bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vasoactive intestinal polypeptide induces per1 and per2 gene expression in the rat suprachiasmatic nucleus late at night
Authors: Nielsen Henriette S. , Hannibal Jens , Fahrenkrug Jan 
Published: March 2003

AbstractCircadian rhythms in behaviour and physiology generated by the suprachiasmatic nucleus (SCN) are entrained to the environmental light/dark cycle via the retinohypothalamic tract. How light is able to adjust the endogenous rhythm is not fully understood, but induction of the two clock genes per1 and per2 in the SCN is believed to be important for the adjustment. Recently, it was shown that vasoactive intestinal polypeptide (VIP), a neurotransmitter found in light‐responsive cells of the SCN, is able to phase shift the circadian rhythm similar to light. In the present study we show by means of an in vitro brain slice model and quantitative in situ hybridization histochemistry that VIP induces both per1 and per2 gene expression in the SCN during late subjective night (CT19). The signalling pathways responsible for the VIP signalling to the clock were investigated using inhibitors of protein kinase A and phospholipase C mediated signalling. Our results demonstrate that both pathways are involved in VIP induced per gene expression and suggest that VIP is important for light‐induced phase shift late at night.
Neural background of glucocorticoid dysfunction‐induced abnormal aggression in rats: involvement of fear‐ and stress‐related structures
Authors: Halász József , Liposits Zsolt , Kruk Menno R. , Haller József 
Published: March 2003

AbstractGlucocorticoid hypofunction is associated with persistent aggression in some psychologically disordered human subjects and, as reported recently, induces abnormal forms of aggression in rats. Here we report on the effects of glucocorticoid hypofunction on aggression‐induced neural activation. Rats were adrenalectomized, and implanted with low‐release glucocorticoid pellets. After one week recovery, they were challenged by an unfamiliar intruder in their home‐cage. Neural activation was studied by c‐Fos protein immunocytochemistry. Aggressive encounters in controls induced c‐Fos activation in all brain areas relevant for the control of aggression (cortex, amygdala, septum, hypothalamus, periaqueductal grey and the locus coeruleus). Very intense c‐Fos activation was observed in the medial amygdala, the hypothalamic attack area and the periaqueductal grey matter which constitute a downward stimulatory stream that activates attack behaviour. The experimentally induced glucocorticoid hypofunction dramatically increased attacks targeted towards vulnerable parts of the opponent's body (mainly the head). This abnormal behaviour was not associated with changes in the activation of brain centres involved in the control of aggression. However, the activation of brain centres involved in both the stress response (the parvocellular part of the hypothalamic paraventricular nucleus) and fear reactions (central amygdala) were markedly increased. An acute glucocorticoid treatment abolished both behavioural and neural consequences of glucocorticoid hypofunction. Our data suggest that glucocorticoid hypofunction‐induced abnormal forms of aggressiveness are related to increased sensitivity to stressors and fear‐eliciting stimuli. This assumption is supported by the finding that fearful situations induce attack patterns in intact rats that are similar to those induced by glucocorticoid hypofunction.
Cortico‐hippocampal APP and NGF levels are dynamically altered by cholinergic muscarinic antagonist or M1 agonist treatment in normal mice
Authors: Seo Hyemyung , Ferree Andrew W. , Isacson Ole 
Published: March 2003

AbstractTo determine whether altered cholinergic neurotransmission can modify the long‐term secretion of amyloid precursor protein (APP), endogenous levels of APP and nerve growth factor (NGF), we administered a selective M1 muscarinic receptor agonist (RS86) or the muscarinic antagonist, atropine, for 7 days in vivo into young adult mice (C57BL/6j). The levels of NGF and total APP in the hippocampus, frontal cortex, striatum, parietal cortex and cerebrospinal fluid (CSF) were examined by ELISA and Western blot. We found that this repeated i.m. administration of M1 receptor agonist resulted in decreased total APP levels in the hippocampus, frontal cortex and parietal cortex, and increased secreted α‐APPs levels in the CSF. M1 agonist treatment also resulted in decreased NGF levels in the hippocampus and CSF. These effects of the M1 muscarinic agonist could be blocked by atropine, which by itself elevated tissue levels of total APP. Interestingly, we found that the decrease of total APP in the hippocampus and striatum after M1 agonist treatment inversely correlated with the change in NGF levels. These data suggest that a sustained increased cholinergic, M1‐mediated neurotransmission will enhance secretion of α‐APPs in CSF and adaptively reduce the levels of total APP and NGF in the corticohippocampal regions of normal mice. The dynamic and adaptive regulation linking total APP and NGF levels in normal adult mice is relevant for understanding the pathophysiology of conditions with cholinergic and APP related pathologies, like Alzheimer's disease and Down's syndrome.
Learning the invariance properties of complex cells from their responses to natural stimuli
Authors: Einhäuser Wolfgang , Kayser Christoph , König Peter , Körding Konrad P. 
Published: March 2003

