bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasticity of μ and δ Opioid Receptors in the Superficial Dorsal Horn of the Adult Rat Spinal Cord Following Dorsal Rhizotomies: A Quantitative Autoradiographic Study
Authors: Besse D. , Lombard M. C. , Besson J. M.
Published: April 2006

The aim was to study the regulation of μ and δ opioid binding sites in the superficial layers (laminae I–II) of the dorsal horn of the adult rat spinal cord 1, 2, 4 and 12 weeks after unilateral dorsal rhizotomies of various extents. Using quantitative autoradiography and highly selective tritiated opioid ligands, we have shown that the decrease in [3H]Tyr*‐d‐Ala‐Gly‐NMe‐Phe‐Gly‐ol ([3H]DAMGO) (μ sites) and [3H]Tyr*‐d‐Thr‐Gly‐Phe‐Leu‐Thr ([3H]DTLET) (δ sites) binding in the side ipsilateral to the lesion as compared to the intact side is related to the number of dorsal roots cut. In the segment central to the lesion, 1 week after the lesion, ipsilateral/contralateral side binding ratios for [3H]DAMGO were 0.70, 0.49, 0.36 and 0.25 when 1, 3, 5 and 7 roots respectively were sectioned. For [3H]DTLET, the ratios were 0.71, 0.54, 0.42 and 0.39. The time‐related analysis of binding ratios showed that, in partially deafferented spinal segments after long‐term deafferentation (12 weeks postlesion) there were greater numbers of μ and δ binding sites than in cases of short‐term deafferentation (1–2 weeks). By contrast, in spinal segments considered as completely deafferented, there was no difference in the remaining μ and δ binding sites at 12 weeks as compared to 1 week postlesion. Consequently, it is deduced that the partial recovery of μ and δ binding observed after long‐term partial deafferentation could be associated with neuronal plasticity (probably collateral sprouting) of fine diameter primary afferent fibres arising from intact dorsal roots.
The Effectiveness of the Gene Which Slows the Rate of Wallerian Degeneration in C57BL/Ola Mice Declines With Age
Authors: Perry V. H. , Brown M. C. , Tsao J. W.
Published: April 2006

The rate of Wallerian degeneration is unusually slow in severed axons of mice of the C57BL/Ola strain. Within mice of that strain we have now found that the rate of degeneration increases with the age of the animal. In 4‐week‐old mice nerve stimulation evokes muscle contractions even 5 days after sciatic nerve section and compound action potentials can be recorded in the distal nerve stump up to 3 weeks after section. In 1‐year‐old animals no action potentials can be excited 5 days after nerve section. Heterozygous mice carrying only one copy of the dominant gene show the same age‐related decline in viability of the distal nerve stump after axotomy, and the rate of decline is no greater than for homozygous mice. The more rapid rate of degeneration of severed axons of mice of the C57BL/6J strain was affected in the opposite way by age, degeneration occurring more slowly in older animals.
The Extent of the Dendritic Tree and the Number of Synapses in the Frog Motoneuron
Authors: Birinyi A. , Antal M. , Wolf E. , Székely G.
Published: April 2006

Frog motoneurons were intracellularly labelled with cobaltic lysine in the brachial and the lumbar segments of the spinal cord, and the material was processed for light microscopy in serial sections. With the aid of the neuron reconstruction system NEUTRACE, the dendritic tree of neurons was reconstructed and the length and surface area of dendrites measured. The surface of somata was determined with the prolate – oblate average ellipsoid calculation. Corrections were made for shrinkage and for optical distortion. The mean surface area of somata was 6710 μm2; lumbar motoneurons were slightly larger than brachial motoneurons. The mean length of the combined dendritic tree of brachial neurons was 29 408 μm and that of lumbar neurons 46 806 μm. The mean surface area was 127 335 μm2 in brachial neurons, and 168 063 μm2 in lumbar neurons. The soma – dendrite surface area ratio was 3 – 5% in most cases. Dendrites with a diameter of ≤ 1.0 μm constituted ∼ 75% of the combined dendritic length in most of the neurons. Unlike in the cat, there was no correlation between the size of stem dendrites and the extent of daughter branches. From the synaptic density estimated in earlier electron microscope investigations of frog motoneuron dendrites (Antal et al., J. Neurocytol., 15, 303–310, 1986; 21, 34–49, 1992), and from the present data, the number of synapses on the dendritic tree was calculated. The calculations indicated 26 949 synapses on the smallest and 61 519 synapses on the largest neuron if the synaptic density was multiplied by the length of the dendritic tree. If the synaptic density was multiplied by the surface area of the dendritic tree the calculation yielded 23 337 synapses for the smallest and 60 682 synapses for the largest neuron. More than 60% of the combined surface area of dendrites was >600 μm from the soma. This suggests that about two‐thirds of the synapses impinged upon distant dendrites >600 μm from the soma. The efficacy of synapses at these large distances is investigated on model neurons in the accompanying paper (Wolf et al., Eur. J. Neurosci., 4, 1013–1021, 1992).
Phase‐dependent Modulation of a Cutaneous Sensory Pathway by Glycinergic Inhibition from the Locomotor Rhythm Generator in Xenopus Embryos
Authors: Sillar Keith T. , Roberts Alan
Published: April 2006

