bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal ganglion cells with NADPH‐diaphorase activity in the chick form a regular mosaic with a strong dorsoventral asymmetry that can be modelled by a minimal spacing rule
Authors: Cellerino Alessandro , Novelli Elena , Galli‐Resta Lucia
Published: March 2003

We have identified a class of retinal ganglion cells in the chick retina that can be labelled by NADPH‐diaphorase histochemistry. These cells have a remarkable topographic distribution, being restricted to the dorsal hemiretina, and form a highly regular mosaic, as revealed by the analysis of nearest neighbour distribution and Delaunay triangulation. Autocorrelation analysis of the mosaic of NADPH‐diaphorase‐positive retinal ganglion cells shows that the mosaic spatial organization could be generated with the single constraint that two elements cannot be closer than a given minimal distance (dmin), which we confirmed by computer simulations. In contrast with what has been observed in other mosaics, here dmin varies with cell density. However, the observed variation of the exclusion area is consistent with an original assembly of the mosaic with a constant dmin (as is the case in other mosaics), followed by differential expansion of the retina during development.
Spatial, temporal and subcellular localization of islet‐brain 1 (IB1), a homologue of JIP‐1, in mouse brain
Authors: Pellet Jean‐Baptiste , Haefliger Jaques‐Antoine , Staple Julia K. , Widmann Christian , Welker Egbert , Hirling Harald , Bonny Christophe , Nicod Pascal , Catsicas Stefan , Waeber Gérard , Riederer Beat M.
Published: March 2003

Islet‐brain 1 (IB1) was recently identified as a DNA‐binding protein of the GLUT2 gene promoter. The mouse IB1 is the rat and human homologue of the Jun‐interacting protein 1 (JIP‐1) which has been recognized as a key player in the regulation of c‐Jun amino‐terminal kinase (JNK) mitogen‐activated protein kinase (MAPK) pathways. JIP‐1 is involved in the control of apoptosis and may play a role in brain development and aging. Here, IB1 was studied in adult and developing mouse brain tissue by in situ hybridization, Northern and Western blot analysis at cellular and subcellular levels, as well as by immunocytochemistry in brain sections and cell cultures. IB1 expression was localized in the synaptic regions of the olfactory bulb, retina, cerebral and cerebellar cortex and hippocampus in the adult mouse brain. IB1 was also detected in a restricted number of axons, as in the mossy fibres from dentate gyrus in the hippocampus, and was found in soma, dendrites and axons of cerebellar Purkinje cells. After birth, IB1 expression peaks at postnatal day 15. IB1 was located in axonal and dendritic growth cones in primary telencephalon cells. By biochemical and subcellular fractionation of neuronal cells, IB1 was detected both in the cytosolic and membrane fractions. Taken together with previous data, the restricted neuronal expression of IB1 in developing and adult brain and its prominent localization in synapses suggest that the protein may be critical for cell signalling in developing and mature nerve terminals.
Abnormal substance P release from the spinal cord following injury to primary sensory neurons
Authors: Malcangio Marzia , Ramer Matt S. , Jones Martyn G. , McMahon Stephen B.
Published: March 2003

The neuropeptide substance P (SP) modulates nociceptive transmission within the spinal cord. Normally, SP is uniquely contained in a subpopulation of small‐calibre axons (Aδ‐ and C‐fibres) within primary afferent nerve. However, it has been shown that after nerve transection, besides being downregulated in small axons, SP is expressed de novo in large myelinated Aβ‐fibres. In this study we investigated whether, following peripheral nerve injury, SP was released de novo from the spinal cord after selective activation of Aβ‐fibres. Spinal cords with dorsal roots attached were isolated in vitro from rats 2 weeks following distal sciatic axotomy or proximal spinal nerve lesion (SNL). The ipsilateral dorsal roots were electrically stimulated for two consecutive periods at low‐ or high‐threshold fibre strength, spinal cord superfusates were collected and SP content was determined by radioimmunoassay. SNL, but not axotomized or control rat cords, released significant amounts of SP after selective activation of Aβ‐fibres. Not only do these data support the idea that Aβ myelinated fibres contribute to neuropathic pain by releasing SP, they also illustrate the importance of the proximity of the lesion to the cell body.
Dual effect of ecdysone on adult cricket mushroom bodies
Authors: Cayre Myriam , Strambi Colette , Strambi Alain , Charpin Pierre , Ternaux Jean‐Pierre
Published: March 2003

Mushroom bodies, which are the main integrative centre for insect sensorial information, play a critical role in associative olfactory learning and memory. This paired brain structure contains interneurons grouped in a cortex, sending their axons into organized neuropiles. In the house cricket (Acheta domesticus) brain, persistent neuroblasts proliferate throughout adult life. Juvenile hormone (JH) has been shown to stimulate this proliferation [Cayre, M., Strambi, C. & Strambi, A. (1994) Nature, 368, 57–59]. In the present study, the effect of morphogenetic hormones on mushroom body cells maintained in primary culture was examined. Whereas JH did not significantly affect neurite growth, ecdysone significantly stimulated neurite elongation. Moreover, ecdysone also acted on neuroblast proliferation, as demonstrated by the reduced number of cells labelled with 5‐bromodeoxyuridine following ecdysone application. Heterospecific antibodies raised against ecdysone receptor protein and ultraspiracle protein, the two heterodimers of ecdysteroid receptors, showed positive immunoreactivity in nervous tissue extracts and in nuclei of mushroom body cells, indicating the occurrence of putative ecdysteroid receptors in cricket mushroom body cells. These data indicate a dual role for ecdysone in adult cricket mushroom bodies: this hormone inhibits neuroblast proliferation and stimulates interneuron differentiation. These results suggest that a constant remodelling of mushroom body structure could result from physiological changes in hormone titres during adult life.
Inositol 1,4,5‐trisphosphate and adenophostin analogues induce responses in turtle olfactory sensory neurons
Authors: Kashiwayanagi Makoto , Tatani Kazuya , Shuto Satoshi , Matsuda Akira
Published: March 2003

