bluuebunny/crossref_metadata_2025 huggingface dataset:
A PET Study of Somatosensory Discrimination in Man. Microgeometry Versus Macrogeometry
Authors: O'Sullivan Brendan T. , Roland Per E. , Kawashima Ryuta
Published: April 2006

The regional cerebral blood flow (rCBF) was measured with 15O‐butanol and positron emission tomography (PET) in 10 healthy subjects in order to compare cerebral activation involved in the somatosensory discrimination of microgeometric features with cerebral activation associated with the discrimination of macrogeometric features. Subjects performed two‐alternative forced choice (2‐AFC) discriminations of pairs of stimuli from a series of quantified standardized stimuli that differed in roughness (microgeometry), and a separate 2‐AFC task of smooth tactile stimuli that differed in length (macrogeometry). Results are presented from three conditions: (1) a roughness discrimination task; (2) a length discrimination task; and (3) a control trial in which subjects were required to reproduce similar exploratory finger movements only, but without a specific stimulus to feel. Mean subtraction images were computed using the computerized adjustable brain atlas of Greitz et al. (1991, J. Comput. Assisted Tomogr., 15, 26–38) and areas of significant blood flow change were identified. Both the roughness and the length discrimination tasks activated overlapping cortical fields contralaterally in the anterior and posterior lip of the postcentral sulcus. However, in the length discrimination, activation of the posterior lip of the postcentral sulcus extended deeper into the sulcus and there was also a separate additional area of activation in the anterior part of the precentral gyrus. Furthermore, the length discrimination task activated fields in the overt part of the supramarginal gyrus bilaterally as well as fields in the angular gyrus bilaterally. Thus roughness discrimination uses only a subset of the cortical regions that are needed for the recovery of length information, which requires more extensive somatosensory processing. This finding may be partly explained in that length perception needs both edge detection of the stimuli used, as well as integrated information of surface length and velocity, which is not necessary for roughness perception. Specific differences in the acquisition of necessary tactile information between the two discrimination tasks was reflected in different sampling strategies.
Auditory Localization Behaviour in Visually Deprived Cats
Authors: Rauschecker Josef P. , Kniepert Ulla
Published: April 2006

The ability to localize sounds in azimuth was tested in five cats that had been binocularly deprived of vision from birth for several months and in three normal age‐matched controls. Brief tone bursts were presented in an eight‐choice apparatus along 360° of the azimuthal plane at constant elevation. Using positive reinforcement techniques, the cats were trained to walk from the centre of the 3 m diameter circular enclosure to the hidden loudspeakers. The distribution of sound localization error from 55 trials per cat at each speaker position was measured, and its standard deviation was used to assess the precision of sound localization. All cats localized tones straight ahead of them most precisely; performance at lateral and rear positions was gradually less precise. When the sound localization ability of normal and binocularly deprived cats was compared across speakers, a significantly enhanced precision was found for binocularly deprived cats overall (P < 0.002; two‐way analysis of variance). An improvement was found at each individual speaker position, but it was greatest at lateral and rear positions. In two sets of control experiments normal cats were retested (i) in the dark with the aid of an infrared camera and (ii) after 3 months of binocular lid suture. Normal cats in the dark did not show any differences in their sound localization behaviour. Late‐deprived cats showed a tendency for better performance, which fell short of statistical significance. Our results in visually deprived cats agree well with some reports on the sound localization ability of blind humans, but disagree with others. Our data provide support for a hypothesis of compensatory plasticity, in which sensory functions get sharpened with the loss of another modality. They seem to rule out the necessity for vision to play a role in the postnatal calibration of auditory space.
Pattern of Development of the Callosal Transfer of Visual Information to Cortical Areas 17 and 18 in the Cat
Authors: Milleret C. , Houzel J. C. , Buser P.
Published: April 2006

The aim of this study was to investigate the development of visual callosal transfer in the normally reared cat. Two‐ to nine‐week‐old kittens and adults (used as controls) underwent section of the optic chiasm. Three days later, the animals were placed under anaesthesia and paralysed; unit activities were recorded from visual cortical areas 17 and 18 and from the white matter in one hemisphere. The units were tested for their responses to visual stimulation of each eye successively. Out of 1036 recorded neurons, 185 could be activated through the eye contralateral to the explored cortex via callosal transfer. Most of them could also be driven through the ipsilateral eye via the ‘direct’ geniculo‐cortical pathway. For animals aged ≤2 weeks, virtually all of these units were located at the 17/18 border zone, with a majority in the supragranular layers. When activated through the corpus callosum, they displayed receptive fields located either on the central vertical meridian of the visual field or in the hemifield ipsilateral to the explored cortex. Such extension into the ipsilateral hemifield as well as receptive field disparities of binocular units decreased with age, while spontaneous activity, strength of response, orientation selectivity and ability to respond to slits moving at middle‐range velocity increased. The main conclusion is that the transient callosal projections described by anatomists, which are present until 3 months of age, do not achieve supraliminar synaptic contacts with parts of areas 17 and 18 other than the 17/18 border zone, at least from 12 days after birth. However the visual callosal transfer in young animals displays some characteristics which disappear with age.
Expression of Soluble Guanylyl Cyclase Gene in Adult Rat Brain
Authors: Burgunder J.‐M. , Cheung P. T.
Published: April 2006

