Cholinergic modulation of intrinsic fibre-evoked excitatory transmission contains a nicotinic component in immature but not adult rat piriform cortex, in vitro

The piriform cortex (PC) is highly prone to epileptogenesis, particularly in immature animals, where decreased muscarinic modulation of PC intrinsic fibre excitatory neurotransmission is implicated as a likely cause. However, whether higher levels of acetylcholine (ACh) release occur in immature vs. adult PC remains unclear. We investigated this using in vitro extracellular electrophysiological recording techniques. Intrinsic fibre-evoked extracellular field potentials (EFPs) were recorded from layers II to III in PC brain slices prepared from immature (P14-18) and adult (P>40) rats. Adult and immature PC EFPs were suppressed by eserine (1muM) or neostigmine (1muM) application, with a greater suppression in immature ( approximately 40%) than adult ( approximately 30%) slices. Subsequent application of atropine (1muM) reversed EFP suppression, producing supranormal ( approximately 12%) recovery in adult slices, suggesting that suppression was solely muscarinic ACh receptor-mediated and that some 'basal' cholinergic 'tone' was present. Conversely, atropine only partially reversed anticholinesterase effects in immature slices, suggesting the presence of additional non-muscarinic modulation. Accordingly, nicotine (50muM) caused immature field suppression ( approximately 30%) that was further enhanced by neostigmine, whereas it had no effect on adult EFPs. Unlike atropine, nicotinic antagonists, mecamylamine and methyllycaconitine, induced immature supranormal field recovery ( approximately 20%) following anticholinesterase-induced suppression (with no effect on adult slices), confirming that basal cholinergic 'tone' was also present. We suggest that nicotinic inhibitory cholinergic modulation occurs in the immature rat PC intrinsic excitatory fibre system, possibly to complement the existing, weak muscarinic modulation, and could be another important developmentally regulated system governing immature PC susceptibility towards epileptogenesis.

Developmental changes in presynaptic muscarinic modulation of excitatory and inhibitory neurotransmission in rat piriform cortex in vitro: relevance to epileptiform bursting susceptibility

Suppression of depolarizing postsynaptic potentials and isolated GABA-A receptor-mediated fast inhibitory postsynaptic potentials by the muscarinic acetylcholine receptor agonist, oxotremorine-M (10 microM), was investigated in adult and immature (P14-P30) rat piriform cortical (PC) slices using intracellular recording. Depolarizing postsynaptic potentials evoked by layers II-III stimulation underwent concentration-dependent inhibition in oxotremorine-M that was most likely presynaptic and M2 muscarinic acetylcholine receptor-mediated in immature, but M1-mediated in adult (P40-P80) slices; percentage inhibition was smaller in immature than in adult piriform cortex. In contrast, compared with adults, layer Ia-evoked depolarizing postsynaptic potentials in immature piriform cortex slices in oxotremorine-M, showed a prolonged multiphasic depolarization with superimposed fast transients and spikes, and an increased 'all-or-nothing' character. Isolated N-methyl-d-aspartate receptor-mediated layer Ia depolarizing postsynaptic potentials (although significantly larger in immature slices) were however, unaffected by oxotremorine-M, but blocked by dl-2-amino-5-phosphonovaleric acid. Fast inhibitory postsynaptic potentials evoked by layer Ib or layers II-III-fiber stimulation in immature slices were significantly smaller than in adults, despite similar estimated mean reversal potentials ( approximately -69 and -70 mV respectively). In oxotremorine-M, only layer Ib-fast inhibitory postsynaptic potentials were suppressed; suppression was again most likely presynaptic M2-mediated in immature slices, but M1-mediated in adults. The degree of fast inhibitory postsynaptic potential suppression was however, greater in immature than in adult piriform cortex. Our results demonstrate some important physiological and pharmacological differences between excitatory and inhibitory synaptic systems in adult and immature piriform cortex that could contribute toward the increased susceptibility of this region to muscarinic agonist-induced epileptiform activity in immature brain slices.