Using the whole‐cell mode of the patch‐clamp technique, we recorded inward currents in response to inositol‐1,4,5‐trisphosphate (IP3) and adenophostin analogues in turtle olfactory sensory neurons. Dialysis of IP3 into the neurons induced inward currents with an increase in membrane conductance in a dose‐dependent manner under the voltage‐clamp conditions (holding potential −70 mV). The application of Ca2+‐free Ringer solution to neurons previously dialysed with IP3 induced inward currents that were reversibly inhibited by application of Na+, Ca2+‐free Ringer solution, normal Ringer solution or 10 μm ruthenium red. Dialysis of the adenophostin analogues, novel IP3 receptor ligands, also induced inward currents with an increase in membrane conductance. The magnitude of the responses to the adenophostin analogues varied among these derivatives. The application of Ca2+‐free Ringer solution to neurons previously dialysed with the adenophostin analogues induced inward currents that were inhibited by the application of normal Ringer solution. The reversal potential of inward currents induced by an adenophostin analogue was similar to that induced by IP3, suggesting that inward currents induced by the adenophostin analogue were generated by a similar ionic mechanism to that induced by IP3. The present study demonstrated that IP3‐mediated transduction pathways exist in turtle olfactory receptor neurons and that adenophostin analogues act as agonists of IP3.
The seasonal pattern of cell proliferation and neuron number in the dentate gyrus of wild adult eastern grey squirrels
Authors: Lavenex Pierre , Steele Michael A. , Jacobs Lucia F.
Published: March 2003

The dentate gyrus is one of two areas in the mammalian brain that produces neurons in adulthood. Neurogenesis (proliferation, survival, and differentiation of new neurons) is regulated by experience, and increased neurogenesis appears to be correlated with improved spatial learning in mammals and birds. We tested the hypothesis that in long‐lived mammals that scatter‐hoard food, seasonal variations in spatial memory processing (i.e. increased processing during caching season in the autumn) might correlate with changes in neurogenesis and neuron number in the granule cell layer of the dentate gyrus (gcl DG). We investigated the rate of cell proliferation and the total number of neurons in the granule cell layer of wild adult eastern grey squirrels (Sciurus carolinensis) at three different times of the year (October, January and June). We found no seasonal differences in cell proliferation rate or in total neuron number in the granule cell layer. Our findings are in agreement with those of previous studies in laboratory mice and rats, and in free‐ranging, food‐caching, black‐capped chickadees, as well as with current hypotheses regarding the relationship between neurogenesis and learning. Our results, however, are also in agreement with the hypothesis that neurogenesis in the dentate gyrus represents a maintenance system that may be regulated by environmental factors, and that changes in total neuron number previously reported in rodents represent developmental changes rather than adult plasticity. The patterns observed in mature wild rodents, such as free‐ranging squirrels, may represent more accurately the extent of hippocampal plasticity in adult mammals.
Neurokinin 1 receptor expression by neurons in laminae I, III and IV of the rat spinal dorsal horn that project to the brainstem
Authors: Todd Andrew J. , McGill Margaret M. , Shehab Safa A. S.
Published: March 2003

Large neurons in laminae III and IV of the spinal cord which express the neurokinin 1 receptor and have dendrites that enter the superficial laminae are a major target for substance P (SP)‐containing (nociceptive) primary afferents. Although some of these neurons project to the thalamus, we know little about other possible projection targets. The main aim of this study was to determine whether all cells of this type are projection neurons and to provide information about brainstem sites to which they project. Injections of cholera toxin B subunit were made into four brainstem areas that receive input from the spinal cord, and the proportion of cells of this type in the L4 spinal segment that were retrogradely labelled was determined in each case. The results suggest that most of these cells (>90%) project to the contralateral lateral reticular nucleus (or to a nearby region), while many (>60%) send axons to the lateral parabrachial area and some to the dorsal part of the caudal medulla. However, few of these cells project to the periaqueductal grey matter. As lamina I neurons with the neurokinin 1 receptor appear to be important in the generation of hyperalgesia, we also examined projection neurons in this lamina and found that for each injection site the great majority possessed the receptor. These results demonstrate that dorsal horn neurons which express the neurokinin 1 receptor contribute to several ascending pathways that are thought to be important in pain mechanisms.
In vivo survival requirement of a subset of nodose ganglion neurons for nerve growth factor
Authors: Forgie Alison , Kuehnel Florian , Wyatt Sean , Davies Alun M.
Published: March 2003

