bluuebunny/crossref_metadata_2025 huggingface dataset:
Sites of [3H]taurine Uptake in the Rat Substantia Nigra in Relation to the Release of Taurine from the Striatonigral Pathway
Authors: Corte L. Delia , Bolam J. P. , Clarke D. J. , Parry D. M. , Smith A. D.
Published: April 2006

The autoradiographic localization of radiolabelled taurine taken up in the rat substantia nigra in vivo together with conditions of release of the [3H]taurine taken up into brain slices were studied to determine whether they are consistent with the hypothesis that taurine may act as a neurotransmitter in the striatonigral pathway.

At the light microscopic level the main cellular elements that became radiolabelled following the injection of [3H]taurine into the substantia nigra could be identified as glial cells. Electron microscope autoradiography confirmed that a subpopulation of glial cells including astrocytes, pericytes, and oligodendrocytes were radiolabelled and that neuronal perikarya were not radiolabelled. In addition, axonal elements including both terminal and preterminal boutons were found to have silver grains overlying them and were thus considered to be radiolabelled. This was supported by a quantitative analysis of the distribution of the silver grains; whereas glial elements had a significantly higher number of grains associated with them than with any other structure, axonal elements had a significantly greater number of grains than dendritic structures.

Release of the preloaded [3H]taurine from superfused slices of substantia nigra occurred in response to veratridine, was calcium‐dependent and was sensitive to inhibition by high magnesium concentrations or tetrodotoxin. Following the destruction of neurons in the striatum by ibotenic acid injections, although the weight of the ipsilateral substantia nigra was reduced, the uptake of [3H]taurine was not altered. In contrast to this, the veratridine‐stimulated release was markedly attenuated, implying that the destruction of striatal neurons causes the loss of sites in the substantia nigra from which exogenous taurine is released.

These results add further support to previous suggestions that taurine might act as a neurotransmitter or neuromodulator in the striatonigral pathway.
Effects of Putative Neurotransmitters of the Carotid Body on its Own Glomus Cells
Authors: Eyzaguirre C. , Monti‐Bloch L. , Woodbury J. W.
Published: April 2006

Carotid body glomus cells produce and release acetylcholine (ACh), catecholamines, and neuropeptides, and there is biochemical evidence that these cells possess receptors for these substances. Thus, we studied the effects of cholinergics [ACh, nicotine (Nic), bethanechol (BN)] and peptides [met‐enkephalin (ME), substance P (SP)] on the membrane potential (Em), voltage noise (Erms), and input resistance (R0) of glomus cells. Sliced carotid bodies (for cell visualization) of cats, rabbits, and mice were used.

The mean Em and R0 of rabbit glomus cells were lower than those of cat and mouse. R0 of mouse cells was the largest, whereas Erms was similar in all species. The various agents had qualitatively similar effects on the cells of the three species although some quantitative differences were sometimes observed. But, for simplicity, results were pooled.

ACh depolarized most cells (effect depressed by zero [Ca2+]0 and Mn2+), reduced their resistance, and induced variable changes in Erms. Different ACh doses produced non‐linear effects on ΔEm. Nic and BN also depolarized most cells, reducing R0 and Erms. Atropine depressed the cell responses to BN; α‐bungarotoxin the depolarizing response to Nic. ME and SP depolarized most cells, but only ME significantly reduced R0. Neither peptide significantly changed voltage noise.

Comparing the effects of all drugs showed that BN was the most effective depolarizing agent, producing the largest reductions in R0. There were negative correlations between ΔEm and ΔR0 with the cholinergics and SP; correlations between ΔErms and ΔR0 were significant and positive only with the cholinergics.

These results confirm the presence of nicotinic, muscarinic, and peptidergic receptors in glomus cells. The similar effects of cholinergics and peptides and those of flow interruption and anoxia suggest that the latter may partly act via autoreceptors for the released transmitters.
Long‐Term Reduction in the Number of C‐Fibre Nociceptors Following Capsaicin Treatment of a Cutaneous Nerve in Adult Rats
Authors: Pini Adrian , Baranowski Richard , Lynn Bruce
Published: April 2006

The structure and function of C‐ and A‐fibres have been studied 3–12 months following a single 30 min exposure of the saphenous nerve of adult rats to 1% capsaicin. Examination of nerve cross‐sections showed that the number of C‐fibres was reduced by 36%, but A‐fibres were unaffected. The remaining C‐fibres included many that were unusually small in size. The changes were not restricted to the treatment site but were found over at least a further 10 mm proximal and distal to it. In treated nerves, the C‐fibre component of the compound action potential was reduced in size relative to the Aαβ component. Single unit studies revealed that an unusually high proportion of C‐fibres had no cutaneous receptive field (54%, compared with 28% in controls). There was no such change for A‐fibres. The conduction velocity range for C‐fibre units in treated nerves was almost normal, but this sample contained an unusually low proportion of polymodal nociceptors. Allowing for the fall in total numbers and the reduction in units with cutaneous receptive fields, it was calculated that overall the numbers of C‐polymodal nociceptor units had fallen by 74%. No significant changes in number had occurred in the other classes of C‐afferents. The reduction in the numbers of nociceptive C‐fibres is likely to be the direct cause of the reduction in pain responses and in neurogenic inflammation that several groups have reported following treatment of adult rats with capsaicin. Reduction in the numbers of C‐fibre is also likely to be the reason for reduced neuropeptide levels seen in tissues innervated by treated nerves.
Neuropeptide Levels after Pentylenetetrazol Kindling in the Rat
Authors: Marksteiner Josef , Lassmann Hans , Saria Alois , Humpel Christian , Meyer Dieter K. , Sperk Günther
Published: April 2006

