In this model, unilateral intrahippocampal kainic acid (KA) injec

In this model, unilateral intrahippocampal kainic acid (KA) injection induced degeneration of CA1, CA3c and hilar neurons, followed by spontaneous recurrent focal seizures. In the contralateral, morphologically preserved MDV3100 hippocampus, a long-lasting increase of PSA-NCAM immunoreactivity was observed. Inactivation of PSA-NCAM by endoneuraminidase (EndoN) administration into the contralateral ventricle of KA-treated mice caused severe degeneration of CA3a,b neurons and dentate gyrus granule cells in the epileptic focus, and led to early onset of focal seizures. This striking trans-hemispheric alteration suggested that PSA-NCAM mediates

GDNF signaling, leading to transport of neuroprotective signals into the lesioned hippocampus. This hypothesis was confirmed by injecting GDNF antibodies into the contralateral hippocampus of KA-treated mice, thereby reproducing the enhanced neurodegeneration seen after PSA-NCAM inactivation. Furthermore, contralateral EndoN and anti-GDNF treatment decreased PCI-32765 molecular weight GDNF family receptor α1 immunoreactivity and FAK phosphorylation in the epileptic focus. Thus, Ret-independent GDNF signaling across the commissural projection might protect CA3a,b neurons and delay seizure onset. These findings implicate GDNF in the control of epileptogenesis and offer a

possible mechanism explaining lesion asymmetry in mesial TLE. “
“We often face the challenge of simultaneously attending to multiple non-contiguous regions of space. There is ongoing debate as to how spatial attention is divided under these situations. Whereas, for several years, the predominant view was that humans could divide the attentional spotlight,

several recent studies argue in favor of a unitary spotlight that rhythmically samples relevant locations. Here, this issue was addressed by the use of high-density electrophysiology in concert with the multifocal m-sequence technique to examine visual evoked else responses to multiple simultaneous streams of stimulation. Concurrently, we assayed the topographic distribution of alpha-band oscillatory mechanisms, a measure of attentional suppression. Participants performed a difficult detection task that required simultaneous attention to two stimuli in contiguous (undivided) or non-contiguous parts of space. In the undivided condition, the classic pattern of attentional modulation was observed, with increased amplitude of the early visual evoked response and increased alpha amplitude ipsilateral to the attended hemifield. For the divided condition, early visual responses to attended stimuli were also enhanced, and the observed multifocal topographic distribution of alpha suppression was in line with the divided attention hypothesis.

Like other H-NS proteins, XrvB may regulate various genes, which

Like other H-NS proteins, XrvB may regulate various genes, which may include pathogenicity-related genes other than hrp. Feng et al. (2009) reported that another H-NS-like protein XrvA functions in the positive regulation of hrp gene expression in the bacterium. They showed that, besides playing a role in hrp gene expression, XrvA Dabrafenib datasheet is also involved in the expression of rpfC, rpfF, rpfG and gumB, which play important roles in

virulence and extracellular polysaccharide production (Tang et al., 1996; Chatterjee & Sonti, 2002; Jeong et al., 2008). When the expression of rpfC was examined by semi-qRT-PCR, little difference was observed between the wild type and the XrvB mutant, and there seems to be no difference in extracellular polysaccharide production between the two strains (data not shown). The target genes of the two H-NS-like proteins, XrvA and XrvB, are likely to be different, but they may function cooperatively to enable the adequate expression of Xoo hrp genes in the infection process. The regulatory mechanisms of XrvB for hrp gene expression remain unclear. In a future study, a microarray assay comparing gene expression between the XrvB mutant and the

wild type or the chromatin immunoprecipitation assay should GSK126 solubility dmso reveal target genes that are directly regulated by XrvB, leading to the clarification of XrvB functions, including the interactions between XrvB and XrvA and/or other hrp regulatory proteins. Y.K.-I. and S.T. contributed

equally to this work. Fig. S1. Alignment of the conserved C-terminal region in H-NS-like proteins XOO0736, XOO2588 and XOO3168 of Xanthomonas oryzae pv. oryzae MAFF311018. Table S1. Bacterial strains and plasmids used Buspirone HCl in this study. Table S2. Primers used in this study. Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. “
“Ninety bacteria isolated from raw composting materials were screened for their cellulolytic activity on solid medium containing carboxymethylcellulose. The bacteria producing the highest cellulolytic activity levels were identified by 16S rRNA sequencing as Bacillus licheniformis strain 1, Bacillus subtilis subsp. subtilis strain B7B, Bacillus subtilis subsp. spizizenii strain 6, and Bacillus amyloliquefaciens strain B31C. Cellulase activity production by the most productive strain B. amyloliquefaciens B31C was optimized in liquid culture varying the carbon source. Comparison of growth curves of B. amyloliquefaciens B31C at temperatures from 28 to 47 °C indicated its thermotolerant nature. Moreover, analysis of time courses of cellulase activity production in this thermal range showed that increase of temperature from 28 to 37 °C causes an increase of cellulase activity levels.

