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Feeding ecology of organisms associated with floating Sargassum in the northwestern Gulf of Mexico was assessed using fatty acids. Nineteen groups were collected from the Sargassum community including four autotrophs, eight invertebrates, five juvenile fishes, and two adult fishes. Spatial and temporal variability in polyunsaturated fatty acid (PUFA) signatures of selected taxa (Sargassum fluitans [autotroph], Leander tenuicornis [primary heterotroph], Balistes capriscus [secondary heterotroph]) was examined to quantify natural variation within these dietary tracers. Although PUFA signatures varied seasonally for all three taxa, no differences were detected between samples collected in year 2000 and 2001 or from different sample locations in the northwest Gulf. PUFA signatures made up 16.3–62.3% of the total fatty acid composition of main autotrophs present in the pelagic environment [particulate organic matter (POM), epiphytic algae, S. fluitans, S. natans], and PUFA profiles of selected primary producers were distinct. Specifically, levels of 20:5n−3, 22:5n−3, and 22:6n−3 were significantly higher in POM than Sargassum spp. or epiphytic algae (Cladophora sp.). Dominant PUFA in the tissue of invertebrate and vertebrate consumers were 18:2n−6, 20:4n−6, 20:5n−3, 22:5n−3, 22:6n−3 and multivariate analyses indicated that PUFA signatures of all consumers were highly similar to POM. As a result, heterotrophs utilizing the Sargassum complex may rely heavily on phytoplankton production rather than production by Sargassum or associated epiphytic algae.

The local synaptic connectivity in the superficial gray layer of the superior colliculus (SC) was assessed following retinal ganglion cell axonal regeneration through a peripheral nerve graft into the SC of Lister Hooded rats, using in vitro brain slice techniques. Repair was effected between the ipsilateral eye and SC, following bilateral lesion of optic nerves and ablation of ipsilateral occipital cortex. Deafferentation surgery alone resulted in a complete loss of synaptic potentials of extrinsic origin, once both retinal and cortical inputs were removed. Stimulation of graft insertion sites elicited synaptic responses comprising monosynaptic and network-mediated depolarising events. This activity, together with similar spontaneous bursts of depolarising events and action potential firing, was generated by the activation of non-N-methyl-D-aspartate glutamate receptors. This behaviour may reflect the development of a local recurrent synaptic connectivity following the repair surgery, as both evoked and spontaneous responses developed into large long-lasting bursts of excitatory activity when inhibition mediated by GABA receptors was blocked. These results suggest that the ultrastructural changes in the superficial layers of the SC resulting from deafferentation are reflected functionally at the synaptic level in the target structure even after repair. Such changes are likely to compromise the ability of the target structure to function normally during information processing. Therefore, although axons regenerating along peripheral nerve grafts can make functional synaptic connections, their efficacy in activating the target structure will probably be compromised by local changes in synaptic connectivity.

Kainate receptors have been studied extensively in vitro, but how they might function physiologically remains unclear. We studied kainate receptor modulation of synaptic responses in the rat ventrobasal thalamus using the novel antagonist LY382884 and the agonist ATPA (selective for GluR5-containing kainate receptors) as tools. No evidence could be found for a direct contribution of kainate receptors to responses of thalamic relay cells to lemniscal (sensory) input in thalamic slices studied with the aid of intracellular and field potential recordings, using selective AMPA and NMDA receptor antagonists and LY382884. However, the GluR5 agonist ATPA reduced the IPSPs originating from the thalamic reticular nucleus. Extracellular single-neurone recordings in anaesthetised rats showed that excitatory responses evoked by physiological vibrissa afferent stimulation were reduced by LY382884 applied iontophoretically at the recording site. This action of the antagonist was occluded when GABA receptors were blocked, indicating that the reduction in excitatory sensory responses by LY382884 is due to an action on GABAergic inhibition arising from the thalamic reticular nucleus. Further experiments showed that these actions depended on whether inhibition was evoked during activation of the excitatory receptive field rather than when inhibition was evoked from a surround vibrissa. We suggest that GluR5 is located presynaptically on inhibitory GABAergic terminals of thalamic reticular nucleus neurones, and that it is normally activated by glutamate spillover from synapses between excitatory afferents and relay neurones during physiological stimulation. We propose that this GluR5-activated disinhibition has an important novel role in extracting sensory information from background noise.

