Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability

Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice

A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro

Cannabis is a potential treatment for epilepsy, although the few human studies supporting this use have proved inconclusive. Previously, we showed that a standardized cannabis extract (SCE), isolated Delta(9)-tetrahydrocannabinol (Delta(9)-THC), and even Delta(9)-THC-free SCE inhibited muscarinic agonist-induced epileptiform bursting in rat olfactory cortical brain slices, acting via CB1 receptors. The present work demonstrates that although Delta(9)-THC (1microM) significantly depressed evoked depolarizing postsynaptic potentials (PSPs) in rat olfactory cortex neurones, both SCE and Delta(9)-THC-free SCE significantly potentiated evoked PSPs (all results were fully reversed by the CB1 receptor antagonist SR141716A, 1microM); interestingly, the potentiation by Delta(9)-THC-free SCE was greater than that produced by SCE. On comparing the effects of Delta(9)-THC-free SCE upon evoked PSPs and artificial PSPs (aPSPs; evoked electrotonically following brief intracellular current injection), PSPs were enhanced, whereas aPSPs were unaffected, suggesting that the effect was not due to changes in background input resistance. Similar recordings made using CB1 receptor-deficient knockout mice (CB1(-/-)) and wild-type littermate controls revealed cannabinoid or extract-induced changes in membrane resistance, cell excitability and synaptic transmission in wild-type mice that were similar to those seen in rat neurones, but no effect on these properties were seen in CB1(-/-) cells. It appears that the unknown extract constituent(s) effects over-rode the suppressive effects of Delta(9)-THC on excitatory neurotransmitter release, which may explain some patients' preference for herbal cannabis rather than isolated Delta(9)-THC (due to attenuation of some of the central Delta(9)-THC side effects) and possibly account for the rare incidence of seizures in some individuals taking cannabis recreationally

Cross-modal preference acquisition: evaluative conditioning of pictures by affective olfactory and auditory cues

In this research, a cross-model paradigm was chosen to test the hypothesis that affective olfactory and auditory cues paired with neutral visual stimuli bearing no resemblance or logical connection to the affective cues can evoke preference shifts in those stimuli. Neutral visual stimuli of abstract paintings were presented simultaneously with liked and disliked odours and sounds, with neutral-neutral pairings serving as controls. The results confirm previous findings that the affective evaluation of previously neutral visual stimuli shifts in the direction of contingently presented affective auditory stimuli. In addition, this research shows the presence of conditioning with affective odours having no logical connection with the pictures.

The neural processing of masked speech: Evidence for different mechanisms in the left and right temporal lobes

It has been previously demonstrated that extensive activation in the dorsolateral temporal lobes associated with masking a speech target with a speech masker, consistent with the hypothesis that competition for central auditory processes is an important factor in informational masking. Here, masking from speech and two additional maskers derived from the original speech were investigated. One of these is spectrally rotated speech, which is unintelligible and has a similar (inverted) spectrotemporal profile to speech. The authors also controlled for the possibility of “glimpsing” of the target signal during modulated masking sounds by using speech-modulated noise as a masker in a baseline condition. Functional imaging results reveal that masking speech with speech leads to bilateral superior temporal gyrus (STG) activation relative to a speech-in-noise baseline, while masking speech with spectrally rotated speech leads solely to right STG activation relative to the baseline. This result is discussed in terms of hemispheric asymmetries for speech perception, and interpreted as showing that masking effects can arise through two parallel neural systems, in the left and right temporal lobes. This has implications for the competition for resources caused by speech and rotated speech maskers, and may illuminate some of the mechanisms involved in informational masking.