In immobilized Xenopus laevis embryos two classes of sensory interneuron are excited by mechanosensory Rohon‐Beard neurons and rhythmically inhibited during fictive swimming. Dorsolateral commissural (DLC) interneurons are inhibited in time with rhythmic motor discharge on the same side as their soma, while unidentified dorsolateral (DLX) interneurons are inhibited in the opposite phase of the swimming rhythm. The inhibition is abolished by bath application of strychnine sulphate at 1–10 μM, but not by the γ‐aminobutyric acid antagonists bicuculline (20–40 μM) or curare (70–100 μM). The inhibitory postsynaptic potentials (IPSPs) involve an increase in chloride conductance since they are reversed in sign to become depolarizing following intracellular injection of chloride ions. The conductance increase during inhibition was able to block impulses evoked by intracellular current in a phase‐dependent manner, suggesting that postsynaptic inhibition is sufficient to account for the gating of afferent input to the spinal cord during swimming. An interneuron receives IPSPs that are predominantly in one phase of the rhythm, but most interneurons are also inhibited sporadically in the opposite phase. The amplitude and time course of the IPSPs closely follow the frequency of the swimming rhythm, with maximal inhibition occurring near the starts of episodes, when swimming frequency is at its highest. Towards the end of an episode, when swimming frequency declines, the level of inhibition is low, the membrane potential of the interneurons returns to rest between cycles, and IPSPs often fail to occur. Inhibition suppresses sensory excitation in a phase‐dependent manner (cf. Sillar and Roberts, Nature, 331, 262–265, 1988). Sensory interneurons fire a single impulse in response to a brief sensory stimulus, but they will usually fire multiple impulses when depolarized with sufficient intracellular current. In some sensory interneurons a short‐latency IPSP follows the impulse evoked by skin stimulation that could curtail impulse activity. However, when the inhibition is blocked by strychnine, sensory interneurons still fire a single short‐latency impulse, favouring the conclusion that brief, synchronized afferent excitation elicits a single impulse in neurons that are capable of firing multiply. Since the inhibition of DLC interneurons occurs in phase with activity on the same side it probably originates from spiking in ipsilateral glycinergic commissural interneurons which have ipsilateral as well as contralateral projections. The inhibition of DLX interneurons in the opposite phase probably originates from the contralateral projections of commissural interneurons.
Ca2+ Channel Expression in the Oligodendrocyte Lineage
Authors: Blankenfeld Gabriela v. , Verkhratsky Alexej N. , Kettenmann Helmut
Published: April 2006

The development of oligodendrocytes from their precursor cells through different developmental stages can be studied in vitro. These stages can be distinguished by specific monoclonal antibodies and by a characteristic K+ channel profile. In this study we demonstrate that the occurrence of Ca2+ currents also undergoes marked changes during the development of mouse oligodendrocytes. Immature precursor cells which can develop into astrocytes or oligodendrocytes expressed two different types of voltage‐activated Ca2+ channels. The expression of Ca2+ channels in precursor cells was strongly correlated with the expression of Na+ channels. When cells started to express the O1 antigen and were committed to the oligodendrocyte lineage, Ca2+ and Na+ currents could no longer be detected. Large Ca2+ currents were, however, recorded later in the development of the oligodendrocytes, correlated with the expression of the O10 antigen. The Ca2+ channels were classified as high and low voltage‐activated Ca2+ channels according to their range of activation, and are further described by their kinetic and pharmacological properties.
GABA Triggers a [Ca2+]i Increase in Murine Precursor Cells of the Oligodendrocyte Lineage
Authors: Kirchhoff Frank , Kettenmann Helmut
Published: April 2006

The development of oligodendrocytes from their precursor cells can be studied in vitro by using a culture system in which cells can be identified at different developmental stages. We used this culture system to compare the effect of the inhibitory neurotransmitter γ‐aminobutyric acid (GABA) on intracellular Ca2+ concentration ([Ca2+]i) using fura‐2 fluorescence systems. Application of GABA evoked transient [Ca2+]i increases in precursor cells. In contrast, [Ca2+]i levels were not affected in oligodendrocytes, which were identified by their positive labelling with the antibody O1. The precursor cells, identified by a lack of O1 staining, responded to GABA in the concentration range between 10−6 and 10−4 M. Since muscimol mimicked and bicuculline as well as picrotoxin blocked the GABA response, we conclude that the response is mediated by activation of GABAA receptors. The involvement of Ca2+ channels is inferred from the observation that the [Ca2+]i changes could be blocked by nifedipine or by omitting Ca2+ from the bath solution. Both GABAA receptors and Ca2+ channels have been previously identified on these precursor cells with the aid of the patch‐clamp technique. We thus propose the following mechanism to explain our observations: the Cl− efflux via the GABA receptor depolarizes precursor cells, and this depolarization leads to activation of Ca2+ channels, resulting in an influx of Ca2+ and the observed rise in cytosolic [Ca2+]. Although its physiological importance is speculative, this event could serve as a signal from GABAergic neurons to glial precursor cells.
Simultaneous Demonstration of Serotonin‐immunoreactive Terminals and GABAergic Neurons in the VPL Nucleus of the Cat Thalamus
Authors: Liu X.‐B. , Jones E. G.
Published: April 2006