The synthesis of the intracellular messenger, cyclic GMP, is catalysed by particulate or soluble guanylyl cyclase (sGCY). sGCY is activated by nitric oxide, a compound with putative neurotransmitter functions, especially in long‐term potentiation. Hybridization histochemistry with a probe complementary to the rat lung large (α1) subunit was used to assess the exact localization of sGCY mRNA in the rat brain. Many cells in the olfactory bulb contained sGCY mRNA. In the whole cerebral cortex, sGCY mRNA was found in all layers, with a predominance in layers II ‐ III. A similar pattern was found in the olfactory tuberculum, in continuation with the piriform cortex and the cortical amygdaloid nucleus. All parts of the striatum expressed sGCY mRNA. sGCY mRNA was also found in the habenula medialis, in the pinealis in some diencephalic nuclei, and in the granule cell layers of the cerebellum. This study provides a description of the normal anatomy of sGCY gene expression in the rat forebrain as a basis for the study of the modulation of expression after physiological and pharmacological manipulations.
Muscarinic Receptor Characteristics and Regulation in Rat Cerebral Cortex: Changes during Development, Aging and the Oestrous Cycle
Authors: van Huizen Frans , March Derrick , Cynader Max S. , Shaw Christopher
Published: April 2006

The effects of postnatal development, aging and the oestrous cycle on muscarinic acetylcholine receptor (mAChR) properties were examined in in vitro living slices of rat neocortex. Using the hydrophilic antagonist ([3H]NMS) to label cell surface mAChRs, an increase in both Bmax and Kd was found during the first postnatal weeks. These values peaked at between 20–40 days postnatally and then declined to adult levels. After 3 months of age, a steady decline in receptor number started: it was 10.1% lower at 10 months and 38.7% lower at 17 months of age. In contrast, Kd values increased, being 31.7 and 20% higher respectively at these ages. Carbachol‐induced (4 h at 37°C) down‐regulation of receptor number was ‐22.2% in newborn and 26.1% in adult (3‐month‐old) rats, but only 16.3% at 20–40 days of age. The degree of carbachol‐induced down‐regulation of mAChR was not affected in the older animals. Veratridine, which increases neural activity, also induced a significant reduction in [3H]NMS binding sites of 11.4% in rats aged 0–20 days and 22.4% in 3‐month‐old rats, but at 20–40 and 40–60 days of age no significant down‐regulation of receptor number was observed. Furthermore, down‐regulation was absent in the 10‐month‐old rats as well. Since a great variation in Smax and Kd values was seen in 3‐month‐old females but not in male rats, we investigated mAChR characteristics during the oestrous cycle of female rats. In pro‐oestrus, mACh receptor number was increased and affinity decreased in comparison with di‐oestrus. The transition from pro‐oestrus into oestrus was accompanied by a significant decrease in receptor number and an increase in receptor affinity. Injection of ovariectomized females with oestradiol and progesterone induced an increase in the number of binding sites and a decrease in affinity. These values are comparable to those seen in pro‐oestrous rats. These results demonstrate (i) that both carbachol‐ and veratridine‐induced down‐regulation of the mACh receptor is limited during the critical period of cortical plasticity, (ii) that after 3 months of age mACh receptor number is gradually declining, and (iii) that the steroid hormones oestrogen and progesterone are capable of modifying the characteristics of muscarinic antagonist binding sites in the female rat cerebral cortex.
Fibroblast Growth Factor‐5 Promotes Differentiation of Cultured Rat Septal Cholinergic and Raphe Serotonergic Neurons: Comparison with the Effects of Neurotrophins
Authors: Lindholm Dan , Hartikka Jukka , da Penha Berzaghi Maria , Castrén Eero , Tzimagiorgis Georgios , Hughes Richard A. , Thoenen Hans
Published: April 2006

Fibroblast growth factor‐5 (FGF‐5) is a member of the fibroblast growth factor gene family, which has a signal sequence characteristic of secretory proteins. FGF‐5 mRNA has previously been shown to be present in the adult mouse brain. Here we demonstrate that recombinant FGF‐5 has neurotrophic activity on cultured rat septal cholinergic and raphe serotonergic neurons. The effect of FGF‐5 on serotonin uptake was stronger than that evoked with either brain‐derived neurotrophic factor or neurotrophin‐3. FGF‐5 also increased the choline acetyltransferase activity of cultured rat septal cholinergic neurons, the effect being additive to that of nerve growth factor. In situ hybridization experiments and immunohistochemistry using a specific anti‐FGF‐5 antibody demonstrated that FGF‐5 is expressed in rat hippocampal neurons. Like nerve growth factor mRNA, the levels of FGF‐5 mRNA in the rat hippocampus increased substantially during early postnatal development. In addition, injection of the muscarinic receptor agonist pilocarpine elevated FGF‐5 mRNA. The presence of the secretory FGF‐5 in the rat hippocampus, a target field of septal cholinergic and raphe serotonergic neurons, suggests that FGF‐5 acts as a trophic factor for these neurons also in vivo.
Development of the Thalamic Reticular Nucleus in Ferrets with Special Reference to the Perigeniculate and Perireticular Cell Groups
Authors: Mitrofanis John
Published: April 2006