Levels of several neuropeptides were measured in the frontal cortex, dorsal hippocampus, striatum, and amygdala/pyriform cortex in rats kindled for 5 weeks by daily injection of pentylenetetrazol (30 mg/kg, i.p.). Significantly increased concentrations (by 30–140%) were found in all examined brain areas for neuropeptide Y, somatostatin (except hippocampus) and neurokinin‐like immunoreactivity 10 days after the last kindling session. Similar but less pronounced changes were also found 24 h after the last seizure. The increase in total neurokinin‐like immunoreactivity was due to a marked increase in neurokinin B as revealed by HPLC analysis. Increases in peptide levels, however, were restricted to fully kindled animals. At the same time no changes in levels of substance P, vasoactive intestinal polypeptide and calcitonin gene‐regulated peptide were observed. Cholecystokinin octapeptide was enhanced only in the hippocampus (by 46%). The increases in neuropeptide Y, somatostatin, and neurokinin‐like immunoreactivity subsided after 3 months. A markedly decreased seizure threshold was observed 10 days and 2 months after the final kindling session.

No nerve cell degeneration was observed in kindled rats 24 h or 10 days after the last pentylenetetrazol injection. Some animals (2 of 4), however, exhibited signs of blood‐brain barrier damage when examined 24 h after the last kindling session which may reflect the preceding convulsions. No such changes were detected after 10 days.

The increases in peptide levels may suggest increased activity of respective neurons which, at least to some degree, may be associated with γ‐aminobutyric acid. The changes in peptide levels may be more closely related to the kindling procedure itself than to the decreased seizure threshold of the animals.
Activation of Calcium Channel Currents in Rat Sensory Neurons by Large Depolarizations: Effect of Guanine Nucleotides and (‐)‐Baclofen
Authors: Dolphin Annette C. , Scott Roderick H.
Published: April 2006

Calcium channel currents have been recorded from cultured rat sensory neurons at clamp potentials of between ‐30 and +120 mV. At large depolarizing potentials between +50 and +120 mV, the current was outward. This outward current was shown to be largely due to ions passing through calcium channels, because it was substantially although generally incompletely blocked by Cd2+ (1 mM) and ω‐conotoxin (1 μM). Internal GTP‐γ‐S (100 μM) and to a lesser extent GTP (1 mM) reduced the amplitude and slowed the activation of the outward, as well as the inward calcium channel current. Baclofen (100 μM) reversibly inhibited both the inward and outward currents. These results suggest that the effect of baclofen and G protein activation on calcium channel currents is not due to a shift in the voltage‐dependence of channel availability.
Differential Effects of Glucocorticoids on Corticotrophin‐Releasing Factor in the Rat Pituitary Neurointermediate Lobe and Median Eminence
Authors: Jessop David S. , Chowdrey Hardial S. , Lightman Stafford L.
Published: April 2006

We have investigated the effects of glucocorticoid manipulation on corticotrophin‐releasing factor (CRF‐41) in the neurointermediate lobe (NIL) and median eminence (ME) of the rat using a radioimmunoassay specific for CRF‐41. CRF‐41 content in the NIL (88 ± 7 fmol, mean ± SEM) was not significantly altered by administration of dexamethasone in drinking water for 12 days (67 ± 9 fmol) or adrenalectomy for 12 days (96 ± 17 fmol). The saline‐stimulated increase in NIL CRF‐41 content (154 ± 24 fmol) was not affected by dexamethasone (152 ± 24 fmol) or adrenalectomy (179 ± 21 fmol). In contrast, the content of CRF‐41 in the ME declined following dexamethasone treatment (1247 ± 92 fmol to 864 ± 26 fmol), or adrenalectomy (854 ± 78 fmol). Our results provide further evidence that CRF‐41 in the NIL and ME can be differentially regulated.
Tracing of Neuronal Connections in the Human Brain by Magnetic Resonance Imaging in vivo
Authors: Danek A. , Bauer M. , Fries W.
Published: April 2006

Axon degeneration after disruption of fibre tracts in the mammalian nervous system is accompanied by myelin breakdown which leads to changes in its magnetic resonance properties. In two patients with pure motor strokes due to small ischaemic lesions restricted to the internal capsule, magnetic resonance imaging disclosed a narrow band of pathological signal increase descending band‐like into the brain stem and ascending to the precentral gyrus, which corresponded to the well‐known path of the pyramidal tract. The findings suggest that in man anterograde and possibly retrograde fibre degeneration can be traced in vivo by conventional magnetic resonance imaging techniques. Critical conditions are the presence of small, strategically located lesions, appropriate choice of imaging plane, and the interval between time of lesion and of imaging. This demonstration may open a new era for functional neuroanatomy of man.
Serotonin Induces a Cyclic AMP‐Mediated Outwardly Rectifying Slow K+ Current in a Single Identified Snail Neuron
Authors: Paupardin‐Tritsch Danièle , Gerschenfeld H. M.
Published: April 2006

