Spatiotemporal atmospheric in-situ carbon dioxide data over the Indian sites-data perspective.

In the current study, atmospheric carbon dioxide (CO2) data covering multiple locations in the Indian subcontinent are reported. This data was collected using a dedicated ground-based in-situ network established as part of the Geosphere-Biosphere Programme (CAP-IGBP) of the Climate and Atmospheric Processes of the Indian Space Research Organisation (ISRO). Data are collected over Ponmudi, Ooty, Sriharikota, Gadanki, Shadnagar, Nagpur, and Dehradun during 2014-2015, 2017-2020, 2012, 2011-2015, 2014-2017, 2017 and 2008-2011, respectively. The atmospheric CO2 generated as part of the CAP-IGBP network would enhance the understanding of CO2 variability in different time scales ranging from diurnal, seasonal, and annual over the Indian region. Data available under this network may be interesting to other research communities for modeling studies and spatiotemporal variability of atmospheric CO2 across the study locations. The work also evaluated the CO2 observations against the Model for Interdisciplinary Research on Climate version 4 atmospheric chemistry-transport model (MIROC4-ACTM) concentrations.

Triamcinolone Acetonide Subconjunctival Injection as Stand-alone Inflammation Prophylaxis after Phacoemulsification Cataract Surgery.

PURPOSE: To compare the effectiveness and safety of a single injection of subconjunctival triamcinolone acetonide (TA) with that of postoperative topical prednisolone acetate (PA) with and without nonsteroidal anti-inflammatory drugs (NSAIDs) for cataract surgery prophylaxis. DESIGN: Retrospective, comparative effectiveness cohort study. PARTICIPANTS: Patients at Kaiser Permanente Northern California from 2018 through 2021. INTERVENTION: Exposure groups included topical PA with or without NSAID and subconjunctival injection of TA (Kenalog; Bristol-Myers-Squibb) 10 mg/ml or 40 mg/ml in a low dose (1.0-3.0 mg) or high dose (3.1-5.0 mg). MAIN OUTCOME MEASURES: The adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of postoperative macular edema (ME) and iritis diagnoses 15 to 120 days after surgery (effectiveness measures) and a glaucoma-related event (safety measure) between 15 days and 1 year after surgery. RESULTS: Of 69 832 eligible patient-eyes, postoperative ME, iritis, and a glaucoma-related event occurred on average in 1.3%, 0.8%, and 3.4% of eyes in the topical groups and 0.8%, 0.5%, and 2.8% of eyes in the injection groups, respectively. In multivariable analysis, compared with the PA reference group, the PA plus NSAID group had a lower OR of ME (OR, 0.88; 95% CI, 0.74-1.04; P = 0.135). and all injection groups had even lower odds, with the high-dose TA 10-mg/ml group reaching statistical significance (OR, 0.64; 95% CI, 0.43-0.97; P = 0.033). A trend of lower odds of a postoperative iritis diagnosis was noted in the high-strength (40 mg/ml) groups. For postoperative glaucoma-related events, compared with PA, the TA 10-mg/ml low-dose group showed lower odds (OR, 0.69; 95% CI, 0.55-0.86; P = 0.001), the TA 10-mg/ml high-dose group showed similar odds (OR, 0.90; 95% CI, 0.70-1.15; P = 0.40), and the TA 40-mg/ml low-dose and high-dose groups showed higher odds of an event occurring (OR, 1.46 [95% CI, 0.98-2.18; P = 0.062] and OR, 2.14 [95% CI, 1.36-3.37; P = 0.001], respectively). CONCLUSIONS: The TA 10-mg/ml high-dose (4 mg) group was associated with a lower risk of postoperative ME and a similar risk of glaucoma-related events compared with the topical groups. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Neighbouring effect of land use changes and fire emissions on atmospheric CO2 and CH4 over suburban region of India (Shadnagar).

