mellonella, thereby enhancing the host defense against B. cenocepacia infection. As shown in Fig. 4c, at 10 h postinfection, the four immune-related genes were

either inactive (uninfected larvae treated with DHA) or expressed at very low levels (infected larvae with and without DHA treatment). However, at 21 h postinfection, the mRNAs of gallerimycin, IMPI and lysozyme were found to be induced either in the infected larvae-treated or untreated with DHA. Nevertheless, the total amount of mRNA encoding gallerimycin reached its highest value in the DHA-treated larvae (120-fold). The housekeeping gene actin was used as a reference for relative quantification of mRNA (Fig. 4c). The antimicrobial property of essential ABT-263 manufacturer LCUFAs and their derivatives has been recognized for many years (Desbois & Smith, 2010). In the present study, we have investigated for the first time the in vitro antimicrobial properties of eight different LCUFAs against B. cenocepacia, an emerging pathogen in patients with CF. We observed that of the LCUFAs tested, only three fatty acids have anti-Burkholderia activity,

namely petroselinic acid, DHA and nervonic acid. The differences in growth inhibition most likely correlates with the geometry and position of the carbon-carbon double bonds as well as the carbon chain lengths of the LCUFAs tested (Huang et al., 2010). DHA showed the highest level of growth inhibition, albeit with moderate efficacy (millimolar concentrations) see more (Fig. 1). This is consistent with previous published studies that indicate that DHA exhibits a broad spectrum of in vitro antibacterial activity against various Gram-positive and Gram-negative pathogenic bacteria (Shin et al., 2007; Martinez

et al., 2009). The mechanism of action of DHA against B. cenocepacia K56-2 is not known. Possibly, as described Hydroxychloroquine for other LCUFAs, DHA primarily affects the integrity of the bacterial plasma membrane, thereby leading to cell damage and cell death (Desbois & Smith, 2010). There are, however, some differences in DHA activity between cell types, whereby DHA has a higher antimicrobial activity against Gram-positive bacteria, which again, probably is a result of structural differences in the cell wall and/or plasma membrane (Shin et al., 2007). To further extend and confirm the in vitro anti-Burkholderia activity of DHA, a panel of 19 isolates representing all 17 Bcc species was tested. Our results indicated that all Bcc isolates were inhibited by 50 mM DHA, although significant differences in the levels of growth inhibition were observed across all species (Fig. 3). No obvious link was observed between DHA and antibiotic or biocide resistance as previously published (Nzula et al., 2002; Rose et al., 2009). The clinical isolate B. cenocepacia J2315 was found to be more susceptible to DHA than other B. cenocepacia strains, yet J2315 was the strain most resistance to meropenem (Nzula et al., 2002). Conversely, strain B.

mellonella, thereby enhancing the host defense against B. cenocepacia infection. As shown in Fig. 4c, at 10 h postinfection, the four immune-related genes were

either inactive (uninfected larvae treated with DHA) or expressed at very low levels (infected larvae with and without DHA treatment). However, at 21 h postinfection, the mRNAs of gallerimycin, IMPI and lysozyme were found to be induced either in the infected larvae-treated or untreated with DHA. Nevertheless, the total amount of mRNA encoding gallerimycin reached its highest value in the DHA-treated larvae (120-fold). The housekeeping gene actin was used as a reference for relative quantification of mRNA (Fig. 4c). The antimicrobial property of essential Akt inhibitor LCUFAs and their derivatives has been recognized for many years (Desbois & Smith, 2010). In the present study, we have investigated for the first time the in vitro antimicrobial properties of eight different LCUFAs against B. cenocepacia, an emerging pathogen in patients with CF. We observed that of the LCUFAs tested, only three fatty acids have anti-Burkholderia activity,

namely petroselinic acid, DHA and nervonic acid. The differences in growth inhibition most likely correlates with the geometry and position of the carbon-carbon double bonds as well as the carbon chain lengths of the LCUFAs tested (Huang et al., 2010). DHA showed the highest level of growth inhibition, albeit with moderate efficacy (millimolar concentrations) CSF-1R inhibitor (Fig. 1). This is consistent with previous published studies that indicate that DHA exhibits a broad spectrum of in vitro antibacterial activity against various Gram-positive and Gram-negative pathogenic bacteria (Shin et al., 2007; Martinez

