bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel temporal configurations of stimuli produce discrete changes in immediate‐early gene expression in the rat hippocampus
Authors: Amin Eman , Pearce John M. , Brown Malcolm W. , Aggleton John P. 
Published: November 2006

AbstractChanges in limbic brain activity in response to novel configurations of visual stimuli were assessed by quantifying two immediate‐early genes, c‐fos and zif268. Rats were first trained to use distal, visual cues to support radial‐arm maze performance. Two separate sets of visual cues were used, one in the morning (Set A) and the other in the afternoon (Set B). On the final day the experimental group was tested with a novel configuration created by combining four of the eight visual cues from Set A with four of the eight visual cues from Set B. Although each individual cue was in a familiar location, the combination of cues was novel. Comparisons with a control group revealed discrete decreases in Fos centred in the hippocampus and retrosplenial cortex. The hippocampal c‐fos findings produced a dissociation with the perirhinal cortex, where no change was observed. Other regions seemingly unaffected by the novel stimulus configuration included the postrhinal, entorhinal and parietal cortices. Zif268 levels in the experimental group increased in the anterior ventral thalamic nucleus. Although previous studies have shown how the rat hippocampus is involved in responding to the spatial rearrangement of visual stimuli, the present study examined temporal rearrangement. The selective immediate‐early gene changes in the hippocampus and two closely related sites (retrosplenial cortex and anterior ventral thalamic nucleus) when processing the new stimulus configuration support the notion that the hippocampus is important for learning the ‘relational’ or ‘structural’ features of arrays of elements, be they spatial or temporal.
Face‐ and gaze‐sensitive neural responses in children with autism: a magnetoencephalographic study
Authors: Kylliäinen Anneli , Braeutigam Sven , Hietanen Jari K. , Swithenby Stephen J. , Bailey Anthony J. 
Published: November 2006

AbstractFace and gaze processing were studied using magnetoencephalography in 10 children with autism and 10 normally developing children, aged between 7 and 12 years. The children performed two tasks in which they had to discriminate whether images of faces presented sequentially in pairs were identical. The images showed four different categories of gaze: direct gaze, eyes averted (left or right) and closed eyes but there was no instruction to focus on the direction of gaze. Images of motorbikes were used as control stimuli. Faces evoked strong activity over posterior brain regions at about 100 ms in both groups of children. A response at 140 ms to faces observed over extrastriate cortices, thought to be homologous to the N170 in adults, was weak and bilateral in both groups and somewhat weaker (approaching significance) in the children with autism than in the control children. The response to motorbikes differed between the groups at 100 and 140 ms. Averted eyes evoked a strong right lateralized component at 240 ms in the normally developing children that was weak in the clinical group. By contrast, direct gaze evoked a left lateralized component at 240 ms only in children with autism. The findings suggest that face and gaze processing in children with autism follows a trajectory somewhat similar to that seen in normal development but with subtle differences. There is also a possibility that other categories of object may be processed in an unusual way. The inter‐relationships between these findings remain to be elucidated.
Contralateral inhibitory and excitatory frequency response maps in the mammalian cochlear nucleus
Authors: Ingham Neil J. , Bleeck Stefan , Winter Ian M. 
Published: November 2006

AbstractThere is increasing evidence that the responses of single units in the mammalian cochlear nucleus can be altered by the presentation of contralateral stimuli, although the functional significance of this binaural responsiveness is unknown. To further our understanding of this phenomenon we recorded single‐unit (n = 110) response maps from the cochlear nucleus (ventral and dorsal divisions) of the anaesthetized guinea pig in response to presentation of ipsilateral and contralateral pure tones. Many neurones showed no evidence of input from the contralateral ear (n = 41) but other neurones from both ventral and dorsal cochlear nucleus showed clear evidence of contralateral inhibitory input (n = 61). Inhibitory response patterns were divided into two groups. In 36 neurones, contralateral tone‐evoked inhibition was closely aligned with the ipsilateral excitatory response map (± 0.33 octaves) often extending to low stimulus levels. In 25 neurones, higher threshold contralateral inhibitory responses were found, mostly centred at frequencies greater than 0.33 octaves below the ipsilateral excitation. A few neurones (n = 8) exhibited responses consistent with excitatory input from the contralateral ear, which was closely aligned with the ipsilateral excitation, and were found exclusively in the dorsal cochlear nucleus. The latency of the contralateral interaction was, on average, longer than the ipsilateral latency. Interaural level difference curves are similar to other reports from the cochlear nucleus. Our results are consistent with the idea that contralateral interactions arise from a variety of direct and indirect neuronal projections.
CaV3 T‐type calcium channel isoforms differentially distribute to somatic and dendritic compartments in rat central neurons
Authors: McKay Bruce E. , McRory John E. , Molineux Michael L. , Hamid Jawed , Snutch Terrance P. , Zamponi Gerald W. , Turner Ray W. 
Published: November 2006