In this review, we summarize three sets of findings that have recently been observed in thalamic astrocytes and neurons, and discuss their significance for thalamocortical loop dynamics. (i) A physiologically relevant ‘window’ component of the low–voltage–activated, T–type Ca 2+ current ( I Twindow ) plays an essential part in the slow (less than 1 Hz) sleep oscillation in adult thalamocortical (TC) neurons, indicating that the expression of this fundamental sleep rhythm in these neurons is not a simple reflection of cortical network activity. It is also likely that I Twindow underlies one of the cellular mechanisms enabling TC neurons to produce burst firing in response to novel sensory stimuli. (ii) Both electrophysiological and dye–injection experiments support the existence of gap junction–mediated coupling among young and adult TC neurons. This finding indicates that electrical coupling–mediated synchronization might be implicated in the high and low frequency oscillatory activities expressed by this type of thalamic neuron. (iii) Spontaneous intracellular Ca 2+ ([Ca 2+ ] i ) waves propagating among thalamic astrocytes are able to elicit large and long–lasting N –methyl–D–aspartate–mediated currents in TC neurons. The peculiar developmental profile within the first two postnatal weeks of these astrocytic [Ca 2+ ] i transients and the selective activation of these glutamate receptors point to a role for this astrocyte–to–neuron signalling mechanism in the topographic wiring of the thalamocortical loop. As some of these novel cellular and intracellular properties are not restricted to thalamic astrocytes and neurons, their significance may well apply to (patho)physiological functions of glial and neuronal elements in other brain areas.

Group I metabotropic glutamate receptors (mGluRs) are expressed in cells in the superficial layers of the rat superior colliculus (SSC) and SSC afferents. The purpose of this study was to investigate the physiological effect of Group I mGluR activation on visual responses of SSC neurones using both in vivo and in vitro techniques. In the in vivo preparation, agonists and antagonists were applied by iontophoresis and single neurone activity was recorded extracellularly in anaesthetised rats. Application of the Group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) resulted in a reversible inhibition of the visual response. The effect of DHPG could be blocked by concurrent application of the Group I (mGluR1/mGluR5) antagonist (S)-4-carboxyphenylglycine (4CPG) or mGluR1 antagonist (+)-2-methyl-4-carboxyphenylglycine (LY367385). Application of 4CPG alone resulted in a facilitation of the visual response and this effect was not changed when the visual stimulus contrast was varied. Response habituation was observed when visual stimuli were presented at 0.5 s intervals, but this was not affected by DHPG or 4CPG. In slices of the superior colliculus, stimulation of the optic tract resulted in a field EPSP recorded from the SSC whose duration was increased in the presence of the GABA antagonists picrotoxin and CGP55845. Application of DHPG (5-100 microM) reduced the field EPSP, and this effect could be reversed by the mGluR1 antagonist LY367385 (200 microM), but not by the mGluR5 antagonist MPEP (5 microM). These data show that activation of mGluR1, but probably not mGluR5, can modulate visual responses of SSC neurones in vivo, and that this could be via presynaptic inhibition of glutamate release from either retinal or, possibly, cortical afferents.

1 Using an in vitro slice preparation of the rat dorsal lateral geniculate nucleus (dLGN), the properties of retinogeniculate and corticothalamic inputs to thalamocortical (TC) neurones were examined in the absence of GABAergic inhibition. 2 The retinogeniculate EPSP evoked at low frequency ( 150 %. This frequency-dependent depression of the retinogeniculate EPSP was maximal after the second stimulus, while the frequency-dependent facilitation of the corticothalamic EPSP was maximal after the fourth or fifth stimulus, at interstimulus frequencies of 1-10 Hz. 4 There was a short-term enhancement of the