This study describes the development of the ferret thalamic reticular nucleus from Nissl‐stained and from parvalbumin‐immunostained sections. From early stages [embryonic day (E) 23‐E25], there is a large group of ventral thalamic cells which lies between the dorsal thalamus and the primordial internal capsule. This group of cells, the primordial reticular nucleus, gives rise to the main body of the reticular nucleus, the perigeniculate nucleus and the perireticular nucleus. In the reticular nucleus, there are two waves of parvalbumin expression during development. The first wave begins prenatally in small cells which are seen rarely after birth. Their fate is not clear: they may have lost immunoreactivity, migrated elsewhere, or died. At the end of the first wave, a second wave begins in a distinct group of larger ovoid reticular cells, which appear to remain into adulthood. At about birth, the dorsocaudal pole of the reticular nucleus first forms the perigeniculate nucleus. During this developmental stage, cells which make up the reticular and perigeniculate nuclei are the only parvalbumin‐immunostained structures in the thalamus. Thus, rather than develop from the dorsal thalamus, the perigeniculate nucleus seems to have its origins in the ventral thalamus together with the reticular nucleus. During development, the reticular nucleus is associated closely with a large mass of cells located in the internal capsule, called the perireticular nucleus. Later, the perireticular nucleus is dramatically reduced in size: that is, there is a large reduction in the number of perireticular cells seen per section and in the extent of the nucleus across the internal capsule. There are two cytoarchitectonically distinct groups of perireticular cells. One group of cells, called the large‐celled perireticular zone (LPR), enters the internal capsule from early prenatal development (E25). Many of these cells reach the globus pallidus and extend as far as the cortical subplate zone. The LPR together with the subplate form an extensive neuronal network in the white matter during early development, which disappears later in development (about postnatal day 20). The second group of perireticular cells is made up of smaller cells and is called the small‐celled perireticular zone (SPR). These small cells enter the internal capsule from the reticular nucleus just prior to birth. Many of the cells in the SPR remain in the adult.
Innervation of Putative Rapidly Adapting Mechanoreceptors by Calbindin‐ and Calretinin‐immunoreactive Primary Sensory Neurons in the Rat
Authors: Duc Christophe , Barakat‐Walter Ibtissam , Droz Bernard
Published: April 2006

Calbindin and calretinin are two homologous calcium‐binding proteins that are expressed by subpopulations of primary sensory neurons. In the present work, we have studied the distribution of the neurons expressing calbindin and calretinin in dorsal root ganglia of the rat and their peripheral projections. Calbindin and calretinin immunoreactivities were expressed by subpopulations of large‐ and small‐sized primary sensory neurons and colocalized in a majority of large‐sized ones. The axons emerging from calbindin‐ or calretinin‐immunoreactive neurons innervated muscle spindles, Pacini corpuscles and subepidermal lamellar corpuscles in the glabrous skin, formed palisades of lanceolate endings around hairs and vibrissae, and gave rise to intraepidermal nerve endings in the digital skin. Since most of these afferents are considered as rapidly adapting mechanoreceptors, it is concluded that calbindin‐ or calretinin‐expressing neurons innervate particular mechanoreceptors that display physiological characteristics of rapid adaptation to stimuli.
Evidence for Excitatory Amino Acid Neurotransmitters in Forward and Feedback Corticocortical Pathways within Rat Visual Cortex
Authors: Johnson Randall R. , Burkhalter Andreas
Published: April 2006

It is a commonly accepted notion that cells which make projections between the multiple cortical areas found in the mammalian visual system are excitatory, but there is little direct evidence that this is the case. Here we demonstrate using retrograde tracing with D‐[3H]aspartate that connections in the rat which project from lower to higher visual areas (i.e. forward) and those which project from higher to lower areas (i.e. feedback) may use excitatory amino acid neurotransmitters. Following injection into the primary visual cortex, clusters of retrogradely labelled cells were found in several extrastriate areas within the cytoarchitectonic subdivisions 18a (‘areas’ LM, AL, PX, FLX, RL, AX) and 18b (‘area’ MX), and in the retrosplenial cortex. In all of these areas D‐[3H]aspartate‐labelled cells were surrounded by diffuse label which may represent anterograde labelling of axon terminals. This suggests that both legs of reciprocal intracortical circuits have similar chemospecificity. To directly demonstrate excitatory amino acid localization in forward projections, D‐[3H]aspartate was injected into extrastriate area LM. As expected, the results revealed retrogradely labelled neurons within area 17. Outside area 17, LM injections labelled neurons in AL, PX, FLX, RL, AX and MX. Taken in the context of the hierarchy of areas in rat cerebral cortex (Coogan and Burkhalter, J. Neurosci., 13, 3749–3772, 1993), these results show that D‐[3H]aspartate labels: (1) forward connections from area 17 to LM, AL, PX, RL, AX and MX, (2) feedback connections from LM, AL, FLX, PX, RL, AX and MX to area 17, (3) feedback connections from AL, PX, RL, AX and MX to LM, and (4) lateral connections between FLX and LM. These findings strongly indicate that both forward and feedback connections as well as lateral connections at several different levels of the cortical hierarchy use excitatory amino acid neurotransmitters.
Chemical Compartmentation and Relationships between Calcium‐binding Protein Immunoreactivity and Layer‐specific Cortical and Caudate‐projecting Cells in the Anterior Intralaminar Nuclei of the Cat
Authors: Molinari M. , Leggio M. G. , Dell'Anna M. E. , Giannetti S. , Macchi G.
Published: April 2006