Contextual modulation of amygdala responsivity to surprised faces

We recently demonstrated a functional relationship between fMRI responses within the amygdala and the medial prefrontal cortex based upon whether subjects interpreted surprised facial expressions positively or negatively. In the present fMRI study, we sought to assess amygdala-medial prefrontal cortex responsivity when the interpretations of surprised faces were determined by contextual experimental stimuli, rather than subjective judgment. Subjects passively viewed individual presentations of surprised faces preceded by either a negatively or positively valenced contextual sentence (e. g., She just found $500 vs. She just lost $500). Negative and positive sentences were carefully matched in terms of length, situations described, and arousal level. Negatively cued surprised faces produced greater ventral amygdala activation compared to positively cued surprised faces. Responses to negative versus positive sentences were greater within the ventrolateral prefrontal cortex, whereas responses to positive versus negative sentences were greater within the ventromedial prefrontal cortex. The present study demonstrates that amygdala response to surprised facial expressions can be modulated by negatively versus positively valenced verbal contextual information. Connectivity analyses identified candidate cortical-subcortical systems subserving this modulation.

Sex-dependent age modulation of frontostriatal and temporo-parietal activation during cognitive control

Developmental functional imaging studies of cognitive control show progressive age-related increase in task-relevant fronto-striatal activation in male development from childhood to adulthood. Little is known, however, about how gender affects this functional development. In this study, we used event related functional magnetic resonance imaging to examine effects of sex, age, and their interaction on brain activation during attentional switching and interference inhibition, in 63 male and female adolescents and adults, aged 13 to 38. Linear age correlations were observed across all subjects in task-specific frontal, striatal and temporo-parietal activation. Gender analysis revealed increased activation in females relative to males in fronto-striatal areas during the Switch task, and laterality effects in the Simon task, with females showing increased left inferior prefrontal and temporal activation, and males showing increased right inferior prefrontal and parietal activation. Increased prefrontal activation clusters in females and increased parietal activation clusters in males furthermore overlapped with clusters that were age-correlated across the whole group, potentially reflecting more mature prefrontal brain activation patterns for females, and more mature parietal activation patterns for males. Gender by age interactions further supported this dissociation, revealing exclusive female-specific age correlations in inferior and medial prefrontal brain regions during both tasks, and exclusive male-specific age correlations in superior parietal (Switch task) and temporal regions (Simon task). These findings show increased recruitment of age-correlated prefrontal activation in females, and of age-correlated parietal activation in males, during tasks of cognitive control. Gender differences in frontal and parietal recruitment may thus be related to gender differences in the neurofunctional maturation of these brain regions.

Prefrontal cortical-ventral striatal interactions involved in affective modulation of attentional performance: implications for corticostriatal circuit function

Anatomically segregated systems linking the frontal cortex and the striatum are involved in various aspects of cognitive, affective, and motor processing. In this study, we examined the effects of combined unilateral lesions of the medial prefrontal cortex (mPFC) and the core subregion of the nucleus accumbens (AcbC) in opposite hemispheres (disconnection) on a continuous performance, visual attention test [five-choice serial reaction-time task (5CSRTT)]. The disconnection lesion produced a set of specific changes in performance of the 5CSRTT, resembling changes that followed bilateral AcbC lesions while, in addition, comprising a subset of the behavioral changes after bilateral mPFC lesions previously reported using the same task. Specifically, both mPFC/AcbC disconnection and bilateral AcbC lesions markedly affected aspects of response control related to affective feedback, as indexed by perseverative responding in the 5CSRTT. These effects were comparable, although not identical, to those in animals with either bilateral AcbC or mPFC/AcbC disconnection lesions. The mPFC/AcbC disconnection resulted in a behavioral profile largely distinct from that produced by disconnection of a similar circuit described previously, between the mPFC and the dorsomedial striatum, which were shown to form a functional network underlying aspects of visual attention and attention to action. This distinction provides an insight into the functional specialization of corticostriatal circuits in similar behavioral contexts.