AbstractNeurons in primary visual cortex are typically classified as either simple or complex. Whereas simple cells respond strongly to grating and bar stimuli displayed at a certain phase and visual field location, complex cell responses are insensitive to small translations of the stimulus within the receptive field [Hubel & Wiesel (1962)J. Physiol. (Lond.), 160, 106–154; Kjaer et al. (1997)J. Neurophysiol., 78, 3187–3197]. This constancy in the response to variations of the stimuli is commonly called invariance. Hubel and Wiesel's classical model of the primary visual cortex proposes a connectivity scheme which successfully describes simple and complex cell response properties. However, the question as to how this connectivity arises during normal development is left open. Based on their work and inspired by recent physiological findings we suggest a network model capable of learning from natural stimuli and developing receptive field properties which match those of cortical simple and complex cells. Stimuli are drawn from videos obtained by a camera mounted to a cat's head, so they should approximate the natural input to the cat's visual system. The network uses a competitive scheme to learn simple and complex cell response properties. Employing delayed signals to learn connections between simple and complex cells enables the model to utilize temporal properties of the input. We show that the temporal structure of the input gives rise to the emergence and refinement of complex cell receptive fields, whereas removing temporal continuity prevents this processes. This model lends a physiologically based explanation of the development of complex cell invariance response properties.
Effects of water on cortical excitability in humans
Authors: Müller Viktor , Birbaumer Niels , Preißl Hubert , Braun Christoph , Lang Florian 
Published: March 2003

AbstractThe effects of water on cortical excitability, measured using magnetoencephalographic recordings, were investigated in a sample of 19 healthy volunteers in a double‐blind, placebo experiment comparing water with saline solution. Spontaneous magnetoencephalogram as well as auditory‐evoked magnetic fields were recorded before and after the drinking of 750 mL water (9 subjects) or saline solution (10 subjects) and during and after hyperventilation following the drinking conditions. Hyperventilation was used to enhance the hypothesized synchronizing effect of water on spontaneous magnetoencephalographic activity. In addition, the magnetic fields were measured during a dichotic listening task under attended and unattended conditions. The prediction, that intake of water, because of induced cell swelling, will increase neuronal excitability and lead to an increased synchronization of the spontaneous magnetoencephalogram during hyperventilation was confirmed. Hyperventilation induced an increase of spectral power in all frequency bands particularly theta and delta power after water drinking. Furthermore, there was an increase of magnetic mismatch negativity (MMNm) amplitude in attended conditions and a simultaneous decrease in unattended conditions after water drinking. N1m (magnetic N1 wave) revealed significant changes during experimental conditions: increase after drinking and decrease after hyperventilation in both groups. MMNm for attended conditions showed a high positive correlation with osmolality changes (difference in the mol solute per kg water before and after drinking); N1m and PNm (magnetic processing negativity) as well as MMNm for unattended conditions showed significant correlations with subjective ratings of thirst and mood state.
Novel expression of AMPA‐receptor subunit GluR1 on mossy cells and CA3 pyramidal neurons in the human epileptogenic hippocampus
Authors: Eid Tore , Kovacs Ilona , Spencer Dennis D. , De Lanerolle Nihal C. 
Published: March 2003