AbstractSpike output in many neuronal cell types is affected by low‐voltage‐activated T‐type calcium currents arising from the Cav3.1, Cav3.2 and Cav3.3 channel subtypes and their splice isoforms. The contributions of T‐type current to cell output is often proposed to reflect a differential distribution of channels to somatic and dendritic compartments, but the subcellular distribution of the various rat T‐type channel isoforms has not been fully determined. We used subtype‐specific Cav3 polyclonal antibodies to determine their distribution in key regions of adult Sprague–Dawley rat brain thought to exhibit T‐type channel expression, and in particular, dendritic low‐voltage‐activated responses. We found a selective subcellular distribution of Cav3 channel proteins in cell types of the neocortex and hippocampus, thalamus, and cerebellar input and output neurons. In general, the Cav3.1 T‐type channel immunolabel is prominent in the soma/proximal dendritic region and Cav3.2 immunolabel in the soma and proximal‐mid dendrites. Cav3.3 channels are distinct in distributing to the soma and over extended lengths of the dendritic arbor of particular cell types. Cav3 distribution overlaps with cell types previously established to exhibit rebound burst discharge as well as those not recognized for this activity. Additional immunolabel in the region of the nucleus in particular cell types was verified as corresponding to Cav3 antigen through analysis of isolated protein fractions. These results provide evidence that different Cav3 channel isoforms may contribute to low‐voltage‐activated calcium‐dependent responses at the somatic and dendritic level, and the potential for T‐type calcium channels to contribute to multiple aspects of neuronal activity.
Persistent rhythmic oscillations induced by nicotine on neonatal rat hypoglossal motoneuronsin vitro
Authors: Lamanauskas Nerijus , Nistri Andrea 
Published: November 2006

AbstractPatch‐clamp recording from hypoglossal motoneurons in neonatal Wistar rat brainstem slices was used to investigate the electrophysiological effects of bath‐applied nicotine (10 µm). While nicotine consistently evoked membrane depolarization (or inward current under voltage clamp), it also induced electrical oscillations (3–13 Hz; lasting for ≥ 8.5 min) on 40% of motoneurons. Oscillations required activation of nicotinic receptors sensitive to dihydro‐β‐erythroidine (0.5 µm) or methyllycaconitine (5 nm), and were accompanied by enhanced frequency of spontaneous glutamatergic events. The slight voltage dependence of oscillations and their block by the gap junction blocker, carbenoxolone, suggest they originate from electrically coupled neurons. Network nicotinic receptors desensitized more slowly than motoneuron ones, demonstrating that network receptors remained active longer to support heightened release of the endogenous glutamate necessary for enhancing the network excitability. The ionotropic glutamate receptor antagonist, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), and the group I metabotropic receptor antagonist, (RS)‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA), suppressed oscillations, while the NMDA receptor antagonist,d‐amino‐phosphonovaleriate (APV), produced minimal depression. Nicotine‐evoked oscillations constrained spike firing at low rates, although motoneurons could still generate high‐frequency trains of action potentials with unchanged gain for input depolarization. This is the first demonstration that persistent activation of nicotinic receptors could cause release of endogenous glutamate to evoke sustained oscillations in the theta frequency range. As this phenomenon likely represented a powerful process to coordinate motor output to tongue muscles, our results outline neuronal nicotinic acetylcholine receptors (nAChRs) as a novel target for pharmacological enhancement of motoneuron output in motor dysfunction.
The cytosolic domain of APP induces the relocalization of dynamin 3 in hippocampal neurons
Authors: Meckler X. , Bertandeau E. , McNiven M. A. , Allinquant B. , Hémar A. 
Published: November 2006