In the F2 neuron of the parietal ganglion of the snail Helix aspersa either bath or iontophoretic application of serotonin (5‐HT) induces an outward current. This current has a long latency (10–60 s) and a slow time course, a 500 ms iontophoretic application of 5‐HT evoking a response lasting 3–5 min. This slow outward current reverses at ‐80 mV, a value equal to EK. After doubling the extracellular K+ concentration the reversal potential of the 5‐HT response is shifted by 19 mV, as predicted by the Nernst equation. The I‐V curves reveal that the 5‐HT‐induced slow outward current is outwardly rectifying. This 5‐HT response is blocked by intracellular Cs+ and tetraethylammonium (TEA+) and by extracellular TEA+ and Ba2+, but is not affected by the removal of extracellular Ca2+ or the intracellular injection of ethyleneglycol‐bis‐(β‐amino‐ethylether)‐N,N,N′,N′‐tetra‐acetic acid (EGTA). These results indicate that the outwardly rectifying slow outward current induced by 5‐HT in the F2 neuron is carried by K+ and is Ca2+‐independent. In the single isolated F2 neuron, 5‐HT induces a 2.5‐fold stimulation of the adenylate cyclase activity. In addition, both the intracellular injection of 3′,5′‐adenosine monophosphate (cAMP) and the application of forskolin mimic the effect of 5‐HT on the F2 neuron. The phosphodiesterase inhibitor isobutylmethylxanthine also induces a slow outward current and potentiates the 5‐HT response. The intracellular injection of a synthetic 20‐residue peptide inhibitor of the cAMP‐dependent protein kinase blocks the slow outward K+ current induced by 5‐HT. These results show that in the F2 neuron, 5‐HT elicits a slow K+ current via the stimulation of adenylate cyclase, an increase in intracellular cAMP and the activation of the cAMP‐dependent kinase which probably phosphorylates a population of outwardly rectifying K+ channels or some protein/s associated with these channels.
Cloning and Characterization of the Rat Gene Encoding GAP‐43
Authors: Grabczyk Ed , Zuber Mauricio X. , Federoff Howard J. , Ng Shi‐Chung , Pack Alison , Fishman Mark C.
Published: April 2006

GAP‐43 is a gene expressed only in the nervous system. The protein product is believed to be important to neuronal growth and plasticity. Most, and likely all, neurons express high levels of GAP‐43 during periods of neurite elongation. To initiate studies of GAP‐43 gene regulation we have cloned the rat gene encoding GAP‐43. The GAP‐43 gene includes three exons. The first exon encodes only the amino terminal 10 amino acids, which corresponds to the membrane targeting domain of GAP‐43. The second exon encodes a putative calmodulin binding domain and a protein kinase C phosphorylation site. The 5′‐flanking sequence is unusual in that it lacks CAAT or TATA elements, and directs RNA transcription initiation from several sites. Some of the transcription start sites are used to a different degree in the central and peripheral nervous systems.
Responses of Regenerating Rat Retinal Ganglion Cell Axons to Contacts with Central Nervous Myelin in vitro
Authors: Vanselow J. , Schwab M. E. , Thanos S.
Published: April 2006

In order to investigate the responses of neurites to myelin in vitro, retinal explants obtained from adult rats were cultured on poly‐L‐lysine and laminin. Regenerating adult ganglion cell axons were confronted with rat central myelin which was adsorbed on culture dishes. When the explants were placed directly on the myelin, axons did not grow out. Alternatively, when the explants were placed at a certain distance from the myelin, massive outgrowth of axons was observed. When axonal growth cones encountered the myelin, they displayed various reactions. All single axons observed immediately stopped growing after encountering the myelin border. All of them remained for at least 4 h at the border. Sixteen per cent of them remained in this ‘resting state’ throughout the time of observation (2–5 days). Nineteen per cent of the axons degenerated following contact with the myelin. The majority of axons were able to circumvent the myelin either by backbranching (21%) or by growing in another direction with the leading growth cone (37%). Eight per cent of the axons were observed to enter the myelin. The results indicate that central myelin represents a non‐permissive obstacle for growing adult axons. This observation is in conformity with the inability to regenerate that is typical of lesioned optic nerve axons in situ.
Effects of Corticotrophin Releasing Factor, Muscarine and Somatostatin on Rubidium and Potassium Efflux from Mouse AtT‐20 Pituitary Cells
Authors: Luini A. , Brown D. A.
Published: April 2006

Effects of secretagogues and anti‐secretagogues of ACTH secretion on K+ permeability in the clonal pituitary cell line AtT‐20 were measured by recording 86Rb or 42K efflux. Efflux was accelerated by the secretagogues K+, corticotrophin, forskolin, isoprenaline, and the Ca‐ionophore A23187. Efflux was reduced by the inhibitors somatostatin, muscarine, and oxotremorine, or by removing external Ca. Efflux was also reduced by the K+‐channel blocking compound d‐tubocurarine but not by tetraethylammonium. Muscarine, oxotremorine, somatostatin, and 0 Ca2+ also reduced intracellular Ca2+ measured by quin‐2 fluorescence. It is suggested that most of the resting 86Rb or 42K efflux measured under these conditions occurs via tubocurarine‐sensitive Ca2+‐dependent K+‐channels, and that changes in efflux rate produced by secretagogues or anti‐secretagogues are secondary to changes in intracellular Ca2+.
Glutamate as the Principal Mossy Fibre Transmitter in Rat Cerebellum: pharmacological evidence
Authors: Garthwaite J. , Brodbelt A. R.
Published: April 2006