Olfactory attractiveness of mixtures of some host plant and conspecific semiochemicals to the banana weevil Cosmopolites sordidus (Germar, 1824)

A simple "Y" shaped olfactometer was used in laboratory studies on the olfactory attractiveness of mixtures in various proportions of industrial analogues of some host plant and conspecific-based semiochemicals, or their combinations with banana rhizome, to the banana weevil. The aim was to identify factors that influence their attractiveness to the weevil, and consider the possibility for their use as lures for trapping the weevil in the field. Cosmopolites sordidus was attracted to the mixtures at specific concentrations and proportions of constituent chemicals. 6-methylhept-5-en-2-one was only attractive on its own at 1 µl/100 ml and in mixture with 4- mercaptophenol, but not at 10 µl, 0.01 µl, or in combination with banana rhizome. 4-mercaptohpenol and 2-n-butylfuran, which were compatible with most host plant-based chemicals and were attractive as a mixture, were perceived to be key elements in the composition of attractants to the weevil. It was concluded that in addition to the composition, other factors that may determine the attractiveness or otherwise of a mixture to C. sordidus are the proportions and concentrations of the constituent chemicals.

The neural processing of masked speech: evidence for different mechanisms in the left and right temporal lobes

It has been previously demonstrated that extensive activation in the dorsolateral temporal lobes associated with masking a speech target with a speech masker, consistent with the hypothesis that competition for central auditory processes is an important factor in informational masking. Here, masking from speech and two additional maskers derived from the original speech were investigated. One of these is spectrally rotated speech, which is unintelligible and has a similar (inverted) spectrotemporal profile to speech. The authors also controlled for the possibility of "glimpsing" of the target signal during modulated masking sounds by using speech-modulated noise as a masker in a baseline condition. Functional imaging results reveal that masking speech with speech leads to bilateral superior temporal gyrus (STG) activation relative to a speech-in-noise baseline, while masking speech with spectrally rotated speech leads solely to right STG activation relative to the baseline. This result is discussed in terms of hemispheric asymmetries for speech perception, and interpreted as showing that masking effects can arise through two parallel neural systems, in the left and right temporal lobes. This has implications for the competition for resources caused by speech and rotated speech maskers, and may illuminate some of the mechanisms involved in informational masking.

Human frontal lobes are not relatively large

One of the most pervasive assumptions about human brain evolution is that it involved relative enlargement of the frontal lobes. We show that this assumption is without foundation. Analysis of five independent data sets using correctly scaled measures and phylogenetic methods reveals that the size of human frontal lobes, and of specific frontal regions, is as expected relative to the size of other brain structures. Recent claims for relative enlargement of human frontal white matter volume, and for relative enlargement shared by all great apes, seem to be mistaken. Furthermore, using a recently developed method for detecting shifts in evolutionary rates, we find that the rate of change in relative frontal cortex volume along the phylogenetic branch leading to humans was unremarkable and that other branches showed significantly faster rates of change. Although absolute and proportional frontal region size increased rapidly in humans, this change was tightly correlated with corresponding size increases in other areas andwhole brain size, and with decreases in frontal neuron densities. The search for the neural basis of human cognitive uniqueness should therefore focus less on the frontal lobes in isolation and more on distributed neural networks.

Umami: a delicious flavor formed by convergence of taste and olfactory pathways in the human brain

Umami taste is produced by glutamate acting on a fifth taste system. However, glutamate presented alone as a taste stimulus is not highly pleasant, and does not act synergistically with other tastes (sweet, salt, bitter and sour). We show here that when glutamate is given in combination with a consonant, savory, odour (vegetable), the resulting flavor can be much more pleasant. Moreover, we showed using functional brain imaging with fMRI that the glutamate taste and savory odour combination produced much greater activation of the medial orbitofrontal cortex and pregenual cingulate cortex than the sum of the activations by the taste and olfactory components presented separately. Supralinear effects were much less (and significantly less) evident for sodium chloride and vegetable odour. Further, activations in these brain regions were correlated with the pleasantness and fullness of the flavor, and with the consonance of the taste and olfactory components. Supralinear effects of glutamate taste and savory odour were not found in the insular primary taste cortex. We thus propose that glutamate acts by the nonlinear effects it can produce when combined with a consonant odour in multimodal cortical taste-olfactory convergence regions. We propose the concept that umami can be thought of as a rich and delicious flavor that is produced by a combination of glutamate taste and a consonant savory odour. Glutamate is thus a flavor enhancer because of the way that it can combine supralinearly with consonant odours in cortical areas where the taste and olfactory pathways converge far beyond the receptors.