Neurons projecting to the parietal cortex or striatum and neurons showing immunoreactivity for the calcium‐binding proteins parvalbumin and 28KD‐calbindin were examined in the anterior intralaminar nuclei (IL) of the cat. Retrograde tracing from deep or superficial parietal cortical layers or from the caudate nucleus was coupled with immunohistochemistry to determine which of these proteins were expressed in the projection neurons. It was found that IL neurons project to deep as well as to superficial layers of the parietal cortex, that IL‐cortical neurons could be differentiated into two populations according to their cortical projection pattern and their soma size, and that IL neurons projecting to the parietal cortex or to the striatum express 28KD calbindin immunoreactivity but not parvalbumin immunoreactivity. The distribution of immunoreactivity to 28KD calbindin and parvalbumin in the neuropil showed a consistent complementary distribution pattern in the IL. The compartments based on differential parvalbumin and 28KD calbindin expression may indicate the presence of functionally segregated units in IL.
Characteristics of Calcium Channels Responsible for Voltage‐activated Calcium Entry in Rat Cerebellar Granule Cells
Authors: Bossu J. L. , De Waard M. , Fagni L. , Tanzi F. , Feltz A.
Published: April 2006

The properties and characteristics of calcium channel openings in cerebellar granule cells were analysed by the cell‐attached patch‐clamp technique. At depolarized potentials, with 110 mM Ba2+ as the divalent charge carrier, 36% of the patches displayed activity that consisted of elementary events whose amplitude ranged from – 0.3 to –1. 75 pA at 0 mV, giving rise to a high threshold current. In this population of events at least four different types of channel openings were identified by their distinct biophysical and pharmacological properties. Two types of channel openings, with conductances around 24 and 7 pS, had similar characteristics in that both opened following two modes of gating characterized by brief (˜ 2 ms) and longer openings (˜ 8 ms) and both were sensitive to dihydropyridines. A further type of channel opening, with a conductance around 11 pS gated mainly with brief openings (∼1 ms), was shown to be insensitive to dihydropyridines but was undetectable in recordings from the cells that had been treated with ω‐conotoxin. The last type of event was revealed after treatment of the cell with nicardipine or nifedipine and ω‐conotoxin. The corresponding channel had a conductance of 19 pS and opened in one dominant mode characterized by brief openings (∼1 ms). The data obtained on single‐channel activity of cerebellar granule cells are compared with the properties of the total current recorded in whole‐cell conditions.
Effects of Transforming Growth Factor β1, on Scar Production in the Injured Central Nervous System of the Rat
Authors: Logan Ann , Berry Martin , Gonzalez Ana Maria , Frautschy Sally A. , Sporn Michael B. , Baird Andrew
Published: April 2006

In the central nervous system (CNS), nerve regeneration after traumatic injury fails. The formation of a dense fibrous scar is thought to restrict in part the growth of axonal projections, providing one of the many reasons that complete lesions of neural pathways in the adult mammalian CNS are rarely followed by significant functional recovery. In order to determine which mechanisms mediate scar formation in the CNS and to investigate whether they can be modulated in vivo, we have attempted to define the potential role of trophic factors. Our previous studies have shown the focal elevation of transforming growth factor β1 (TGFβ1) expression in lesioned CNS tissue. In the studies described here, we demonstrate that TGFβ1 participates in the scarring response in the rat brain. First, the elevated protein levels of TGFβ1 are localized to specific populations of injury‐responsive cells in the traumatized CNS. Furthermore, the injection of TGFβ1 into the brains of injured rats causes a dramatic increase in the scarring response. Conversely, when neutralizing TGFβ1 antibodies are administered, the deposition of fibrous scar tissue and the formation of a limiting glial membrane that borders the lesion is significantly attenuated, thus establishing a role for the endogenous growth factor in regulation of the non‐glial component of the scar. In implicating TGFβ1 in the scarring response in the CNS, the potential use for TGFβ1 antagonists as inhibitors of scar formation in the injured mammalian CNS is self‐evident.
Muscarinic Regulation of Ca2+ Currents in Rat Sensory Neurons: Channel and Receptor Types, Dose ‐ response Relationships and Cross‐talk Pathways
Authors: Wanke Enzo , Bianchi Laura , Mantegazza Massimo , Guatteo Ezia , Mancinelli Enzo , Ferroni Arnaldo
Published: April 2006

We studied, in rat sensory neurons, the modulation of high voltage‐activated Ca2+ currents (ICa mediated by the pertussis toxin‐sensitive activation of muscarinic receptors, which were found to be of subtypes M2, or M4. Muscarine reversibly blocked somatic Ca2+ spikes but strong predepolarizations only partially relieved the inhibited Ca2+ current. On the other hand, the putative coupling messenger could not rapidly diffuse towards channels whose activity was recorded from a macro‐patch. The perforated patch technique virtually prevented the response rundown present during whole‐cell experiments. Both ω‐conotoxin GVIA (ω‐CgTx)‐sensitive channels and ω‐CgTx‐ and dihydropyridine‐resistant channels are coupled to the muscarinic receptor, but not the L‐channel. When measured in the same neuron, dose ‐ response relationships for the first and subsequent agonist applications differed; maximal inhibition, the reciprocal of half‐maximal concentration and the Hill coefficient were always highest in the first trial. Muscarine and oxotremorine exhibited monotone dose ‐ response curves, but oxotremorine‐M showed non‐linear relationships which became monotonic when cells were intracellularly perfused with inhibitors of protein kinase A (PKA) and C (PKC), suggesting that either PKA or receptor‐induced PKC could phosphorylate and thus inactivate G‐proteins or other unknown proteins involved in inhibitory muscarinic actions on ICa. In summary, these data provide a preliminary pharmacological characterization of the muscarinic inhibition of the Ca2+ channels in sensory neurons, with implications about agonist specificity and the interplay between signalling pathways.
Intracellular Action of Spermine on Neuronal Ca2+ and K+ Currents
Authors: Drouin Herbert , Hermann Anton
Published: April 2006