Multidecadal modulation of El Nino-Southern Oscillation (ENSO) variance by Atlantic Ocean sea surface temperatures

Observations suggest a possible link between the Atlantic Multidecadal Oscillation (AMO) and El Nino Southern Oscillation (ENSO) variability, with the warm AMO phase being related to weaker ENSO variability. A coupled ocean-atmosphere model is used to investigate this relationship and to elucidate mechanisms responsible for it. Anomalous sea surface temperatures (SSTs) associated with the positive AMO lead to change in the basic state in the tropical Pacific Ocean. This basic state change is associated with a deepened thermocline and reduced vertical stratification of the equatorial Pacific ocean, which in turn leads to weakened ENSO variability. We suggest a role for an atmospheric bridge that rapidly conveys the influence of the Atlantic Ocean to the tropical Pacific. The results suggest a non-local mechanism for changes in ENSO statistics and imply that anomalous Atlantic ocean SSTs can modulate both mean climate and climate variability over the Pacific.

Solar modulation in surface atmospheric electricity

The solar wind modulates the flux of galactic cosmic rays impinging on Earth inversely with solar activity. Cosmic ray ionisation is the major source of air’s electrical conductivity over the oceans and well above the continents. Differential solar modulation of the cosmic ray energy spectrum modifies the cosmic ray ionisation at different latitudes,varying the total atmospheric columnar conductance. This redistributes current flow in the global atmospheric electrical circuit, including the local vertical current density and the related surface potential gradient. Surface vertical current density and potential gradient measurements made independently at Lerwick Observatory,Shetland,from 1978 to 1985 are compared with modelled changes in cosmic ray ionisation arising from solar activity changes. Both the lower troposphere atmospheric electricity quantities are significantly increased at cosmic ray maximum(solar minimum),with a proportional change greater than that of the cosmic ray change.

Top-down solar modulation of climate: evidence for centennial-scale change

During the descent into the recent ‘exceptionally’ low solar minimum, observations have revealed a larger change in solar UV emissions than seen at the same phase of previous solar cycles. This is particularly true at wavelengths responsible for stratospheric ozone production and heating. This implies that ‘top-down’ solar modulation could be a larger factor in long-term tropospheric change than previously believed, many climate models allowing only for the ‘bottom-up’ effect of the less-variable visible and infrared solar emissions. We present evidence for long-term drift in solar UV irradiance, which is not found in its commonly used proxies. In addition, we find that both stratospheric and tropospheric winds and temperatures show stronger regional variations with those solar indices that do show long-term trends. A top-down climate effect that shows long-term drift (and may also be out of phase with the bottom-up solar forcing) would change the spatial response patterns and would mean that climate-chemistry models that have sufficient resolution in the stratosphere would become very important for making accurate regional/seasonal climate predictions. Our results also provide a potential explanation of persistent palaeoclimate results showing solar influence on regional or local climate indicators.

Dual carrier modulation soft demapper

An Orthogonal Frequency Division Multiplexing (OFDM) communication system with a transmitter and a receiver. The transmitter is arranged to transmit channel estimation sequences on each of a plurality of band groups, or bands, and to transmit data on each of the band groups or bands. The receiver is arranged to receive the channel estimation sequences for each band group or band to calculate channel state information from each of the channel estimation sequences transmitted on that band group or band and to form an average channel state information. The receiver receives the transmitted data, transforms the received data into the frequency domain, equalizes the received data using the channel state information, demaps the equalized data to re-construct the received data as soft bits and modifies the soft bits using the averaged channel state information.

Fixed point dual carrier modulation performance for wireless USB

Dual Carrier Modulation (DCM) is currently used as the higher data rate modulation scheme for Multiband Orthogonal Frequency Division Multiplexing (MB-OFDM) in the ECMA-368 defined Ultra-Wideband (UWB) radio platform. ECMA-368 has been chosen as the physical radio platform for many systems including Wireless USB (W-USB), Bluetooth 3.0 and Wireless HDMI; hence ECMA-368 is an important issue to consumer electronics and the user’s experience of these products. In this paper, Log Likelihood Ratio (LLR) demapping method is used for the DCM demaper implemented in fixed point model. Channel State Information (CSI) aided scheme coupled with the band hopping information is used as the further technique to improve the DCM demapping performance. The receiver performance for the fixed point DCM is simulated in realistic multi-path environments.