The action of ethosuximide (ETX) on Na+, K+, and Ca2+currents and on tonic and burst-firing patterns was investigated in rat and cat thalamic neuronsin vitroby using patch and sharp microelectrode recordings. In thalamocortical (TC) neurons of the rat dorsal lateral geniculate nucleus (LGN), ETX (0.75–1 mm) decreased the noninactivating Na+current,INaP, by 60% but had no effect on the transient Na+current. In TC neurons of the rat and cat LGN, the whole-cell transient outward current was not affected by ETX (up to 1 mm), but the sustained outward current was decreased by 39% at 20 mV in the presence of ETX (0.25–0.5 mm): this reduction was not observed in a low Ca2+(0.5 mm) and high Mg2+(8 mm) medium or in the presence of Ni2+(1 mm) and Cd2+(100 μm). In addition, ETX (up to 1 mm) had no effect on the low-threshold Ca2+current,IT, of TC neurons of the rat ventrobasal (VB) thalamus and LGN and in neurons of the rat nucleus reticularis thalami nor on the high-threshold Ca2+current in TC neurons of the rat LGN.Sharp microelectrode recordings in TC neurons of the rat and cat LGN and VB showed that ETX did not change the resting membrane potential but increased the apparent input resistance at potentials greater than −60 mV, resulting in an increase in tonic firing. In contrast, ETX decreased the number of action potentials in the burst evoked by a low-threshold Ca2+potential. The frequency of the remaining action potentials in a burst also was decreased, whereas the latency of the first action potential was increased. Similar effects were observed on the burst firing evoked during intrinsic δ oscillations.These results indicate an action of ETX onINaPand on the Ca2+-activated K+current, which explains the decrease in burst firing and the increase in tonic firing, and, together with the lack of action on low- and high-threshold Ca2+currents, the results cast doubts on the hypothesis that a reduction ofITin thalamic neurons underlies the therapeutic action of this anti-absence medicine.

Recordings were made from single neurones responsive to somatosensory input in the ventrobasal thalamus of the anaesthetised rat. GABAergic afferent inhibition arising from the thalamic reticular nucleus was evoked using a condition-test vibrissal stimulation paradigm. Local iontophoretic application of the group II metabotropic glutamate receptor (mGluR) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) in the vicinity of the recorded neurones produced a reduction of the afferent inhibition (from 78+/-3.0% to 25+/-5.3%), presumably via a presynaptic mechanism. This effect could be antagonised by LY307452, a known group II mGluR antagonist. In contrast, two selective group I mGluR agonists, (S)-3,5-dihydroxyphenylglycine (DHPG) and trans-azetidine-2,4-dicarboxylate (tADA), were without effect on the GABAergic inhibition. These data show that group II but not group I mGluRs can have a significant role in the modulation of GABAergic afferent inhibition in the ventrobasal thalamus. This could be of importance in the control of sensory discriminative processes and functions of sleep, arousal and seizure generation.

Previous work has shown that responses of thalamic neurons in vivo to the metabotropic glutamate receptor agonists 1S,3R-aminocyclopentane-1,3-dicarboxylate and S-3,5-dihydroxyphenylglycine can be reduced by a variety of phenylglycine antagonists. Responses of thalamic neurons to noxious thermal somatosensory stimuli were reduced in parallel by these antagonists, indicating that these responses are mediated by Group I metabotropic glutamate receptors (i.e. metabotropic glutamate receptor-1 and/or metabotropic glutamate receptor-5), which are known to be linked to phosphoinositol phosphate hydrolysis. The recent development of S-2-methyl-4-carboxyphenylglycine as an antagonist which is highly selective for metabotropic glutamate receptor-1 compared to metabotropic glutamate receptor-5 on human receptors expressed in AV-12 cells, now offers the possibility of discriminating between these two receptor subtypes in order to distinguish which is involved in thalamic responses. We have made recordings from single somatosensory neurons in the thalamus of the rat, and find that S-2-methyl-4-carboxy-phenylglycine is able to reduce responses of neurons to 1S,3R-aminocyclopentane-1,3-dicarboxylate, S-3,5-dihydroxyphenylglycine, and noxious stimuli without significant effect on responses to either N-methyl-D-aspartate or (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. These results suggest that excitatory responses of thalamic neurons to 1S,3R-aminocyclopentane-1,3-dicarboxylate and S-3,5-dihydroxyphenylglycine may be mediated by metabotropic glutamate receptor-1. Furthermore, the reduction of nociceptive responses by S-2-methyl-4-carboxy-phenylglycine indicates that metabotropic glutamate receptor-1 is involved in thalamic nociceptive processing and that such antagonists may have analgesic properties.