To examine the possibility that glutamate may be widely used as the transmitter for cerebellar mossy fibres, population responses of granule cells following electrical stimulation of these fibres were recorded in rat cerebellar slices using a gap technique. Several different vermal lobules (II, V, VIb, VIII, IXc and X) whose main mossy fibre afferents originate in different nuclei, were compared. The mossy fibre response was remarkably similar in appearance in all lobules. With 1.2 mM Mg2+ in the perfusing solution, and with a low rate of stimulation (0.05 Hz), the N‐methyl‐D‐aspartate (NMDA) antagonist, D‐2‐amino‐5‐phosphonovalerate (APV, 30 μM), had little or no effect but all components of the response could be inhibited by the broad spectrum excitatory amino acid antagonist, kynurenate (3 mM), or by the relatively selective non‐NMDA antagonist, 6‐cyano‐2,3‐dihydroxy‐7‐nitro‐quinoxaline (CNQX, 10 μM). Slow APV‐sensitive components emerged during high frequency stimulation (30 ‐ 150 Hz) or, with a low stimulation rate, on removal of Mg2+ or addition of bicuculline (30 μM). The results suggest that an excitatory amino acid, presumably glutamate, is the major mossy fibre transmitter in the cerebellum and that it activates both NMDA and non‐NMDA receptors on granule cells.
Hipppcampal Electrical Activity and Behaviour in Rabbits during Adaptation to a Novel Semi‐Natural Environment
Authors: Fontani Giuliano , Vegni Virginia
Published: April 2006

The aim of the present experiment was to show possible modifications in behaviour and hippocampal electrical activity during adaptation to a novel semi‐natural environment. Rabbits with chronic implanted electrodes in the hippocampus were introduced into a large, natural, open‐air enclosure. Their spontaneous behaviour was studied for 3 days. Electrical activity was recorded by telemetry, stored with behaviour on a video‐tape, and then analysed. Behaviour was divided into categories and variables. The categories were: activity directed towards the environment (including exploratory movements, scanning, marking, etc.) and self‐directed activities (such as eating, drinking, self‐grooming, etc.). Exploratory elements were observed and classified according to a spatial and a temporal criterion. The rabbits showed a progressive adaptation to the environment with quantitative and qualitative reduction in exploration and an increment in quiet immobility and inspective activities. Three EEG patterns were recognized from autocorrelation and spectral analysis: high rhythmicity theta (HRSA) with specific relationship to voluntary movements, such as exploration and running; low rhythmicity theta (LRSA) in signalling activities or self‐directed behaviour and during postural and reactive immobility; and irregular activity (IA) sometimes seen in the same immobile behaviour. The results show that some behaviours (exploration, alert and postural immobility, self‐directed activity) are correlated to specific patterns of electrical activity in the hippocampus and, as exploratory behaviour decreased with time, there was a concomitant increase in EEG frequency.
Organization of the Visual Sector of the Thalamic Reticular Nucleus in Galago
Authors: Conley Michael , Diamond Irving T.
Published: April 2006

Projections to and from the visual sector of the thalamic reticular nucleus were studied in the prosimian primate genus Galago by anterograde and retrograde transport of WGA‐HRP injected into the dorsal lateral geniculate nucleus (GLd), pulvinar nucleus, and their cortical targets. Contrary to the idea that thalamic connections with the reticular nucleus are not delimited sharply between nuclei associated with the same modality, our results show a distinct laminar segregation of the projections from the GLd and pulvinar nuclei. The GLd is connected reciprocally with the lateral 2/3 of the caudal part of the reticular nucleus, and the striate cortex sends projections to the same lateral tier. Both sets of projections are organized topographically, lines of projection taking the form of slender elongated strips that run from caudo‐dorsal to rostro‐ventral within the nucleus. The pulvinar nucleus, which projects to several areas of the temporal, parietal, and occipital lobes, including the striate cortex, is connected reciprocally with the medial 1/3 of the caudal part of the reticular nucleus. Every injection into the pulvinar nucleus labelled a wide area of the medial tier, with no indication of visuotopic organization. The projections from the middle temporal area, one of the principal targets of the pulvinar nucleus, also terminate only in the medial tier of the visual sector. And we would expect that, in general, a thalamic nucleus and its cortical target would project to the same part of the reticular nucleus. The case of the striate area is an exception but only in the sense that it projects to the pulvinar nucleus as well as GLd. Thus an injection into a single locus in area 17 produces two parallel strips in the visual sector of the reticular nucleus, but both are in the lateral tier. We propose that each strip arises from a separate population of cells with cortical layer VI, one with an allegiance to the GLd and the other to the pulvinar nucleus.
The Effects of Prenatal Intracranial Infusion of Tetrodotoxin on Naturally Occurring Retinal Ganglion Cell Death and Optic Nerve Ultrastructure
Authors: Friedman S. , Shatz C. J.
Published: April 2006