The present study investigated the effects of land use/land cover (LU/LC) changes on atmospheric carbon dioxide (CO2) and methane (CH4) concentrations over the sub-urban region of India (Shadnagar) using continuous decadal CO2 and CH4in-situ data measured by the greenhouse gas analyser (GGA). Data was collected from 2013 to 2022 at a 1 Hz frequency. Analysis of the current study indicates that during pre-monsoon, the seasonal maximum of CO2 was 409.91 ± 9.26 ppm (µ ± 1σ), while the minimum during monsoon was about 401.64 ± 7.13 ppm. Post-monsoon has a high seasonal mean CH4 concentration of 2.08 ± 0.06 ppm, while monsoon has a low seasonal mean CH4 concentration of 1.88 ± 0.03 ppm. The primary classes, such as forest, crop, and built-up, were considered to estimate the effect of LU/LC changes on atmospheric CO2 and CH4 concentrations. Between 2005 and 2021, the study's results show that the built-up area at radii of 10 km, 20 km, and 50 km increased by 0.17 %, 0.10 %, and 0.4 %, respectively. While other LU/LC categories declined by 30 %, agriculture areas increased by 30 % on average. As a result, the CO2 and CH4 concentrations at the study site are increased by 6 % (26 ppm) and 6.5 % (140 ppb), respectively. The present study utilised the fire-based carbon emissions data from the Global Fire Emissions Database (GFED) to understand the impact on atmospheric CO2 and CH4. Analysis of the present work investigated the influence of transported airmass on CO2 and CH4 during the pre-monsoon and post-monsoon seasons using the HYSPLIT trajectories and found emissions were from the northwest, southeast, and northeast of the study site. Further, in-situ CO2 and CH4 records are compared against the MIROC4-ACTM simulation, and strong agreement was found with bias of 1.80 ppm and 0.98 ppb for CO2 and CH4, respectively.

Characterizing the regional XCO2 variability and its association with ENSO over India inferred from GOSAT and OCO-2 satellite observations.

India is primarily concerned with comprehending regional carbon source-sink response in the context of changes in atmospheric CO2 concentrations or anthropogenic emissions. Recent advancements in high-resolution satellite's fine-scale XCO2 measurements provide an opportunity to understand unprecedented details of source-sink activity on a regional scale. In this study, we investigated the long-term variations of XCO2 concentration and growth rates as well as its covarying relationship with ENSO and regional climate parameters (temperature, precipitation, soil moisture, and NDVI) over India from 2010 to 2021 using GOSAT and OCO-2 retrievals. The results show since the launch of OCO-2 in 2014, the number of monthly high-quality XCO2 soundings over India has grown nearly 100-fold compared to GOSAT, launched in 2009. Also, the discrepancy in XCO2 increase of 2.54(2.43) ppm/yr was observed in GOSAT (OCO-2) retrieval during an overlapping measurement period (2015-2021). Additionally, wavelet analysis indicated that the OCO-2 retrieval is able to capture a better frequency of local-scale XCO2 variability compared to GOSAT, owing to its high-resolution cloud-free XCO2 soundings, providing more well-defined regional-scale source-sink features. Furthermore, dominant spatial pattern of XCO2 variability observed over south and southeast of India in both satellites, with XCO2 semi-annual and annual variability more distinctly present in OCO-2 compared to GOSAT. A cross-correlation analysis suggested GOSAT XCO2 growth rate positively correlates with ENSO in different homogeneous monsoon regions of India, with ENSO leading the GOSAT XCO2 growth rate in all homogeneous regions by 3-9 months. The South Peninsular region sensitive to ENSO changes, especially during 2015-2016 ENSO event, where a decrease in CO2 uptake was observed is closely linked with precipitation, soil moisture, and temperature anomalies. However, regional climate parameters show a low correlation with XCO2 growth since CO2 is a long-lived well-mixed gas primarily having an imprint of large-scale transport in column CO2.

Management of intussusception in children: A comparative study of hydrostatic reduction with saline under ultrasound guidance versus laparoscopic assistance.

Introduction: Intussusception is a common cause of intestinal obstruction in infants and children. Ultrasound-guided hydrostatic reduction (USGHR) with saline is considered the gold standard with a success rate of more than 90%. Hydrostatic reduction with laparoscopic assistance has its own advantage of direct visualisation, assessment of bowel vascularity and controlled distension. The choice of procedure depends on available resources and surgeon's preference. This study aims to compare the outcomes of the two methods, i.e., laparoscopic-assisted hydrostatic reduction (LAHR) and USGHR under general anaesthesia (GA). Materials and Methods: This was a prospective study carried out at two different centres over a 3-year period. All patients of intussusception were managed by either hydrostatic reduction with saline under ultrasound guidance or hydrostatic reduction with laparoscopic assistance. Both the procedures were done in operation theatre under GA. The operating time and amount of fluid used for reduction were noted. Results: There were 27 patients in Group 1 (USGHR) and 20 patients in Group 2 (LAHR). The two groups were similar in terms of demographic parameters. The various outcomes such as number of attempts for reduction, fluid required for reduction, time to start oral feeds, complication and length of stay were similar in both the groups. The mean operating time for Group 1 was 19.4 ± 4.5 min and for Group 2 was 34.9 ± 4.8 min (P < 0.001). Conclusion: Both the procedures fare equally in terms of outcome except mean operating time, therefore, LAHR is a good alternative to USGHR in resource-poor nations where logistics of intraoperative ultrasound may not be present.