The development of membrane properties, firing patterns, and δ oscillations in neurons of the cat dorsal lateral geniculate nucleus (dLGN) was investigatedin vitroduring the first 7 postnatal weeks. Compared with adult neurons, the resting membrane potential was more depolarized at postnatal days 1–9 (P1–P9), the input resistance was higher at P1–P7, and action potentials had a higher threshold and a smaller amplitude at P1–P3 and a longer duration at P1–P9. At P1–P3 trains longer than 200 msec were rarely observed, and trains with more than three action potentials were only present in 41% of the neurons, whereas at P1–P7 the normalized slope of the instantaneous frequencies at the first five interspike intervals was smaller than in the adult. A long-lasting (up to 6 sec) afterhyperpolarization followed a short train of action potentials in 88 and 30% of neurons at P1–P3 and P30–P32, respectively, but it was rarely observed in the adult. The low-threshold Ca2+potential could evoke a burst of action potentials since P1. However, at P1–P7 the number of action potentials per burst was smaller (range, one to five), and at P1–P9 their maximum instantaneous frequency was lower (

We evaluated the cross-sensor compatibilities of the normalized difference vegetation index (NDVI) across the Visible/Infrared Imager/Radiometer Suite (VIIRS), Moderate Resolution Imaging Spectroradiometer (MODIS), and the National Oceanic and Atmospheric Administration (NOAA)-14 and NOAA-19 Advanced Very High Resolution Radiometer (AVHRR) (AVHRR/2 and AVHRR/3) bandpasses using a global set of Earth Observing One Hyperion hyperspectral data. Five levels of atmospheric correction were simulated to examine the impact of the atmosphere on intersensor NDVI compatibility. These were the uncorrected 'top-of-atmosphere'; Rayleigh (RAY); Rayleigh and ozone (RO); Rayleigh, ozone, and water vapor (ROW); and total atmosphere-corrected 'top-of-canopy (TOC)' reflectances. Among all possible sensor pairs examined, the highest compatibility was observed for VIIRS versus MODIS. Cross-sensor NDVI relationships between the two sensor bandpasses remained nearly the same throughout all levels of atmospheric correction. AVHRR/3-versus-AVHRR/2 NDVI relationships changed very little and also showed an equivalent level of compatibility to VIIRS versus MODIS across all levels of atmospheric correction although they were subject to systematic differences. Intersensor NDVI compatibilities of VIIRS and MODIS to AVHRR/2 and to AVHRR/3 were lower due primarily to the differential sensitivities of these sensors' near-infrared bands to the atmospheric water vapor effects. Comparisons of cross-sensor NDVI compatibilities where operational atmospheric correction schemes were assumed for each of the sensors suggest the need of VIIRS TOC NDVI for long-term continuity with MODIS and AVHRR, which is not currently produced as part of the standard VIIRS Vegetation Index Environmental Data Record. © 2012 IEEE.

The presence and role of presynaptic GABA(B) receptors in the control of excitatory amino acid-medicated transmission were investigated (using sharp electrode recordings) in the rat dorsal lateral geniculate nucleus and ventrobasal thalamus in vitro by comparing the effects of the selective GABA(B) receptor agonist, (+ or -)-baclofen, and of two antagonists, CGP 35348 and 2-hydroxy-saclofen, on the excitatory postsynaptic potentials evoked in thalamocortical neurons by stimulation of the sensory afferents. Application of CGP 35348 alone blocked the GABA(B) receptor-mediated inhibitory postsynaptic potential evoked in the dorsal lateral geniculate nucleus by stimulation of the optic tract (n = 5), but had no effect on the resting membrane potential and input resistance of thalamocortical cells (n = 6). In contrast, 2-hydroxy-saclofen caused a hyperpolarization (6.9 + or - 0.5 mV, n = 10) and a decrease in the apparent input resistance (26.3 + or - 2.6%, n = 10). This effect of 2-hydroxy-saclofen was antagonized by CGP 35348. When bicuculline was present in the perfusion medium and following intracellular injection of QX 314, GABA(A) and GABA(B) receptors in the recorded neurons were blocked. Under this condition, application of baclofen decreased the amplitude of the medial lemniscus- and optic tract-evoked excitatory postsynaptic potentials in the two thalamic nuclei investigated. This effect was fully antagonized by CGP 35348 and only partially by 2-hydroxy-saclofen. CGP 35348 alone increased (19.3 + or - 4.3%, n = 5) and 2-hydroxy-saclofen alone decreased (29.9 + or - 8.6%, n = 5) the amplitude of the excitatory postsynaptic potential. This effect of 2-hydroxy-saclofen was not blocked by CGP 35348. These results indicate that presynaptic GABA(B) receptors are present on the terminals of the sensory afferents in the rat dorsal lateral geniculate nucleus and in the ventrobasal thalamus. These receptors are tonically activated by endogenous GABA, at least in vitro, and provide a negative control mechanism by which the excitatory amino acid-mediated transmission within these nuclei can be regulated. In contrast, the endogenous GABA level is not sufficient for a tonic activation of postsynaptic GABA(B) receptors. Furthermore, these results indicate that 2-hydroxy-saclofen acts as a partial agonist on postsynaptic CGP 35348-sensitive GABA(B) receptors, and that, in addition to its antagonist action on presynaptic CGP 35348-sensitive GABA(B) receptors, it also has an effect on either presynaptic, CGP 35348-insensitive GABA(B) receptors and/or another presynaptic receptor type.