The anterior temporal lobes support residual comprehension in Wernicke’s aphasia

Wernicke’s aphasia occurs following a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory-verbal comprehension is significantly impaired in Wernicke’s aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used fMRI to investigate the neural basis of written word and picture semantic processing in Wernicke’s aphasia, with the wider aim of examining how the semantic system is altered following damage to the classical comprehension regions. Twelve participants with Wernicke’s aphasia and twelve control participants performed semantic animate-inanimate judgements and a visual height judgement baseline task. Whole brain and ROI analysis in Wernicke’s aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke’s aphasia group displayed an “over-activation” in comparison to control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke’s aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results concord with models which indicate that the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions.

Olfactory selection of Plantago lanceolata by snails declines with seedling age

Background and Aims Despite recent recognition that (1) plant–herbivore interactions during the establishment phase, (2) ontogenetic shifts in resource allocation and (3) herbivore response to plant volatile release are each pivotal to a comprehensive understanding of plant defence, no study has examined how herbivore olfactory response varies during seedling ontogeny. Methods Using a Y-tube olfactometer we examined snail (Helix aspersa) olfactory response to pellets derived from macerated Plantago lanceolata plants harvested at 1, 2, 3, 4, 5, 6 and 8 weeks of age to test the hypothesis that olfactory selection of plants by a generalist herbivore varies with plant age. Plant volatiles were collected for 10 min using solid-phase microextraction technique on 1- and 8-week-old P. lanceolata pellets and analysed by gas chromatography coupled with a mass spectrometer. Key Results Selection of P. lanceolata was strongly negatively correlated with increasing age; pellets derived from 1-week-old seedlings were three times more likely to be selected as those from 8-week-old plants. Comparison of plant selection experiments with plant volatile profiles from GC/MS suggests that patterns of olfactory selection may be linked to ontogenetic shifts in concentrations of green leaf volatiles and ethanol (and its hydrolysis derivatives). Conclusions Although confirmatory of predictions made by contemporary plant defence theory, this is the first study to elucidate a link between seedling age and olfactory selection by herbivores. As a consequence, this study provides a new perspective on the ontogenetic expression of seedling defence, and the role of seedling herbivores, particularly terrestrial molluscs, as selective agents in temperate plant communities.

Detection of flood extent in urban areas using high resolution TerraSAR-X data

Flooding is a major hazard in both rural and urban areas worldwide, but it is in urban areas that the impacts are most severe. An investigation of the ability of high resolution TerraSAR-X data to detect flooded regions in urban areas is described. An important application for this would be the calibration and validation of the flood extent predicted by an urban flood inundation model. To date, research on such models has been hampered by lack of suitable distributed validation data. The study uses a 3m resolution TerraSAR-X image of a 1-in-150 year flood near Tewkesbury, UK, in 2007, for which contemporaneous aerial photography exists for validation. The DLR SETES SAR simulator was used in conjunction with airborne LiDAR data to estimate regions of the TerraSAR-X image in which water would not be visible due to radar shadow or layover caused by buildings and taller vegetation, and these regions were masked out in the flood detection process. A semi-automatic algorithm for the detection of floodwater was developed, based on a hybrid approach. Flooding in rural areas adjacent to the urban areas was detected using an active contour model (snake) region-growing algorithm seeded using the un-flooded river channel network, which was applied to the TerraSAR-X image fused with the LiDAR DTM to ensure the smooth variation of heights along the reach. A simpler region-growing approach was used in the urban areas, which was initialized using knowledge of the flood waterline in the rural areas. Seed pixels having low backscatter were identified in the urban areas using supervised classification based on training areas for water taken from the rural flood, and non-water taken from the higher urban areas. Seed pixels were required to have heights less than a spatially-varying height threshold determined from nearby rural waterline heights. Seed pixels were clustered into urban flood regions based on their close proximity, rather than requiring that all pixels in the region should have low backscatter. This approach was taken because it appeared that urban water backscatter values were corrupted in some pixels, perhaps due to contributions from side-lobes of strong reflectors nearby. The TerraSAR-X urban flood extent was validated using the flood extent visible in the aerial photos. It turned out that 76% of the urban water pixels visible to TerraSAR-X were correctly detected, with an associated false positive rate of 25%. If all urban water pixels were considered, including those in shadow and layover regions, these figures fell to 58% and 19% respectively. These findings indicate that TerraSAR-X is capable of providing useful data for the calibration and validation of urban flood inundation models.