Observational constraints reduce model spread but not uncertainty in global wetland methane emission estimates.

The recent rise in atmospheric methane (CH4 ) concentrations accelerates climate change and offsets mitigation efforts. Although wetlands are the largest natural CH4 source, estimates of global wetland CH4 emissions vary widely among approaches taken by bottom-up (BU) process-based biogeochemical models and top-down (TD) atmospheric inversion methods. Here, we integrate in situ measurements, multi-model ensembles, and a machine learning upscaling product into the International Land Model Benchmarking system to examine the relationship between wetland CH4 emission estimates and model performance. We find that using better-performing models identified by observational constraints reduces the spread of wetland CH4 emission estimates by 62% and 39% for BU- and TD-based approaches, respectively. However, global BU and TD CH4 emission estimate discrepancies increased by about 15% (from 31 to 36 TgCH4 year-1 ) when the top 20% models were used, although we consider this result moderately uncertain given the unevenly distributed global observations. Our analyses demonstrate that model performance ranking is subject to benchmark selection due to large inter-site variability, highlighting the importance of expanding coverage of benchmark sites to diverse environmental conditions. We encourage future development of wetland CH4 models to move beyond static benchmarking and focus on evaluating site-specific and ecosystem-specific variabilities inferred from observations.

Palladium-Catalyzed Regioselective Intermolecular Hydroalkoxylation of 1-Arylbutadienes.

An efficient method for the synthesis of (E)-(3-alkoxybut-1-enyl)benzenes by Pd-catalyzed regioselective intermolecular hydroalkoxylation of 1-arylbutadienes has been developed. This method can be executed in a simple operation with no dry reaction conditions required and having tolerance to a wide range of substrates. Chloromethyl methyl ether (MOMCl) as an additive was found to be essential for the success of the reaction.

Olfactory rule learning-induced enhancement in intrinsic neuronal excitability is maintained by shutdown of the cholinergic M-current.

Training rats in a particularly difficult olfactory discrimination task initiates a period of accelerated learning, manifested as a dramatic increase in the rats' capacity to discriminate between pairs of odors once they have learned the discrimination task, implying that rule learning has taken place. At the cellular biophysical level, rule learning is maintained by reduction in the conductance of the slow current (sIAHP) simultaneously in most piriform cortex layer II pyramidal neurons. Such sIAHP reduction is expressed in attenuation of the post-burst afterhyperpolarization (AHP) potential and thus in enhanced repetitive action potential firing. Previous studies have shown that a causal relationship exists between long-lasting post-burst AHP reduction and rule learning. A specific channel through which the sIAHP flows has not been identified. The sIAHP in pyramidal cells is critically dependent on membrane phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)]. PtdIns(4,5)P(2) regulates the calcium sensitivity of the sIAHP by acting downstream from the rise in intracellular calcium. These findings led to the interesting hypothesis that PtdIns(4,5)P(2) activates a variety of potassium channels. Thus, the sIAHP would not represent a unitary ionic current but the embodiment of a generalized potassium channel gating mechanism. We thus hypothesized that the learning-induced increase in intrinsic excitability is mediated by reduced conductance of one or more of the currents that contribute to the sIAHP. Here we first show, using current-clamp recordings, that the post-burst AHP in piriform cortex pyramidal neurons is also mediated by the Ih, and the contribution of this current to the post-burst AHP is also affected by learning. We also show, using whole-cell patch-clamp recordings, that the sIAHP in neurons from trained rats is not sensitive to blocking membrane phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)], and to the blocking of the current mediated by the cholinergic muscarinic acetylcholine receptor (M-current). Further current-clamp recordings also show that blocking PtdIns(4,5)P(2) synthesis and application of a specific IKCa blocker have no effect on the post-burst AHP in neurons from trained as well as control rats. Taken together with results from our previous studies, these data suggest that rule learning-induced long-lasting enhancement in intrinsic neuronal excitability results from reduced conductance of the M-current and thus the slow potassium currents, which control repetitive spike firing.