Intra‐and extracellular effects of the polyamine spermine on electrical activity and membrane currents of identified neurons in the abdominal ganglion of Aplysia californica were studied under current‐and voltage‐clamp conditions. Lonophoretic injection of spermine reduced the amplitude of action potentials and altered their time course as well as spontaneous discharge activity. Investigation of membrane currents showed that intracellular spermine suppressed the total outward current but increased the inward rectifier current. After separation of ion currents it was found that the voltage‐activated, delayed K+ outward current and the Ca2+ inward current were reduced by intracellular spermine in a dose‐ and voltage‐dependent manner. The block of the K+ current can be described by a voltage‐dependent reaction, where one spermine molecule binds to one channel. The binding constant Kb, at zero voltage, and the effective valency, zδ, had values of 176/M and 0.41 for cell R‐15, 223/M and 0.64 for cell L‐11, and 137/M and 0.42 for cell L‐3. Apparently, more than one spermine cation is needed to block one Ca2+ channel, since the coefficient n, which absorbs the molecularity and cooperativity of the reaction, had non‐integral values between 1.34 and 2.22. The binding constant Kb and the effective valency zδ had values of 265/M and 0.64 for cell R‐15, 821M and 0.56 for cell L‐4, and 263/M and 0.51 for cell L‐6. Intracellular spermine also blocked the Ca2+‐activated K+ current induced by ionophoretic Ca2+‐injections, but increased the current at prolonged times after spermine injection. Extracellular spermine had no effect on electrical activity or on membrane currents. The results indicate that intracellular spermine affects the electrical discharge activity of neurons by acting as a blocker and/or modulator at voltage‐dependent membrane conductances.
Different Domains of the F3 Neuronal Adhesion Molecule are Involved in Adhesion and Neurite Outgrowth Promotion
Authors: Durbec Pascale , Gennarini Gianfranco , Buttiglione Mara , Gomez Sophie , Rougon Geneviève
Published: April 2006

The mouse F3 cell surface protein is preferentially expressed on axons of subpopulations of neurons and is anchored to the membrane by a glycosyl‐phosphatidylinositol group. It consists of six immunoglobulin‐like domains and four fibronectin type III homologous repeats, and can be found both in membrane‐anchored and soluble forms. We have previously established that F3 fulfils the operational criteria of a cell adhesion molecule when anchored to the plasma membrane and that its soluble form stimulates neurite initiation and neurite outgrowth. To further characterize F3‐mediated adhesion and to investigate whether adhesion and neurite outgrowth promoting activities are displayed by different parts of the molecule, we (i) selected F3 transfected CHO cells expressing increasing levels of F3 at their surface and (ii) prepared transfectants expressing an F3 molecule with its fibronectin type III repeats deleted. We show that the F3 molecule mediates divalent‐cation‐independent, temperature‐dependent binding. The levels of aggregation of F3 transfectants are proportional to the level of F3 expression. Transfectants expressing F3 deleted of the fibronectin type Ill repeats lose their adhesive properties; conversely, cells expressing wild‐type F3 and treated with collagenase, specifically removing the immunoglobulin‐like domains, are still able to aggregate. Therefore, in this model adhesion site(s) mapped to the fibronectin type III repeats. By contrast, transfectants expressing deleted F3, as well as the soluble forms of this F3 deleted molecule, were able to stimulate neurite outgrowth of sensory neurons similarly to wild‐type F3. Our data indicate that F3 is a multifunctional molecule and that adhesion and neurite outgrowth promoting properties are expressed by distinct and independent domains.
Motor Neuron Death Induced by Axotomy in Neonatal Mice Occurs More Slowly in a Mutant Strain in Which Wallerian Degeneration is Very Slow
Authors: Lapper S. R. , Brown M. C. , Perry V. H.
Published: April 2006

In contrast to motor neurons of adults, motor neurons of neonatal mice die if their axons are cut. We have examined the extent, the time course and the loss of susceptibility with age to such induced death in C57BLWlds mice. This is a strain which has a dominant autosomal mutation which dramatically slows the rate of degeneration of axons separated from their cell bodies. Following axotomy in neonatal animals the total number of motor neurons killed is no less in C57BL/Wdls mice than in two other strains (C57BL/6J/Ola and BALB/c/Ola). Indeed, the susceptibility to axotomy persists to a later age in C57BL/Wlds mice. However, the rate of cell death is significantly slower than in the two other strains; in C57BL/Wlds mice under a week old at the time of sciatic nerve section only‐16% of motor neurons have been lost 3 days after axotomy, whereas in the other mice ‐45–84% of the final loss has by then occurred. This result extends previous work which showed that retrograde degeneration of retinal ganglion cells of adult mice was slower in C57BL/Wlds mice (V. H. Perry et al., Eur. J. Neurosci., 2, 408–413, 1991). It is therefore possible that Wallerian degeneration of axons shares features in common with retrograde nerve cell death and that the Wlds mutation may throw light on aspects of this complex process.
Expression of Neuronal Nicotinic Acetylcholine Receptor Subunit Genes in the Rat Autonomic Nervous System
Authors: Rust G. , Burgunder J.‐M. , Lauterburg T. E. , Cachelin A. B.
Published: April 2006