Investigation of the effects of the novel anticonvulsant compound carisbamate(RWJ-333369) on rat piriform cortical neurones in vitro

Background and purpose: Carisbamate is being developed for adjuvant treatment of partial onset epilepsy. Carisbamate produces anticonvulsant effects in primary generalized, complex partial and absence-type seizure models, and exhibits neuroprotective and antiepileptogenic properties in rodent epilepsy models. Phase IIb clinical trials of carisbamate demonstrated efficacy against partial onset seizures; however, its mechanisms of action remain unknown. Here, we report the effects of carisbamate on membrane properties, evoked and spontaneous synaptic transmission and induced epileptiform discharges in layer II-III neurones in piriform cortical brain slices. Experimental approach: Effects of carisbamate were investigated in rat piriform cortical neurones by using intracellular electrophysiological recordings. Key results: Carisbamate (50–400 mmol·L-1) reversibly decreased amplitude, duration and rise-time of evoked action potentials and inhibited repetitive firing, consistent with use-dependent Na+ channel block; 150–400 mmol·L-1 carisbamate reduced neuronal input resistance, without altering membrane potential. After microelectrode intracellular Cl- loading, carisbamate depolarized cells, an effect reversed by picrotoxin. Carisbamate (100–400 mmol·L-1) also selectively depressed lateral olfactory tract-afferent evoked excitatory synaptic transmission (opposed by picrotoxin), consistent with activation of a presynaptic Cl conductance. Lidocaine (40–320 mmol·L-1) mimicked carisbamate, implying similar modes of action. Carisbamate (300–600 mmol·L-1) had no effect on spontaneous GABAA miniature inhibitory postsynaptic currents and at lower concentrations (50–200 mmol·L-1) inhibited Mg2+-free or 4-aminopyridine-induced seizure-like discharges. Conclusions and implications: Carisbamate blocked evoked action potentials use-dependently, consistent with a primary action on Na+ channels and increased Cl- conductances presynaptically and, under certain conditions, postsynaptically to selectively depress excitatory neurotransmission in piriform cortical layer Ia-afferent terminals.

Subglacial bedform evidence for a major palaeo-ice stream and its retreat phases in Amundsen Gulf, Canadian Arctic Archipelago

Ascertaining the location of palaeo-ice streams is crucial in order to produce accurate reconstructions of palaeo-ice sheets and examine interactions with the ocean-climate system. This paper reports evidence for a major ice stream in Amundsen Gulf, Canadian Arctic Archipelago. Mapping from satellite imagery (Landsat ETM+) and digital elevation models, including bathymetric data, is used to reconstruct flow-patterns on southwestern Victoria Island and the adjacent mainland (Nunavut and Northwest Territories). Several flow-sets indicative of ice streaming are found feeding into the marine trough and cross-cutting relationships between these flow-sets (and utilising previously published radiocarbon dates) reveal several phases of ice stream activity centred in Amundsen Gulf and Dolphin and Union Strait. A large erosional footprint on the continental shelf indicates that the ice stream (ca. 1000 km long and ca. 150 km wide) filled Amundsen Gulf, probably at the Last Glacial Maximum. Subsequent to this, the ice stream reorganised as the margin retreated back along the marine trough, eventually splitting into two separate low-gradient lobes in Prince Albert Sound and Dolphin and Union Strait. The location of this major ice stream holds important implications for ice sheet-ocean interactions and specifically, the development of Arctic Ocean ice shelves and the delivery of icebergs into the western Arctic Ocean during the late Pleistocene. Copyright (C) 2006 John Wiley & Sons, Ltd.