The sensory neurons of the nodose ganglion are the classic example of a population of peripheral nervous system neurons that do not require nerve growth factor (NGF) for survival during development but are dependent on other neurotrophins. We have re‐examined this assertion by studying the development of the nodose ganglion of mice that have a null mutation in the NGF gene. Compared with wild‐type embryos, the number of neurons undergoing apoptosis was elevated in NGF –/– mice, resulting in a significant reduction in the total number of neurons in the ganglion by the end of embryonic development. TrkA, the NGF receptor tyrosine kinase, was expressed in the nodose ganglion throughout development and there was a marked decrease in TrkA mRNA expression in the nodose ganglion of NGF –/– embryos. Although the in vitro survival of the majority of nodose neurons was promoted by brain‐derived neurotrophic factor (BDNF), a minor proportion was supported by NGF in cultures established over a range of embryonic stages. These results clearly demonstrate that a subset of nodose ganglion neurons depends on NGF for survival during development. The finding that the expression of tyrosine hydroxylase (TH) mRNA was unaffected in the nodose ganglia of NGF‐deficient embryos indicates that this NGF‐dependent subset is distinct from the subset of catacholaminergic neurons in the nodose ganglion.
Oxytocin induces preservation of social recognition in male rats by activating α‐adrenoceptors of the olfactory bulb
Authors: Dluzen Dean E. , Muraoka Shinichiro , Engelmann Mario , Ebner Karl , Landgraf Rainer
Published: March 2003

In this report, a series of four experiments was performed to evaluate the relationship between the olfactory bulb norepinephrine system and intra‐olfactory bulb infusion of oxytocin in the preservation of social memory responses. The present data indicate that oxytocin exerts this preservation of social recognition through a specific, receptor‐mediated mechanism within the olfactory bulb (experiment 1). The involvement of the olfactory bulb norepinephrine system is revealed by the demonstration that retrodialysis of oxytocin into the olfactory bulb increases norepinephrine release (experiment 4). Our data suggest that the increased output of olfactory bulb norepinephrine resulting from oxytocin appears to activate α‐adrenoceptors to produce this preservation in recognition because infusions of clonidine into the olfactory bulb preserve recognition responses in a manner similar to that observed with oxytocin (experiment 2). In addition, a co‐infusion of oxytocin with phentolamine abolishes recognition responses (experiment 3). Accordingly, this model affords the opportunity to study neuropeptide–catecholamine interactions, link these interactions with a specific behavioural outcome and identify a novel function/site of action for oxytocin in the male.
Hippocampal stem cells differentiate into excitatory and inhibitory neurons
Authors: Vicario‐Abejón Carlos , Collin Carlos , Tsoulfas Pantelis , McKay Ronald D. G.
Published: March 2003

Stem cell technology promises new and rapid advances in cell therapy and drug discovery. Clearly, the value of this approach will be limited by the differentiated functions displayed by the progeny of stem cells. The foetal and adult central nervous system (CNS) harbour stem cells that can be expanded in vitro and differentiate into immature neurons and glia. Surprisingly, we do not know if neurons derived from stem cells form synapses, a definitive feature of neuronal function. Neuronal differentiation is a complex process and in this paper we establish conditions that permit extensive maturation of neurons in the presence of neurotrophins. These conditions permit the differentiation of rat hippocampal stem cells into both excitatory (glutamatergic) and inhibitory (GABAergic) neurons. The proportion of excitatory and inhibitory synapses was strongly influenced by specific neurotrophins, and these responses reflect the region of origin of the stem cells in the brain. These data show that stem cells can be used to study mechanisms of excitation and inhibition in the nervous system.
Effects of monoamines on interneurons in four spinal reflex pathways from group I and/or group II muscle afferents
Authors: Jankowska E. , Hammar I. , Chojnicka B. , Hedén C. H.
Published: March 2003

Effects of locally applied serotonin (5‐HT) and noradrenaline (NA) were tested on extracellularly recorded responses of single spinal interneurons in deeply anaesthetized cats. These effects were tested on: (i) interneurons mediating reciprocal inhibition from group Ia afferents; (ii) interneurons mediating non‐reciprocal inhibition from group Ia and Ib afferents; (iii) intermediate zone interneurons co‐excited by group I and II afferents; and (iv) dorsal horn interneurons excited by group II afferents. Effects of monoamines were tested on responses evoked at latencies compatible with monosynaptic coupling. Responses evoked by group Ia and/or Ib muscle afferents were facilitated in all of the tested interneurons both by NA and 5‐HT. Responses evoked by group II muscle afferents were depressed in the majority of the interneurons but were facilitated in some of them. 5‐HT depressed these responses in all dorsal horn interneurons and in one subpopulation of intermediate zone interneurons, while it facilitated them in another subpopulation of intermediate zone interneurons. NA depressed them in all intermediate zone interneurons and in one subpopulation of dorsal horn interneurons, while it facilitated them in another subpopulation of dorsal horn interneurons. The results of this study lead to the conclusions that: (i) modulation of synaptic actions of muscle spindle and tendon organ afferents on spinal interneurons by 5‐HT and NA is related to both the type of the afferent and the functional type of the interneuron; and that (ii) 5‐HT and NA counteract each others' actions on some interneuronal types but mutually enhance them on the others.
Afferent‐specific modulation of short‐term synaptic plasticity by neurotrophins in dentate gyrus
Authors: Asztely Fredrik , Kokaia Merab , Olofsdotter Klara , Örtegren Unn , Lindvall Olle
Published: March 2003