et al., 2009). The mechanism of action of DHA against B. cenocepacia K56-2 is not known. Possibly, as described Aldehyde dehydrogenase for other LCUFAs, DHA primarily affects the integrity of the bacterial plasma membrane, thereby leading to cell damage and cell death (Desbois & Smith, 2010). There are, however, some differences in DHA activity between cell types, whereby DHA has a higher antimicrobial activity against Gram-positive bacteria, which again, probably is a result of structural differences in the cell wall and/or plasma membrane (Shin et al., 2007). To further extend and confirm the in vitro anti-Burkholderia activity of DHA, a panel of 19 isolates representing all 17 Bcc species was tested. Our results indicated that all Bcc isolates were inhibited by 50 mM DHA, although significant differences in the levels of growth inhibition were observed across all species (Fig. 3). No obvious link was observed between DHA and antibiotic or biocide resistance as previously published (Nzula et al., 2002; Rose et al., 2009). The clinical isolate B. cenocepacia J2315 was found to be more susceptible to DHA than other B. cenocepacia strains, yet J2315 was the strain most resistance to meropenem (Nzula et al., 2002). Conversely, strain B.

This is a normal tendency of biofilm-forming bacteria such as mycobacteria. On treatment with alcohol, most of the bacteria lose their cell shape and morphology and as a consequence remain unattached and occur mostly as single cells. Thus, the growth inhibitory activity of decanol can be attributed partly, if not exclusively, to its ability to damage the cellular envelope. Perhaps INCB024360 research buy this damage is a result of the well-known event of accumulation of alkanols in the membrane thus affecting the general membrane functions. Biofilm formation in many cases is important for bacterial virulence and survival (Parsek & Singh, 2003). So a successful attenuation of biofilm formation can be of wide interest for

the management of disease progression and elimination of the pathogen. An intact cellular envelope and its hydrophobicity helps in cell to cell adhesion and thus promotes biofilm formation in microorganisms such as mycobacteria. Thus, any damage to the cell envelope may hinder its ability to adhere to each other and subsequently inhibits biofilm formation. In this context we have assessed the TSA HDAC datasheet ability of long-chain fatty alcohols in biofilm formation

by performing CV assay and acridine orange staining of the biofilm. Interestingly, our result showed that decanol concentrations of 0.1 and 0.2 mM, far lower than its MIC (0.4 mM), were able to attenuate biofilm formation (Fig. 3a). Furthermore, the quantitative CV assay also revealed that 9-decene-1-ol concentrations of 0.05 and 0.1 mM, again lower than its MIC (0.2 mM), were able to attenuate biofilm formation considerably (Fig. 3b). The same concentration of the alcohols tested had

no effect on planktonic growth as measured by OD600 nm. These results clearly suggest that a sublethal dose of both 1-decanol and 9-decene-1-ol is able to attenuate biofilm formation in vitro. This inhibition may result from the ability of these agents to damage the cellular envelope and thus in turn perturb the cell to cell adhesion, which from is a key factor in biofilm formation. Exploring new agents that can attenuate biofilm formation and insight into the mechanism involved may shed light into therapeutic strategies for infections with microbes such as mycobacteria whose pathogenic potential strongly depends on successful biofilm formation within the host. Surface active agents such as surfactants and other membrane-damaging compounds are drawing significant attention in the field of antimicrobial chemotherapy. Drugs such as daptomycin clofazimine derivatives that are known to disrupt membrane integrity are already being used either clinically or are at the final stage of drug development (Adams et al., 1999; Pogliano et al., 2012). Membrane active agents generally have multiple target sites and diverse modes of action against the organism, reducing the chance of mutation at the target site (Andries et al., 2005; Koul et al., 2008).

Supernatant solubility was tested in different polar solvents: 2 × ethyl acetate, chloroform or butanol were added,

respectively, to a 250-mL flask with 50 mL of the different culture filtrates. Extraction of potentially active fractions was Selleck STA-9090 carried out as described (Rydberg et al., 2004). The organic phase was vaporized to remove the organic solvent using a vacuum at 50 °C followed by the addition of sterile distilled water until the original volume was restored. The aqueous phase and aqueous solution components of the respective organic extracts were then tested for nematicidal activity. The molecular size of the nematicidal components was determined by dialyzing the culture filtrates against a Millipore ultrafiltration membrane (1000 nominal molecular weight limit) using a vacuum PI3K inhibitor rotary evaporator. The culture filtrates in the Buchner flask and the residual portion in the Buchner

