bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radioautographic Evidence that the GABAA Receptor Antagonist SR 95531 is a Substrate Inhibitor of MAO‐A in the Rat and Human Locus Coeruleus
Authors: Luque J. M. , Erat R. , Kettler R. , Cesura A. , Prada M. Da , Richards J. G. 
Published: April 2006

AbstractThe locus coeruleus (LC), a major noradrenergic nucleus in the brain, probably has a functional role in the regulation of anxiety states as well as vigilance, attention, learning and memory. LC neurons are under the inhibitory control of γ‐aminobutyric acid (GABA) via ionotropic GABAA receptors. However, to date, little is known of the receptor binding characteristics of these neurons. In the present investigation we therefore examined by receptor radioautography the localization of the binding sites for different components of the GABAA receptor complex in the rat and human LC. Both rat and human LC neurons have a high density of binding sites for the pyridazinyl‐GABA derivative [3H]SR 95531 (gabazine, a GABAA receptor antagonist for low affinity GABA recognition sites). However, at the concentrations used, no binding sites in the LC were detectable for the benzodiazepine receptor antagonist [3H]flumazenil, the GABAA receptor agonist (for high affinity sites) [3H]muscimol or the ionophore ligand [35S]t ‐butyl bicyclophosphorothionate (TBPS). Unexpectedly, the pharmacological specificity of [3H]SR 95531 binding to the LC differed markedly from that to most brain regions (IC50 values for GABA and RU 5135 respectively in the LC were > 10‐2 and 10‐3 M; and, for example, in the dentate gyrus the most labelled structure after the LC, 8 × 10‐7 and 1.8 × 10‐9 M). These differences prompted the further characterization of [3H]SR 95531 binding in the LC, revealing a significant affinity for monoamine oxidase type A (MAO‐A), which is highly concentrated in this nucleus. In a competition binding study, a reduction of up to 25% of the [3H]SR 95531 binding was observed with MAO‐A but not MAO‐B inhibitors, at concentrations which produce maximum but selective enzyme inhibition. Correspondingly, 2 h after the oral administration of supramaximal doses of the MAO‐A inhibitors moclobemide and Ro 41 ‐1049 (but not the MAO‐B inhibitor lazabemide) the in vitro binding of [3H]SR 95531 was markedly reduced (by 77 and 82% of controls respectively). Moreover, enzyme radioautography with [3H]Ro 41 ‐1049 revealed that SR 95531 has a significant affinity for MAO‐A (ICgo values were 10‐5 and 4x 10‐6 M in the LC and dentate gyrus respectively) but not for MAO‐B ([3H]lazabemide binding). Altogether, these findings suggest that the high‐affinity binding of [3H]SR 95531 to the LC mainly reflects its affinity for MAO‐A, which questions its utility as a selective ligand for low‐affinity GABA recognition sites in the CNS. It remains to be seen whether the dual pharmacological profile of SR 95531 (desinhibition of LC neurons and facilitation of noradrenergic transmission) can be exploited as a principle in the development of new anxiolytics or antidepressants.
MCPG Antagonizes Metabotropic Glutamate Receptors but not Long‐term Potentiation in the Hippocampus
Authors: Manzoni Olivier J. , Weisskopf Marc G. , Nicoll Roger A. 
Published: April 2006

AbstractIn the CA1 and CA3 regions of the guinea pig hippocampus, we have tested the ability of the new antagonist (RS)‐α‐methyl‐4‐carboxyphenylglycine (MCPG) to inhibit the well‐known effects of (trans)‐1‐amino‐cyclopentyl‐1,3‐dicarboxylate (ACPD), a specific agonist of glutamate metabotropic receptors. Whole‐cell recordings showed that MCPG was able to antagonize the blocking action of ACPD on IAHP in the CA1 region. In addition, we report here that MCPG also antagonized the presynaptic inhibitory actions of ACPD on field excitatory postsynaptic potentials in both areas CA1 and CA3. Thus, MCPG proved to be an effective tool for determining physiological roles of the glutamate metabotropic receptors in synaptic transmission in the hippocampus. We next tested the possible effects of this antagonist on long‐term potentiation (LTP). In completely blind experiments MCPG was without effect on LTP in both areas CA1 and CA3. In conclusion, our results suggest that, although MCPG is a valuable antagonist of the ACPD‐sensitive receptors, it has no inhibitory effect on LTP.
Influences of Horizontal Connections on Visual Responses in Rabbit Striate Cortex
Authors: Morin C. , Molotchnikoff S. 
Published: April 2006