In the autonomic nervous system efferent signals are relayed in sympathetic and parasympathetic ganglia. Fast synaptic transmission between pre‐ and postsynaptic neurons is achieved by neuronal nicotinic acetylcholine receptors (nAChRs). There is still little known about the subunit composition of these receptors. Establishing the subunit composition of native neuronal nAChRs is important for the understanding of their functional properties both in vivo and after expression in heterologous expression systems. We have combined in situ hybridization and autoradiography to detect the presence of mRNAs encoding subunits of neuronal nAChRs in sympathetic and parasympathetic ganglia. Inspection of the autoradiographs showed that the hybridization signal of five riboprobes (α3, 014–1, α7, β2 and β4) was significantly higher than the unspecific signal obtained with sense riboprobes. The distribution of α7 was tissue‐dependent: a7 riboprobe binding was detected in the neurons of the superior cervical ganglion, adrenal medulla and ciliary ganglion. In contrast, the α7 hybridization signal was found only in a small fraction (1 ‐3%) of the neurons of the sphenopalatine and otic ganglia. Our results are consistent with the idea that α3 mRNA expression levels are somewhat higher than those of α7, α4 ‐1, β2 and β4.
Correlation Dimension of the Human Sleep Electroencephalogram: Cyclic Changes in the Course of the Night
Authors: Achermann Peter , Hartmann Rolf , Gunzinger Anton , Guggenbüh Walter , Borbély Alexander A.
Published: April 2006

The complexity of the electroencephalogram (EEG) during human sleep can be estimated by calculating the correlation dimension. Due to the large number of calculations required by this approach, only selected short (4–164 s) segments of the sleep EEG have been analysed previously. By using a new type of personal supercomputer, we were able to calculate the correlation dimension of overlapping 1 min EEG segments for the entire sleep episode (480 min) of 11 subjects and thereby delineate the time course of the changes. The correlation dimension was high in episodes of rapid eye movement (REM) sleep, declined progressively within each non‐REM sleep episode, and reached a low level at times when EEG slow waves (0.75–4.5 Hz) were dominant. However, whereas slow‐wave activity showed its typical progressive decline from non‐REMIREM sleep cycle 1 to 4, no such trend was present for the correlation dimension. By providing an estimate of the complexity of a signal and being independent of amplitude and frequency measures, the correlation dimension represents a novel approach to exploring the dynamics of sleep and the processes underlying its regulation.
A Unique Achiasmatic Anomaly Detected in Non‐albinos with Misrouted Retinal‐fugal Projections
Authors: Apkarian Patricia , Bour Lo , Barth Peter G.
Published: April 2006

In mammals with binocular vision, projections of retinal sons to primary retino‐recipient nuclei establish a strict visuotopic and eye‐segregated arrangement. Normal primate visual pathway organization is characterized by orderly hemiretina separation in which nasal‐retinal axons cross at the optic chiasm and project to primary contralateral subcortical and cortical structures while temporal‐retinal fibres project ipsilaterally to corresponding visual structures. We report here, in two unrelated children, an unusual visual pathway malformation in which nasal‐retinal cortical projections, unable to decussate due to the inborn absence of an optic chiasm, erroneously route ipsilaterally to visual projection targets. We have termed this newly documented achiasmatic condition the non‐decussating retinal‐fugal fibre syndrome (Apkarian er al., Invest. Ophthalmol. Vis. Sci., 34, Suppl., 711, 1993).
Expression of GAP‐43 in the Granule Cells of Rat Hippocampus After Seizure‐induced Sprouting of Mossy Fibres: In Situ Hybridization and Immunocytochemical Studies
Authors: Bendotti Caterina , Pende Mario , Samanin Rosario
Published: April 2006

The axonal growth‐associated protein GAP‐43 is believed to play some role in the synaptic remodelling that takes place in the hippocampus of adult rats after certain experimental lesions. GAP‐43 mRNA is highly expressed in adult CA3 pyramidal cells but almost absent in the dentate granule cells. We analysed whether the sprouting of granule cell axons, the mossy fibres of the hippocampus, caused by kainic acid‐induced seizures in adult rats was associated with any induction of GAP‐43 mRNA in granule cells and with any changes in the immunostaining pattern of GAP‐43 in the hippocampus. Increased GAP‐43 mRNA expression was found to be induced in granule cells 18, 24 and 30 h after a systemic injection of kainic acid which induced generalized seizures in adult rats, and returned to control levels by 48 h post‐treatment. No effect was observed in other regions of the hippocampus. However, when kainic acid was injected into 15‐day‐old rats, which responded with generalized seizures but no sprouting of mossy fibres, there was no induction of GAP‐43 mRNA in the granule cells, suggesting a close relation between GAP‐43 expression and sprouting of these cells. Seven days after kainic acid injections, GAP‐43 immunostaining was decreased in the inner molecular layer of the dentate gyrus except for a thin supragranular band, whereas 30 days after treatment all animals showed increased GAP‐43 immunoreactivity in the whole inner molecular layer. Since collaterals of mossy fibres grow in the inner molecular layer after kainic acid‐induced seizures, these results support the theory that GAP‐43 plays a role in synaptic remodelling in the adult central nervous system.
Loss of the Compound Action Potential: an Electrophysiological, Biochemical and Morphological Study of Early Events in Axonal Degeneration in the C57BL/Ola Mouse
Authors: Tsao J. W. , Brown M. C. , Carden M. J. , McLean W. G. , Perry V. H.
Published: April 2006