Neurotrophins modulate synaptic transmission and plasticity in the adult brain. We here show a novel feature of this synaptic modulation, i.e. that two populations of excitatory synaptic connections to granule cells in the dentate gyrus, lateral perforant path (LPP) and medial perforant path (MPP), are differentially influenced by the neurotrophins BDNF and NT‐3. Using field recordings and whole‐cell patch‐clamp recordings in hippocampal slices, we found that paired‐pulse (PP) depression at MPP–granule cell synapses was impaired in BDNF knock‐out (+/–) mice, but PP facilitation at LPP synapses to the same cells was not impaired. In accordance, scavenging of endogenous BDNF with TrkB–IgG fusion protein also impaired PP depression at MPP–granule cell synapses, but not PP facilitation at LPP–granule cell synapses. Conversely, in NT‐3+/– mice, PP facilitation was impaired at LPP–granule cell synapses whilst PP depression at MPP–granule cell synapses was unaffected. These deficits could be reversed by application of exogenous neurotrophins in an afferent‐specific manner. Our data suggest that BDNF and NT‐3 differentially regulate the synaptic impact of different afferent inputs onto single target neurons in the CNS.
Altering the concentration of GABA in the synaptic cleft potentiates miniature IPSCs in rat occipital cortex
Authors: Perrais David , Ropert Nicole
Published: March 2003

We have tested the effect of dextran (40 kDa, 5%) on miniature IPSCs (mIPSCs) recorded in layer V cortical pyramidal cells. This compound increases the amplitude of mIPSCs at room and physiological temperatures by 15%, leaving their duration unaffected at room temperature and slightly increased at physiological temperature. The amplitude increase is attributable to an increase in the number of receptors bound by GABA during synaptic transmission, as shown by the occlusion between the effects of dextran and zolpidem on mIPSC amplitude at room temperature. As dextran presumably enhances the concentration and dwell time of GABA in the synaptic cleft, these results demonstrate that the postsynaptic GABAA receptors are not saturated at room and physiological temperatures.
Inhibition of 11β‐hydroxysteroid dehydrogenase, the foeto‐placental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety‐like behaviour in the offspring
Authors: Welberg Leonie A. M. , Seckl Jonathan R. , Holmes Megan C.
Published: March 2003

Glucocorticoids may underlie the association between prenatal stress, low birth weight and adult stress‐associated disorders, e.g. hypertension and type 2 diabetes, increased hypothalamic–pituitary–adrenal (HPA) activity and affective dysfunction. Normally, 11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2) rapidly inactivates glucocorticoids in placenta and many foetal tissues, thus acting as a ‘barrier’ to maternal steroids. We investigated the effect of inhibiting foeto‐placental 11β‐HSD in rats, using carbenoxolone (CBX), on subsequent HPA activity and regulation and stress‐induced behaviour in adult offspring. Pregnant Wistar rats were injected with CBX (12.5 mg s.c.) or vehicle daily throughout pregnancy. CBX treatment reduced birth weight. Adult offspring of CBX‐treated dams had persistently reduced body weight, increased basal corticosterone (CORT) levels, increased corticotropin‐releasing hormone (CRH) and reduced glucocorticoid receptor (GR) mRNA in the hypothalamic paraventricular nucleus, though hippocampal GR and mineralocorticoid receptor (MR) mRNA expression were unaltered. In addition, these animals showed less grooming and rearing in an open field and reduced immobility in a forced swim test, and had increased GR mRNA expression in the basolateral (BLA), central (CEA) and medial (MEA) nuclei of the amygdala, with unaltered MR mRNA. These data suggest that disturbance of the foeto‐placental enzymatic barrier to maternal glucocorticoids reduces birth and body weight, and produces permanent alterations of the HPA axis and anxiety‐like behaviour in aversive situations. The behavioural and HPA effects may reflect GR gene programming in amygdala and hypothalamus, respectively. Foetal overexposure to endogenous glucocorticoids (prenatal stress or reduced activity of foeto‐placental 11β‐HSD) may represent a common link between the prenatal environment, foetal growth and adult neuroendocrine and affective disorders.
Gq protein α subunits Gαq and Gα11 are localized at postsynaptic extra‐junctional membrane of cerebellar Purkinje cells and hippocampal pyramidal cells
Authors: Tanaka Jun , Nakagawa Shin , Kushiya Etsuko , Yamasaki Miwako , Fukaya Masahiro , Iwanaga Toshihiko , Simon Melvin I. , Sakimura Kenji , Kano Masanobu , Watanabe Masahiko
Published: March 2003

Following cell surface receptor activation, the α subunit of the Gq subclass of GTP‐binding proteins activates the phosphoinositide signalling pathway. Here we examined the expression and localization of Gq protein α subunits in the adult mouse brain by in situ hybridization and immunohistochemistry. Of the four members of the Gq protein α subunits, Gαq and Gα11 were transcribed predominantly in the brain. The highest transcriptional level of Gαq was observed in cerebellar Purkinje cells (PCs) and hippocampal pyramidal cells, while that of Gα11 was noted in hippocampal pyramidal cells. Antibody against the C‐terminal peptide common to Gαq and Gα11 strongly labelled the cerebellar molecular layer and hippocampal neuropil layers. In these regions, immunogold preferentially labelled the cytoplasmic face of postsynaptic cell membrane of PCs and pyramidal cells. Immunoparticles were distributed along the extra‐junctional cell membrane of spines, dendrites and somata, but were almost excluded from the junctional membrane. By double immunofluorescence, Gαq/Gα11 was extensively colocalized with metabotropic glutamate receptor mGluR1α in dendritic spines of PCs and with mGluR5 in those of hippocampal pyramidal cells. Together with concentrated localization of mGluR1α and mGluR5 in a peri‐junctional annulus on PC and pyramidal cell synapses (Baude et al. 1993, Neuron, 11, 771–787; Luján et al. 1996, Eur. J. Neurosci., 8, 1488–1500), the present molecular‐anatomical findings suggest that peri‐junctional stimulation of the group I metabotropic glutamate receptors is mediated by Gαq and/or Gα11, leading to the activation of the intracellular effector, phospholipase Cβ.
Dissociable roles of the central and basolateral amygdala in appetitive emotional learning
Authors: Parkinson John A. , Robbins Trevor W. , Everitt Barry J.
Published: March 2003