The Feulgen reaction has been utilized to localize DNA in nuclei throughout the cycle of mouse duodenal crypt cells using Epon-embedded 1 micron thick sections. The observed changes indicate that the 12.3 h long mitotic cycle of these cells can be subdivided into eleven stages, seven of which take place during the interphase. Computer measurements of Feulgen-stained nuclei and previous radioautographic studies indicate that DNA synthesis begins during stage I and ends during stage IV. The staining pattern shows no distinctive feature in the nuclei of the 1.5 h long stage I. Thereafter, marked changes occur during the rest of the interphase--that is during the 6.3 h that precede karyokinesis and the 3.5 h that follow it. Thus, at stage II the background of the nuclei darkens; at stage III, there appear stained threads interpreted as densifying chromosomes and dots interpreted as chromomeres, both of which thicken from 0.2 to 0.4 micron; at stage IV they further thicken to about 0.5 micron and at stage V, to about 0.7 micron. At this stage, which approximately corresponds to prophase, the intensely stained, discrete dots are localized within the less intensely stained sausage-shaped threads. As the breakup of the nuclear envelope introduces stage VI, whose early part corresponds to prometaphase, the intensely stained dots become close to one another within the threads and eventually fuse. The staining of the threads thus intensifies, and, by the late part of the stage that corresponds to metaphase, they have become the homogeneously dense metaphase chromosomes. At stage VII, the anaphase chromosomes reach each pole where they associate into a compact mass.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Depolarizing responses to DL-2-amino-4-phosphonobutyrate (AP4) and related amino acids have been studied in the rat cerebral cortex slice following the application of quisqualate (Quis). 2. Before exposure to Quis, 500 microM DL-AP4 had little or no effect. However, following a single application of 40 microM Quis for 2 min, DL-AP4 produced depolarizing responses. With repeated applications of DL-AP4, there was a decline in response amplitude. A second application of Quis restored the depolarizing potency of DL-AP4 to a level above that for the first DL-AP4 response after the first Quis application. With a sequence of alternate applications of Quis and DL-AP4, the amplitude of DL-AP4 responses became maximal after the second Quis application. Responses to DL-AP4 could also be induced by the application of 1 microM Quis for 60 min, but were smaller in amplitude. 3. Responses to the normally inactive amino acids L-cysteine (Cys), L-cystathionine (CTN) and L-alpha-aminoadipate (AA) were also induced once Quis was applied. These responses were also maximized after a second application of Quis, except those to L-Cys, which failed to reach a plateau after three Quis applications. 4. The co-application of DL-AP4 with the first Quis application depressed the subsequent mean DL-AP4 response by 47%. Re-application of Quis restored the amplitude of DL-AP4 responses to levels comparable to control. L-alpha-AA also suppressed the induction of DL-AP4 responses, when co-applied with the first Quis exposure, reducing mean response amplitude by 98%. Unlike DL-AP4, however, the effect with L-alpha-AA persisted so that DL-AP4 responses were significantly suppressed compared to control, even after further applications of Quis. 5. The effects of the anion transport blockers, 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 4-acetoamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS) on the induction process and the DL-AP4 responses themselves were examined. DIDS (100 microM) significantly inhibited the DL-AP4 responses, and to a lesser extent the induction of the responses by 40 microM Quis (2 min), while SITS (300 microM) only inhibited the DL-AP4 responses. However, the induction of responses by 1 microM Quis (60 min) was significantly affected by this concentration of SITS. 6. DIDS (100 microM) had no effect on responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA), but selectively potentiated those to Quis. Examination of the full concentration-response curve for Quis revealed that, while the Rmax remained constant, the Hill slope was increased and the EC50 was decreased in the presence of DIDS. SITS (300 microM), however, antagonized responses to AMPA, and had little effect on responses to Quis except at the highest concentration of Quis tested (20 microM), where a potentiation was observed, suggesting that it is a non-NMDA receptor antagonist.7. These observations indicate that the production of depolarizing responses to a number of amino acids, including DL-AP4, in the cerebral cortex is mediated via an anion transport mechanism sensitive to DIDS and SITS, and that the exchange of DL-AP4 for a sequestered excitatory amino acid receptor agonist, probably Quis, could underlie the production of these responses. Indeed, Quis is apparently sequestered via a similar process. However, the involvement of such a process in the induction of these responses remains inconclusive.

