of neuronal apoptosis compared with PAF‐treated CGN cultures that have ceased to migrate. PAF‐mediated inhibition of neuronal migration in reaggregated CGNs or induction of apoptosis in CGNs that have ceased to migrate can be reversed by either PAF receptor antagonists, or the GSK‐3β inhibitors lithium or valproic acid, in a dose‐dependent manner. Abnormal PAF signalling that results in GSK‐3β overactivation may represent a common mechanism for pathological defects in neuronal migration in the prenatal period and neuronal apoptosis in the postnatal period.
Purely temporal figure–ground segregation
Authors: Kandil Farid I. , Fahle Manfred 
Published: March 2003

AbstractVisual figure–ground segregation is achieved by exploiting differences in features such as luminance, colour, motion or presentation time between a figure and its surround. Here we determine the shortest delay times required for figure–ground segregation based on purely temporal features. Previous studies usually employed stimulus onset asynchronies between figure‐ and ground‐containing possible artefacts based on apparent motion cues or on luminance differences. Our stimuli systematically avoid these artefacts by constantly showing 20 × 20 ‘colons’ that flip by 90° around their midpoints at constant time intervals. Colons constituting the background flip in‐phase whereas those constituting the target flip with a phase delay. We tested the impact of frequency modulation and phase reduction on target detection. Younger subjects performed well above chance even at temporal delays as short as 13 ms, whilst older subjects required up to three times longer delays in some conditions. Figure–ground segregation can rely on purely temporal delays down to around 10 ms even in the absence of luminance and motion artefacts, indicating a temporal precision of cortical information processing almost an order of magnitude lower than the one required for some models of feature binding in the visual cortex [e.g. Singer, W. (1999), Curr. Opin. Neurobiol., 9, 189–194]. Hence, in our experiment, observers are unable to use temporal stimulus features with the precision required for these models.
Amphetamine and cocaine induce different patterns of c‐fos mRNA expression in the striatum and subthalamic nucleus depending on environmental context
Authors: Uslaner Jason , Badiani Aldo , Norton Camille S. , Day Heidi E. W. , Watson Stanley J. , Akil Huda , Robinson Terry E. 
Published: March 2003

AbstractIn the dorsal striatum, there are two major populations of medium spiny projection neurons. One population is positive for dynorphin mRNA (DYN+), and these cells project preferentially to the substantia nigra, forming the so‐called ‘direct pathway’. A second population is positive for enkephalin mRNA (ENK+), and these cells influence the substantia nigra indirectly, via the globus pallidus and subthalamic nucleus. Psychostimulant drugs, such as amphetamine and cocaine, are reported to induce immediate early genes (IEGs) in only one subpopulation of dorsal striatal projection neurons, DYN+ cells. However, this apparent selectivity appears to be a function of environmental context. We found that when given in the animal's home cage, amphetamine and cocaine increased expression of the IEG, c‐fos, almost exclusively in DYN+ cells. However, when given in a novel environment, amphetamine and cocaine increased c‐fos mRNA in both DYN+ and ENK+ cells. Furthermore, amphetamine and cocaine increased c‐fos mRNA expression in the subthalamic nucleus when administered in the novel environment, but not when given at home. We conclude that the neural circuitry engaged by psychostimulant drugs, and their ability to induce specific patterns of gene expression, are determined by the environmental context in which they are experienced. This may be related to the ability of environmental novelty to facilitate psychostimulant drug‐induced neuroplasticity.
Dopaminergic retinal cell differentiation in culture: modulation by forskolin and dopamine
Authors: Guimarães Marília Zaluar P. , Hokoç Jan Nora , Duvoisin Robert , Reis Ricardo A. M. , De Mello Fernando Garcia 
Published: March 2003

AbstractWe examined the effects of dopamine and cAMP on the differentiation of dopaminergic retinal cells in the chick retina, using an in vitro system and tyrosine hydroxylase immunocytochemistry. Tyrosine hydroxylase‐positive cells were detected in cultures prepared from embryonic day 10 retinas. These increased in number as a function of time in vitro and by treatment for 4 days with forskolin. Besides causing a 3.4‐fold increase in the tyrosine hydroxylase‐positive population, forskolin also caused these cells to developed morphogenetic features of more mature cells. As opposed to forskolin, cultures treated with dopamine exhibited a 55% reduction of the tyrosine hydroxylase‐positive cell population, as compared to untreated cultures. Quinpirole was able to mimic the dopamine effect. This dopamine effect could only be blocked by clozapine, whereas raclopride and eticlopride were ineffective. Our results suggest the existence of a narrow window during development when undifferentiated dopaminergic cells are capable of being influenced by specific signals, possibly via cAMP production. The data also indicate that dopamine may act as a regulatory factor limiting the tyrosine hydroxylase‐positive population in the retina.
Post‐weaning social isolation of rats leads to an abnormal gait
Authors: Roberts L. , Clarke K. A. , Greene J. R. T. 
Published: March 2003