The amygdala is considered to be a core component of the brain's fear system. Data from neuroimaging studies of normal volunteers and brain‐damaged patients perceiving emotional facial expressions, and studies of conditioned freezing in rats, all suggest a specific role for the amygdala in aversive motivation. However, the amygdala may also be critical for emotional processing in positive or appetitive settings. Using an appetitive Pavlovian approach procedure we show a theoretically important dissociation in the effects of excitotoxic lesions of the central nucleus and basolateral area of the amygdala, in the rat. Whilst central nucleus lesions impair appetitive Pavlovian conditioning, basolateral lesions do not. Together with other data, these results not only support the hypothesis that the amygdala is critical for appetitive as well as aversive learning, but are also consistent with amygdala subsystems subserving distinct aspects of emotional learning. Lesions of the dorsal or ventral subiculum were without effect on autoshaping, indicating the lack of involvement of hippocampal processing in this form of emotional behaviour and emphasizing further the neural specificity of the effects seen following central amygdala lesions.
Endothelial and neuronal nitric oxide synthases are present in the suprachiasmatic nuclei of Syrian hamsters and rats
Authors: Caillol Monique , Devinoy Eve , Lacroix Marie‐Christine , Schirar Alain
Published: March 2003

Nitric oxide (NO) is involved in the transmission of light information to suprachiasmatic nuclei (SCN). By immunocytochemistry, we showed that both neuronal and endothelial NO synthase isoforms (nNOS and eNOS) were present in the SCN of rats and hamsters. nNOS‐immunoreactive neurons were located mainly around the SCN with only a few nNOS neurons within the nucleus. By double‐label immunocytochemistry, we also found, within the population of SCN glial fibrillary acidic protein (GFAP)‐immunoreactive astrocytes, a subpopulation of eNOS‐immunoreactive astrocytes. Using Western blot analysis, we detected in SCN protein extracts eNOS and nNOS proteins having the expected 140 and 150 kDa molecular weights, respectively. By in situ hybridization of a 2.4‐kb murine eNOS probe, mRNA for eNOS was located in the SCN of rats and hamsters. The transcript was further identified by detection of a RT‐PCR product of the predicted size, after amplification of total RNA with primers specific for eNOS. In the SCN and cerebellum, the size of the mRNA for nNOS, detected with a rat probe on Northern blot, was ∼ 10.5 kb, corresponding to that previously published. In the same tissues, we found two transcripts, one weakly expressed at ∼ 4.0 kb and another more strongly expressed at ∼ 2.6 kb, both hybridizing with two non‐overlapping murine and rat eNOS probes. These results suggested the existence in the SCN of alternate transcripts for eNOS. We propose that two pathways could link light stimuli and NO release in the SCN: one involving N‐methyl‐ d‐aspartate (NMDA) receptors and nNOS in neurons; the other linking α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors and eNOS in astrocytes.
Neuroanatomical correlates of the near response: voluntary modulation of accommodation/vergence in the human visual system
Authors: Richter Hans O. , Lee Joel T. , Pardo José V.
Published: March 2003

This study identifies brain regions participating in the execution of eye movements for voluntary positive accommodation (VPA) during open‐loop vergence conditions. Neuronal activity was estimated by measurement of changes in regional cerebral blood flow (rCBF) with positron emission tomography and 15O‐water. Thirteen naive volunteers viewed a checkerboard pattern with their dominant right eye, while a lens interrupted the line of gaze during alternate 1.5 s intervals. Three counterbalanced tasks required central fixation and viewing of a stationary checkerboard pattern: (i) through a 0.0 diopter (D) lens; (ii) through a −5.0‐D lens while avoiding volitional accommodation and permitting blur; and (iii) through a −5.0‐D lens while maintaining maximal focus. The latter required large‐amplitude, high‐frequency VPA. As an additional control, seven of the subjects viewed passively a digitally blurred checkerboard through a 0.0‐D lens as above. Optometric measurements confirmed normal visual acuity and ability to perform the focusing task (VPA). Large‐amplitude saccadic eye movements, verified absent by electro‐oculography, were inhibited by central fixation. Image averaging across subjects demonstrated multifocal changes in rCBF during VPA: striate and extrastriate visual cortices; superior temporal cortices; and cerebellar cortex and vermis. Decreases in rCBF occurred in the lateral intraparietal area, prefrontal and frontal and/or supplementary eye fields. Analysis of regions of interest in the visual cortex showed systematic and appropriate task dependence of rCBF. Activations may reflect sensorimotor processing along the reflex arc of the accommodation system, while deactivations may indicate inhibition of systems participating in visual search.
Role of basal ganglia and ectostriatum in the context‐dependent properties of the optocollic reflex (OCR) in the pigeon (Columba livia): a lesion study
Authors: Gioanni H. , Sansonetti A.
Published: March 2003