AbstractPrevious immunocytochemical investigations performed in our laboratory on the human hippocampus surgically resected for the treatment of mesial temporal lobe epilepsy (MTLE) have demonstrated an increased expression of the AMPA‐receptor subunit GluR1 on neurons in the hilus and area CA3. Light microscopically, many of these neurons exhibited peculiar filamentous extensions and grape‐like excrescences that protruded from their somata and proximal dendrites, suggesting that these neurons may be mossy cells and CA3 pyramidal neurons, respectively. The present electron microscopic study was carried out to further characterize these cells. The filamentous extensions were identified as dendrites from which spines often protruded, and the grape‐like excrescences represented clusters of closely associated dendrites and spines. A variety of synapses were formed by the GluR1‐positive profiles. These arrangements ranged from simple contacts between a single unlabelled axon terminal and a single labelled postsynaptic element, to complex contacts involving multiple unlabelled axon terminals and labelled postsynaptic elements. Many of the axon terminals involved in these arrangements were mossy fibre boutons. Thus, a large proportion of the GluR1‐positive neurons were identified as hilar mossy cells and CA3 pyramidal neurons, cells hitherto thought to be absent or greatly reduced in the MTLE hippocampus. Taken together, these data suggest the presence of a highly efficient excitatory circuit involving AMPA receptors, mossy cells and CA3 pyramidal neurons in the sclerotic hippocampus. Such a circuit could be critically involved in the genesis and maintenance of temporal lobe epilepsy.
Crossed unilateral lesions of temporal lobe structures and cholinergic cell bodies impair visual conditional and object discrimination learning in monkeys
Authors: Barefoot H. C. , Baker H. F. , Ridley R. M. 
Published: March 2003

AbstractMonkeys with excitotoxic lesions of the CA1/subiculum region in the right hemisphere and with immunotoxic lesions of the cholinergic cells of the diagonal band in the left hemisphere were impaired on a visual conditional task. In this task, correct choice of one of two objects depends on which of two background fields both objects are presented against, irrespective of the spatial positions of the objects. They were not impaired on simple object or shape discrimination tasks. The pattern of impairments is the same as that seen after bilateral excitotoxic lesions of CA1/subiculum, implying that the diagonal band lesion disables the ipsilateral CA1/subiculum. It also argues that CA1/subiculum, sustained by its cholinergic input, is necessary for some forms of nonspatial conditional learning. Addition of an inferotemporal (IT) cortical ablation to the left hemisphere did not affect simple visual discrimination learning, although all the monkeys then failed to learn a new visual conditional task. This demonstrates that intact IT cortex in only one hemisphere is sufficient to sustain simple visual discrimination learning but implies that the cholinergic input and the inferotemporal cortical input to the hippocampus both contribute to visual conditional learning. The subsequent addition of an immunotoxic lesion of the basal nucleus of Meynert in the right hemisphere resulted in an additional impairment on a difficult shape discrimination. This argues that it is the cholinergic projection to the inferotemporal cortex, rather than to the rest of the cortex, which contributes to visual discrimination learning and memory.
Cortical representation of acoustic motion in the Rufous Horseshoe bat, Rhinolophus rouxi
Authors: Firzlaff U. , Schuller G. 
Published: March 2003

AbstractResponses of neurons to apparent auditory motion in the azimuth were recorded in three different fields of auditory cortex of the rufous horseshoe bat. Motion was simulated using successive stimuli with dynamically changing interaural intensity differences presented via earphones. Seventy‐one percent of sampled neurons were motion‐direction‐sensitive. Two types of responses could be distinguished. Thirty‐four percent of neurons showed a directional preference exhibiting stronger responses to one direction of motion. Fifty‐seven percent of neurons responded with a shift of spatial receptive field position depending on direction of motion. Both effects could occur in the same neuron depending on the parameters of apparent motion. Most neurons with contralateral receptive fields exhibited directional preference only with motion entering the receptive field from the opposite direction. Receptive field shifts were opposite to the direction of motion. Specific combinations of spatiotemporal parameters determined the motion‐direction‐sensitive responses. Velocity was not encoded as a specific parameter. Temporal parameters of motion and azimuth position of the moving sound source were differentially encoded by neurons in different fields of auditory cortex. Neurons with a directional preference in the dorsal fields can encode motion with short interpulse intervals, whereas direction‐preferring neurons in the primary field can best encode motion with medium interpulse intervals. Furthermore, neurons with a directional preference in the dorsal fields are specialized for encoding motion in the midfield of azimuth, whereas direction‐preferring neurons in the primary field can encode motion in lateral positions. The results suggest that motion information is differentially processed in different fields of the auditory cortex of the rufous horseshoe bat.
Emergence of axons from distal dendrites of adult mammalian neurons following a permanent axotomy
Authors: Rose P. K. , MacDermid V. , Joshi M. , Neuber‐Hess M. 
Published: March 2003