Modelling the lava dome extruded at Soufrière Hills Volcano, Montserrat, August 2005–May 2006. Part I: Dome shape and internal structure

Lava domes comprise core, carapace, and clastic talus components. They can grow endogenously by inflation of a core and/or exogenously with the extrusion of shear bounded lobes and whaleback lobes at the surface. Internal structure is paramount in determining the extent to which lava dome growth evolves stably, or conversely the propensity for collapse. The more core lava that exists within a dome, in both relative and absolute terms, the more explosive energy is available, both for large pyroclastic flows following collapse and in particular for lateral blast events following very rapid removal of lateral support to the dome. Knowledge of the location of the core lava within the dome is also relevant for hazard assessment purposes. A spreading toe, or lobe of core lava, over a talus substrate may be both relatively unstable and likely to accelerate to more violent activity during the early phases of a retrogressive collapse. Soufrière Hills Volcano, Montserrat has been erupting since 1995 and has produced numerous lava domes that have undergone repeated collapse events. We consider one continuous dome growth period, from August 2005 to May 2006 that resulted in a dome collapse event on 20th May 2006. The collapse event lasted 3 h, removing the whole dome plus dome remnants from a previous growth period in an unusually violent and rapid collapse event. We use an axisymmetrical computational Finite Element Method model for the growth and evolution of a lava dome. Our model comprises evolving core, carapace and talus components based on axisymmetrical endogenous dome growth, which permits us to model the interface between talus and core. Despite explicitly only modelling axisymmetrical endogenous dome growth our core–talus model simulates many of the observed growth characteristics of the 2005–2006 SHV lava dome well. Further, it is possible for our simulations to replicate large-scale exogenous characteristics when a considerable volume of talus has accumulated around the lower flanks of the dome. Model results suggest that dome core can override talus within a growing dome, potentially generating a region of significant weakness and a potential locus for collapse initiation.

Numerical simulation of the 12 May 1997 CME Event: The role of magnetic reconnection

We perform a numerical study of the evolution of a Coronal Mass Ejection (CME) and its interaction with the coronal magnetic field based on the 12 May 1997, CME event using a global MagnetoHydroDynamic (MHD) model for the solar corona. The ambient solar wind steady-state solution is driven by photospheric magnetic field data, while the solar eruption is obtained by superimposing an unstable flux rope onto the steady-state solution. During the initial stage of CME expansion, the core flux rope reconnects with the neighboring field, which facilitates lateral expansion of the CME footprint in the low corona. The flux rope field also reconnects with the oppositely orientated overlying magnetic field in the manner of the breakout model. During this stage of the eruption, the simulated CME rotates counter-clockwise to achieve an orientation that is in agreement with the interplanetary flux rope observed at 1 AU. A significant component of the CME that expands into interplanetary space comprises one of the side lobes created mainly as a result of reconnection with the overlying field. Within 3 hours, reconnection effectively modifies the CME connectivity from the initial condition where both footpoints are rooted in the active region to a situation where one footpoint is displaced into the quiet Sun, at a significant distance (≈1R ) from the original source region. The expansion and rotation due to interaction with the overlying magnetic field stops when the CME reaches the outer edge of the helmet streamer belt, where the field is organized on a global scale. The simulation thus offers a new view of the role reconnection plays in rotating a CME flux rope and transporting its footpoints while preserving its core structure.