The possible participation of basal ganglia and associated structures [dorsal striato‐pallidum, nucleus spiriformis lateralis (SpL), ectostriatum] in the elaboration of the optocollic reflex (OCR) was investigated by making bilateral chemical lesions (ibotenic acid). Previous data have shown that both the slow and fast phases of the OCR are dependent on the behavioural context. The slow phase velocity (SPV) and the peak velocity of fast phases obtained in non‐flying pigeons (‘resting condition’) were enhanced in pigeons in which a flying posture was experimentally provoked (‘flying condition’). Therefore, the effect of lesions was analysed in pigeons standing in the ‘resting’ or ‘flying’ condition. In the ‘resting’ as in the ‘flying’ condition, all the lesions provoked a decrease in SPV, which augmented with the stimulation velocity. Velocity step stimuli revealed greater OCR deficits than velocity ramp stimuli. Extensive lesions (including the striato‐pallidum, ectostriatum and a part of the neostriatum), as well as SpL lesions, provoked a greater SPV decrease over a longer time than lesions restricted to the striato‐pallidum or the ectostriatum. The peak velocity of fast phases was only reduced by the ‘extensive lesion’ in the ‘flying condition’. The present data show that the basal ganglia system is involved in the elaboration of optokinetic responses and suggest that, to work in an optimal range, the optokinetic centres need to receive integrated information from basal ganglia in addition to direct visual input.
Cell type‐ and synapse‐specific variability in synaptic GABAA receptor occupancy
Authors: Hájos Norbert , Nusser Zoltan , Rancz Ede A. , Freund Tamás F. , Mody Istvan
Published: March 2003

The degree of postsynaptic type A γ‐aminobutyric acid receptor (GABAA receptor) occupancy was investigated by using the benzodiazepine agonist zolpidem. This drug increases the affinity of GABAA receptors for γ‐aminobutyric acid (GABA) at room temperature (Perrais & Ropert 1999, J. Neurosci., 19, 578) leading to an enhancement of synaptic current amplitudes if receptors are not fully occupied by the released transmitter. We recorded miniature inhibitory postsynaptic currents (mIPSCs) from eight different cell types in three brain regions of rats and mice. Receptors in every cell type were benzodiazepine sensitive, as 10–20 μm zolpidem prolonged the decays of mIPSCs (151–184% of control). The amplitude of the GABAA receptor‐mediated events was significantly enhanced in dentate granule cells, CA1 pyramidal cells, hippocampal GABAergic interneurons, cortical layer V pyramidal cells, cortical layer V interneurons, and in cortical layer II/III interneurons. An incomplete postsynaptic GABAA receptor occupancy is thus predicted in these cells. In contrast, zolpidem induced no significant change in mIPSC amplitudes recorded from layer II/III pyramidal cells, suggesting full GABAA receptor occupancy. Moreover, different degrees of receptor occupancy could be found at distinct GABAergic synapses on a given cell. For example, of the two distinct populations of zolpidem‐sensitive mIPSCs recorded in olfactory bulb granule cells, the amplitude of only one type was significantly enhanced by the drug. Thus, at synapses that generate mIPSCs, postsynaptic receptor occupancy is cell type and synapse specific, reflecting local differences in the number of receptors or in the transmitter concentration in the synaptic cleft.
GABAB receptors mediate frequency‐dependent depression of excitatory potentials in rat perirhinal cortex in vitro
Authors: Ziakopoulos Zoe , Brown Malcolm W. , Bashir Zafar I.
Published: March 2003

Excitatory synaptic transmission in the perirhinal cortex exhibits marked homosynaptic paired pulse depression (PPD) at inter‐pulse intervals between 100 and 1000 ms, being maximal at 200 ms. Additionally, there is greater PPD with stimulation of the pathway from the temporal cortex side than with stimulation of the pathway from the entorhinal cortex side. We establish that this frequency‐dependent depression relies on the activation of GABAB (γ‐aminobutyric acid) receptors. PPD in both temporal and entorhinal pathways is abolished by either of the selective GABAB receptor antagonists, 3‐N[1‐(s)‐(3,4‐dichlorophenyl)ethyl]amino‐2‐(s)‐hydroxypropyl‐p‐benzyl‐phosphinic acid (CGP55845A) or 3‐amino‐propyl(diethoxymethyl)phosphinic acid (CGP35348). Barium which blocks G‐protein‐coupled, inwardly rectifying potassium channels, does not block PPD. Heterosynaptic depression mediated by GABAB receptors was also observed. The depression of the entorhinal pathway by stimulation of the temporal pathway is greater than depression of the temporal pathway by stimulation of the entorhinal pathway. Moreover, PPD increases with stimulus strength and the depression is enhanced by short trains of stimuli, consistent with stronger stimulation resulting in more GABA reaching GABAB receptors on excitatory glutamatergic synapses. Synaptic activation of GABAB receptors may be important in regulating excitability in a frequency‐dependent manner with maximal depression occurring at ∼ 5 Hz, which approximates to the theta rhythm. That homosynaptic and heterosynaptic depression by stimulation of the temporal pathway is greater than by stimulation of the entorhinal pathway suggests that activation of temporal feedforward connections to the perirhinal cortex can dominate the GABAergic control of synaptic activity within the perirhinal cortex.
Differences in Bcl‐2‐ and Bax‐independent function in regulating apoptosis in sensory neuron populations
Authors: Middleton Gayle , Cox Sean Wyatt andrew , Korsmeyer Stanley , Davies Alun M.
Published: March 2003