Pre‐embedding immunoperoxidase (for serotonin) and postembedding immunogold (for γ‐aminobutyric acid; GABA) labelling were combined at light and electron microscopic levels to demonstrate the neuronal targets of serotonin (5‐HT) afferents in the ventral posterior lateral nucleus (VPL) of the cat thalamus. 5‐HT‐immunoreactive fibres and terminal varicosities were found in close proximity to GABA‐immunoreactive interneurons and non‐GABAergic relay neurons. Ultrastructurally, the vast majority of 5‐HT terminals made close membrane contacts without overt membrane specializations with GABAergic axon terminals, GABAergic presynaptic dendrites and GABAergic somata. A very small number of 5‐HT terminals formed typical asymmetrical synapses with GABAergic presynaptic dendrites and with dendritic shafts of relay cells. Some 5‐HT terminals participated with the presynaptic dendrites in triadic synaptic arrangements. These findings suggest a dual innervation pattern by 5‐HT afferents in VPL and the release of 5‐HT in large part at sites not associated with morphologically detectable synapses.
Evidence for a Slowly Inactivating K+ Current in Prefrontal Cortical Cells
Authors: Hammond C. , Crépel F.
Published: April 2006

The in vitro slice preparation of rat prefrontal cortical cells was used to analyse the presence and characteristics of a slowly inactivating outward current and its effect on the delayed integration of synaptic inputs. Pyramidal cells were identified as regular firing or bursting cells. In a fraction of these cells a depolarizing current pulse to –40 mV from a holding potential of –95 mV evoked the fast outward IA current followed by a slower outward current (IKs) which inactivated slowly during the 3‐s pulse. This slowly inactivating outward current was completely inactivated at holding potentials near –40 mV and was fully deinactivated by large hyperpolarizing pulses of 1 s duration. It was sensitive to micromolar concentrations of 4‐aminopyridine and to 10 mM tetraethylammonium. In current clamp experiments, when the cells were maintained at –80 mV, they responded to subliminal depolarizing current pulses by a slow rising depolarization which reached threshold for spike firing after a delay of several seconds. This delay was considerably reduced either by maintaining the cell at less hyperpolarized potentials or by bath application of 40 μM 4‐aminopyridine, or by repeated application of depolarizing pulses. The inactivation of IKs by the last procedure also led to plateau depolarization of the cell. These results suggest that the activation of the slowly inactivating outward current IKs can shunt excitatory inputs, preventing the cell from reaching spike threshold as long as it is not largely inactivated.
Effect of Temperature and Calcium on the Binding Properties of the AMPA Receptor in Frozen Rat Brain Sections
Authors: Tocco G. , Massicotte G. , Standley S. , Thompson R. F. , Baudry M.
Published: April 2006

The elucidation of the mechanisms regulating the properties of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) subtype of glutamate receptors is important for understanding glutamatergic transmission. Here we report that qualitative as well as quantitative analysis of tritiated ligand binding to the AMPA receptor on thin frozen rat brain tissue sections reveals the existence of several mechanisms regulating the binding properties of AMPA receptors. Preincubation of tissue sections at 35°C results in a decreased amount of [3H]AMPA binding as compared to that measured following preincubation at 0°C. The decrease in binding appears to be mainly localized to cell bodies as evaluated by autoradiography, and could be due to proteolysis. Preincubation with calcium at 35°C produces increased levels of [3H]AMPA binding. The effect of calcium is mimicked by manganese and to a lesser extent by magnesium; it is concentration‐dependent with a 50% effective concentration for calcium of ∼150 μM, time‐dependent and temperature‐dependent. The calcium‐induced increase in [3H]AMPA binding is different among various brain structures, being larger in area CA1 of the hippocampus and in the superficial layers of the cerebral cortex. The effect of calcium is partly reduced by preincubation with the calpain inhibitor leupeptin and potentiated by preincubation with purified calpain II. The calcium‐induced increase in [3H]AMPA binding is associated with a decrease in the binding of an antagonist of AMPA receptors, [3H]6‐nitro‐7‐cyanoquinoxaline‐2,3‐dione. The results indicate that the binding properties of the AMPA receptor are rapidly regulated by calcium‐dependent processes, and possibly by calcium‐dependent proteases. They suggest that modulation of the binding properties involves changes in the configuration of the receptor, producing opposite changes in the affinities of the receptor for agonists and antagonists. Finally, these results strengthen the hypothesis that changes in the properties of AMPA receptors might underlie various forms of synaptic plasticity.
Learning‐dependent Changes in the Responses to Visual Stimuli of Neurons in a Recognition Memory System
Authors: McLennan J. G. , Horn G.
Published: April 2006