4 Dimensional XStrain speckle tracking echocardiography: comprehensive evaluation of left ventricular strain and twist parameters in healthy Indian adults during COVID-19 pandemic.

INTRODUCTION: 4D XStrain speckle tracking echocardiography (STE) is a feasible newer technology to evaluate the strain and rotational deformation of left ventricle (LV). We aimed to exhaustively present the normal value ranges of LV strain and twist parameter in healthy Indian adults during COVID-19 pandemic and furthermore to analyse their relationship with age and gender. METHOD: Study population consisted of 80 adults of 18-60 years (58 men, 22 women), which was arbitrarily divided into two groups: Group A <30 years and Group B >31 years. RESULTS: GLS was higher in females (P<0.01) and in Group A (P<0.01). On the contrary GCS and GRS were higher in men (P=NS) and in Group B (P<0.01), at the mitral valve level. At the papillary muscle level GCS and GRS values are more in men (P<0.01) and in <30 years of age (P<0.01 and P<0.05 respectively). Furthermore, the values of numerous other strain parameters-GLSR, GCSR, GRSR, LGV, TV, TS, TSR, Shear, Shear rate, ROV and RV, reflected heterogeneous variation across gender and various age groups. Twist was greater in men and increased with increasing age (P<0.01). CONCLUSION: We have demonstrated a comprehensive data obtained in the current study utilizing 4D XStrain STE in healthy subjects. The LV speckle tracking software simultaneously provided 4D volumetric, strain, rotation and twist data in great detail. However, this distinctive technology has not been widely adopted and its evaluation is still limited to research applications. Therefore, further clinical studies are needed to validate our findings.

Respiratory loss during late-growing season determines the net carbon dioxide sink in northern permafrost regions.

Warming of northern high latitude regions (NHL, > 50 °N) has increased both photosynthesis and respiration which results in considerable uncertainty regarding the net carbon dioxide (CO2) balance of NHL ecosystems. Using estimates constrained from atmospheric observations from 1980 to 2017, we find that the increasing trends of net CO2 uptake in the early-growing season are of similar magnitude across the tree cover gradient in the NHL. However, the trend of respiratory CO2 loss during late-growing season increases significantly with increasing tree cover, offsetting a larger fraction of photosynthetic CO2 uptake, and thus resulting in a slower rate of increasing annual net CO2 uptake in areas with higher tree cover, especially in central and southern boreal forest regions. The magnitude of this seasonal compensation effect explains the difference in net CO2 uptake trends along the NHL vegetation- permafrost gradient. Such seasonal compensation dynamics are not captured by dynamic global vegetation models, which simulate weaker respiration control on carbon exchange during the late-growing season, and thus calls into question projections of increasing net CO2 uptake as high latitude ecosystems respond to warming climate conditions.

The Safety Profile of FDA-Approved Epithelium-Off Corneal Cross-Linking in a US Community-Based Healthcare System.

Purpose: To determine the occurrence of early post-operative complications following FDA-approved epithelium-off corneal cross-linking in the United States. Materials and Methods: This multicenter, retrospective cohort study identified patients who underwent epithelium-off (epi-off) corneal cross-linking (CXL) for keratoconus and post-refractive keratectasia within the Kaiser Permanente Northern California healthcare system between 2016 and 2018. Post-operative complications including delayed epithelial healing, infection, and loss of visual acuity were recorded. Results: The study included 878 eyes of 654 patients. The mean age was 27±9.4 years (range 7-71). Five hundred ninety-nine patients (91.6%) had keratoconus while 55 had post-refractive corneal ectasia (8.4%). Forty-seven eyes had prolonged follow-up because of the occurrence of complications in the early post-operative period. The respective rates of delayed epithelial healing, and keratitis were 3.9% (95% CI 2.7-5.3%), and 1.5% (95% CI 0.8-2.5%). Four approaches for management of delayed epithelial healing were compared; epithelium healing duration was the longest in the repeat bandage contact lens (BCL) group (23.8 days) and the shortest in the antibiotic ointment group (14.3 days), with statistically significant differences (p < 0.05) in the healing time between these 2 groups. Conclusion: The concern for early clinical complications after epi-off CXL often leads to delayed CXL intervention and further keratoconus progression with increased economic burdens. A large retrospective review of 878 eyes found that FDA-approved epi-off CXL protocol appears to be safe with low occurrence rates of early post-operative complications. The recommended management for delayed epithelial healing is using antibiotic ophthalmic ointment.