AbstractThe distinctive features of axons and dendrites divide most neurons into two compartments. This polarity is fundamental to the ability of most neurons to integrate synaptic signals and transmit action potentials. It is not known, however, if the polarity of neurons in the adult mammalian nervous system is fixed or plastic. Following axotomy, some distal dendrites of neck motoneurons in the adult cat give rise to unusual processes that, at a light microscopic level, resemble axons (Rose, P.K. & Odlozinski, M., J. Comp. Neurol., 1998, 390, 392). The goal of the present experiments was to characterize these unusual processes using well‐established ultrastructural and molecular criteria that differentiate dendrites and axons. These processes were immunoreactive for growth‐associated protein‐43 (GAP‐43), a protein that is normally confined to axons. In contrast, immunoreactivity for a protein that is widely used as a marker for dendrites, microtubule‐associated protein (MAP)‐2a/b, could not be detected in the unusual distal arborizations. At the electron microscopic level, unusual distal processes contained dense collections of neurofilaments and were frequently myelinated. These molecular and structural characteristics are typical of axons and suggest that the polarity of adult neurons in the mammalian nervous system can be disrupted by axotomy. If this transformation in neuronal polarity is common to other types of neurons, axon‐like processes emerging from distal dendrites may represent a mechanism for replacing connections lost due to injury. Alternatively, the connections formed by these axons may be aberrant and therefore maladaptive.
Abnormal trafficking and subcellular localization of an N‐terminally truncated serotonin transporter protein
Authors: Ravary Anne , Muzerelle Aude , Darmon Michèle , Murphy Dennis L. , Moessner Rainald , Lesch K. Peter , Gaspar Patricia 
Published: March 2003

AbstractWe report here that a truncated 5‐HTT protein is produced in the neurons of the raphe, in serotonin transporter (5‐HTT) knockout (KO) mice. The 5‐HTT gene has exon 2 deleted and we found that one main transcript, shortened by 450 bp, is produced in these KO mice. The mutated 5‐HTT protein is only recognized by antibodies against the C‐terminal portion of 5‐HTT. This protein is not functional as there is no high‐affinity serotonin uptake in 5‐HTT KO mice, in adults or during development. Conversely, low‐affinity serotonin uptake was detected in vitro, and in dopaminergic neurons of the substantia nigra in vivo. The truncated 5‐HTT, recognized by antibodies to the C‐terminus, is present exclusively in the somatodendritic compartment of the raphe neurons instead of being exported to axons. As shown with confocal and electron microscopy, the truncated 5‐HTT does not reach the plasma membrane and is essentially retained in the endoplasmic reticulum. However, this does not seem to trigger refolding or degradation responses, as no upregulation of the chaperone BiP or of the degradation signal ubiquitin was detected. Last, as observed in heterozygous mice, the presence of the truncated 5‐HTT protein, although produced in large quantities, does not disturb the normal trafficking of the wild‐type protein. This study therefore validates the 5‐HTT KO model despite the occurrence of an incomplete translation, and brings novel information on the in vivo 5‐HT uptake and cellular processing of an abnormal 5‐HTT protein.
Somatosensory cortical neuronal population activity across states of anaesthesia
Authors: Erchova Irina A. , Lebedev Mikhail A. , Diamond Mathew E. 
Published: March 2003