funnel were, respectively, diluted to their starting volumes with ddH2O (solutions E and F, which were then tested for nematicidal activity). Genomic DNA was extracted from Bacillus spp. as described (Hoflack et al., 1997). Plasmids from E. coli and Bacillus spp. were both extracted with an AxyPrep™ plasmid miniprep kit (Axygen Scientific Inc., Union City, CA), except that Bacillus spp. were resuspended in solution I and treated with 10 mg mL−1 lysozyme (Sigma, pH 8.0) at 37 °C for 20 min. Escherichia coli DH5α and B. subtilis OKB105 strains were transformed as described (Spizizen, 1958; Sambrook et al., 1989) as was the OKB105 mutant library (Breton et al., 2006). Southern hybridizations were performed using DIG High Prime DNA Labeling and the Detection Starter Kit I as described by the manufacturer (Roche Applied Science, Mannheim, Germany). All enzymes used in this study were purchased from TaKaRa Bio Inc. (Japan). The specific primers used are described in Table 2. For complementation of the

M1 mutant, two types of plasmids were constructed. pMA5-purL (multicopy shuttle expression vector) was constructed as follows. The entire purL gene was amplified from strain OKB105 chromosomal DNA using primers P1/P2. The sequences of Cm were obtained from pDG1661 using primers P3/P4. The two fragments were ligated by overlap PCR using primers P1/P4. The PCR product was purified, Astemizole digested with BamHI and NdeI, and cloned into the E. coli–B. subtilis pMA5 shuttle vector (Dartois et al., 1994) to generate expression vector pMA5-purL. The pMA5-purL was transformed into strain M1, and selected on solid LB agar medium supplemented with 5 μg mL−1 chloramphenicol and 50 μg mL−1 kanamycin. M1∷pMA5-purL was confirmed by PCR and BamHI/NdeI digestion, and the resulting transformant was designated M1-1. M1-1 used the constitutive promoter HpaII for purL expression. pUC18-purL (suicide vector) was constructed as follows.

In addition, the ssg mutation also significantly altered the exopolysaccharide composition devoid of fucose

and mannose. Based on the results of our analysis of sugar composition of exopolysaccharide, we speculate that the product Trichostatin A manufacturer of ssg might be involved in the transfer of a specific sugar residue from its nucleotide-activated sugar precursor to the growing chain of exopolysaccharide as proposed above for the role of Ssg protein in lipopolysaccharide biosynthesis. The precise mechanism by which Ssg acts on O-antigen and exopolysaccharide biosynthesis deserves further study. Mutations that alter the lipopolysaccharide biosynthesis have been shown to affect motility and biofilm formation in many bacteria including P. aeruginosa and Stenotrophomonas maltophilia (Huang et al., 2006; Lindhout et al., 2009). As expected, the mutant Tyrosine Kinase Inhibitor Library order KL28Δssg exhibited many defects, especially in adhesion-related properties such as surface motility, circular pellicles, biofilm and aerial structure formation. The observed defects in the mutant strain are probably due to the cumulative effect of lipopolysaccharide truncation and altered exopolysaccharide composition. Thus, the ssg gene has important

relevance in the ecological fitness of this bacterium. Although homologs of Ssg are found in many plant and animal pathogenic Pseudomonas species, the reaction catalyzed by members of this glycosyltransferase family remains unknown at present (King et al., 2009). In conclusion, we have shown that the product encoded by ssg plays a critical role in lipopolysaccharide and exopolysaccharide biosynthesis in strain KL28. More work is required

before we can fully understand the biochemical activities of Ssg in lipopolysaccharide and/or exopolysaccharide biosynthesis pathways in Pseudomonas. Carnitine dehydrogenase This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (No. 2009-0073913 and 2007-0055799) and by Changwon National University in 2009–2010. Work in the lab of J.S.L. is funded by the Canadian Cystic Fibrosis Foundation, and J.S.L. is a holder of a Canada Research Chair award. “
“The thermophilic bacterium Thermus thermophilus HB27 is known for its highly efficient natural transformation system, which has become a model system to study the structure and function of DNA transporter in thermophilic bacteria. The DNA transporter is functionally linked to type IV pili (T4P), which are essential for twitching motility and adhesion to solid surfaces. However, the pilus structures themselves are dispensable for natural transformation. Here, we report that the cellular mRNA levels of the major structural subunit of the T4P, PilA4, are regulated by environmental factors. Growth of T. thermophilus in minimal medium or low temperature (55 °C) leads to a significant increase in pilA4 transcripts.