Pterins accumulate in the head capsules of horn flies, Haematobia irritans irritans (L.), as a linear function of time and temperature. Pterin concentrations were used to estimate chronological ages and to establish correlations between chronological age and ovarian development and reproductive success in 12 horn fly populations in 1988 and 1989. Male ages were estimated spectrofluorometrically. There were statistically significant differences between years in population age structure measured by pterins. Survival rates estimated from pterin concentration distributions were consistent with a one-parameter exponential model with constant survival rate. Mean daily survival rates were 0.81 for females and 0.84 for males in 1988 and 0.66 and 0.75 in 1989. Mean lifetime egg production was approximately 26 eggs per female in 1988 and 8 in 1989. Female reproductive success was close to the maximum possible, i.e., there were no net delays in oviposition. Analysis of gonotrophic age distributions provided survival estimates that suggested an increasing risk of mortality with age or age-related biases in sampling.

1. The effects of L-glutamate diethyl ester (GDEE) HCl, glutarate diethyl ester (GlrDEE) and glutarate dimethyl ester (GlrDME) on depolarizing responses to alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionate (AMPA), kainate (Kain), N-methyl-D-aspartate (NMDA) and quisqualate (Quis), and spontaneous paroxysmal discharges (SPDs) were examined. Experiments were performed on slices of rat cingulate cortex using the in vitro grease gap recording technique in nominally Mg(2+)-free Krebs medium. 2. GDEE HCl (3-14 mM) caused a concentration-dependent depolarization of the d.c. baseline potential. L-Glutamate (0.1-0.5 mM), HCl (15 mM) and sucrose (30 mM) also depolarized the baseline. GlrDEE (3-12 mM) and GlrDME (4-26 mM) had no consistent effect on baseline potential. 3. GDEE HCl (10 mM) had no effect on depolarizing responses to AMPA, Kain and NMDA, but caused potentiation of those to Quis with a dose-ratio of 0.53 (0.44-0.63) (n = 4). In two other experiments, where the depolarization of the baseline induced by GDEE HCl was large, a depression of Quis response amplitude was observed. 4. GlrDEE (10 mM) antagonized depolarizing responses to Kain, and to a lesser extent NMDA, with dose-ratios of 2.14 (1.92-2.38) and 1.61 (1.39-1.87), respectively. This concentration of GlrDEE had no effect on AMPA responses, but potentiated Quis responses, with a dose-ratio of 0.64 (0.58-0.71). 5. GlrDME (10 mM) antagonized depolarizing responses to Kain and to Quis, with dose-ratios of 1.66 (1.48-1.85) and 1.22 (1.15-1.29), respectively, and had no effect on responses to NMDA. 6. The SPDs were inhibited by GDEE HCI (IC50 6.7 +/- 0.37mM), GlrDEE (IC50 5.6 +/- 0.38 mM) and GlrDME (IC50 10.4 +/- 0.73 mM). 7. In conclusion, there is little evidence that GDEE HCI is an antagonist of the postsynaptic excitatory amino acid receptors in the rat neocortex, and its effects may result from its contamination with Lglutamate and increased osmolarity of the bathing medium at high concentrations. The deaminated analogues of GDEE are very weak Kain antagonists.

There are two thrust systems in the Southwest Pyrenees: a NW-SE trending, thin-skin system exposed in the post-Triassic cover and a larger, thick-skin system of NE-SW thrusts in the Palaeozoic basement. The ‘cover’ thrust system propagated and migrated both southward and westward in response to the non-orthogonal collision of Iberia with Europe during Palaeogene mountain building. The ‘basement’ thrust system is interpreted to be a longer-lived structure, initiated during the extensional tectonic regime in mid Cretaceous time, and inverted during the main episode of Pyrenean collision. A model in which interaction of the two thrust systems controlled the timing and magnitude of thrust-induced, flexural subsidence is presented. The development of the basement thrust system caused regional subsidence along the South Pyrenean foreland margin that was subsequently halted by local uplift associated with the west-migratingcover thrust system.