When young chicks are trained by exposing them to a conspicuous object they learn its characteristics. The learning process is known as imprinting. In the present study neuronal activity in a region crucial for imprinting was shown to be affected by training and by the object on which the chicks had been trained. The region is the intermediate and medial part of the left hyperstriatum ventrale (left IMHV). No such effects were found in a visual projection area, the left hyperstriatum accessorium. Domestic chicks were imprinted on either a rotating red box (n= 7 chicks) or a rotating blue box (n= 8). When the chicks were ∼48 h old they were anaesthetized and multiple‐unit activity was recorded in simultaneous, single penetrations through each of the two regions. Records were also made from eight dark‐reared chicks. Whilst recording, the red or blue box, placed in front of the contralateral eye, was switched on to give a total of 20 rotations, the interval between each rotation being 10 s. The alternative stimulus was then presented 20 times. Unit activity in the 3 s before and after stimulus onset was compared and the data for each of the 20 presentations were combined. In the left IMHV 18 out of a total of 115 recording sites (16%) responded significantly to the stimuli; in the left hyperstriatum accessorium 39 out of 126 recording sites (26%) did so. Measures of unit activity at each recording site were combined for a given penetration to provide a ‘mean penetration response’. The response to the red box differed from the response to the blue box in the left IMHV of dark‐reared chicks. After training with the blue box the response to both boxes was similar to the response to the blue box in dark‐reared birds. After training with the red box the response to both boxes was similar to the response to the red box in dark‐reared birds. No significant effects were found in the left hyperstriatum accessorium. The two training boxes were virtually identical apart from the differences in colour and brightness. Training appeared to stabilize the response of the visually naive left IMHV to the training stimulus whilst changing its response to the alternative, but similar stimulus. That is, one consequence of training is that the two stimuli are placed in the same category, and this neural change may provide a basis for stimulus generalization. The underlying neural system is modelled and a mechanism that allows such stimuli to be discriminated is proposed.
Somatic Acetylcholine Release in Rabbit Nodose Ganglion
Authors: Palouzier‐Paulignan B. , Chamoin M.‐C. , Ternaux J.‐P.
Published: April 2006

In the rabbit, as in various other species, the presence of a cholinergic vagal afferent contingent has been demonstrated previously using biochemical and immunohistological approaches at the nodose ganglion level, where vagal afferent cell bodies are located. This structure is completely devoid of synaptic contacts. In the present study, somatic acetylcholine release is demonstrated on different types of in vitro rabbit nodose ganglion preparations (fragments of nodose tissue or isolated cell bodies) using chemiluminescent detection. Acetylcholine endogenous content was measured and was shown to be greater in the right nodose ganglion compared to the left. This difference was also observed when spontaneous and potassium chloride‐evoked acetylcholine release was measured in extracellular fluid after a 15‐min incubation of nodose ganglion fragments. Calcium removal totally blocked this somatic release. A kinetic study of acetylcholine release was also performed by placing the samples (nodose ganglion fragments or isolated cell bodies) directly in front of the photomultiplier, allowing the direct monitoring of (acetylcholine + choline) and choline effluxes. The net acetylcholine release was then deduced by subtraction. Identical kinetics was obtained with the two different nodose ganglion preparations used. This somatic release is calcium‐dependent. The occurrence of acetylcholine release at the nodose ganglion level is discussed in comparison with the events occurring in the cholinergic nerve endings. These mechanisms could be implicated in the premodulation of the vagal afferent messages conveyed from the periphery to the central nervous system.
An Electromyographic Study of the Hindlimb Locomotor Movements in the Acute Thalamic Rat
Authors: Goudard I. , Orsal D. , Cabelguen J.‐M.
Published: April 2006

In this paper we have analysed the patterns of muscular activities that underlie hindlimb locomotor movements in the acute thalamic rat. Electromyographic activities of muscles representative of the functional muscle groups of the hindlimbs were recorded bipolarly during locomotion in acute thalamic rats. Locomotor movements occurred spontaneously, but could also be induced by electrical stimulation (0. 1 ms pulses; 30–70 Hz; 75–300 μA) of the lateral hypothalamic area. The two hindlimbs displayed a wide variety of coordination patterns during both types of locomotion. However, alternated coordination of the hindlimbs occurred more frequently during induced than during spontaneous locomotion. Correspondingly, the duration of the spontaneous step cycles had a tendency to be shorter than that of the evoked step cycles, although they had a quite similar range. The patterns of muscular activities within one hindlimb were similar during spontaneous and induced locomotion. During each step cycle, (i) the hip and ankle flexors usually displayed a single burst in alternation with that displayed by the hip, knee and ankle extensors, (ii) a double bursting pattern was sometimes observed in flexors during fast locomotor movements, (iii) within flexors and extensors, muscles were recruited sequentially, and (iv) the activation of other muscles (semitendinosus, rectus femoris, extensor and flexor digitorum longus) consisted of single or double bursting patterns.
Early Development of Olivocerebellar Projections in the Fetal Rat Using CGRP Immunocytochemistry
Authors: Chedotal Alain , Sotelo Constantino
Published: April 2006