AbstractAmyloid precursor protein (APP) has been the subject of intense research to uncover its implication in Alzheimer's disease. Its physiological function is, however, still poorly understood. Herein, we investigated its possible influence on the development of cultured hippocampal neurons. A peptide corresponding to the APP intracellular domain linked to a cell‐penetrating peptide was used to alter the interactions of APP with its cytosolic partners. This treatment promoted the concentration of the cytosolic GTPase dynamin 3 (Dyn3) in neurite segments when most untreated cells displayed a homogenous punctate distribution of Dyn3. The Dyn3‐labelled segments were excluded from those revealed by APP staining after aldehyde fixation. Interestingly, after aldehyde fixation MAP2 also labelled segments excluded from APP‐stained segments. Thus APP is also a marker for the spacing pattern of neurites demonstrated by Taylor & Fallon (2006)J. Neurosci., 26, 1154–4463.
Mechanism of progesterone neuroprotection of rat cerebellar Purkinje cells following oxygen–glucose deprivation
Authors: Ardeshiri A. , Kelley M. H. , Korner I. P. , Hurn P. D. , Herson P. S. 
Published: November 2006

AbstractThe survival of rat Purkinje cell (PCs) cerebellar cultures was used to test the hypothesis that progesterone is protective against oxygen–glucose deprivation through potentiation of GABAA receptor activity. Electrophysiological recordings confirm that PCs develop robust excitatory and inhibitory synapses in culture. Exposure of cultured PCs to increasing concentrations of progesterone during oxygen–glucose deprivation revealed a concentration‐dependent protection by progesterone, with significant protection observed at physiological concentrations, as low as 10 nm. The concurrent application of the GABAA receptor antagonist picrotoxin (100 µm) completely abolished the neuroprotection afforded by progesterone, indicating that progesterone is neuroprotective through activation of GABAA receptors. Progesterone potentiates GABAA receptor activity indirectly through its metabolites, such as allopregnanolone (ALLO). Therefore, ALLO was applied to PC cultures and was observed to produce significant protection at all concentrations tested, from 10 to 1000 nm. Finally, the inhibition of progesterone metabolism with finasteride abolished the protection afforded by progesterone without having any effect on the neuroprotection caused by ALLO. These data indicate that progesterone protects cerebellar PCs at physiological concentrations through a GABA‐active metabolite.
Age‐related decline in striatal dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse model of Parkinson's disease
Authors: Colebrooke Rebecca E. , Humby Trevor , Lynch Patrick J. , McGowan Daniel P. , Xia Jing , Emson Piers C. 
Published: November 2006

AbstractDopamine cytotoxicity is thought to contribute towards the selective loss of substantia nigra pars compacta dopamine neurons and disease progression in Parkinson's disease. However, the long‐term toxicity of dopamine in vivo has not previously been established. The vesicular monoamine transporter 2 (VMAT2) sequesters monoamines into synaptic vesicles, a process that, in addition to being important in normal transmission, may also act to keep intracellular levels of monoamine neurotransmitters below potentially toxic thresholds. The homozygous VMAT2‐hypomorphic mouse has an insertion in the VMAT2 gene (Slc18a2). Consequently, VMAT2‐deficient mice (VD–/–) have an ∼ 95% reduction in VMAT2 expression and an equivalent level of dopamine depletion in the striatum which results in moderate motor impairment. Here, we show that L‐DOPA induces locomotor hyperactivity in VD–/– mice and reverses the deficit in motor coordination and balance as tested with the rotarod. We report that evidence for cytosolic accumulation of dopamine in substantia nigra neurons in these mice is two‐fold: firstly, there is reduced phosphorylation of tyrosine hydroxylase at the residue associated with catechol feedback inhibition; and, secondly, there are increased rates of dopamine turnover at 6, 12 and 24 months of age. These animals exhibit a progressive decline in striatal monoamine levels and rotarod performance with increasing age. However, despite these data, there was no loss of nigral dopamine neurons as estimated by quantification of tyrosine hydroxylase‐immunoreactive cells in the substantia nigra pars compacta of old VD–/– mice (24‐month‐old), implying that these age‐dependent manifestations may be due to senescence alone.
dextro‐Naloxone orlevo‐naloxone reverses the attenuation of morphine antinociception induced by lipopolysaccharide in the mouse spinal cord via a non‐opioid mechanism
Authors: Wu Hsiang‐En , Sun Han‐Sen , Cheng Caleb W. , Terashvili Maia , Tseng Leon F. 
Published: November 2006