Homologous systems were identified in the genomes of distinct tax

Homologous systems were identified in the genomes of distinct taxonomic groups of Bacteria and Archaea, which provides

evidence that horizontal gene transfer has contributed to the wide dissemination of R-M modules – even between domains. Analysis of the cleavage specificity of the R.PamI endonuclease revealed that this protein is an isoschizomer of restriction enzyme NcoI. Interestingly, bioinformatic analyses suggest that R.PamI and NcoI are accompanied by methyltransferases of different methylation specificities (C5-methylcytosine and N4-methylcytosine methyltransferases, respectively), which possibly exemplifies recombinational shuffling of genes coding for individual components of R-M systems. The PamI system can stabilize plasmid pAMI7 in a bacterial population, most probably at the postsegregational level. Therefore, it functions in an analogous manner to plasmid-encoded Selleckchem Tofacitinib toxin-antitoxin (TA) systems. Since the TA system

of pAMI7 is nonfunctional, it is highly Veliparib chemical structure probable that this lack is compensated by the stabilizing activity of PamI. This indicates the crucial role of the analyzed R-M system in the stable maintenance of pAMI7, which is, to our knowledge, the first report of ‘symbiosis’ between a R-M system and a plasmid in the Alphaproteobacteria. Restriction-modification (R-M) systems are exclusive to unicellular organisms and are ubiquitous in the bacterial world. These systems encode (1) a restriction endonuclease (REase), which recognizes a specific DNA sequence and introduces a double-strand break, and (2) a cognate DNA methyltransferase (MTase) that transfers the methyl group from S-adenosyl-l-methionine

(AdoMet) onto specific nucleobases within the same target, thereby protecting it from cleavage. Methylation of DNA occurs either at adenine or cytosine, yielding N6-methyladenine (m6A), N4-methylcytosine (m4C) or C5-methylcytosine (m5C). The m4C and m6A DNA MTases, which modify exocyclic NH2 groups, Florfenicol are grouped together as N-MTases (Tock & Dryden, 2005). Based on their genetic and biochemical characteristics, R-M systems have been classified into four types (I–IV) (Roberts et al., 2003). The vast majority (more than 3800) of the systems belong to type II, which comprises two-gene genetic modules encoding separate proteins: MTase and REase. Both enzymes recognize a specific short nucleotide sequence (commonly a palindrome) and the REase cleaves double-stranded DNA at specific sites within or adjacent to these sequences (Roberts et al., 2003). It is widely believed that the R-M modules act as ‘a natural bacterial immune system’ which discriminates ‘self ’ (methylated) DNA from ‘foreign’ (not protected by methylation) DNA acquired by horizontal gene transfer. These systems are therefore efficient tools for defense against infection by viral, plasmid, and other exogenous DNA (Tock & Dryden, 2005).

History of HIV infection and hepatitis A, B or C was obtained fro

History of HIV infection and hepatitis A, B or C was obtained from the interview and confirmed serologically and using medical charts. Serological proof of coinfection with HCV and HIV was obtained using the Procleix HIV-1/HCV nucleic acid testing kit (Gen-Probe, San Diego, CA, USA) [23]. Plasma MDA was tested as the marker of oxidative stress using the TBAR kit (ZeptoMetrix, Buffalo, NY, USA). In this test, thiobarbituric acid was reacted with MDA, and the concentration of MDA in plasma determined by fluorimetry at an excitation wavelength of 530 nm and emission of 550 nm. Plasma glutathione peroxidase activity was determined using the Total Glutathione Peroxidase assay kit (ZeptoMetrix).