AbstractThe purpose of this study was to further characterize the phenotype of rats that have experienced prolonged postweaning social isolation, a paradigm that produces changes relevant to neuropsychiatric disorders. At weaning, male Wistar rats from three litters were housed socially (n = 12) or in isolation (n = 13) for 10 weeks. Isolated rats could see, hear and smell other rats. A sophisticated analysis of gait revealed that the stride duration was increased in isolates (12%, P = 0.0024) as a result of increased stance duration (18%, P = 0.0005), but there was no difference in vertical reaction force or velocity. Adrenal glands were heavier in isolates (19%, P = 0.0047). There was no difference in cross‐sectional area of the brain or lateral ventricles anywhere along the anterior–posterior axis. All experiments and analysis were performed blind to housing condition. This is the first study to demonstrate that socially isolated rats have an abnormal gait. Further analysis, including pharmacological manipulation, is needed in order to understand the nature of the abnormality.
Involvement of the central nucleus of the amygdala and nucleus accumbens core in mediating Pavlovian influences on instrumental behaviour
Authors: Hall Jeremy , Parkinson John A. , Connor Thomas M. , Dickinson Anthony , Everitt Barry J. 
Published: March 2003

AbstractPavlovian conditioned cues exert a powerful influence on instrumental actions directed towards a common reward, this is known as Pavlovian‐to‐instrumental transfer (PIT). The nucleus accumbens (NAcc) has been hypothesized to function as an interface between limbic cortical structures required for associative conditioning, like the amygdala, and response mechanisms through which instrumental behaviour can be selected and performed. Here we have used selective excitotoxic lesions to investigate the involvement of subnuclei of the amygdala as well as the core and shell regions of the nucleus accumbens on PIT in rats. Within the amygdala, selective lesions of the central nucleus (CeN), but not of the basolateral nucleus (BLA), abolished the PIT effect. In addition, selective lesions of the NAcc core, but not the NAcc shell, also abolished PIT. None of the lesions impaired the acquisition of Pavlovian food cup approaches or instrumental responding itself. These data demonstrate that the CeN and NAcc core are central components of the neural system mediating the impact of Pavlovian cues on instrumental responding. We suggest that this effect may depend upon the regulation of the dopaminergic innervation of the NAcc core by projections from the CeN to the ventral tegmental area.
DNA elements of the type 1 adenylyl cyclase gene locus enhance reporter gene expression in neurons and pinealocytes
Authors: Chan Guy C.‐K. , Lernmark Ulrika , Xia Zhengui , Storm Daniel R. 
Published: March 2003

AbstractThe Ca2+‐stimulated type 1 adenylyl cyclase (AC1) contributes to several forms of synaptic plasticity and is the only known neurospecific adenylyl cyclase. Furthermore, the protein and mRNA levels of AC1 undergo a circadian oscillation in the pineal gland, and AC1 may play a pivotal role in regulating nocturnal melatonin synthesis. To better understand the expression of AC1, we isolated mouse genomic DNA clones of AC1. The transcription and translation start regions of mouse AC1 share extensive homologies with the bovine counterpart. The upstream proximal region has potential binding sites for transcription factors, including the steroid receptor family, the E‐box factors, and Sp1. A 280‐bp fragment that contains the transcription start site directed reporter gene expression in cultured cortical neurons and pinealocytes functioning as a basal neuro‐ and pineal‐directed promoter. Interestingly, pinealocyte expression of the reporter gene was inhibited by increases in cAMP. This cAMP sensitivity may explain why AC1 mRNA in the pineal is low at night when cAMP is elevated and high during the day when cAMP signals drop. An adjacent 330‐bp fragment interacted specifically with nuclear factor(s) that we designate binary E‐box factor (BEF). Methylation interference and DNase I footprinting identified the BEF‐binding site sequence as 5′‐CCAAGGTCACGTGGC‐3′. When linked to the basal tissue‐directed promoter, this 15‐bp sequence further enhanced reporter expression in neurons and pinealocytes. We propose that this 15‐bp sequence may contribute to increased expression of AC1 in neurons and pinealocytes relative to other cells.
Comparison of the aggregation properties, secondary structure and apoptotic effects of wild‐type, Flemish and Dutch N‐terminally truncated amyloid β peptides
Authors: Demeester N. , Mertens C. , Caster H. , Goethals M. , Vandekerckhove J. , Rosseneu M. , Labeur C. 
Published: March 2003

AbstractThe Dutch (E22Q) and Flemish (A21G) mutations in the βAPP region of the amyloid precursor protein (APP) are associated with familial forms of Alzheimer dementia. However, patients with these mutations express substantially different clinical phenotypes. Therefore, secondary structure and cytotoxic effects of the three Aβ(12–42) variants [wild‐type (WT), Dutch and Flemish] were tested. At a concentration of 5 µm the aggregation of these peptides followed the order: Aβ(1–42) WT > Aβ(12–42) WT > Aβ(12–42) Flemish > Aβ(12–42) Dutch. The stability of the secondary structure of these peptides upon decreasing the trifluoroethanol (TFE) concentration in the buffer was followed by circular dichroism measurements. WT peptides progressively lost their α‐helical structure; this change occurred faster for both the Flemish and Dutch peptides, and at higher percentages of TFE in the buffer, and was accompanied by an increase in β‐sheet and random coil content. Apoptosis was induced in neuronal cells by the Aβ(12–42) WT and Flemish peptides at concentrations as low as 1–5 µm, as evidenced by propidium iodide (PI) staining, DNA laddering and caspase‐3 activity measurements. Even when longer incubation times and higher peptide concentrations were applied the N‐truncated Dutch peptide did not induce apoptosis. Apoptosis induced by the full length Aβ(1–42) peptide was weaker than that induced by its N‐truncated variant. These data suggest that N‐truncation enhanced the cytotoxic effects of Aβ WT and Flemish peptides, which may play a role in the accelerated progression of dementia.