AbstractGlial stimulation by intrathecal injection of lipopolysaccharide (LPS) attenuated the tail‐flick inhibition produced by morphine given intrathecally in the spinal cord of the male CD‐1 mice. The phenomenon has been defined as antianalgesia. The effects ofdextro‐naloxone orlevo‐naloxone on the attenuation of morphine‐produced tail‐flick inhibition induced by LPS were then studied. Pretreatment withdextro‐naloxone orlevo‐naloxone reversed the attenuation of the morphine‐produced tail‐flick inhibition induced by LPS. Pretreatment withdextro‐naloxone orlevo‐naloxone alone did not affect the morphine‐produced tail‐flick inhibition. It is concluded thatdextro‐naloxone andlevo‐naloxone block the LPS‐induced antianalgesia against morphine antinociception via a non‐opioid mechanism.
Lack of effects of GHB precursors GBL and 1,4‐BD following i.c.v. administration in rats
Authors: Carter Lawrence P. , Koek Wouter , France Charles P. 
Published: November 2006

AbstractGamma‐hydroxybutyrate (GHB) is used therapeutically and recreationally worldwide. Since the scheduling of GHB by the USA and the United Nations in 2000–2001, the recreational use of GHB precursors has reportedly increased. The aim of this study was to examine if potency differences of GHB and GHB‐like compounds are due to their blood–brain barrier permeability. The effects of peripheral and central administration of GHB, GHB precursors gamma‐butyrolactone (GBL) and 1,4‐butanediol (1,4‐BD), and the gamma‐aminobutyric acid (GABA)B receptor agonist baclofen on schedule‐controlled responding were examined in rats. GHB and baclofen were 276‐ and 253‐fold more potent, respectively, after intracerebroventricular (i.c.v.) administration than after intraperitoneal (i.p.) administration, whereas GBL and 1,4‐BD, up to a dose of 1780 µg were without effect after i.c.v. administration. These data suggest that GBL and 1,4‐BD are not metabolically converted to GHB in the brain, that enhanced brain penetration cannot account for potency differences between compounds, and that baclofen, like GHB, can readily cross the blood–brain barrier.
Mapping continuous neuronal activation without an ON–OFF paradigm: initial results of BOLD ceiling fMRI
Authors: Haller Sven , Wetzel Stephan G. , Radue Ernst W. , Bilecen Deniz 
Published: November 2006