Plasma levels of zinc and selenium were determined by flame atomic absorption spectrophotometry. Plasma vitamin A and vitamin E levels were determined by http://www.selleckchem.com/products/gsk1120212-jtp-74057.html high-performance liquid chromatography (HPLC). Weight and height were obtained in participants wearing light clothing and no shoes utilizing a standard scale calibrated prior to each measurement. Height was measured with the participant’s heels touching the base of the vertical board of the stadiometer. The moveable headboard was brought to the most superior point on the head with sufficient pressure to compress the hair. Body mass index (BMI) was calculated using the standard formula that divides weight in kilograms by the square of height in

metres (kg/m2). To estimate liver disease stage, we calculated the aminotransferase to platelet ratio index (APRI) and fibrosis index (FIB-4) indexes, http://www.selleckchem.com/GSK-3.html which include routine tests to predict liver fibrosis in patients with HIV/HCV coinfection [24]. The objectives were (1) to determine whether there was a significant difference in the proportion and degree of liver damage between the HIV/HCV-coinfected and HIV-monoinfected groups and (2) to determine whether there was a relationship between the stage of

liver disease and oxidative stress and plasma antioxidants, regardless of the aetiology of liver damage and HCV status. The APRI was calculated according to the formula: [AST (× upper limit of normal range) × 100]/platelet count (109 cells/L). The upper limit of normal for the present study was 0.45. The FIB-4 formula uses age and the relatively inexpensive test of transaminases (AST and ALT) and platelet counts Ureohydrolase (PLT): [age (years) × AST (U/L)]/[PLT (109 cells/L) × ALT1/2 (U/L)]. At a cut-off of <1.45, the negative predictive value to exclude advanced fibrosis (stages 4–6 of the Ishak scale) was 90% with a sensitivity of 70%. A cut-off of >3.25 had a positive predictive value of 65% and a specificity of 97% to predict advanced disease [24]. Animal and human studies have associated obesity, type 2 diabetes and hypertriglyceridaemia with increased oxidative stress and nonalcoholic liver disease [25,26]. For this reason, only the values for participants without diabetes, whose BMI was <28 kg/m2, and who had plasma triglycerides <150 mg/dL were used in the final analysis.

They might thus play a role in modulating spinal activity in adva

They might thus play a role in modulating spinal activity in advance of any control exerted via the cerebellar loop. “
“Plaid stimuli are often used to investigate the mechanisms involved in the integration and segregation of motion information. Considering the perceptual importance of such mechanisms, only a very limited number of visual brain areas have been found to be specifically involved in motion integration. These are the human (h)MT+ complex, area V3 and the pulvinar. The hMT+ complex can be functionally subdivided RG7204 solubility dmso into two separate areas, middle temporal area (MT) and medial superior temporal area (MST); however, it is currently unclear

whether these distinct sub-regions have different responses to plaid stimuli. To address this issue we used functional magnetic resonance imaging to quantify the relative response of MT and MST Adriamycin to component and pattern

motion. Participants viewed plaid stimuli that were constrained to result in the perception of either component motion (segregation of motion information) or pattern motion (integration of motion information). MT/MST segregation was achieved using a moving dot stimulus that allowed stimulation of each visual hemifield either in unison or separately. We found pattern motion selective responses in both MT and MST. Consistent with previous reports, activity indicative of pattern motion selectivity was also found in the pulvinar as well as in other extrastriate areas. These results

demonstrate that MT, MST and the pulvinar are involved Sclareol in the complex motion integration mechanisms that are triggered by plaid stimuli. This reinforces the concept that integrative computations take place in a distributed neuronal circuit both in cortical and sub-cortical networks. “
“Magnetic compass orientation in a night-migratory songbird requires that Cluster N, a cluster of forebrain regions, is functional. Cluster N, which receives input from the eyes via the thalamofugal pathway, shows high neuronal activity in night-migrants performing magnetic compass-guided behaviour at night, whereas no activation is observed during the day, and covering up the birds’ eyes strongly reduces neuronal activation. These findings suggest that Cluster N processes light-dependent magnetic compass information in night-migrating songbirds. The aim of this study was to test if Cluster N is active during daytime migration. We used behavioural molecular mapping based on ZENK activation to investigate if Cluster N is active in the meadow pipit (Anthus pratensis), a day- and night-migratory species. We found that Cluster N of meadow pipits shows high neuronal activity under dim-light at night, but not under full room-light conditions during the day.