AbstractThe goal of this study was to examine the role of horizontal connections in rabbit striate neurons. Anaesthetized rabbits were prepared in the usual fashion for single‐cell recordings in area 17 of the visual cortex. We compared responses evoked by moving and stationary stimuli prior to, during and after recovery from lateral microinjection of either lidocaine (n= 61), γ‐aminobutyric acid (GABA, n = 18) or bicuculline (n= 8) 2 mm from the recording site. This procedure allows evaluation of the contribution of neighbouring neurons in visual responses. Results showed that striate neurons are dependent on the adjacent cells1 excitability. Modification of responses to stationary targets suggests that lateral interactions play a role in the generation of discharges to fixed stimuli. Lateral inactivation preferentially influenced non‐directional over direction‐selective units. This influence usually resulted in the non‐directional neuron becoming directional by attenuation of the visually driven response in one direction. Simple and complex cells tended to be influenced differently by lateral inactivation. Simple cells became less responsive, whereas complex cells became more responsive. This dichotomy among cellular types suggests that simple cells receive mainly excitatory horizontal influences, while complex cells are contacted mostly by lateral inhibitory inputs.
The Effect of Corticosterone on Reactivity to Spatial Novelty is Mediated by Central Mineralocorticosteroid Receptors
Authors: Oitzl Melly S. , Fluttert Marc , Ron de Kloet E. 
Published: April 2006

AbstractCorticosterone, secreted by the adrenal glands, binds to central mineralocorticoid receptors with high affinity and to glucocorticoid receptors with a tenfold lower affinity. In previous studies we have shown that the selective activation of either mineralocorticoid receptors or glucocorticoid receptors exerts distinctly different behavioural effects. In this study we examined in particular the mineralocorticoid receptor‐mediated effect of corticosterone on the control of the behavioural response of male Wistar rats to spatial novelty. This analysis was based on our observation that in adrenal‐intact rats the presence of an object in the centre of an open field alters the time spent and distance walked in the centre compared to the peripheral area, i.e. the pattern of reactive locomotor activity is changed. Using this paradigm we found that 1 day after removal of the adrenals the rats increased their behavioural reactivity towards the object. Treatment of adrenalectomized rats with a low dose of corticosterone (50 μg/kg s.c.) 1 h prior to testing restored the behavioural reactivity to the level of sham‐operated, intact rats. Surprisingly, a high dose of corticosterone (1000 μg/kg s.c.) also increased the rat's reactivity towards the object. The same high dose of corticosterone given to adrenal‐intact rats also increased behavioural reactivity. Pretreatment of these rats with an intracerebroventricular injection of the selective mineralocorticoid receptor antagonist RU28318 (100 ng/μl) prevented the corticosterone‐induced increase in behavioural reactivity, while the blockade of glucocorticoid receptors with the antagonist RU38486 (100 ng/μl) was not effective. Administration of the mineralocorticoid receptor antagonist without corticosterone to adrenal‐intact rats also increased behavioural reactivity, but this increase did not reach statistical significance. General locomotor activity was not affected by either treatment. In conclusion, we found a U‐shaped relationship between the pattern of behavioural reactivity in a novel environment and the circulating plasma corticosterone level. The response to spatial novelty appeared to be sensitive with respect to the activation and blockade of central, presumably hippocampal mineralocorticoid receptors.
Rectification Properties and Ca2+ Permeability of Glutamate Receptor Channels in Hippocampal Cells
Authors: Lerma J. , Morales M. , Ibarz J. M. , Somohano F. 
Published: April 2006