In the C57BL/Ola (Ola) mouse strain there is a marked slowing of axonal disintegration during Wallerian degeneration. The locus of the mutation controlling this phenomenon (slow Wallerian degeneration‐ Wlds) has been mapped to chromosome 4, and its protective effect decreases with advancing age. Using biochemical, electrophysiological and histological techniques, the present study was undertaken to determine whether neurofilament phosphorylation and stability are altered or whether calcium‐activated proteases are absent in the sciatic nerves of Ola mice. A compound action potential was detectable only when neurofilaments were present and normal axonal architecture was seen. In 1‐month‐old Ola mice, compound action potentials and neurofilaments were still detectable at 21 days post‐transection, whereas both were undetectable by 2 days in BALB/c and C57BL/6J (6J) mice of the same age. Neurofilament levels declined faster with advancing Ola age, confirming previous results, whereas degeneration slowed in ageing BALB/c and 6J mice. In vitro and in vivo degeneration rates were comparable in BALB/c and 6J nerves. Ola nerves, however, showed more rapid decline in vitro than in vivo. Ola and BALB/c nerves frozen and then thawed and incubated in the presence of calcium ions and the ionophore A23187 were not resistant to degradation by intrinsic proteases. Even when a compound action potential could no longer be elicited, however, a majority of nerves still had >50% of myelinated and unmyelinated axons whose electron microscopic profiles appeared normal. Thus, it appears that the first event in Wallerian degeneration in the Ola mouse is a change at the plasma membrane‐a transected nerve becomes unable to conduct a compound action potential. Degeneration of the cytoskeleton is a later, separable event.
Localization of Aminopeptidase N and Dipeptidyl Peptidase IV in Pig Striatum and in Neuronal and Glial Cell Cultures
Authors: Barnes Kay , Kenny A. John , Turner Anthony J.
Published: April 2006

The subcellular distribution of the plasma membrane ectoenzymes, aminopeptidase N (aminopeptidase M) and dipeptidyl peptidase IV, has been examined by fractionating homogenates of porcine striata by a discontinuous Percoll gradient centrifugation procedure which distinguishes fractions containing pre‐ and post‐synaptic elements. The two enzymes showed different distributions–dipeptidyl peptidase IV did not show a significant pre‐synaptic location, whereas aminopeptidase N was present on both pre‐ and post‐synaptic fractions. Immunofluorescent staining on mixed and neuron‐enriched primary cultures of pig striatal tissue using affinity purified antibodies to the aminopeptidase and to the dipeptidyl peptidase revealed the ectoenzymes on distinct populations of cells. The astrocytic identity of the aminopeptidase N‐staining cells was established by correlation with immunostaining for glial fibrillary acidic protein and for vimentin by confocal microscopy. Ultracryosections of striatum immunostained with gold‐labelled immunoglobulins of differing diameters demonstrated aminopeptidase N on pericytes and confirmed its location on endothelial and astrocytic glial cells. Thus, several independent approaches indicated that aminopeptidase N, in addition to being present on endothelial and synaptic membranes, is found on astrocytes and pericytes in the perivascular neuropil, whereas dipeptidyl peptidase IV is less widely distributed on microvessels and appears not to have a synaptosomal location.
Creatine Kinase Isoenzymes in Chicken Cerebellum: Specific Localization of Brain‐type Creatine Kinase in Bergmann Glial Cells and Muscle‐type Creatine Kinase in Purkinje Neurons
Authors: Hemmer Wolfram , Zanolla Else , Furter‐Graves Elizabeth M. , Eppenberger Hans M. , Wallimann Theo
Published: April 2006

Creatine kinase isoenzymes were localized in the chicken cerebellum by the use of isoenzyme‐specific anti‐chicken creatine kinase antibodies. Brain‐type creatine kinase was found in high amounts in the molecular layer, particularly in Bergmann glial cells but also in other cells of the cerebellar cortex, e.g. in astrocytes and in the glomerular structures, as well as in cells of the deeper nuclei. A mitochondrial creatine kinase isoform was primarily localized to the glomerular structures in the granule cell layer and was also identified in Purkinje neurons. Surprisingly, a small amount of the muscle‐type creatine kinase isoform was identified in cerebellar extracts by immunoprecipitation, immunoblotting and native enzyme electrophoresis, and was shown to be localized exclusively in Purkinje neurons. Cell type‐specific expression of brain‐ and muscle‐type creatine kinase in Bergmann glial cells and Purkinje neurons, respectively, may serve to adapt cellular ATP regeneration to the different energy requirements in these specialized cell types. The presence of brain‐type creatine kinase in Bergmann glial cells and astrocytes is discussed within the context of the energy requirements for ion homeostasis (K+ resorption), as well as for metabolite and neurotransmitter trafficking. In addition, the presence of muscle‐type creatine kinase in Purkinje neurons, which also express other muscle‐specific proteins, is discussed with respect to the unique calcium metabolism of these neurons and their role in cerebellar motor learning.
Brain Insults in Rats Induce Increased Expression of the BDNF Gene through Differential Use of Multiple Promoters
Authors: Kokaia Zaal , Metsis Madis , Kokaia Merab , Bengzon Johan , Elmér Eskil , Smith Maj‐Lis , Timmusk Tõnis , Siesjö Bo K. , Persson Håkan , Lindvall Olle
Published: April 2006