“Proteorhodopsins (PRs), light-driven proton pumps, consti


“Proteorhodopsins (PRs), light-driven proton pumps, constitute the largest family of the microbial rhodopsins. PRs are widely distributed in the oceanic environment and freshwater, but no bacteria with PRs have been isolated from freshwater so far. To facilitate isolation of the bacteria with PR genes, we constructed

INK 128 cost a vector system that can be used to clone potential PR genes and render color changes when overexpressed in Escherichia coli. Using this method, we successfully isolated a strain with PR gene from freshwater and identified it as Exiguobacterium sp. JL-3. The full length PR gene was then cloned using the SEFA PCR method. Protein sequence alignment showed that JL-3_PR shares high sequence identity (84–89%) with the PRs from Exiguobacterium strains, but low sequence identity (< 38%) with other PRs. Surprisingly, we could not detect any proton-pumping activity in the native JL-3 cells and protoplasts, but the recombinant JL-3_PR do pump protons when overexpressed in E. coli. Sequence analysis further revealed that the PRs from Exiguobacterium had an unusual lysine as the proton donor instead of the typical acidic residue. These data suggest that JL-3_PR is a sensory PR rather than a proton pump. "
“Pseudomonas aeruginosa

are known to have a wide physiological potential allowing them to constantly populate diverse environments leading to severe infections of humans such as septicemia, leg ulcers, and burn wounds. We set out to probe physiological characteristics of P. aeruginosa isolates from diabetic Ku-0059436 leg ulcers collected from Helsinki metropolitan area. A total of 61 clinical isolates were obtained. Detailed phenotypic (physiological) characteristics [outer membrane (OM) permeability, membrane voltage, and activity of multidrug

resistance pumps] were determined in several growth phases leading to the division of the analyzed set of P. aeruginosa strains into five distinct clusters including Doxacurium chloride cells with similar physiological properties. In addition, their antibiotic resistance patterns and genetic heterogeneity were determined. Multiple isolates from the same patient were genetically very closely related and belonged to the same phenotypic cluster. However, genetically close isolates from different patients expressed very different phenotypic properties. The characteristics of infected patients seem to determine the growth environments for microorganisms that adapt by changing their physiological and/or genetic properties. “
“Cysteine synthase A encoded by cysK catalyzes the synthesis of cysteine from O-acetylserine. Expression of cysK in Escherichia coli is under the control of CysB, a LysR family transcription factor. Herein we showed that the expression of cysK is regulated by several genetic and environmental factors in addition to CysB: two genetic factors, OmpR and CysE, and lithium. Based on the findings, we constructed the high-level expression system of cysK.

Sunbathing, swimming, skiing, and other outdoor pursuits remain p

Sunbathing, swimming, skiing, and other outdoor pursuits remain popular activities among travelers despite associations between excessive UV radiation and skin cancer. Some special populations are at high risks of solar UV radiation-associated skin cancers, including children, persons taking certain photosensitive drugs, organ transplant recipients, and persons with rare genetic skin diseases. Recommended photoprotection strategies

for everyone and especially for travelers to high UV index regions should include: (1) practicing Ion Channel Ligand Library datasheet responsible sun exposure behaviors, (2) wearing photoprotective clothing, (3) wearing sunglasses, (4) applying broad-spectrum sunscreens, and (5) selecting the right sunscreen for one’s skin type. Travel medicine practitioners should always advise their patients to avoid sunburns that could spoil vacations and damage skin and should encourage them to reapply broad-spectrum sunscreens frequently and to wear photoprotective clothing, including broad-brimmed hats. Hotels and resort communities should encourage their guests to Ku-0059436 concentration adopt responsible sun exposure and protection behaviors by making sunscreens available at swimming pools, tennis courts, golf courses, and all other outdoor venues enjoyed by vacationers. Although the impact of UV radiation on the development

of CMM, retinal melanoma, and macular degeneration will require further study, travelers may anticipate future advances in sunscreen composition including the addition of silica-shell microencapsulated