AbstractExcitatory amino acids exert a depolarizing action on central nervous system cells through an increase in cationic conductances. Non‐NMDA receptors have been considered to be selectively permeable to Na+ and K+, while Ca2+ influx has been thought to occur through the NMDA receptor subtype. Recently, however, the expression of cloned non‐NMDA receptor subunits has shown that α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors are permeable to Ca2+ whenever the receptor lacks a particular subunit (edited GluR‐B). The behaviour of recombinant glutamate receptor channels predicts that Ca2+ would only permeate through receptors that show strong inward rectification and vice versa, i.e. AMPA receptors with linear current‐voltage relationships would be impermeable to Ca2+ . Using the whole‐cell configuration of the patch‐clamp technique, we have studied the Ca2+ permeability and the rectifying properties of AMPA receptors, when activated by kainate, in hippocampal neurons kept in culture or acutely dissociated from differentiated hippocampus. Cells were classified according to whether they showed outward rectifying (type I), inward rectifying (type II) or almost linear (type III) current‐voltage relationships for kainate‐activated responses. AMPA receptors of type I cells (52.2%) were mostly Ca2+‐impermeable (PcaIPcs= 0.1) while type II cells (6.5%) expressed Ca2+‐permeable receptors (PcaIPcs=0.9).Type III cells (41.3%) showed responses with low but not negligible Ca2+ permeability (PcaIPcs= 0.18). The degree of Ca2+ permeability and inward rectification were well correlated in cultured cells, i.e. more inward rectification corresponded to higher Ca2+ permeability. In acutely dissociated neurons, the restricted activation of the receptors located either in dendritic or somatic membranes revealed that inward rectifying (i.e. Ca2+‐permeable) AMPA receptors are preferentially located in the dendritic shaft (i.e. synaptic field). Our results indicate that oligomeric AMPA receptors of different subunit composition are coexpressed in dissimilar proportions in different cells, which would explain the incomplete inward rectification and graded Ca2+ permeability. In addition, Ca2+‐permeable AMPA receptors may exhibit non‐homogeneous subcellular distribution.
GABA‐activated Chloride Currents of Postnatal Mouse Retinal Ganglion Cells are Blocked by Acetylcholine and Acetylcarnitine: How Specific are Ion Channels in Immature Neurons?
Authors: Bähring R. , Standhardt H. , Martelli E. Arrigoni , Grantyn R. 
Published: April 2006

AbstractThe goal of this study was to clarify pharmacological properties of GABAA receptors in cells of the mouse retinal ganglion cell layer in situ. Spontaneous synaptic currents and responses to exogenous GABA were recorded from individual neurons in retinal whole mounts (postnatal days 1–3) or retinal stripe preparations (postnatal days 4–6). Drugs were applied by a fast local superfusion system. Current responses were measured with the patch‐clamp technique in the whole‐cell configuration. All cells responded to exogenous GABA (average EC50 and Hill coefficient: 16.7 μM and 0.95 respectively) and generated GABAergic synaptic currents in response to elevated KCI. GABA‐induced currents of retinal ganglion cells were blocked by bicuculline, picrotoxin and Zn2+, as well as strychnine, and increased by pentobarbital, clonazepam and 3α‐hydroxy‐5α‐pregnan‐20‐one. In some retinal ganglion cells GABA caused an increase in the frequency of spontaneous synaptic currents, which points to a partially depolarizing action of this traditionally inhibitory neurotransmitter in the neural retina. Our major observation is that acetylcholine and acetylcarnitine blocked or reduced GABAergic inhibitory postsynaptic currents and responses to exogenous GABA. This effect was seen in only a fraction of retinal ganglion cells and occurred in both the undesensitized and the desensitized state of the GABAA receptor. The block was voltage‐independent and persisted during coapplication with the nicotinic and muscarinic acetylcholine receptor antagonists D‐tubocurarine and atropine. In contrast to GABA‐activated Cl− currents, glycine‐activated Ch currents remained unaffected by acetylcholine and acetylcarnitine. Acetylcarnitine had no effect on voltage‐activated Ca2+ channel currents and glutamate‐activated currents. Similar results were obtained in a dissociated cell culture preparation from the neonatal rat superior colliculus. In these cells acetylcholine induced a rightward shift in the dose ‐ response curve for GABA. Taken together, these results indicate that acetylcholine and acetylcarnitine can act directly at the GABAA binding site and thereby reduce the action of GABA in the immature retina.
Shaker Mutants Lack Post‐tetanic Potentiation at Motor End‐plates
Authors: Delgado Ricardo , Latorre Ramon , Labarca Pedro 
Published: April 2006