The expression of calcitonin gene‐related peptide (CGRP) immunoreactivity in certain inferior olivary neurons is transient and developmentally regulated. Labelled neurons begin to appear at embryonic day 16 (E16), and reach their maximal extent by postnatal day 2 (P2). The extinction of the labelling occurs between P13 and P16. Expression of CGRP immunoreactivity is also observed in a few cerebellar fibres from E17, when axons in the restiform bundle begin to enter medially the cerebellar parenchyma. Their maximal extent is reached by P6, and thereafter they slowly disappear following a precise pattern, although fibre extinction is not complete. The spatio‐temporal changes in the olivary distribution of the labelled neurons and the changes in the cerebellar labelled fibres follow the known pattern of topographic arrangement of the olivocerebellar system in adult rats. Moreover, the developmental phases of the CGRP‐labelled fibres in postnatal rats correspond to those known for climbing fibre phenotypic acquisition. Thus, CGRP immunocytochemistry identifies in the fetal rat a subset of inferior olivary neurons and their corresponding cerebellar climbing fibres. Using this approach, we have analysed some of the initial events leading to the formation of the olivocerebellar projection, and obtained the following information: (i) Olivocerebellar axons are not randomly distributed in the restiform bundle before they enter the cerebellum. (ii) In the presence of a large spectrum of choices at the surface of the rostral half of the cerebellar plate the labelled olivary axons begin to enter the cerebellum at a precise medial point to abut a region composed solely of migrating Purkinje cells, and establish contacts with their targets before these neurons reach their final cortical location. (iii) From E18 to E19, the bundle of labelled fibres loses its superficial location, being bypassed by migrating Purkinje cells, to occupy a region corresponding to the prospective white matter. This translocation is coincident with the occurrence of a second axonal entry point, somewhat more lateral than the previous one, and with the appearance of a new lateral stripe of labelled fibres. (iv) Both the early and the late appearing labelled stripes remain confined from the time of their formation in precise cerebellar territories, indicating that only some clusters of Purkinje cells are contacted by the CGRP fibres. The results obtained imply that there is neither a waiting period nor an initial phase of randomness in the formation of the olivocerebellar projection map. This absence of chaotic cerebellar invasion, and the high selectivity of the entry points, suggest that the orientation of CGRP‐positive olivocerebellar fibres towards their targets is regulated by positional information shared between subsets of olivary neurons and clusters of Purkinje cells. The result of this process would be the formation of a precocious coarse topography that would need further refinement.
Long‐term Potentiation and Field EPSPs in the Lateral and Medial Perforant Paths in the Dentate Gyrus In Vitro: a Comparison
Authors: Hanse Eric , Gustafsson Bengt
Published: April 2006

The entorhinal cortex projects monosynaptically to the granule cells in the dentate gyrus via the lateral and medial perforant paths. These two subdivisions of the perforant path differ with respect to synaptic properties, and recent studies suggest that they also differ with respect to long‐term potentiation (LTP). In the present study, using the in vitro slice preparation of the guinea‐pig hippocampus, field excitatory postsynaptic potentials (EPSPs) and LTP in the lateral and medial perforant paths were compared. The two pathways were distinguished on the basis of their different termination in the dendritic layer, their different pharmacology and short‐term synaptic facilitation. The field EPSP [obtained in the presence of γ‐aminobutyric acid (GABA) A and B receptor antagonists] consisted of a non‐N‐methyl‐d‐aspartate (NMDA) component with different time characteristics in the two pathways, the decay being monoexponential in the lateral perforant path and biexponential in the medial one. In addition, the field EPSP in both pathways contained a small NMDA‐mediated component that could also be observed after complete blockade of the non‐NMDA one. LTP induction in both lateral and medial perforant paths was facilitated by blockade of GABAA inhibition, showed associative properties, and was blocked by NMDA receptor antagonists. Following the induction event, LTP in both pathways developed to a peak value within 30–40 s, and the stability of LTP was correlated with the amount of postsynaptic, but not presynaptic, activity during the induction event. During blockade of GABAA inhibition the opioid receptor antagonist naloxone and the β‐adrenergic antagonist timolol had no effect on the magnitude or stability of LTP. It is concluded that LTP in the lateral and medial perforant paths does not differ with respect to induction mechanisms and early temporal characteristics.
The Effect of Apomorphine and Buspirone on Regional Cerebral Blood Flow During the Performance of a Cognitive Task—Measuring Neuromodulatory Effects of Psychotropic Drugs in Man
Authors: Grasby P. M. , Friston K. J. , Bench C. J. , Frith C. D. , Paulesu E. , Cowen P. J. , Liddle P. F. , Frackowiak R. S. J. , Dolan R.
Published: April 2006

Psychopharmacological activation, in conjunction with positron emission tomographic measurements of regional cerebral blood flow (rCBF), was used to investigate the neurotransmitter basis of a specific cognitive function in man. Monoaminergic neurotransmission was pharmacologically manipulated during performance of auditory – verbal memory tasks. Statistical parametric mapping was used to identify the brain sites of interaction between memory‐induced increases in rCBF and active drugs. Memory task‐induced increases in rCBF in the left prefrontal cortex were attenuated by apomorphine, a non‐selective dopamine agonist, whilst buspirone, a serotonin1A partial agonist, augmented rCBF increases in this area. In addition, apomorphine and buspirone augmented memory‐induced increases in rCBF centred in the posterior cingulate cortex, whilst buspirone alone attenuated rCBF increases in the retrosplenial cortex and posterior parahippocampal gyrus. These regionally selective interactions may represent neuromodulatory effects of monoaminergic neurotransmission on a specific cognitive function in man.
The Effect of Removing Superior Temporal Cortical Motion Areas in the Macaque Monkey: I. Motion Discrimination Using Simple Dots
Authors: Cowey Alan , Marcar Valentine L.
Published: April 2006

We compared the pre‐ and postoperative performance of macaque monkeys on visual discrimination tasks entailing the perception of differences in the motion of two luminous spots. Animals in which area MT and adjacent regions had been surgically removed were not significantly impaired as long as there were differences in the temporal frequency of the two stimuli. When the latter were eliminated the postoperative performance of the MT animals was significantly impaired compared to their preoperative performance and compared to the animals in the control groups. The same animals were also impaired at perceiving which of two moving dots, presented in the dark, changed its direction.
The Effect of Removing Superior Temporal Cortical Motion Areas in the Macaque Monkey: II. Motion Discrimination Using Random Dot Displays
Authors: Marcar Valentine L. , Cowey Alan
Published: April 2006