UV filters to enhance UV protection, antioxidants to limit DNA damage, and DNA repair stimulants to repair any sun damage.[68] Astemizole The authors state they have no conflicts of interest to declare. “
“Travel-related diarrhea is common among tourists to developing countries. We report two cases of diarrhea due to Cryptosporidium hominis and Isospora belli, respectively, in a child and an adult returning from Africa, without other associated microorganisms. We emphasize the need to detect underdiagnosed coccidiosis in diarrheic travelers with specific methods Most episodes of travelers’ diarrhea have a self-limited course and the pathogens do not cause any major damage to the intestine. Bacterial enteropathogens, particularly enterotoxigenic Escherichia coli, account for most acute diarrheal episodes in travelers,1 but the etiology of persistent travelers’ diarrhea lasting more than 3 weeks often remains unknown. Spore-forming protozoa, such as Cryptosporidium, Cyclospora, Isospora, and fungi as Microsporidia are now well-documented causes of persistent diarrhea in returning travelers.2–4 We report a case of chronic Cryptosporidium hominis diarrhea and a case of acute Isospora belli diarrhea in immunocompetent travelers both returning from West Africa. A 1-year-old child born in France to a Guinean immigrant couple living in Amiens (Picardy, France) traveled with these parents returning to their village in Guinea on holiday from May 11 to June 11, 2008.

The mean velocity over a 90-min recording period was calculated i

The mean velocity over a 90-min recording period was calculated in the control and treatment condition. To measure a change in the directionality of migrating interneurons after treatment conditions, the angle change between the track path of the control condition

and of the wash condition was calculated. For quantification of the distribution of GAD65-GFP+ interneurons, sections from GAD65-GFP mice and adra2a/2c-ko GAD65-GFP mice were obtained at P21 and quantified in the somatosensory cortex (bregma -1.34; mouse brain atlas, Paxinos and click here Franklin, 2001). Composite epifluorescent images (Nikon Plan 10× objective) were obtained with GAD65-GFP+ and Hoechst labelling, a grid was apposed on the corresponding somatosensory cortex using the Metamorph software (version 7.4) and GAD65-GFP+ cells were manually counted in the different cortical layers (n = 6 GAD65-GFP+ brains, total of 881 cells; n = 6 adra2a-ko GAD65-GFP+ brains, total of 1015 cells). Epifluorescent images (Nikon Plan 10× objective) were Roscovitine taken at the level of the somatosensory cortex to quantify the percentage of GAD65-GFP+ interneurons located in upper (I–IV) and lower (V and VI) cortical layers and expressing VIP (n = 3, 529 cells), reelin (n = 3, 685 cells), NPY (n = 3, 644 cells), calretinin (n = 3,

673 cells), parvalbumin (n = 3, 726 cells) and somatostatin (n = 3, 623 cells). Statistical analysis (GraphPad prism software, version 4.0) was done using unpaired Student’s t-test, one-way anova with Tukey’s multiple comparison test, or χ2 Edoxaban test. Statistical significance was defined at *P < 0.05, **P < 0.01. Values given are means ± SEM. Transgenic mice expressing GFP under the control of the GAD65 promoter were used to study cortical interneuron migration as previously described (Riccio et al., 2009). Given the high subtype diversity of cortical interneurons, we first characterised the identity of GAD65-GFP interneurons

using molecular markers. As previously reported (Lopez-Bendito et al., 2004; Riccio et al., 2011), we found that GAD65-GFP+ interneurons preferentially express markers that label cortical interneurons derived from the caudal ganglionic eminences but not the medial ganglionic eminences (Fig. S1). Quantification at postnatal day 21 in the somatosensory cortex revealed that GAD65-GFP+ cortical interneurons hardly expressed parvalbumin or somatostatin (Fig. S1), which are classical markers of cortical interneuron subtypes derived from the medial ganglionic eminences (Rudy et al. 2011). In contrast, GAD65-GFP+ interneurons expressed markers such as reelin, NPY, VIP and calretinin, which preferentially label cortical interneuron subtypes derived from the caudal ganglionic eminences (Fig. S1; Rudy et al. 2011). Migration of GAD65-GFP+ interneurons was monitored between E17.5 and E18.