Seasonal and annual variations of CO2 and CH4 at Shadnagar, a semi-urban site.

Carbon dioxide (CO2) and methane (CH4) are the most important greenhouse gases (GHGs) due to their significant role in anthropogenic global climate change. The spatio-temporal variations of their concentration are characterized by the terrestrial biosphere, seasonal weather patterns and anthropogenic emissions. Hence, to understand the variability in regional surface GHG fluxes, high precision GHGs measurements were initiated by the National Remote Sensing Center (NRSC) of India. We report continuous CO2 and CH4measurements during 2014 to 2017 for the first time from Shadnagar, a suburban site in India. Annual mean CO2 and CH4 concentrations are 399.56 ± 5.46 ppm and 1.929 ± 0.09 ppm, respectively, for 2017. After the strong El Niño of 2015-2016, an abnormal rise in CO2 growth rate of 5.5 ppm year-1 was observed in 2017 at the study site, compared to 3.03 ppm year-1 at Mauna Loa. Thus, the repercussion of the El Niño effect diminishes the net uptake by the terrestrial biosphere accompanied by increased soil respiration. Seasonal tracer to tracer correlation between CO2 and CH4 was also analyzed to characterize the possible source-sink relationship between the species. We compared CO2 and CH4 concentrations to simulations from an atmospheric chemistry transport model (ACTM). The seasonal phases of CH4 were well captured by the ACTM, whereas the seasonal cycle amplitude of CO2 was underestimated by about 30%.

Regional trends and drivers of the global methane budget.

The ongoing development of the Global Carbon Project (GCP) global methane (CH4 ) budget shows a continuation of increasing CH4 emissions and CH4 accumulation in the atmosphere during 2000-2017. Here, we decompose the global budget into 19 regions (18 land and 1 oceanic) and five key source sectors to spatially attribute the observed global trends. A comparison of top-down (TD) (atmospheric and transport model-based) and bottom-up (BU) (inventory- and process model-based) CH4 emission estimates demonstrates robust temporal trends with CH4 emissions increasing in 16 of the 19 regions. Five regions-China, Southeast Asia, USA, South Asia, and Brazil-account for >40% of the global total emissions (their anthropogenic and natural sources together totaling >270 Tg CH4  yr-1 in 2008-2017). Two of these regions, China and South Asia, emit predominantly anthropogenic emissions (>75%) and together emit more than 25% of global anthropogenic emissions. China and the Middle East show the largest increases in total emission rates over the 2000 to 2017 period with regional emissions increasing by >20%. In contrast, Europe and Korea and Japan show a steady decline in CH4 emission rates, with total emissions decreasing by ~10% between 2000 and 2017. Coal mining, waste (predominantly solid waste disposal) and livestock (especially enteric fermentation) are dominant drivers of observed emissions increases while declines appear driven by a combination of waste and fossil emission reductions. As such, together these sectors present the greatest risks of further increasing the atmospheric CH4 burden and the greatest opportunities for greenhouse gas abatement.

Strong Southern Ocean carbon uptake evident in airborne observations.

The Southern Ocean plays an important role in determining atmospheric carbon dioxide (CO2), yet estimates of air-sea CO2 flux for the region diverge widely. In this study, we constrained Southern Ocean air-sea CO2 exchange by relating fluxes to horizontal and vertical CO2 gradients in atmospheric transport models and applying atmospheric observations of these gradients to estimate fluxes. Aircraft-based measurements of the vertical atmospheric CO2 gradient provide robust flux constraints. We found an annual mean flux of ­0.53 ± 0.23 petagrams of carbon per year (net uptake) south of 45°S during the period 2009­2018. This is consistent with the mean of atmospheric inversion estimates and surface-ocean partial pressure of CO2 (Pco2)­based products, but our data indicate stronger annual mean uptake than suggested by recent interpretations of profiling float observations.

Application of remote sensing in alpine grasslands cover mapping of western Himalaya, Uttarakhand, India.