Nine macaque monkeys were trained to discriminate between a display in which all the dots moved randomly (visual dynamic noise) and an adjacent display in which a proportion of the dots oscillated coherently from side to side. Two monkeys in which area MT (middle temporal visual area) and adjacent regions were surgically removed were unable to perform even the simplest version of this task where the coherent motion was not masked by any visual dynamic noise. The other seven animals tolerated between 60% and 65% of random movement in the otherwise coherently oscillating display before they failed to discriminate between the two displays. In contrast, shape discrimination tasks containing luminance boundaries were unaffected by the removal of area MT. However, the removal of area MT did impair the animals' ability to use a kinetic boundary as the basis for shape discrimination. Their performance with a kinetic boundary between a moving and a stationary random dot field and a kinetic boundary between two random dot fields moving in opposite directions was the most severely impaired. Their performance with a kinetic boundary defined by two random dot fields moving orthogonally to each other was unimpaired. None of the animals from either group was able to use the kinetic boundary defined by coherent motion and visual dynamic noise as the basis for shape discrimination. The ease with which the control animals were able to employ the different types of kinetic boundaries to perform the shape discrimination reflected previously published proportions of cells in area MT that are specialized for detecting the different types of kinetic boundaries.
Spontaneous Gaze Shifts in Intact Head‐free Rats and Following Inferior Olive and Cerebellar Lesions
Authors: Tempia Filippo , Ghirardi Mirella , Dotta Michele , Strata Piergiorgio
Published: April 2006

Recent experiments have shown that after lesions of the inferior olive or of the flocculus and paraflocculus of the cerebellum, in the pigmented rat, spontaneous saccades made when the head is completely restrained are followed by a large postsaccadic drift. The aims of the present paper were to study (i) the strategies and the characteristics of spontaneous eye – head coordinated gaze shifts in intact pigmented rats and to compare them with those described in other mammals, (ii) how they are affected by inferior olive and flocculus – paraflocculus lesions, and (iii) whether in these groups of animals the stability of the gaze is more deficient when the head is free to rotate in the horizontal plane (head‐free condition) relative to the head‐fixed condition. Three types of gaze shift strategy of intact rats are described and characterized. Following inferior olive or flocculus – paraflocculus lesion the dynamic parameters of such gaze shifts (the main sequences of head, gaze and eye and the timing of eye and head movement onset) are not significantly affected. The main deficits of lesioned animals affect the stability of gaze at the end of gaze shifts. After inferior olive lesion the amplitude of the postsaccadic drift of the gaze is 43.2% of the gaze saccade in the head‐fixed condition, which is reduced to 22.9% in the head‐free condition. Following flocculus – paraflocculus lesion the postsaccadic drift of gaze is even more reduced than after inferior olive lesion, changing from 39.2% in the head‐fixed condition to only 9.7% in the head‐free condition.
Tunicamycin Dissociates Depolarization‐induced Calcium Entry From Transmitter Release. Involvement of Glycosylated Protein(s) in the Process of Neurosecretion in PC‐12 Cells
Authors: Schwartz Lydia , Diamant Sophia , Barhanin Jacques , Atlas Daphne
Published: April 2006

The process of regulated secretion in PC‐12 cells is tightly coupled to calcium entry, which is absolutely dependent on extracellular Ca2+([Ca2+]ex). Tunicamycin treatment of the cells dissociated depolarization‐triggered Ca2+ influx from depolarization (high K+)‐induced transmitter release into two distinct and independent phases. Deplarization‐evoked Ca2+ influx was not affected by tunicamycin treatment (1 μg/ml, 72 h), whereas depolarization‐evoked transmitter release was strongly inhibited (>60%), suggesting at least a two‐step process, and the participation of glycosylated protein(s) in the actual fusion/secretion step. Similarly, bradykinin‐mediated transmitter release was linearly related to and absolutely dependent on Ca2+ entry, and was inhibited by tunicamycin treatment (>80%), whereas bradykinin‐evoked Ca2+ entry was not impaired, indicating that glycosylated protein(s) are essential for bradykinin‐evoked release at a step subsequent to Ca2+ influx. The heavily glycosylated α2 subunit of the dihydropyridine‐sensitive channel, which was used to monitor tunicamycin inhibition of glycosylation, was not expressed in the tunicamycin‐treated cells, as shown by Western blot analysis. This observation allowed us to conclude that the a, subunit of the heteromeric dihydropyridine voltage‐sensitive Ca2+ channel, which is responsible for Ca2+ entry, is also fully functional when not assembled with its corresponding α2 subunit. The molecular properties of the α2 subunit, whose role in the complex structure of the channel is not yet understood, are shown for the first time for the L‐type Ca2+ channel of PC‐12 cells. Similar to cardiac and skeletal muscle cells, the α2 subunit appears to be a glycosylated polypeptide of molecular weight 170 kD and to display a characteristic mobility shift to 140 kD under reducing conditions.
Kynurenic Acid in the Quinolinate‐lesioned Rat Hippocampus: Studies In Vitro and In Vivo
Authors: Wu Hui‐Qiu , Baran Halina , Ungerstedt Urban , Schwarcz Robert
Published: April 2006