In the developing vertebrate nervous system, cell death is known to play an important role in determining final neuron number. Retinal ganglion cells in the cat's visual system undergo a massive elimination by cell death during the prenatal period between E44 (age of embryo in days) and birth (=E65). We have examined whether neural activity contributes to ganglion cell death by infusing tetrodotoxin (TTX), a blocker of the voltage‐sensitive sodium channel. TTX was infused intracranially via osmotic minipumps implanted in utero at E42. The effects of the TTX treatment on ganglion cell death and optic nerve ultrastructure were examined at either E49 or E57 by electron microscopy and quantitative analysis of optic axon number. The numbers of optic nerve axons counted in the optic nerves of animals after either 1 or 2 weeks of TTX treatment were not significantly different from the counts in normal animals at comparable ages: E49 TTX—3.2 × 105; E48 normal—3.3 × 105; E57 TTX—2.1 × 105; E59 normal—2.4 × 105. These results suggest that retinal ganglion cells cannot be rescued from death by blockade of neural activity central to the optic chiasma. However, the ultrastructure of optic nerves following 2 weeks of TTX infusion was quite abnormal. The usual packaging of axons into fascicles by glia was disrupted by the presence of many pale, organelle‐poor processes that were about 10 times larger in their cross‐sectional areas than axons in either normal or TTX‐treated nerves. Examination of these processes in serial transverse or in longitudinal electron microscope (EM) sections of the nerve revealed that they were most likely glial in origin. The ultrastructural organization of the optic nerve following 1 week of TTX treatment was normal, indicating that this effect on glial ultrastructure is either cumulative or delayed in onset. These results suggest that while the conduction of action potentials to the terminals of retinogeniculate axons may not play a significant role in regulating ganglion cell number prenatally, it may affect the normal maturation of optic nerve glia.
Protection Against N‐methyl‐D‐aspartate Receptor‐Mediated Neuronal Degeneration In Rat Brain by 7‐chlorokynurenate and 3‐amino‐1‐hydroxypyrrolid‐2‐one, Antagonists at The Allosteric Site for Glycine
Authors: Foster A. C. , Willis C. L. , Tridgett R.
Published: April 2006

7‐Chlorokynurenate (7‐Cl KYNA) and 3‐amino‐1‐hydroxypyrrolid‐2‐one (HA‐966), two selective antagonists of the glycine site on the N‐methyl‐D‐aspartate (NMDA) receptor, have been used to assess the involvement of this site in the neurodegeneration resulting from injection of excitotoxins in the rat brain. In the rat striatum, reductions in the enzymes choline acetyltransferase (CAT) and glutamate decarboxylase (GAD), occurring 7 days after a unilateral, intrastriatal injection of quinolinate (200 nmol), were prevented in a dose‐dependent manner by intrastriatal administration of 7‐Cl KYNA (10–50 nmol) and HA‐966 (200–500 nmol) 1 h after the excitotoxin. In the rat hippocampus, degeneration of pyramidal and granule neurons caused by direct injection of quinolinate (60 nmol) was completely prevented by 7‐Cl KYNA (50 nmol) and partially by HA‐966 (500 nmol) injected intrahippocampally 1 h after the excitotoxin. In the rat striatum, 7‐Cl KYNA (50 nmol) and HA‐966 (500 nmol) also reduced neurotoxicity caused by intrastriatal injection of NMDA (200 nmol), but not that caused by the ‘non‐NMDA’ receptor agonists DL‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) or kainate. The time course of protective effects of 7‐Cl KYNA and HA‐966 in the striatum was similar to that previously observed with the uncompetitive NMDA receptor antagonist MK‐801, indicating that activation of the glycine site contributes to the delayed degeneration of neurons which occurs over the first 5 h following quinolinate injection. The neuroprotective effects of both 7‐Cl KYNA and HA‐966 in the rat striatum appear to be mediated via the glycine site on the NMDA receptor as they were completely reversed by D‐serine, but not L‐serine. These results indicate that activation of the glycine site is essential for the expression of the delayed degeneration of neurons resulting from intracerebral injection of an NMDA receptor agonist, a process which bears similarities to the delayed neurodegeneration which results from a period of cerebral ischaemia.
Glutamate Receptors of a Quisqualate‐Kainate Subtype are Involved in the Presynaptic Regulation of Dopamine Release in the Cat Caudate Nucleus in vivo
Authors: Barbeito L. , Chéramy A. , Godeheu G. , Desce J. M. , Glowinski J.
Published: April 2006

Experiments were conducted with halothane‐anesthetized cats implanted with a push‐pull cannula in the caudate nucleus in order to estimate the effects of glutamate (GLU) agonists on the release of 3H‐dopamine continuously synthesized from 3H‐tyrosine. In the presence of tetrodotoxin (TTX), glutamate (10−8 M, 10−4 M) and kainate (KAI) (10−5 M) stimulated the release of 3H‐dopamine while quisqualate (10−5 M) and N‐methyl‐D‐aspartate (NMDA) (10−5 M) were without effect. The stimulatory effect of kainate (10−5 M) on 3H‐dopamine release did not seem to be mediated by glutamate released from corticostriatal fibers, as not only kainate, but also quisqualate (QUI) and N‐methyl‐D‐aspartate enhanced the efflux of glutamate through a tetrodotoxin‐resistant process. Riluzole (10−5 M), gamma‐D‐glutamyl‐glycine (GDGG) (10−5 M) and glutamine‐diethyl‐ester (10−5 M) prevented the stimulatory effect of kainate (10−5 M) while 6‐cyano‐7‐nitro‐quinoxaline‐2,3‐dione (CNQX) (10−5 M), kynurenate (10−5 M) and 2‐amino‐5‐phosphonovalerate (APV) (10−5 M) were without effect. In the presence of concanavalin A (CONA) (10−7 M), a lectin which is known to prevent the quisqualate‐evoked desensitization of glutamate receptors, quisqualate (10−5 M) stimulated the release of 3H‐dopamine. In addition, in the absence of concanavalin A, quisqualate (10−5 M) blocked the stimulatory effects of kainate (10−5 M) or glutamate (10−4 M) on 3H‐dopamine release. These results suggest the involvement of receptors of the quisqualate/kainate subtype in the direct glutamate‐induced presynaptic facilitation of dopamine release. In contrast to what was observed in the presence of tetrodotoxin, in the absence of the neurotoxin, high concentrations of glutamate (10−4 M) and kainate (10−5 M) reduced rather than stimulated the release of 3H‐dopamine. A weak inhibitory effect was also observed with quisqualate (10−5 M) while N‐methyl‐D‐aspartate (10−5 M) was without effect. In the light of previous studies, these latter observations suggest that glutamate can also exert an indirect inhibitory presynaptic influence on the release of dopamine from nerve terminals of the nigrostriatal dopaminergic neurons by acting on receptors of the quisqualate/kainate subtype located on striatal GABAergic neurons.
Horizontal Interactions in Cat Striate Cortex: III. Ectopic Receptive Fields and Transient Exuberance of Tangential Interactions
Authors: Luhmann H. J. , Greuel J. M. , Singer W.
Published: April 2006