The metabotropic glutamate receptor (mGluR) agonists CCG-I and L-AP4, acting at Group II and Group III mGluRs respectively, can reduce GABAergic synaptic inhibition on single neurones in the rat thalamus in vivo via a presumed presynaptic mechanism. The actions of L-AP4 were antagonized by (+/-)-alpha-methyl-4-phosphonophenylglycine (MPPG), whereas CCG-I was significantly less affected. Thus MPPG may be a useful tool for detecting physiological roles for Group III mGluRs.

Intracellular recordings were made from thalamocortical neurons in slices of rat dorsal lateral geniculate nucleus in vitro, where ionotropic glutamate receptors and ionotropic and metabotropic GABA receptors had been blocked. The activation of specific metabotropic glutamate receptors by exogenous agonists and by the electrical stimulation of the corticothalamic pathway was then assessed using selective antagonists. The specific group I agonist (S)-3,5-dihydoxyphenylglycine and the non-selective agonist (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylic acid both caused a concentration-dependent depolarization of membrane potential. These effects were associated with an increase in the apparent input resistance, and a more robust expression of both the depolarizing sag of the voltage response and the low-threshold Ca2+ potential and an increase in thalamocortical neuron excitability. However, group I agonists selective for the mGlu5 receptor and agonists selective for group II and III receptors did not have these effects. Consequently, these data suggested that these actions were mediated specifically by the group I mGlu1 receptor. The activation of cortical fibres, with trains of 50 stimuli at 50 Hz, resulted in a two-component depolarizing response. The first part of this synaptic response and the agonist-induced depolarization of membrane potential were depressed by the novel group I receptor antagonists LY367366 and LY367385, which are active at mGlu1 receptors. However, they were not blocked by 6-methyl-2-(phenylethyl)-pyridine, a highly selective mGlu5 receptor antagonist. Thus, the membrane potential depolarization of thalamocortical neurons caused either by exogenous agonists or by the stimulation of cortical fibres resulted from the specific activation of mGlu1 but not mGlu5 receptors. This result is consistent with the location of this receptor type on the distal dendrites of thalamocortical neurons in the dorsal lateral geniculate nucleus of the thalamus.

Recordings were made from single neurones in the ventrobasal thalamus of anaesthetised rats in order to evaluate the properties of several agonists and antagonists of Group I mGlu receptors. The selective mGlu1 receptor antagonist LY367385 was found to reduce excitatory responses to iontophoretically applied ACPD and DHPG whereas the mGlu5 agonist CHPG was resistant to antagonism. The antagonists LY367366 and LY393053 reduced responses to all three agonists, but without reducing responses to NMDA or AMPA. Although AIDA was also found to reduce mGlu agonist-evoked responses, this antagonist also produced significant reductions in responses to NMDA and AMPA. These data suggest that there are functional mGlu1 and mGlu5 receptors in the thalamus. Furthermore, LY367385 is a useful tool for investigating mGlu1 functions whereas LY367366 and LY393053 have a broader spectrum of action. The usefulness of AIDA as an antagonist in physiological experiments would appear to be limited by its effects against NMDA and AMPA.

1. Corticothalamic (CT) EPSPs evoked at

Our previous work has shown that Group I mGlu receptors participate in thalamic sensory processing in vivo. However, unequivocal demonstration of mGlu5 participation has not been possible due to the lack of specific ligands. We have therefore made a preliminary study of the in vivo actions of the agonist (R,S)-2-Chloro-5-hydroxyphenylglycine [CHPG] and the novel mGlu5 antagonist 6-methyl-2-(phenylethynyl)-pyridine [MPEP] in order to characterize their suitability for functional studies. Iontophoretically administered MPEP selectively antagonized excitatory responses of single rat thalamic neurones to CHPG compared to the broad-spectrum mGlu agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate. In contrast, the established mGlu1 and mGlu5 antagonist (S)-4-carboxyphenylglycine reduced responses to both agonists. These findings are the first demonstration of an in vivo action of CHPG and its antagonism by a selective mGlu5 antagonist. Furthermore MPEP appears to be a good tool for functional studies of mGlu5.