Systemic gut microbial modulation of bile acid metabolism in host tissue compartments

We elucidate the detailed effects of gut microbial depletion on the bile acid sub-metabolome of multiple body compartments (liver, kidney, heart, and blood plasma) in rats. We use a targeted ultraperformance liquid chromatography with time of flight mass-spectrometry assay to characterize the differential primary and secondary bile acid profiles in each tissue and show a major increase in the proportion of taurine-conjugated bile acids in germ-free (GF) and antibiotic (streptomycin/penicillin)-treated rats.Although conjugated bile acids dominate the hepatic profile (97.0 ± 1.5%) of conventional animals, unconjugated bile acids comprise the largest proportion of the total measured bile acid profile in kidney (60.0±10.4%) andheart (53.0 ± 18.5%) tissues. In contrast, in the GF animal, taurine-conjugated bile acids (especially taurocholic acid and tauro-β-muricholic acid) dominated the bile acid profiles (liver: 96.0 ± 14.5%; kidney: 96 ± 1%; heart: 93 ± 1%; plasma: 93.0 ± 2.3%), with unconjugated and glycine-conjugated species representing a small proportion of the profile. Higher free taurine levels were found in GF livers compared with the conventional liver (5.1-fold; P < 0.001). Bile acid diversity was also lower in GF and antibiotic-treated tissues compared with conventional animals. Because bile acids perform important signaling functions, it is clear that these chemical communication networks are strongly influencedbymicrobial activitiesormodulation, as evidenced by farnesoid X receptor-regulated pathway transcripts. The presence of specific microbial bile acid co-metabolite patterns in peripheral tissues (including heart and kidney) implies a broader signaling role for these compounds and emphasizes the extent of symbiotic microbial influences in mammalian homeostasis.

Bone morphogenetic protein (BMP) ligands and receptors in bovine ovarian follicle cells: actions of BMP-4,-6 and-7 on granulosa cells and differential modulation of Smad-1 phosphorylation by follistatin

Given the paucity of information on the potential roles of bone morphogenetic proteins (BMPs) in the ruminant ovary we conducted immunolocalization and functional studies on cells isolated from bovine antral follicles. Immunocytochemistry revealed expression of BMP-4 and -7 in isolated theca cells whereas granulosa cells and oocytes selectively expressed RMP-6. All three cell types expressed a range of BMP-responsive type-I (BMPRIB, ActRI) and type-II (BMPRII, ActRII, ActRIIB) receptors supporting autocrine/paracrine roles within the follicle. This was reinforced by functional experiments on granulosa cells which showed that BMP-4, -6 and -7 promoted cellular accumulation of phosphorylated Smad-1 but not Smad-2 and enhanced 'basal' and IGF-stimulated secretion of oestradiol (E2), inhibin-A, activin-A and follistatin (FS). Concomitantly, each BMP suppressed 'basal' and IGF-stimulated progesterone secretion, consistent with an action to prevent or delay atresia and/or luteinization. BMPs also increased viable cell number under 'basal' (BMP-4 and -7) and IGF-stimulated (BMP-4, -6 and -7) conditions. Since FS, a product of bovine granulosa cells, has been shown to bind several BMPs, we used the Biacore technique to compare its binding affinities for activin-A (prototype FS ligand) and BMP-4, -6 and -7. Compared with activin-A (K-d 0.28 +/- 0.02 nM; 100%), the relative affinities of FS for BMP-4, -6 and -7 were 10, 5 and 1% respectively. Moreover, studies on granulosa cells showed that preincubation of ligand with excess FS abolished activin-A-induced phosphorylation of Smad-2 and BMP-4-induced phosphorylation of Smad-1. However, FS only partially reversed BMP-6-induced Smad-1 phosphorylation and had no inhibitory effect on BMP-7-induced Smad-1 phosphorylation. These findings support functional roles for BMP-4, -6 and -7 as paracrine/autocrine modulators of granulosa cell steroidogenesis, peptide secretion and proliferation in bovine antral follicles. The finding that FS can differentially modulate BMP-induced receptor activation and that this correlates with the relative binding affinity of FS for each BMP type implicates FS as a potential modulator of BMP action in the ovary.