Grasslands are the world's most extensive terrestrial ecosystem, which provides a variety of services for humans, such as carbon storage, food production, crop pollination, pest regulation, and are a major feed source for livestock. However, grasslands are today one of the most endangered ecosystems due to land-use change, agricultural intensification, land abandonment, as well as climate change. Grasslands are an integral part of human societies across the globe, which are broadly known as tropical savannah and temperate grasslands. In the Himalayan region, grasslands are found in more than 55% of the area and different climatic conditions lead to different varieties of grasslands like Danthonia grasslands, kobresia sedge meadow, etc. Grasslands deal with the spatial and temporal distribution of heterogeneous landscapes, which support a high diversity of various species. Owing to very rugged terrain and inaccessibility, the information on the extent of alpine grassland and percent grass cover (%) across the meadows is limited. Therefore, the present attempt was made to assess the current status of grassland in the alpine region of Uttarakhand above 3000 m asl. LANDSAT-8 (OLI and TIRS sensors) satellite data were used to delineate the grasslands using normalized difference vegetation indices (NDVIs) of the alpine region with the help of over 179 ground truth points out of which 50 points are testing points and 129 points are training points. Grass covers (%) were also assessed in the whole alpine region of Western Himalaya of Uttarakhand which nearly consists of over 75 meadows by using random plots (1 × 1 m, total 10 per site) in each meadow. Overall, 89.52% accuracy was achieved based on 50 randomly selected testing points. A total of 4949.25 sq. km area is under the different percentage of grass cover in the alpine region of Uttarakhand, Western Himalaya. Danthonia grasslands below 4000 m and Kobresia sedge meadows above 4000 m elevation are dominant in the state. In the alpine region, over 1056 sq. km grassland area have less than 10% grass cover indicating higher degraded and cold desert areas and only 565.69 sq. km area have more than 60% grass cover, which is highly favorable for rich biodiversity and grazing.

Comparison of outcomes between 2 week versus 4 week stenting in pediatric pyeloplasty-A single centre observational study.

OBJECTIVE: To compare the surgical outcomes, improvement in renal function and complications between early stent removal (2 weeks) and late stent removal (4 weeks) after pediatric open pyeloplasty. METHODS: A total of 72 open pyeloplasty were included in the study. Forty-three underwent late stent removal (Group 1) and 29 underwent early stent removal (Group 2). Pre-operative and post-operative follow-up data were compared to see the effect of early stent removal on the postoperative drainage pattern at 6 months after surgery and improvement in split function of affected kidney. The complications between the two groups were also compared. RESULTS: Both the groups were matched with respect to age, sex, side and antero-posterior diameter of pelvis. Pre-operative mean split function in Group 1 was 42% (26%-54%) while it was 39% (19%-42%) in Group 2 (p=0.37). Postoperative improvement in drainage pattern was seen in 69 out of 72 (96%) patients, 41 out of 43 (95%) in Group 1 and 28 out of 29 (97%) in Group 2. Improvement in split function occurred in 35 of 38 (97%) in Group 1 and 23 of 26 (88%) patients in Group 2 (p=0.51). Complications were seen in nine out of 72 (12.5%) patients. Incidence of complication in Group 1 was 16% (7/43) and Group 2 was 7% (2/29), and relative risk was 2.36. CONCLUSION: A shorter duration of double J stenting is as effective as a longer stenting period in terms of surgical success outcomes and improvement in split renal function along with a decreased risk of stent related complications.

A Cellular Mechanism Underlying Enhanced Capability for Complex Olfactory Discrimination Learning.

The biological mechanisms underlying complex forms of learning requiring the understanding of rules based on previous experience are not yet known. Previous studies have raised the intriguing possibility that improvement in complex learning tasks requires the long-term modulation of intrinsic neuronal excitability, induced by reducing the conductance of the slow calcium-dependent potassium current (sIAHP) simultaneously in most neurons in the relevant neuronal networks in several key brain areas. Such sIAHP reduction is expressed in attenuation of the postburst afterhyperpolarization (AHP) potential, and thus in enhanced repetitive action potential firing. Using complex olfactory discrimination (OD) learning as a model for complex learning, we show that brief activation of the GluK2 subtype glutamate receptor results in long-lasting enhancement of neuronal excitability in neurons from controls, but not from trained rats. Such an effect can be obtained by a brief tetanic synaptic stimulation or by direct application of kainate, both of which reduce the postburst AHP in pyramidal neurons. Induction of long-lasting enhancement of neuronal excitability is mediated via a metabotropic process that requires PKC and ERK activation. Intrinsic neuronal excitability cannot be modulated by synaptic activation in neurons from GluK2 knock-out mice. Accordingly, these mice are incapable of learning the complex OD task. Moreover, viral-induced overexpression of Gluk2 in piriform cortex pyramidal neurons results in remarkable enhancement of complex OD learning. Thus, signaling via kainate receptors has a central functional role in higher cognitive abilities.