N-methyl-D-aspartate (NMDA) receptors (NMDArs) may facilitate experience-dependent changes in the visual system. Early sensory experience has an influence over the production of the molecular components from which NMDArs are assembled, and thereby alters the properties of functional receptors. Using the antagonists D-2-amino-5-phosphonovalerate (AP5) and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP), which have some selectivity for different variants of the NMDAr, we demonstrate that visual deprivation (by dark rearing) has functional consequences for NMDArs in the superior colliculus. An increase in the sensitivity of visual responses to AP5 in dark-reared rats indicated that NMDArs were more important for visual transmission in these individuals. We also observed a relative change in the efficacy of the antagonists against the visual responses of normal versus dark-reared rats. AP5 reduced the visual responses of both groups, but CPP was ineffective against visual responses after dark rearing. In the same neurons, CPP blocked NMDA induced activity indicating that molecular adaptations of NMDArs are specific to those synapses mediating visual activity.

Mike Coward, who died in 2003, was one of the late 20th century’s most influential, versatile and eclectic structural geologists. This Geological Society special publication is composed of a diverse selection of papers that were presented, mainly by former research students, colleagues and collaborators of Mike’s, at a two-day conference held at Burlington House to commemorate his work. At almost 600 pages, the book contains some thirty substantial papers that reflect the impressive breadth of Coward’s interests. The main scientific papers are preceded by a Foreword, Portrait of a structural geologist , an introduction to the papers contained in the book that ties them in nicely to the wide-ranging impact of Coward’s work on the understanding of …

A four-month post in general practice was included as an option available to doctors applying for a year-long medical senior house officer (SHO) rotation since August 1993. This study sought the views of SHOs before and after undertaking the general practice post. SHOs gained an understanding of modern general practice and changed their views about certain aspects of general practice. They reported gaining a range of generic skills, which included communication, consultation, and clinical skills. These perceived benefits suggest that such experience merits wider adoption and further evaluation.

1. The mechanism underlying a novel form of input signal amplification and bistability was investigated by intracellular recording in rat and cat thalamocortical (TC) neurones maintained in slices and by computer simulation with a biophysical model of these neurones.2. In a narrow membrane potential range centred around -60 mV, TC neurones challenged with small (10-50 pA), short (50-200 ms) current steps produced a stereotyped, large amplitude hyperpolarization (> 20 mV) terminated by the burst firing of action potentials, leading to amplification of the duration and amplitude of the input signal, that is hereafter referred to as input signal amplification.3. In the same voltage range centred around -60 mV, single evoked EPSPs and IPSPs also produced input signal amplification, indicating that this behaviour can be triggered by physiologically relevant stimuli. In addition, a novel, intrinsic, low frequency oscillation, characterized by a peculiar voltage dependence of its frequency and by the presence of plateau potentials on the falling phase of low threshold Ca2+ potentials, was recorded.4. Blockade of pure Na+ and K+ currents by tetrodotoxin (1 uM) and Ba2+ (0.1-2 0 mM), respectively, did not affect input signal amplification, neither did the presence of excitatory or inhibitory amino acid receptor antagonists in the perfusion medium.5. A decrease in [Ca2(+)](o) (from 2 to 1 mM) and an increase in [Mg2+](o) (from 2 to 10 mM), or the addition of Ni2+ (2-3 mM), abolished input signal amplification, while an increase in [Ca2+](o) (from 2 to 8 mM) generated this behaviour in neurones where it was absent in control conditions. These results indicate the involvement of the low threshold Ca2+ current (I-T) in input signal amplification, since the other Ca2+ currents of TC neurones are activated at potentials more positive than -40 mV.6. Blockade of the slow inward mixed cationic current (I-h) by 4-(N-ethyl-N-phenylamino)-1,2 dimethyl -6-(methylamino)-pyrimidinium chloride (ZD 7288) (100-300 mu M) did not affect the expression of the large amplitude hyperpolarization, but abolished the subsequent repolarization to the original membrane potential. In this condition, therefore, input signal amplification was replaced by bistable membrane behaviour, where two stable membrane potentials separated by 15-30 mV could be switched between by small current steps.7. Computer simulation with a model of a TC neurone, which contained only I-T, I-h, K+ leak current (I-Leak) and those currents responsible for action potentials, accurately reproduced the qualitative and quantitative properties of input signal amplification, bistability and low frequency oscillation, and indicated that these phenomena will occur at some value of the injected DC if, and only if, the 'window' component of I-T (I-T,I-Window) and the leak conductance (g(Leak)) satisfy the relation (dI(T. Window)/dV)(max)) g(Leak).8. The physiological implications of these findings for the electroresponsiveness of TC neurones are discussed, and, as I-T is widely expressed in the central nervous system, we suggest that 'window' I-T will markedly affect the integrative properties of many neurones.