Bcl‐2 and Bax are cytoplasmic proteins that have antagonistic actions on apoptosis. To investigate the extent to which these proteins function independently in regulating neuronal apoptosis, we studied the in vivo and in vitro development of two populations of sensory neurons of mouse embryos that lack one or both proteins. Absence of Bcl‐2 increased neuronal apoptosis and reduced the number of neurons in both the trigeminal and nodose ganglia during the period of naturally occurring neuronal death. Absence of Bax reduced neuronal apoptosis and increased the number of surviving neurons in these ganglia and promoted sustained neuronal survival in neurotrophin‐free cultures. In contrast, the elimination of both Bcl‐2 and Bax had different consequences for these populations of neurons. In nodose ganglia, apoptosis was suppressed just as effectively in embryos lacking both proteins as in embryos lacking Bax alone, and neurons that lacked both proteins survived just as effectively in neurotrophin‐free medium as Bax‐deficient neurons. This suggests that for nodose neurons, the suppression of apoptosis by Bcl‐2 is entirely dependent on the presence of Bax. In trigeminal ganglia, although neuronal apoptosis was reduced in embryos lacking both proteins compared with wild‐type embryos, there were significantly more apoptotic neurons and significantly fewer surviving neurons in embryos lacking both proteins compared with Bax‐deficient embryos, and significantly fewer trigeminal neurons from embryos lacking both proteins survived in neurotrophin‐free medium compared with trigeminal neurons that lacked Bax alone. This suggests that for trigeminal neurons, Bcl‐2 functions partly independently of Bax in regulating survival. Our results therefore suggest that the relative independence of Bcl‐2 and Bax in regulating neuronal survival differs from one population of neurons to another.
Galanin knockout mice reveal nociceptive deficits following peripheral nerve injury
Authors: Kerr Bradley J. , Cafferty William B. J. , Gupta YurI. K. , Bacon Andrea , Wynick David , McMahon Stephen B. , Thompson Stephen W. N.
Published: March 2003

The neuropeptide galanin has been identified as a potential neurotransmitter/neuromodulator within the central nervous system. In the present study, the role of endogenous galanin in nociceptive processing in the nervous system has been analysed by using mice carrying a targeted mutation in the galanin gene. Supporting this, the effect of chronic administration of exogenous galanin on nociceptive sensory inputs has been assayed in adult rats. In the absence of peripheral nerve injury, the sensitivity to threshold noxious stimuli is significantly higher in galanin mutant mice than wild‐type controls. Following peripheral nerve injury, in conditions under which endogenous galanin levels are elevated, spontaneous and evoked neuropathic pain behaviours are compromised in mutant mice. Conversely, chronic intrathecal delivery of exogenous galanin to nerve‐intact adult rats is associated with persistent behavioural hypersensitivity, a significant increase in c‐fos expression and an increase in PKCγ immunoreactivity within the spinal cord dorsal horn. The present results demonstrate that a relationship exists between the degree of nerve injury‐induced galanin expression and the degree of behavioural hypersensitivity, and show that galanin may play a role in nociceptive processing in the spinal cord, with interrelated inhibitory and excitatory effects.
Basal expression of c‐Fos and Zif268 in the rat basal ganglia: immunohistochemical characterization of striatal Zif268‐positive neurons
Authors: Ishida Yasushi , Hashiguchi Hiroyuki , Ishizuka Yuta , Todaka Kazunari , Kuwahara Itsumi , Mitsuyama Yoshio , Nishimori Toshikazu
Published: March 2003

Basal expression of the protein products of the inducible immediate early genes (IEGs), c‐Fos and Zif268, was investigated in five regions of the rat basal ganglia using immunohistochemistry. In particular, high basal levels of Zif268 but very low levels of c‐Fos were seen in the caudate‐putamen (CPu). Double immunostaining revealed that many of the constitutively expressed Zif268‐positive neurons were GABAergic but very few were cholinergic or neuronal nitric oxide synthase (nNOS)‐positive, and some of the Zif268‐positive neurons were also immunopositive for a glutamate NMDA receptor subunit NR1 or NR2A. No regional difference between the medial and lateral parts of the CPu was observed in the cellular phenotypes of Zif268‐positive neurons. Almost no basal levels of Zif268 were seen in the other four regions: the globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata. As in the CPu, negligible levels of c‐Fos were seen in these four regions. Differential expression of these two IEGs may suggest gene‐specific and region‐specific functions of c‐Fos and Zif268 in the basal ganglia. Constitutive expression of Zif268 existing mainly in the GABAergic neurons in the CPu may at least in part be maintained by glutamatergic afferents.
Chronic psychosocial stress reduces the density of dopamine transporters
Authors: Isovich Eleonora , Mijnster M. Janneke , Flügge Gabriele , Fuchs Eberhard
Published: March 2003

The effect of different types of physical stress on brain dopaminergic function has been well established in rodents; however, the role of the dopaminergic system in more naturalistic stress situations is poorly understood. Therefore, the aim of the current study was to investigate the effect of chronic psychosocial stress on the dopamine transporter, which is an important component in the regulation of dopaminergic neurotransmission. For this purpose, we used the well‐characterized paradigm of subordination stress in male tree shrews (Tupaia belangeri). In the present study, the animals were subjected to psychosocial stress for 28 days. Animals were daily videotaped and locomotor activity was quantified. In subordinate animals, urinary cortisol and noradrenaline, as well as adrenal weight, were increased, whereas body weight, locomotor activity and testicular function were decreased. Brain dopamine transporter binding sites were quantified by in vitro autoradiography using [3H] WIN 35,428 as ligand. Chronic stress reduced the number of binding sites (Bmax) in the caudate nucleus and the putamen without affecting the affinity (Kd). Stress did not influence the binding parameters in the nucleus accumbens, the substantia nigra or the ventral tegmental area. Furthermore, we found a positive correlation between locomotor activity and the Bmax values for [3H] WIN 35,428 binding in the caudate nucleus, the putamen and the nucleus accumbens. The present study shows that a naturalistic stressor, such as chronic psychosocial conflict, decreases dopamine transporter binding sites in motor‐related brain areas, suggesting that the reduction in locomotor activity in subordinate tree shrews is related to the downregulation of dopamine transporter binding sites.
Perineuronal nets ensheath fast spiking, parvalbumin‐immunoreactive neurons in the medial septum/diagonal band complex
Authors: Morris Neil P. , Henderson Zaineb
Published: March 2003