In this study the developmental changes of intracortical connectivity are related to changes of cortical receptor fields (RFs). The RFs of striate cortex neurons of 4‐ to 8.5‐week‐old kittens, reared under normal conditions (NR) or in a selective visual environment (SE), were analysed quantitatively and compared with adult cats. To unmask weak inputs from outside the conventional RF (CRF), cell excitability was raised by iontophoretic application of glutamate (GLU) and/or bicuculline methiodide (BIC) or by light stimulation of the CRF. Both the dominant discharge region (DDR) and the total RF (TRF) area were significantly larger in NR and SE kittens than in adult cats. Moreover, in kittens 18% of the cells had additional ectopic fields that were excitatory, had similar orientation preferences as the CRF, and ranged 4° to 23° from the centre of the CRF. In 74% of the cases the ectopic fields were direction‐selective and 70% of them preferred stimuli moving toward the CRF. Ectopic fields occurred mainly in supragranular cells, were similarly frequent in simple and complex cells and slightly more frequent in SE (20.7%) than in NR (13.3%) kittens. In adult cats only one of 83 cells tested had an ectopic field. It is concluded that the age‐dependent decrease in the RF size, the laminar distribution of cells having an ectopic RF, and the numerical reduction of these cells with age correlate well with the organization and postnatal pruning of tangential projections, suggesting that these contribute to the elaboration of specific response properties. Moreover, the authors infer from the early presence and from the selectivity of ectopic fields that the system of horizontal intrinsic connections mediates far‐reaching, excitatory interactions between cortical neurons with similar functional properties and serves as a substrate for the processing of global aspects of visual patterns.
Maintenance of Intermediolateral Spinal Cord Neurons by Fibroblast Growth Factor Administered to the Medullectomized Rat Adrenal Gland: Dependence on Intact Adrenal Innervation and Cellular Organization of Implants
Authors: Blottner Dieter , Unsicker Klaus
Published: April 2006

We have previously shown that basic fibroblast growth factor (bFGF; 2 μg), when administered in gelfoams implanted to medullectomized adult rat adrenal glands, maintains target‐deprived preganglionic neurons located in the intermediolateral column (IML) of the spinal cord. We show now that administration of 600 or 60 ng/implant/organ of the biologically active recombinant protein also maintains IML‐neurons. The effects depend on an intact organ nerve supply since administration of bFGF‐implants to the medullectomized and denervated (splanchnicotomized) organ abolishes the maintenance effects for IML‐neurons. A possible regeneration of cholinergic nerve fibres was assessed by quantitative determination of choline acetyltransferase (ChAT)‐activity and ultrastructurally under various treatments. When compared to a cytochrome‐(Cyto)‐C treatment, bFGF significantly increased ChAT‐activity in the innervated adrenal gland after 4 weeks, suggesting that sprouting of cholinergic nerve fibres and/or recovery of enzyme activity had occurred. Electron microscopically, unmyelinated axons associated with Schwann cells were only found in bFGF, but not in Cyto‐C‐implants. We conclude that exogenous bFGF or a yet unidentified trophic molecule possibly induced by bFGF in the adrenal gland acts as a retrogradely transported messenger serving for the maintenance of spinal cord IML‐neurons in vivo. By stimulating axonal sprouting, bFGF might facilitate access of trophic material to nerve fibres.
B‐50/GAP43 Gene Expression in the Rat Olfactory System During Postnatal Development and Aging
Authors: Verhaagen J. , Greer C. A. , Margolis F. L.
Published: April 2006

The olfactory neuroepithelium exhibits neurogenesis throughout adult life, and in response to lesions, a phenomenon that distinguishes this neural tissue from the rest of the mammalian brain. The newly formed primary olfactory neurons elaborate axons into the olfactory bulb. Thus, denervation and subsequent re‐innervation of olfactory bulb neurons may occur throughout life. In this study the authors demonstrate the distribution of the growth‐associated phosphoprotein B‐50/GAP43 and its mRNA in the olfactory neuroepithelium and olfactory bulb during development and aging. In neonatal rats B‐50/GAP43 mRNA was expressed in primary olfactory neurons throughout the olfactory epithelium and in their target neurons in the olfactory bulb, the mitral, juxtaglomerular and tufted cells. In contrast, in adult (7.5 weeks) and aging animals (6–18 months of age) B‐50/GAP43 mRNA expression was progressively restricted to neurons in the basal region of the neuroepithelium and to some of their target mitral and juxtaglomerular cells in the olfactory bulb. The continuing expression of B‐50/GAP43 mRNA in mitral‐ and juxtaglomerular cells in mature animals is thought to be related to their capacity to respond to continuously changing input from the primary olfactory neurons present in the olfactory neuroepithelium.
Synaptic and Nonsynaptic Localization of Benzodiazepine/GABAA Receptor/Cl− Channel Complex Using Monoclonal Antibodies in the Dorsal Lateral Geniculate Nucleus of the Cat
Authors: Soltesz Ivan , Roberts J. David B. , Takagi Hiroshi , Richards J. Grayson , Mohler Hans , Somogyi Peter
Published: April 2006