The analysis of the mutants should continue, especially with respect to changes in membrane properties caused by the presence and absence of the distinct modifications. Hand in hand should go a structural determination of the products of the OlsD- and OlsE-catalyzed reactions.

The exact structure of both modifications is required to understand the function/properties of the different lipids on a biophysical level. M.Á.V.-G. is a PhD student from the Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, and is a recipient of a scholarship from the Consejo Nacional de Ciencia y Tecnología, México. http://www.selleckchem.com/products/Fulvestrant.html Work in our laboratory has been financed by grants from CONACyT-Mexico (46020-N and 153200) and DGAPA/UNAM (IN217907

and IN201310) to C.S. “
“Most of our limited knowledge of microbes in corals comes from stony and soft corals; the microbial diversity of black corals is still poorly understood. Microbial diversity of the South China Sea black coral Antipathes dichotoma was investigated using a culture-dependent method followed by analysis of bacterial 16S rRNA gene and fungal internal transcribed spacer sequences. A total of 36 bacterial and 24 fungal isolates were recovered and identified, belonging to three bacterial phyla (Firmicutes, Actinobacteria and Alphaproteobacteria) and four fungal orders (Eurotiales, Hypocreales, Pleosporales and Botryosphaeriales). The high level microbial diversity of A. dichotoma is in accordance with previous studies on those of some stony and soft corals. However,

the lack of bacterial Gammaproteobacteria phylum in A. dichotoma is in sharp contrast Birinapant chemical structure to the stony and soft corals, in which the Gammaproteobacteria phylum is relatively common and abundant. Antimicrobial activities of 21 bacterial and 10 fungal representative isolates (belonging to 21 different bacterial and 10 different fungal species, respectively) were tested against two marine pathogenic bacteria and two marine coral pathogenic fungi. A relatively high proportion (51.6%) of microbial isolates displayed distinct antibacterial and antifungal activities, suggesting that the black Diflunisal coral-associated microorganisms may aid their host in protection against marine pathogens. This is the first report on the diversity of culturable microorganisms associated with black coral. It contributes to our knowledge of black coral-associated microorganisms and further increases the pool of microorganisms available for natural bioactive product screening. Coral reefs around the world are in decline, and infectious diseases are one of the main visible causes (Richardson & Aronson, 2002). As a result, more attention has been focused on the coral-associated microbes that may play a role in establishing diseases and the connections existing between the microbial communities and the overall health of the corals (Kellogg, 2004).

Recently, Carnobacterium maltaromaticum UAL307, which has been approved in the United States (USDA and FDA) and Canada to preserve processed meat products, was shown to produce at least three bacteriocins: carnocyclin A (CclA), a 60 residue circular peptide, and carnobacteriocin BM1 (CbnBM1) and piscicolin 126 (PisA), which are both type IIa bacteriocins (Martin-Visscher et al., 2008b, 2009). Herein, we evaluate the activity selleck chemical of CclA, CbnBM1 and PisA toward three Gram-negative

organisms, at various concentrations, in the absence and presence of EDTA. The activity of these three bacteriocins is compared with that of nisin A (a positive control) and gallidermin, which are both lantibiotics, and to subtilosin A (SubA), which is a 35-residue cyclic peptide with selleck chemicals unusual cross-links (Fig. 1). Our report highlights the potential of UAL307 and its bacteriocins for use in alternative strategies to specifically target Gram-negative bacteria. All solutions and

materials were sterilized before use, either by autoclaving (121 °C, 15 min) or by filter sterilization (0.22 μm). Cell buffer contained 50 mM Tris-Cl, pH 7.2, 4 mM CaCl2, 100 mM NaCl and 0.1% gelatin (Stevens et al., 1991). Gram-positive organisms were grown at 25 °C on an all-purpose tween agar or broth, unless otherwise stated. The Gram-negative strains used were Escherichia coli DH5α, Pseudomonas aeruginosa ATCC 14207 and Salmonella Typhimurium ATCC 23564, and were grown on Luria–Bertani (LB) agar or Luria broth at 37 °C. Bacterial cultures were maintained as frozen stocks at −80 °C, in appropriate media supplemented with 20% glycerol. Testing was designed so that equivalent volumes of bacterial culture and bacteriocin testing solutions were mixed. Thus, testing solutions were prepared at twice their desired final concentrations. Two sets of testing solutions were prepared Interleukin-3 receptor for each bacteriocin: set A was prepared without EDTA and set B with EDTA (40 mM). For set A, the bacteriocin stock solutions were diluted with cell buffer. For set B, the same bacteriocin stock solutions were diluted with cell buffer containing EDTA. Nisin and gallidermin were tested at final concentrations