AbstractThe two‐electrode voltage clamp technique was employed to measure end‐plate currents in larval neuromuscular junctions of wild‐type (Canton‐S) and of three different Drosophila Shaker mutants: ShakerKS133, Shaker102 and f5Shaker5. In the Shaker mutants, nerve‐evoked end‐plate currents (neepc) were 4–5‐fold larger than those measured in Canton‐S. Shaker motor end‐plates were found to lack post‐tetanic potentiation (PTP), but could undergo facilitation. Moreover, PTP but not facilitation was lost in wild‐type larvae if the neuromuscular junction was exposed to 4‐aminopyridine (4‐AP), a blocker of Shaker A‐type K+ currents. End‐plate currents were depressed by Ca2+ channel blockers like Mg2+, at millimolar concentrations, and Co2+ and Cd2+, at micromolar concentrations, but not by nifedipine (100 nM) and verapamil (100 nM). After exposure to Ca2+ channel blockers, Shaker end‐plates exhibited PTP. In particular, Cd2+ was most effective in depressing neepes and in restoring PTP in all Shaker mutants. The results obtained indicate the abnormal function of Shaker K+ channels at motor nerves specifically abolishes PTP in Drosophila larval neuromuscular junctions.
Inverted Pyramidal Neurons and Interneurons in Cat Cortical Subplate Zone are Labelled by Monoclonal Antibody SP1
Authors: Wahle Petra , Lübke Joachim , Naegele Janice R. 
Published: April 2006

AbstractDuring development, the subplate zone of the cat neocortex contains neuronal populations with distinct morphological and neurochemical phenotypes. A subset of those are specifically recognized by a mouse monoclonal antibody termed SUBPLATE‐1 (SP1), which was generated against tissue homogenates of kitten cortical white matter. SP1 stains cell bodies and proximal dendrites, but rarely distal dendrites, axonal arbors or spines. In order to characterize morphologically the SP1 imunoreactive subplate cell types, we combined SP1 immunohistochemistry with intracellular iontophoretic injections of Lucifer yellow. The majority of double‐labelled neurons were inverted pyramids with a single thicker spine‐covered dendrite that descended into the white matter and a tuft of thinner spinous dendrites that ascended from the upper somatic pole, but generally remained confined to the white matter. Other double‐labelled neurons were multipolar to bitufted, although often equipped with one thicker descending dendrite. In inverted pyramidal cells, the axons originated from the descending dendrite or, more rarely, from the lower portion of the soma, and descended into the white matter. They formed collaterals recurring toward the grey matter. The presence of dendritic spines on double‐labelled pyramidal cells and the axonal arborization patterns were two novel features not revealed previously by SP1 immunohistochemistry alone. The inverted pyramidal morphology was typical for double‐labelled neurons located in the subplate szone below the apices of the gyri, whereas those located below the flanks or sulci or deep in the white matter soften displayed a bitufted or multipolar spinous morphology. A minority of the double‐labelled neurons were multipolar with smooth dendrites and locally branching axons. These results suggest that in the cat subplate zone, a majority of the cells expressing the SP1 antigen are spinous, and we termed the spinous subplate cells ‘subplate pyramidal neurons’.
Requirement of Metabotropic Glutamate Receptors for the Generation of Inflammation‐evoked Hyperexcitability in Rat Spinal Cord Neurons
Authors: Neugebauer Volker , Lücke Thomas , Schaible Hans‐Georg 
Published: April 2006

AbstractIn the central nervous system the transmitter L‐glutamate activates both ionotropic receptors coupled to cation channels and metabotropic receptors coupled to G‐proteins. The role of metabotropic receptors in the processing of mechanosensory and nociceptive information was studied in a subset of spinal cord neurons with afferent input from the knee joint in anaesthetized rats using electrophysiological methods. The ionophoretic administration of L‐2‐amino‐3‐phosphonopropionic acid (L‐AP3), an antagonist at the metabotropic receptor, had no effect on the responses to innocuous and noxious pressure applied to the normal knee joint, although the antagonist prevented the potentiation of these responses evoked by the ionophoretic administration of a specific agonist at the metabotropic receptor, trans‐(±)‐1‐amino‐(1S,3R)‐cyclopentane‐dicarboxylic acid (t‐ACPD). By contrast, in neurons that were rendered hyperexcitable by acute inflammation in the knee joint L‐AP3 reduced the responses to pressure applied to the knee. When L‐AP3 was applied during induction of inflammation and throughout the subsequent 1.5 h the spinal neurons did not develop hyperexcitability over this time period. L‐AP3 did not impair the activation of ionotropic N‐methyl‐D‐aspartate (NMDA) and non‐NMDA receptors by the specific agonists. We conclude that spinal metabotropic glutamate receptors are not involved in the mediation of responses to innocuous and noxious mechanical stimuli applied under normal conditions. They are required, however, for the generation of inflammation‐evoked hyperexcitability of spinal cord neurons, a form of functional plasticity underlying the painfulness in pathophysiological conditions such as inflammation.
The Length – Response Properties of Cells in the Feline Perigeniculate Nucleus
Authors: Jones H. E. , Sillito A. M. 
Published: April 2006