Perineuronal nets, composed of extracellular matrix material, have previously been associated with parvalbumin‐immunoreactive neurons in the medial septum/diagonal band (MS/DB) complex of the rat. The aim of this study was to correlate the presence of perineuronal nets with electrophysiological properties and parvalbumin immunoreactivity in MS/DB neurons. Intracellular recordings were made from cells in a brain slice preparation maintained in vitro, and neurons were characterized into four populations: (i) slow‐firing neurons, (ii) burst‐firing neurons, (iii) fast spiking neurons with narrow action potentials and a small degree of spike frequency adaptation, and (iv) regular spiking neurons with broader action potentials and a high degree of spike frequency adaptation. Following electrophysiological characterization, neurons were filled with biocytin, processed for parvalbumin immunoreactivity and stained for perineuronal nets using Wisteria floribunda lectin. The three substances were viewed with triple fluorescence. Fast spiking, nonadapting neurons, shown previously to contain parvalbumin immunoreactivity, were nearly all ensheathed by perineuronal nets. There was a population of small parvalbumin‐immunoreactive neurons which did not possess perineuronal nets, and which were not encountered with the intracellular electrodes. The other three neuron types in the MS/DB did not contain parvalbumin immunoreactivity or perineuronal nets. In keeping with this neurochemical profile for electrophysiologically identified neurons, burst‐firing neurons had action potential parameters more similar to those of regular spiking than of fast spiking neurons. We conclude that fast spiking neurons, presumed to be GABAergic septohippocampal projection neurons, are surrounded by supportive structures to enable the high level of neuronal discharge required for producing disinhibition of hippocampal pyramidal neurons.
Cannabinoid withdrawal is dependent upon PKA activation in the cerebellum
Authors: Tzavara Eleni TH. , Valjent Emmanuel , Firmo Cedric , Mas Magdalena , Beslot Françoise , Defer Nicole , Roques Bernard P. , Hanoune Jacques , Maldonado Rafael
Published: March 2003

Region‐specific up‐regulation of the cyclic AMP pathway is considered an important molecular mechanism in the origin of the somatic manifestations of the withdrawal syndrome to known drugs of abuse. Nevertheless, the existence of a withdrawal syndrome after prolonged cannabinoid administration has long been a controversial issue. Recent studies, in different species, have shown that withdrawal to prolonged cannabinoid exposure precipitated by the cannabinoid antagonist SR141716A is characterized by physical signs underlying impairment of motor coordination. Interestingly, cannabinoid withdrawal is accompanied by an increase of adenylyl cyclase activity in the cerebellum. Here, we investigate the functional role of the cyclic AMP pathway in the cerebellum in the establishment of cannabinoid withdrawal. We show that after SR141716A precipitation of cannabinoid withdrawal, basal and calcium‐calmodulin‐stimulated adenylyl cyclase activities as well as active PKA in the cerebellum increase in a transient manner with a temporal profile which matches that of the somatic expression of abstinence. Selectively blocking the up‐regulation of the cyclic AMP pathway in the cerebellum, by microinfusing the cyclic AMP blocker Rp‐8Br‐cAMPS in this region, markedly reduced both PKA activation and the somatic expression of cannabinoid withdrawal. Our results (i) directly link the behavioural manifestations of cannabinoid withdrawal with the up‐regulation of the cyclic AMP pathway in the cerebellum, pointing towards common molecular adaptive mechanisms for dependence and withdrawal to most drugs of abuse; (ii) suggest a particular role for the cerebellum as a major neurobiological substrate for cannabinoid withdrawal.
Physiological role of group III metabotropic glutamate receptors in visually responsive neurons of the rat superficial superior colliculus
Authors: Cirone J. , Salt T. E.
Published: March 2003

There is evidence from immunohistochemical and in situ hybridization studies for the presence of Group I, II and III metabotropic glutamate receptors (mGluRs) in the rat superficial superior colliculus (SSC). The purpose of this study was to investigate if manipulation of Group III mGluRs affects visual responses in the SSC. Drugs were applied by iontophoresis and single neuron activity was recorded extracellularly. L‐AP4 (Group III agonist) resulted in a reduction of visual responses in most neurons, but also a potentiation in others. The effect of L‐AP4 is drug‐ and stereospecific in that application of D‐AP4 did not significantly affect visual responses. L‐AP4 application also resulted in a potentiation of the response to iontophoretically applied NMDA. The effects of MPPG and CPPG (Group III antagonists) were compared with the effect of L‐AP4 in the same neuron and were found to produce the opposite effect to L‐AP4. Furthermore, the effect of L‐AP4 could be blocked by coapplication of MPPG or CPPG. Presynaptic depression of glutamate release is a possible mechanism by which L‐AP4 could reduce visual responses in the SSC whereas the potentiation of visual responses by L‐AP4 could be due to a reduction of GABAergic inhibition. The finding that MPPG and CPPG, as well as antagonizing the L‐AP4 effect, have a direct effect on visual responses suggests that Group III mGluRs are activated by endogenous transmitter released during visual stimulation.