AbstractExperiments were carried out to learn about changes in sensory cortical processing associated with different levels of anaesthesia. Traditionally this question has been addressed by studying single neurons. Because state changes are likely to influence the relationships between neurons, the present experiments were undertaken to investigate the spatial and temporal firing patterns distributed across cortex. Using 5 × 5 or 10 × 10 microelectrode arrays, spontaneous and stimulus‐evoked activity of multineuron clusters was recorded from rat somatosensory ‘barrel’ cortex (the whisker representation) during a light surgical stage of urethane anaesthesia, and after two supplemental doses of urethane which led to intermediate and deep levels of anaesthesia. At all depths of anaesthesia, spontaneously occurring action potentials at a single electrode tended to be clustered into ‘bursts.’ With increasing anaesthetic depth, bursts became more prominent and rhythmic, and increasingly synchronized between cortical barrel‐columns. Burst frequency decreased and fewer spikes occurred outside bursts, leading to a decrease in the overall spontaneous firing rate. The cortical territory engaged by individual whiskers contracted with increasing depth of anaesthesia, leading to the spatial segregation of whisker representations. At all stages of anaesthesia, whisker stimulation produced the maximal cortical response when delivered close to burst onset. These observations show that ongoing spontaneous activity modulates sensory response properties and makes peripheral tactile information accessible to a cortical territory whose size is determined by the phase of burst cycle. The possible significance of the cyclic cortical responsiveness encountered during urethane anaesthesia to cortical processing in awake rats is considered.
Modulation of secretion by the endoplasmic reticulum in mouse chromaffin cells
Authors: Rigual Ricardo , Montero Mayte , Rico Alberto J. , Prieto‐Lloret Jesús , Alonso María Teresa , Alvarez Javier 
Published: March 2003

AbstractThe endoplasmic reticulum (ER) has been suggested to modulate secretion either behaving as a Ca2+ sink or as a Ca2+ source in neuronal cells. Working as a Ca2+ sink, through ER‐Ca2+ pumping, it may reduce secretion induced by different stimuli. Instead, working as a Ca2+ source through the Ca2+ induced Ca2+ release (CICR) phenomenon, it may potentiate secretion triggered by activation of plasma membrane Ca2+ channels. We have previously demonstrated the presence of CICR in bovine chromaffin cells, but we now find that mouse chromaffin cells almost lack functional caffeine‐sensitive ryanodine receptors in the ER and, consistently, no CICR from the ER could be observed. In addition, inhibition of ER Ca2+ pumping with ciclopiazonic acid or thapsigargin strongly stimulated high‐K+‐evoked catecholamine secretion and cytosolic [Ca2+] ([Ca2+]c) transients. Surprisingly, 5 mm caffeine reduced high‐K+‐induced [Ca2+]c peaks but considerably potentiated secretion induced by high‐K+ stimulation. However, this potentiation was insensitive to ryanodine and additive to that induced by emptying the ER of Ca2+ with thapsigargin, suggesting that it is unrelated to the activation of ryanodine receptors. We conclude that, in mouse chromaffin cells, CICR is not functional and the ER strongly inhibits secretion by acting as a damper of the [Ca2+]c signal.
The neuronal α6 subunit forms functional heteromeric acetylcholine receptors in human transfected cells
Authors: Fucile Sergio , Matter Jean‐Marc , Erkman Linda , Ragozzino Davide , Barabino Benedetta , Grassi Francesca , Alemà Stefano , Ballivet Marc , Eusebi Fabrizio 
Published: March 2003

AbstractWe examine some of the biological and physiological properties of the avian α6 neuronal nicotinic acetylcholine receptor (nAChR) subunit. We show here that, beginning at embryonic day 5, α6 mRNA is abundantly expressed in the developing chick neuroretina, where it coexists with other nicotinic receptor subunit mRNAs such as α3, β2 and β4. In contrast, α6 mRNA is absent from the optic tectum and from the peripheral ganglia. Despite numerous efforts, the α6 subunit has long failed the critical test of functional reconstitution. Here we use patch‐clamp techniques and confocal laser microscopy to measure ACh‐activated currents and nicotine‐elicited Ca2+ transients in human BOSC 23 cells transfected with chick α6 in combination with other chick nAChR neuronal subunits. Heterologously expressed α6 and β4 subunits form functional heteromeric nAChRs, which are permeable to Ca2+ ions and blocked by the nicotinic antagonist methyllycaconitine (10 μm). Likewise, ACh elicits measurable currents in cells transfected with α6 and β2. Hill analysis of the dose–response curves in cells transfected with α3, β4 and α6 cDNAs, suggests the assembly of functional α3β4α6 receptor, with an apparent affinity for ACh threefold lower than α3β4. Our results indicate that α6‐containing nAChRs assemble in heterologous expression systems and are probably present in retinal cells.