AbstractPerigeniculate cells receive visual input from the dorsal lateral geniculate nucleus (dLGN) and from the visual cortex. In contrast to the extensive literature documenting dLGN and cortical cell responses, comparatively little quantitative data exists for perigeniculate nucleus cells, and very little is known about the role of the corticofugal input to the perigeniculate nucleus. We have previously shown that dLGN relay cells have sharply length‐tuned receptive fields and that a significant component of this is dependent on the corticofugal system. In this report, we have explored the length – response properties of perigeniculate nucleus cells in the presence and absence of corticofugal feedback. The response profiles of most perigeniculate nucleus cells contrasted markedly with the sharply length‐tuned fields of dLGN cells, but exhibited a notable resemblance to those exhibited by VI cells with short summation lengths, which have recently been shown to constitute a considerable proportion of the layer VI cell population. This might suggest that the responses of perigeniculate nucleus cells to long bars derive from their cortical input. However, our data failed to reveal a discernible change in their profiles after removal of the corticofugal drive. This surprising observation implies that their length‐tuning profiles follow from subcortical circuitry. The ways in which this might occur are discussed.
Anatomical and Electrophysiological Evidence for an Excitatory Amino Acid Pathway from the Thalamic Mediodorsal Nucleus to the Prefrontal Cortex in the Rat
Authors: Pirot Sylvain , Jay Thérèse M. , Glowinski Jacques , Thierry Anne‐Marie 
Published: April 2006

AbstractThis study was undertaken to identify the neurotransmitter of the projection from the thalamic mediodorsal nucleus (MD) to the prefrontal cortex (PFC) using both retrograde transport of D‐[3H]aspartate and electrophysiological approaches in the rat. Unilateral microinjections of D‐[3H]aspartate performed into the prelimbic area of the PFC resulted in dense labelling of numerous cells in the ipsilateral MD. Excitatory responses were observed in PFC neurons after electrical stimulation of the MD. However, since cortical neurons project to the MD, these excitatory responses could have resulted either from the activation of the MD‐PFC pathway and/or from the activation of recurrent collaterals of antidromically driven cortico‐thalamic fibres. The conduction time of each of these two reciprocal pathways was determined by antidromic activation. Short latency excitatory responses resulted from activation of the MD‐PFC pathway. They were predominantly observed in PFC neurons located in layer III and evoked at low frequency stimulation (0.3–1 Hz). These excitatory responses disappeared or were replaced by longer latency responses when higher frequency stimulations (3–10 Hz) were used. MD‐evoked responses were blocked by the iontophoretic application of the AMPA receptor antagonist CNQX into the PFC. These results indicate that the MD‐PFC pathway utilizes glutamate and/or aspartate as the neurotransmitter and that its activation induces excitation in PFC neurons through AMPA receptors. Even though the local application of the NMDA receptor antagonist APV was ineffective, a contribution of these receptors in MD‐PFC transmission cannot be excluded.
Interhemispheric Structural Asymmetry Induced by a Lateralized Reaching Task in the Rat Motor Cortex
Authors: Díaz Eugenia , Pinto‐Hamuy Teresa , Fernández Víctor 
Published: April 2006

AbstractThe effects of a lateralized reaching task on the morphological structure of the rat motor cortex were studied during the early postweaning period. Our results show that the consistent use of one forelimb accounts for a significant decrease in the numerical density of cells and an increase in cortical thickness of the contralateral‘forelimb’motor cortex. As a consequence of the early motor training the cell distribution, which is lower rostrally than caudally in nontrained hemispheres, is reversed in the trained hemispheres. This may be interpreted as the specific motor training triggering a higher neuronal branching in the corresponding cortical region. The present findings may further the understanding of the mechanisms involved in the generation of morphological brain asymmetries.