of 6.25, 12.5, 25 and 50 μM. CclA, PisA, CbnBM1 and SubA were tested at final concentrations of 0.5, 6.25, 12.5 and 25 μM. A 2.5% preparation of nisin A was purchased (Sigma) and HPLC purified, as described previously (Silkin et al., 2008). A 200 μM stock solution was prepared by dissolving the sample in water. Gallidermin (≥90% purity) was purchased (Axxora) and used without further purification. A 400 μM stock solution was prepared by dissolving the sample in water. CclA was obtained by growing C. maltaromaticum UAL307 and isolating the bacteriocin from the culture supernatant and purifying it to homogeneity by RP-HPLC (Martin-Visscher et al., 2008b). A 200 μM stock solution was prepared by dissolving the peptide in water. CbnBM1 was isolated from C.

However, many amacrine types have not been studied systematically because, in particular, amacrine cells with large dendritic fields, i.e. wide-field amacrine cells, have a low abundance and are therefore difficult to target. Here, we used a transgenic mouse line expressing the coding sequence of enhanced green fluorescent protein under the promoter for choline acetyltransferase (ChAT-EGFP mouse) and characterized a single wide-field amacrine

cell population monostratifying in layer 2/3 of the inner plexiform layer (WA-S2/3 cell). Somata of WA-S2/3 cells are located either in the inner nuclear layer or are displaced to the ganglion cell layer and exhibit a low cell density. Using immunohistochemistry, we show that WA-S2/3 cells are presumably GABAergic but may also release acetylcholine as their somata are weakly positive for ChAT. Two-photon-guided patch-clamp http://www.selleckchem.com/products/pci-32765.html recordings from intact retinas revealed WA-S2/3 cells to be ON-OFF cells with a homogenous receptive field even larger than the dendritic field. The large spatial extent of the receptive field is most likely due to the extensive homologous and heterologous coupling among WA-S2/3 cells and to other amacrine cells, respectively, as

indicated by tracer injections. In summary, we have characterized a novel type of GABAergic ON-OFF wide-field amacrine cell which is ideally suited to providing long-range inhibition to ganglion cells due to its strong coupling. “
“Pain in infancy influences pain reactivity in later life, but how and why this occurs is poorly understood. Dasatinib molecular weight Here we review the evidence for developmental plasticity of nociceptive pathways in animal models and discuss the peripheral and central mechanisms that underlie this plasticity. Adults who have experienced neonatal injury display increased pain and injury-induced hyperalgesia in the affected region but mild injury can also induce widespread baseline hyposensitivity across the rest of the body surface, suggesting the involvement of several underlying mechanisms, depending upon the

type of early life experience. Peripheral nerve sprouting and dorsal horn central sensitization, disinhibition and neuroimmune priming are discussed in relation to the increased pain and hyperalgesia, while altered descending pain control ID-8 systems driven, in part, by changes in the stress/HPA axis are discussed in relation to the widespread hypoalgesia. Finally, it is proposed that the endocannabinoid system deserves further attention in the search for mechanisms underlying injury-induced changes in pain processing in infants and children. “
“We investigated the sensitivity of visual mismatch negativity (vMMN) to an abstract and non-semantic category, vertical mirror symmetry. Event-related potentials (ERPs) elicited by random and symmetric square patterns, delivered in passive oddball paradigm (participants played a video game), were recorded.

mAChRs on inhibitory neurons, by contrast, help to maintain low levels of correlations in response to increases in excitation that come from both top-down attention and mAChRs on excitatory neurons. When excitatory drive was increased to a column due to top-down attention or BF stimulation, excitatory–inhibitory correlations decreased and excitatory–excitatory correlations remained constant.