The two monoclonal antibodies, bd‐17 and bd‐24, are specific for β‐ and α‐subunits of the GABAA/benzodiazepine receptor/chloride channel complex respectively. An abundance of both subunits has been revealed in the visual thalamus of the cat by light microscopic immunocytochemistry using these antibodies. The α‐subunit specific antibody and electron microscopy were used to determine the subcellular distribution of immunoreactivity with respect to specific cell classes in the dorsal lateral geniculate nucleus. Immunoreactivity was always associated with membranes and the degree of immunoreactivity varied greatly between different types of cell as defined by: (i) immunoreactivity for GABA; (ii) soma area; (iii) presence or absence of cytoplasmic laminated bodies (CLB). GABA negative neurons with the smallest soma area showed the strongest immunoreactivity, mainly in the endoplasmic reticulum and also on the somatic plasma membrane. Cytoplasmic laminated bodies could be found in the majority of these neurons. Large GABA negative cells without CLBs were strongly immunoreactive on the plasma membrane of the soma and dendrites, but showed scant if any intracellular immunoreactivity. GABA‐positive cells showed weak intracellular immunoreactivity but negligible if any immunoreactivity at the somatic and proximal dendritic plasma membrane. A similar reaction pattern was found in GABA negative cells which contained no CLBs and which constituted a medium sized cell population. It is suggested that the degree of intracellular receptor immunoreactivity is positively correlated with receptor turnover. The dendrites of projection cells, particularly outside the glomeruli, showed strong immunoreactivity on the plasma membrane. The synaptic junctions formed by many boutons (F terminals) establishing symmetrical synapses with dendrites of relay cells were immunopositive, but no immunoreactivity could be detected at the synapses established by the presynaptic dendrites of the local interneurons. Many axo‐somatic F1 junctions were also immunoreactive. However, immunoreactivity for the receptor/channel complex was also widely distribution on nonsynaptic plasma membranes of somata and dendrites. Thus GABA may act at both synaptic and non‐synaptic sites. Furthermore, the correlation of immunoreactivity for the GABAA receptor complex with previously published properties of physiologically identified cells suggests that the strongly immunoreactive, small, GABA negative cells with CLBs might correspond to the ‘lagged’ X‐type cells, and the large GABA negative receptor outlined cells without CLBs might correspond to some of the Y‐type neurons.
Monoaminergic and Peptidergic Innervation of the Intermedio‐Lateral Horn of the Spinal Cord
Authors: Fuxe K. , Tinner B. , Bjelke B. , Agnati L. F. , Verhofstad A. , Steinbusch H. G. W. , Goldstein M. , Kalia M.
Published: April 2006

In the rat the monoaminergic and neuropeptidergic innervation of the sympathetic visceral nuclei of the entire thoracic spinal cord has been analysed in serial horizontal sections using immunocytochemistry. Tyrosine hydroxylase (TH), Phenyl‐ethanolamine‐N‐methyl‐transferase (PNMT), 5‐hydroxytryptamine (5‐HT), substance P (SP) and enkephalin (ENK) immunoreactive (IR) nerve terminals form tufts of plexa with strong IR in the principal part of the intermediolateral nucleus (ILp) with the terminals in an extraperikaryal location. High densities of these strongly IR terminals are also found in the principal part of the intercalated nucleus (ICp) and in the paraependymal part of the intercalated nucleus (ICpe). The various types of IR nerve terminals also form rostro‐caudally oriented and latero‐medially oriented strands of strongly IR nerve terminals at regular intervals within each segment. Outside these sympathetic nuclei the terminals are absent or only weakly to moderately IR. The similar pattern of monoamine and peptide innervation of the putative preganglionic sympathetic neurons along the entire thoracic spinal cord may be related to the general three dimensional architecture of the preganglionic multipolar neurons. Thus, these inputs tend to cover the entire surface area of the preganglionic neurons in a uniform way. Some heterogeneities have been observed for the TH, PNMT and neuropeptide Y (NPY) innervation which may contribute to a differential control of sympathetic preganglionic neurons. It is suggested that the unique features of the descending monoaminergic or peptidergic neurons to sympathetic spinal nuclei are related to a demand for maintained transmission upon prolonged activation in these cardiovascular systems, allowing the maintenance of cardiovascular homeostasis.
The Adhesion Molecule on Glia (AMOG) Is Widely Expressed by Astrocytes in Developing and Adult Mouse Brain
Authors: Pagliusi S. R. , Schachner M. , Seeburg P. H. , Shivers B. D.
Published: April 2006