The present study was designed to examine the cellular localization and biosynthetic machinery of the broad‐spectrum excitatory amino acid receptor antagonist kynurenic acid in the lesioned rat hippocampus. Seven days after an intrahippocampal injection of 120 nmol quinolinic acid, which causes massive neurodegeneration in the dorsal hippocampus, kynurenic acid tissue levels and the activity of kynurenic acid's anabolic enzyme, kynurenine aminotransferase, were increased by 92% and 67%, respectively, as compared to controls. The steady‐state levels of extracellular kynurenic acid, examined by microdialysis in unanaesthetized rats, were also increased in the lesioned tissue (from 93.6 ± 10.2 to 207.6 ± 18.6 fmol/30 μl dialysate). Using microdialysis, three compounds which are known to decrease kynurenic acid production from its bioprecursor l‐kynurenine in brain slices and in vivo were tested for their ability to reduce the levels of endogenous kynurenic acid. In unlesioned tissue, aminooxyacetic acid (300 μM), veratridine (50 μM) and glutamate (5 mM), all administered through the dialysis probe, decreased extracellular kynurenic acid concentrations by 30 – 40%, i.e. to a lesser degree than in previous experiments in which kynurenine was used as a bioprecursor. Only the effect of veratridine was abolished in the quinolinate‐lesioned hippocampus. These data indicate that kynurenic acid is produced in and liberated from astrocytes, and that aminooxyacetic acid and glutamate (but not veratridine) exert their action by directly affecting glial kynurenic acid biosynthesis. The results also suggest the existence of two distinct intracellular kynurenic acid pools, which are responsible for kynurenic acid storage and rapid kynurenic acid mobilization, respectively. Taken together, these features of kynurenic acid neurobiology may be of relevance in the control of excitatory amino acid receptor function under physiological and pathological conditions.
Excitatory Amino Acid Pathway from the Hippocampus to the Prefrontal Cortex. Contribution of AMPA Receptors in Hippocampo‐prefrontal Cortex Transmission
Authors: Jay Thérèse M. , Thierry Anne‐Marie , Wiklund Leif , Glowinski Jacques
Published: April 2006

Previous experiments in the rat have demonstrated that field CA1 and the subiculum project to the prefrontal cortex and that this direct unilateral pathway is excitatory. In the present study, anatomical and electrophysiological approaches were used to determine the transmitter mediating the excitatory responses in prefrontal cortex neurons to low‐frequency stimulation of the hippocampus. The method of selective retrograde d‐[3H]aspartate labelling was used to identify putative glutamatergic and/or aspartatergic hippocampal afferent fibres to the prefrontal cortex. Unilateral microinjection of d‐[3H]aspartate into the prelimbic area of the prefrontal cortex resulted in the retrograde labelling of a fraction of hippocampal neurons. Some labelled cell bodies were distributed in field CA1 and the subiculum but larger numbers of neurons were detected in the ventral and intermediary subiculum. In a second series of experiments, the excitatory transmission from the hippocampus to the prefrontal cortex was pharmacologically analysed to provide further evidence for the involvement of glutamate and/or aspartate in the pathway. All prefrontal cortex neurons responding to the stimulation of the hippocampus were activated by selective agonists of the glutamate receptor subtypes α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid (AMPA) and N‐methyl‐d‐aspartate (NMDA), and these effects were selectively antagonized by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and 2‐amino‐5‐phosphonopentanoic acid (APV) respectively. Most of the excitatory responses of prefrontal cortex neurons to single and paired‐pulse stimulation of the hippocampus were antagonized by CNQX. APV only affected the excitatory response in a few cells. These results suggest that the hippocampal input to the prefrontal cortex utilizes glutamate and/or aspartate as a transmitter. Even though prefrontal cortex neurons responding to the stimulation of the hippocampus appear to have both AMPA and NMDA receptors, low‐frequency stimulation of the hippocampo‐prefrontal cortex pathway activates cortical neurons mostly through AMPA receptors.
Inferotemporal‐frontal Disconnection: The Uncinate Fascicle and Visual Associative Learning in Monkeys
Authors: Eacott M. J. , Gaffan David
Published: April 2006

We report a series of six experiments in which we examined the behavioural effects of disconnecting the inferior temporal cortex from the prefrontal cortex in cynomolgus monkeys by sectioning the direct cortico‐cortical pathway between them, the uncinate fascicle. In experiment 1, monkeys with bilateral section of the uncinate fascicle showed a marked deficit in learning visuomotor conditional problems. Experiments 2 and 3 demonstrated that this deficit was not the result of a mild motor impairment, nor of a visual discrimination impairment. However, experiment 4 showed that the impairment extended to visual – visual conditional learning. In contrast, following bilateral section of the uncinate fascicle monkeys were unimpaired at two other tasks of visual associative learning: a reward – visual associative task (experiment 5), in which the presence or absence of a food reward served as a cue to the correct choice between two visual stimuli, and a time – visual associative task (experiment 6), in which the cue to the correct choice was the length of the intertrial interval. Thus, animals with uncinate fascicle section showed no impairment in learning to choose between visual stimuli based on their differential association with food reward or other non‐visual cues, but were unable to learn to choose between visual stimuli based on their differential association with another visual stimulus. They were equally unable to choose between two motor responses on the basis of the visual cue.
Post‐crucial Period Effects of Auditory Experience and Deprivation on the Guinea‐pig Superior Collicular Map of Auditory Space
Authors: Binns K. E. , Withington D. J. , Keating M. J.
Published: April 2006