A non-synaptic mechanism of complex learning: Modulation of intrinsic neuronal excitability.

Training rats in a particularly difficult olfactory discrimination task initiates a period of accelerated learning of other odors, manifested as a dramatic increase in the rats' capacity to acquire memories for new odors once they have learned the first discrimination task, implying that rule learning has taken place. At the cellular level, pyramidal neurons in the piriform cortex, hippocampus and bsolateral amygdala of olfactory-discrimination trained rats show enhanced intrinsic neuronal excitability that lasts for several days after rule learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the post-burst after-hyperpolarization (AHP) which is generated by repetitive spike firing, and is maintained by persistent activation of key second messenger systems. Much like late-LTP, the induction of long-term modulation of intrinsic excitability is protein synthesis dependent. Learning-induced modulation of intrinsic excitability can be bi-directional, pending of the valance of the outcome of the learned task. In this review we describe the physiological and molecular mechanisms underlying the rule learning-induced long-term enhancement in neuronal excitability and discuss the functional significance of such a wide spread modulation of the neurons' ability to sustain repetitive spike generation.

Protective Effect of Pluchea lanceolata against Aluminum Chloride-induced Neurotoxicity in Swiss Albino Mice.

BACKGROUND: Aluminum chloride (AlCl3) is a known potent environmental neurotoxin causing progressive neurodegenerative changes in the brain. The herb Pluchea lanceolata is commonly known as "Rasana" and used as a nerve tonic in neuroinflammatory conditions in Indian system of medicine. OBJECTIVE: To evaluate the neuroprotective activity of hydroalcoholic extract of P. lanceolata in chronic AlCl3-induced neurotoxicity in Swiss albino mice. MATERIALS AND METHODS: Albino mice were categorized into four different groups; Group 1served as vehicle control, Group 2 mice were administered with AlCl3, 40 mg/kg body weight by intraperitoneal route for 45 consecutive days. Groups 3 and 4 mice were administered with AlCl3, 40 mg/kg body weight intraperitoneal for 45 consecutive days along with hydroalcoholic extract of P. lanceolata at 200 and 400 mg/kg body weight. RESULTS: Chronic administration of AlCl3 resulted in behavioral deficits, triggered lipid peroxidation, increased acetylcholinesterase (AChE) activity, and histological alterations. Co-administration of hydroalcoholic extract of P. lanceolata attenuated many of the AlCl3-induced alterations such as behavioral, lipid peroxidation, AChE, and histological changes of brain tissue. CONCLUSION: The results of the present study have demonstrated the protective role of hydroalcoholic extract of P. lanceolata against AlCl3-induced neurotoxicity in Swiss albino mice. The neuroprotective efficacy of P. lanceolata can help reduce the symptoms caused by toxic protein aggregates in several degenerative diseases. SUMMARY: The hydro alcoholic extract of Pluchea lanceolata showed neuroprotective activity in albino mice against AlCl3 toxicityThe benefits of Pluchea lanceolata against AlCl3 toxicity includes reduced lipid peroxidation and acetylcholine esterase activity with improved behavioral functionsThe hydro alcoholic extract of Pluchea lanceolata rendered protection against AlCl3 in forebrain, midbrain, cerebellum and hippocampusTherefore Pluchea lanceolata holds pharmacological potentials for treating diseases associated with neuronal toxicity. Abbreviations used: HAPL: Hydro alcoholic extract of Pluchea lanceolata; CAT: Catalase; GSH-Px: Glutathione peroxidase; SOD: Superoxide dismutase; TBARS: Thio-barbituric acid reactive substances; MDA: Malondialdehyde; AChE: Acetylcholine esterase; AOT: Acute oral toxicity; CNS: Central nervous system; H2O2: Hydrogen peroxide; ML: molecular layer; GL: granular layer; MC: microcytic changes; BV: blood vessels; DG: dentate gyrus; PC: pyramidal cells; LD: Lethal dose; ANOVA: Analysis of variance; SEM: Standard error of mean; PCL: Pyramidal cell layer; OCL: Outer granular layer; BV: blood vessels; PM: Pia mater.