AbstractStandard functional magnetic resonance imaging (fMRI) requires alternations between activation (ON) and baseline (OFF) periods to map the haemodynamic response to neuronal activation. Consequently, standard fMRI cannot map continuous activations in conditions like tinnitus without an ON–OFF paradigm. We present a novel approach to fMRI that allows mapping of continuous neuronal activation. Compared with standard fMRI, we introduced the application of CO2 as potent vasodilator. CO2 induces a ‘global’ blood oxygenation level‐dependent (BOLD) response. The neurovascular coupling in conjunction with the limited cerebral vasodilation implies a limitation or ceiling of the BOLD response. We hypothesize that active areas exhibit a reduced CO2‐induced ΔBOLD due to pre‐existing ‘local’ task‐induced BOLD response. This putative reduction in ΔBOLD might be exploited for mapping of continuous neuronal activation. BOLD ceiling fMRI was tested in the auditory system. Six healthy subjects performed three runs: only continuous monaural auditory; only 10% CO2; simultaneous auditory and CO2 stimulation. First, we demonstrated the ceiling of ΔBOLD during continuous auditory activation. According to the known predominantly contralateral auditory processing, monaural auditory stimulation reduced predominantly contralateral (0.41 ± 0.13%; P < 0.00001) and significantly less (P < 0.0001) ipsilateral ΔBOLD (0.33 ± 0.17%; P < 0.00001). The non‐auditory area was not affected. Second, this BOLD ceiling was exploited to generate an initial activation map of continuous auditory activation (ON period). In contrast to standard fMRI, an OFF period without neuronal activation was not required. BOLD ceiling fMRI is proposed as a complement to standard fMRI for those conditions where ON–OFF paradigms are impossible.
Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice
Authors: Noaín Daniela , Avale M. Elena , Wedemeyer Carolina , Calvo Daniel , Peper Marcela , Rubinstein Marcelo 
Published: November 2006

AbstractThe dopamine D4 receptor (D4R) has received considerable interest because of its higher affinity for atypical antipsychotics, the extremely polymorphic nature of the human gene and the genetic association with attention deficit and hyperactivity disorder (ADHD). Several efforts have been undertaken to determine the D4R expression pattern in the brain using immunohistochemistry, binding autoradiography and in situ hybridization, but the overall published results present large discrepancies. Here, we have explored an alternative genetic approach by studying bacterial artificial chromosome (BAC) transgenic mice that express enhanced green fluorescent protein (EGFP) under the transcriptional control of the mouse dopamine D4 receptor gene (Drd4). Immunohistochemical analysis performed in brain sections of Drd4‐EGFP transgenic mice using an anti‐EGFP polyclonal antibody showed that transgenic expression was predominant in deep layer neurons of the prefrontal cortex, particularly in the orbital, prelimbic, cingulate and rostral agranular portions. In addition, discrete groups of Drd4‐EGFP labelled neurons were observed in the anterior olfactory nucleus, ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD.
Vaccination of Alzheimer's model mice with Aβ derivative in alum adjuvant reduces Aβ burden without microhemorrhages
Authors: Asuni Ayodeji A. , Boutajangout Allal , Scholtzova Henrieta , Knudsen Elin , Li Yong Sheng , Quartermain David , Frangione Blas , Wisniewski Thomas , Sigurdsson Einar M. 
Published: November 2006

AbstractImmunotherapy holds great promise for Alzheimer's disease (AD) and other conformational disorders but certain adverse reactions need to be overcome. The meningoencephalitis observed in the first AD vaccination trial was likely related to excessive cell‐mediated immunity caused by the immunogen, amyloid‐β (Aβ) 1–42, and the adjuvant, QS−21. To avoid this toxicity, we have been using Aβ derivatives in alum adjuvant that promotes humoral immunity. Other potential side effects of immunotherapy are increased vascular amyloid and associated microhemorrhages that may be related to rapid clearance of parenchymal amyloid. Here, we determined if our immunization strategy was associated with this form of toxicity, and if the therapeutic effect was age‐dependent. Tg2576 mice and wild‐type littermates were immunized from 11 or 19 months and their behaviour evaluated prior to killing at 24 months. Subsequently, plaque‐ and vascular‐Aβ burden, Aβ levels and associated pathology was assessed. The therapy started at the cusp of amyloidosis reduced cortical Aβ deposit burden by 31% and Aβ levels by 30–37%, which was associated with cognitive improvements. In contrast, treatment from 19 months, when pathology is well established, was not immunogenic and therefore did not reduce Aβ burden or improve cognition. Significantly, the immunotherapy in the 11–24 months treatment group, that reduced Aβ burden, did not increase cerebral bleeding or vascular Aβ deposits in contrast to several Aβ antibody studies. These findings indicate that our approach age‐dependently improves cognition and reduces Aβ burden when used with an adjuvant suitable for humans, without increasing vascular Aβ deposits or microhemorrhages.