Adhesion molecule on glia (AMOG) is a 45–50 kD cell surface glycoprotein structurally similar to the Na, K‐ATPase β‐subunit and associated with the catalytic subunit of this enzyme. Previous immunofluorescence results had suggested that AMOG is transiently expressed on Bergmann glia during mouse cerebellar development, and antibody‐inhibition results have implicated it in the migration of granule neurons. We report that, while AMOG mRNA is detected in Bergmann glia during the migratory period, this astrocyte derivative continues to express AMOG mRNA at similar levels in adult mice suggesting a functional role for AMOG in adulthood. Evidence from RNA and protein blot analyses that AMOG is present before birth, increasing about ten fold in adult mouse brain and cerebellum is also provided. RNA blot analysis of astrocyte‐enriched cell populations and in situ hybridization results show that astrocytes synthesize AMOG mRNA in all regions of the developing and adult brain. In the adult, AMOG mRNA is more abundant in grey than white matter and, among grey matter regions, highest in cerebellar cortex. These results indicate a relationship between density of neuronal elements and AMOG expression. It is further speculated that AMOG is part of a Na,K‐ATPase complex expressed preferentially by astrocytes in mouse brain.
B‐50/GAP43 Expression Correlates with Process Outgrowth in the Embryonic Mouse Nervous System
Authors: Biffo S. , Verhaagen J. , Schrama L. H. , Schotman P. , Danho W. , Margolis F. L.
Published: April 2006

The hypothesis that B‐50/GAP43, a membrane‐associated phosphoprotein, is involved in process outgrowth has been tested by studying the developmental pattern of expression of B‐50/GAP43 mRNA and protein during mouse neuroembryogenesis. B‐50/GAP43 mRNA is first detectable at embryonic day 8.5 (E8.5) in the presumptive acoustico‐facialis ganglion. Subsequently, both B‐50/GAP43 mRNA and protein were co‐expressed in a series of neural structures: in the ventral neural tube (from E9.5) and dorsal root ganglia (from E10.5), in the marginal layer of the neuroepithelium surrounding the brain vesicles and in the cranial ganglia (from E9.5), in the autonomic nervous system (from E10.5), in the olfactory neuroepithelium and in the mesenteric nervous system (from E11.5), in a continuum of brain regions (from E12.5) and in the retina (from E13.5). Immunoreactive fibers were always seen arising from these regions when they expressed B‐50/GAP43 mRNA. The spatial and temporal pattern of B‐50/GAP43 expression demonstrates that this protein is absent from neuroblasts and consistently appears in neurons committed to fiber outgrowth. The expression of the protein in immature neurons is independent of their embryological origin. Our detailed study of B‐50/GAP43 expression during mouse neuroembryogenesis supports the view that this protein is involved in a process common to all neurons elaborating fibers.
Hippocampal Complex Spike Cells do not Change Their Place Fields if the Goal is Moved Within a Cue Controlled Environment
Authors: Speakman A. , O'Keefe J.
Published: April 2006

It has been shown that most hippocampal complex‐spike cells fire at specific locations in relation to a set of controlled spatial cues and that they continue to fire in the appropriate places when the cues are removed (O'Keefe and Conway, 1978; O'Keefe and Speakman, 1987). However, the goal remained in a constant position relative to the controlled cues throughout these experiments. It is therefore possible that the unit firing was related to the goal location and not to the controlled cues as was suggested. For example, firing in a particular location might signal the rat's intention to make a particular turn towards the goal from that location and not the location itself. There are many reasons for believing that this is an unlikely class of explanations; nevertheless a test of this hypothesis was undertaken in the present experiment. Nineteen place units were recorded from three rats as they performed the task of finding the goal location. After obtaining an accurate picture of the place fields in relation to the controlled cues and the goal, the location of the goal relative to the cues was moved and the animal retrained to the new goal. After the new goal was being consistently chosen, a second picture of the place fields of the same units was obtained. If the fields were related to the environment created by the cues then they would remain the same during the two stages of the experiment. If they were related to the goal, or to the intended movements towards the goal, then they would rotate relative to the cues. As expected, the majority of place fields remained in the same place in relation to the cues during the two stages of the experiment and were not influenced by the goal relocation. In only two cases was there any suggestion that the place fields changed their location after the goal was moved. It was concluded that the activity of place cells is related to an animal's location in an environment and that the results accord with cognitive map theory of hippocampal function (O'Keefe and Nadel, 1978).
Neural Transplantation in Animal Models of Dementia
Authors: Dunnett S. B.
Published: April 2006

Neural transplantation provides a powerful novel technique for investigating the neurobiological basis and potential strategies for repair of a variety of neurodegenerative conditions. The present review considers applications of this technique to dementia. After a general introduction (section 1), attempts to replace damaged neural systems by transplantation are considered in the context of distinct animal models of dementia. These include grafting into aged animals (section 2), into animals with neurotransmitter‐selective lesions of subcortical nuclei, in particular involving basal forebrain cholinergic systems (section 3), and into animals with non‐specific lesions of neocortical and hippocampal systems (section 4). The next section considers the alternative use of grafts as a source of growth/trophic factors to inhibit degeneration and promote regeneration in the aged brain (section 5). Finally, a number of recent studies have employed transplanted tissues to model and study the neurodegenerative processes associated with ageing and Alzheimer's disease taking place within the transplant itself (section 6). It is concluded (section 7) that although neural transplantation does not offer any immediate prospect of therapeutic repair in clinical dementia, the technique does offer a powerful neurobiological tool for studying the neuropathological processes involved in both spontaneous degeneration and specific diseases of ageing. New understandings derived from neural transplantation may be expected to lead to rational development of novel strategies to inhibit the neurodegenerative process and to promote regeneration in the aged brain.