(2) Male expatriates reported more frequent intensive sun exposur

(2) Male expatriates reported more frequent intensive sun exposures and more skin exposures during nautical and mountain sports than male nonexpatriates. Ezzedine and colleagues have registered a large cohort of French adults to observe for sun exposure

and protection behaviors in tropical and high UV-index countries for short and prolonged stays, and their results have repeatedly demonstrated that travelers would benefit from more pre-travel advice regarding sun exposures and sun protective behaviors.[20, 21] Observational studies have demonstrated that the public often misuses sunscreens for intentional UV overexposures and knows little about proper sunscreen protection, selection, CB-839 manufacturer and use. In 2001,

Wright and colleagues evaluated attitudes toward sunscreen effectiveness and found that 47% of study subjects reported staying out longer in the sun after applying sunscreen.[22] Later, Autier defined this behavior as sunscreen abuse or the misuse of sunscreens by sun-sensitive subjects engaging in intentional sun exposure to increase their duration of exposure without decreasing sunburn occurrence.[23] In 2008, Ezzedine and colleagues reported the results of a cross-sectional this website study on artificial and natural tanning behaviors in a French national cohort of 7,200 adults.[24] The investigators determined that indoor tanners were also regular sunbathers unconcerned about the risks of combined indoor and outdoor UV exposures.[24] In a 2009 survey assessment of sunscreen knowledge, Wang observed that only 48.2% of survey

respondents knew that “SPF” was the acronym for “sun protection factor.”[25] The confusing measurement systems for UV protection afforded by sunscreens and photoprotective clothing are compared in Table 1.[18, 26, 27] The quantity and frequency of sunscreen use are the most important factors determining sunscreen efficacy. The international standard quantity of sunscreen application used to determine SPF is 2 mg/cm2.[28, 29] However, Diffey observed that most people apply only 0.5 to 1.5 mg/cm2 Immune system of sunscreen and do not reapply sunscreens after swimming or excessive sweating.[29] Drug-induced photosensitivity reactions occur commonly and are characterized by cutaneous eruptions in sun-exposed areas and result from either toxic or allergic reactions between drugs and UV radiation, primarily UVA.[30-33] Phototoxic reactions are more common than photoallergic reactions, which occur when drug haptens combine with skin proteins producing an immune cellular reaction.[31] Chronic therapy with certain photosensitizing drugs has been associated with the subsequent development of skin cancers, such as PUVA therapy for psoriasis which increases risks of SCC and CMM.

During high-frequency stimulation, AZ endocytosis operated mainly

During high-frequency stimulation, AZ endocytosis operated mainly in the early phase, whereas non-AZ endocytosis operated in the late phase. Thus, intense synaptic transmission is coordinately maintained by synaptic vesicle recycling initiated by Ca2+ influx through the two this website types of Ca2+ channel. “
“Repetitive behaviors and hyperactivity are common features of developmental disorders, including autism. Neuropathology of the cerebellum is also a frequent occurrence in autism and other developmental

disorders. Recent studies have indicated that cerebellar pathology may play a causal role in the generation of repetitive and hyperactive behaviors. In this study, we examined the relationship between cerebellar pathology and these behaviors in a mouse model of Purkinje cell loss. Specifically, we made aggregation chimeras between Lc/+ mutant embryos and +/+ embryos. Lc/+ mice lose 100% of their Purkinje cells postnatally due to a cell-intrinsic NVP-BGJ398 research buy gain-of-function mutation. Through our histological examination, we demonstrated that Lc/++/+ chimeric mice have Purkinje cells ranging from zero to normal numbers. Our analysis of these chimeric cerebella confirmed previous studies on Purkinje cell lineage. The results of both open-field activity and hole-board exploration testing indicated negative relationships between Purkinje cell number and measures of activity and

investigatory nose-poking. Additionally, in a progressive-ratio operant paradigm, we found that Lc/+

mice lever-pressed significantly less than +/+ controls, which led to significantly lower breakpoints in this group. In contrast, chimeric mice lever-pressed significantly more than controls and this repetitive lever-pressing behavior was significantly and negatively correlated with total Purkinje cell numbers. Although the performance of Lc/+ mice is probably related to their motor deficits, the significant relationships between Purkinje cell number and repetitive lever-pressing behavior as well as open-field activity measures provide support for a role of cerebellar pathology in generating repetitive behavior and increased activity in chimeric mice. “
“Fast inhibitory synaptic inputs, which cause conductance Diflunisal changes that typically last for 10–100 ms, participate in the generation and maintenance of cortical rhythms. We show here that these fast events can have influences that outlast the duration of the synaptic potentials by interacting with subthreshold membrane potential oscillations. Inhibitory postsynaptic potentials (IPSPs) in cortical neurons in vitro shifted the oscillatory phase for several seconds. The phase shift caused by two IPSPs or two current pulses summed non-linearly. Cholinergic neuromodulation increased the power of the oscillations and decreased the magnitude of the phase shifts.