The auditory space map in the superior colliculus of the guinea‐pig requires for its normal emergence at 32 days after birth (DAB) bimodal, auditory and visual experience during a 4‐day crucial period (26–30 DAB) (Withington‐Wray et al., Neurosci. Lett., 116, 280–286, 1990d). The need for auditory experience has been proposed to be linked to the rapid changes in the cues for auditory localization brought about by head growth. Head growth is particularly rapid during the first postnatal month but continues more slowly until ∼70 DAB. This suggests that sensory experience may be required beyond the initial crucial period to accommodate later growth. In this paper the role of auditory experience beyond the crucial period has been investigated. Deprivation of ordinary auditory experience was effected by placement of the animals in an environment in which continuous omnidirectional noise obscured the cues of sound direction. Animals deprived of auditory experience during the crucial period and then allowed normal experience showed limited ability to construct an auditory space map and the resulting map was less accurate than that found in normally reared animals. Auditory deprivation following normal experience during the crucial period caused a profound degradation, of both spatial tuning and topography, of auditory multi‐unit receptive fields in the superior colliculus. The spatial tuning and topography of auditory fields from older animals (100 DAB) deprived of ordinary auditory cues for a 4‐week period were normal. Thus, in the guinea‐pig, susceptibility of the superior collicular space map to deprivation of auditory cues is limited by the age of the animal. The timing of the cessation of vulnerability may, in part, be due to the stabilization of directional cues affected by head growth.
The Somatotopic Organization Within the Rabbit's Thalamic Reticular Nucleus
Authors: Crabtree John W.
Published: April 2006

The organization of the somatosensory representation within the rabbit's thalamic reticular nucleus (TRN) was studied. Focal injections of horseradish peroxidase (HRP), wheatgerm agglutinin conjugated to HRP, or [3H]proline were made into somatosensory cortical area 1 (S1). The resultant labelling in the thalamus was analysed. Single injections into S1 result in single zones of terminal labelling in TRN that are restricted to the centroventral part of the sheet‐like nucleus. In reconstructions from horizontal sections these zones of labelling resemble ‘slabs’, which lie in the plane of the nucleus parallel to its borders, occupy only a fraction of the thickness of the reticular sheet, and are elongated in the dorsoventral and oblique rostrocaudal dimensions. Thus, the slabs of S1 terminals, which represent various loci of the body surface, and the main distribution of the reticular dendrites have a similar orientation. In comparisons of the zones of labelling following single or double injections at different cortical sites in S1, an inner (medial) to outer (lateral) shift in labelling in the ventrobasal complex (VB) is accompanied by an inner (medial) to outer (lateral) shift in labelling along the thickness of the reticular sheet; a rostral to caudal shift in labelling in VB is accompanied by a rostral to caudal shift in labelling along the plane of the reticular sheet. Thus, like VB, the reticular nucleus receives a topographically accurate projection from S1. Further, the somatotopic map conveyed from S1 to TRN lies perpendicular to the plane of the nucleus and repeats the spatial organization of the map in VB. These findings, together with those for the visual sector of the rabbit's TRN, indicate that the representation of the cortical sheet is broken up into significant parcels at the inner and outer borders of the reticular sheet.
The Somatotopic Organization Within the Cat's Thalamic Reticular Nucleus
Authors: Crabtree John W.
Published: April 2006

The organization of the somatosensory representation within the cat's thalamic reticular nucleus (TRN) was studied. Focal injections of horseradish peroxidase (HRP), wheatgerm agglutinin conjugated to HRP, and/or [3H]proline were made into somatosensory cortical areas 1 (S1) and 2 (S2). The resultant labelling in the thalamus was analysed. Single injections into S1 result in single zones of terminal labelling in TRN that are restricted to the centroventral part of the sheet‐like nucleus. In reconstructions from horizontal sections these zones of labelling resemble thin ‘slabs’, which lie in the plane of the nucleus parallel to its borders, occupy only a fraction of the thickness of the reticular sheet, and are broadly elongated in the dorsoventral and oblique rostrocaudal dimensions. Thus, the slabs of S1 terminals, which represent large loci of the body surface, and the main distribution of the reticular dendrites have a similar orientation. In comparisons of the zones of labelling following single or double injections at different cortical sites in S1, an inner (medial) to outer (lateral) shift in labelling in the ventrobasal complex (VB) is accompanied by an inner (medial) to outer (lateral) shift in labelling along the thickness of the reticular sheet. Thus, like VB the reticular nucleus receives a topographically accurate projection from S1. Further, the somatotopic map conveyed from S1 to TRN is orientated perpendicular to the plane of the nucleus and repeats the spatial organization of the map in VB. S2 injections result in zones of terminal labelling in that part of TRN that receives S1 inputs. On the basis of these findings, together with those in other mammalian species, two conclusions can be reached about corticoreticular relations. First, although there can be continuity in individual maps of cortical inputs to TRN, there are discontinuities in cortical representations at the inner and outer borders of the reticular sheet. Second, TRN can receive a significant convergence of inputs from different cortical areas.