The rat brain‐derived neurotrophic factor (BDNF) gene consists of four short 5‐exons linked to separate promoters and one 3′‐exon encoding the mature BDNF protein. Using in situ hybridization we demonstrate here that kindling‐induced seizures, cerebral ischaemia and insulin‐induced hypoglycaemic coma increase BDNF mRNA levels through insult‐ and region‐specific usage of three promoters within the BDNF gene. Both brief (2 min) and longer (10 min) periods of forebrain ischaemia induced significant and major increases only of exon III mRNA in the dentate gyrus. Following hypoglycaemic coma (1 and 30 min), exon III mRNA was markedly elevated in the dentate gyrus and, in addition, exon I mRNA showed a moderate increase. Single and recurrent (n= 40) hippocampal seizures significantly increased expression of exon I, II and III mRNAs in the dentate gyrus granule cells. After recurrent seizures, including generalized convulsions, there were also major increases of both exon I and III mRNAs in the CA3 region, amygdala, piriform cortex and neocortex, whereas in the hippocampal CA1 sector marked elevations were detected only for exon III mRNA. The insults had no effect on the level of exon IV mRNA in the brain. The region‐ and insult‐specific pattern of promoter activation might be of importance for the effectiveness of protective responses as well as for the regulation of plastic changes following brain insults.
The Extracellular Matrix Molecule Janusin Regulates Neuronal Morphology in a Substrate‐ and Culture Time‐dependent Manner
Authors: Lochter André , Taylor Joanne , Fuss Babette , Schachner Melitta
Published: April 2006

Janusin is an extracellular matrix glycoprotein with structural homology to tenascin. In search of extracellular matrix components which govern the differentiation of neurons in the central nervous system, we have investigated the influence of janusin on the differentiation of hippocampal neurons in vitro. Janusin coated onto nitrocellulose was a good substrate for attachment of cell bodies and neurite outgrowth after 21 h of culture. Most cells exhibited a polarized morphology with one long major neurite and one or two short minor neurites. When janusin was coated onto a polyornithine‐conditioned plastic surface, it increased the polarity of neurons in that the length of major neurites was increased and the length and number of minor neurites were decreased when compared with the control polyornithine‐conditioned plastic without janusin. As we have shown before for tenascin, laminin and fibronectin, polarization was preceded by an increase in the number and length of all neurites during the first hours after cell plating. This study therefore adds janusin to the increasing number of extracellular matrix glycoproteins which promote axonal but not dendritic growth.
Voltage‐dependent Kinetics of N‐Methyl‐d‐aspartate Synaptic Currents in Rat Cerebellar Granule Cells
Authors: D'Angelo Egidio , Rossi Paola , Taglietti Vanni
Published: April 2006

Decay kinetics of N‐methyl‐d‐aspartate excitatory postsynaptic currents (NMDA‐EPSCs) have been voltage‐dependent in some, but not all neurons studied so far, and almost no information has been available on the voltage‐dependence of the rising phase. In this work we investigated the effect of membrane potential on rising and decay kinetics of the NMDA‐EPSC in cerebellar granule cells using the tight‐seal whole‐cell recording technique. NMDA‐EPSCs were evoked by electrical mossy fibre stimulation in the presence of 10 μM 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione, 1.2 mM Mg2+ and 5 μM glycine. The rate of rise of NMDA‐EPSCs remained substantially unchanged when the cell was depolarized, indicating that the limiting step of channel opening was voltage‐insensitive. The NMDA‐EPSC, however, flattened around the peak and the time‐to‐peak increased. This observation was explained by the influence of decay. Decay was biphasic and slowed down with membrane depolarization. Moreover, the fast component of decay increased less than the slow component. This complex voltage‐dependence may extend the integrative role of the NMDA current during synaptic transmission.
Up‐regulation of Neurotensin mRNA in the Rat Striatum After Acute Methamphetamine Treatment
Authors: Castel M. N. , Morino P. , Dagerlind Å. , Hökfelt T.
Published: April 2006

The effect of acute subcutaneous administration of methamphetamine on the expression of neurotensin mRNA was investigated in the adult rat striatum. At different time points (2, 6 and 24 h) following drug administration rats were killed, and mRNA levels were quantified both on films and emulsion‐dipped tissue sections from two striatal levels. Two hours after methamphetamine injection, a dramatic increase in neurotensin mRNA levels was detected in different areas of the striatum at both rostral and caudal levels. Numerous positive cells were observed in the dorsomedial, dorsolateral and ventrolateral parts of the striatum. This up‐regulation reflected an increase both in the number of cells expressing neurotensin mRNA and in the mean mRNA levels. This increase was still present after 6 h and was similar to the 2 h treated group at the rostral level of the striatum, but lower at the caudal one. Twenty‐four hours after methamphetamine injection, neurotensin mRNA levels were back to control values, or in some areas even below. A strong increase in neurotensin mRNA‐expressing cells was also seen in the olfactory tubercle, and the time‐course was similar to the one observed in the striatum. In a second set of experiments, the effect of methamphetamine was evaluated on adjacent striatal sections hybridized with probes directed against neurotensin and substance P mRNAs, respectively. Two hours after drug administration, a significant increase in the levels of both peptide mRNAs was observed (+ 190% for neurotensin, +80% for substance P). These results demonstrate that methamphetamine is able to induce a dramatic, rapid and transient increase in striatal neurotensin mRNA levels, which may partly account for the elevation in neurotensin peptide levels observed in the striatonigral pathway after methamphetamine. The different anatomical localization of neurotensin mRNA‐expressing cells observed after haloperidol and methamphetamine treatments, as well as the fact that the D1 receptor antagonist SCH‐23390 is able to counteract the effect of methamphetamine but not that of haloperidol on neurotensin mRNA expression, suggests that there are at least two different subpopulations of neurotensin cells in the striatum. One population is regulated via D1 receptors and projects to the substantia nigra pars reticulata. The second is sensitive to D2 receptor stimulation and may project to the globus pallidus and/or may represent interneurons.