This decrease in correlations was further mediated by mAChRs. When the firing pattern of inhibitory neurons was changed from fast-spiking to regular-spiking, excitatory–excitatory and excitatory–inhibitory correlations increased with top-down attention and BF stimulation. This suggests an important role for inhibition in maintaining low excitatory–excitatory correlation levels when excitation is Selleckchem Trametinib increased due to mAChR stimulation on excitatory neurons or added inputs, such as top-down attention. The present model accounts for experimental results demonstrating BF’s role in the enhancement of both bottom-up sensory input and top-down attention. While it has been traditionally accepted that activation of the BF cholinergic system amplifies bottom-up sensory input to the cortex while reducing cortico-cortical and top-down attention (Hasselmo & McGaughy, 2004; this website Yu & Dayan, 2005; Disney et al., 2007), it has also been shown that ACh may be important for enhancing top-down attentional signals

in visual cortex (Herrero et al., 2008). To resolve these seemingly contradictory results, we propose a circuit that involves global and local modes of action by which the BF can enhance sensory and top-down attentional input, respectively. When the BF is stimulated (Fig. 13A, Avelestat (AZD9668) top), it releases ACh in V1 and disinhibits thalamic relay nuclei (via GABAergic projections to the TRN) in a non-specific manner. This leads to a global enhancement of sensory input to the cortex and may correspond to a heightened state of arousal. In contrast, when top-down attentional signals stimulate visual cortex, they can cause a local release of ACh within the context

of our model, which enhances attention locally (Fig. 13A, bottom). The exact mechanisms underlying BF enhancement of sensory information in visual cortex are not completely understood, although it has been suggested that nicotinic receptors play an important role (Disney et al., 2007). We propose that this balance of bottom-up sensory input and top-down input may also be occurring at the level of the thalamus. Topographic projections from the PFC to the TRN, which bias salient input coming from the sensory periphery, may be inhibited via GABAergic projections from the BF. This gives the BF a graded control over top-down attentional biases that PFC may be having on the thalamus. We also suggest that local release of ACh modulates attention by enhancing the firing rates of attended regions in the cortex (Fig. 7).

mAChRs on inhibitory neurons, by contrast, help to maintain low levels of correlations in response to increases in excitation that come from both top-down attention and mAChRs on excitatory neurons. When excitatory drive was increased to a column due to top-down attention or BF stimulation, excitatory–inhibitory correlations decreased and excitatory–excitatory correlations remained constant.

This decrease in correlations was further mediated by mAChRs. When the firing pattern of inhibitory neurons was changed from fast-spiking to regular-spiking, excitatory–excitatory and excitatory–inhibitory correlations increased with top-down attention and BF stimulation. This suggests an important role for inhibition in maintaining low excitatory–excitatory correlation levels when excitation is Selleckchem ABT737 increased due to mAChR stimulation on excitatory neurons or added inputs, such as top-down attention. The present model accounts for experimental results demonstrating BF’s role in the enhancement of both bottom-up sensory input and top-down attention. While it has been traditionally accepted that activation of the BF cholinergic system amplifies bottom-up sensory input to the cortex while reducing cortico-cortical and top-down attention (Hasselmo & McGaughy, 2004; SGI-1776 solubility dmso Yu & Dayan, 2005; Disney et al., 2007), it has also been shown that ACh may be important for enhancing top-down attentional signals

in visual cortex (Herrero et al., 2008). To resolve these seemingly contradictory results, we propose a circuit that involves global and local modes of action by which the BF can enhance sensory and top-down attentional input, respectively. When the BF is stimulated (Fig. 13A, Clomifene top), it releases ACh in V1 and disinhibits thalamic relay nuclei (via GABAergic projections to the TRN) in a non-specific manner. This leads to a global enhancement of sensory input to the cortex and may correspond to a heightened state of arousal. In contrast, when top-down attentional signals stimulate visual cortex, they can cause a local release of ACh within the context

of our model, which enhances attention locally (Fig. 13A, bottom). The exact mechanisms underlying BF enhancement of sensory information in visual cortex are not completely understood, although it has been suggested that nicotinic receptors play an important role (Disney et al., 2007). We propose that this balance of bottom-up sensory input and top-down input may also be occurring at the level of the thalamus. Topographic projections from the PFC to the TRN, which bias salient input coming from the sensory periphery, may be inhibited via GABAergic projections from the BF. This gives the BF a graded control over top-down attentional biases that PFC may be having on the thalamus. We also suggest that local release of ACh modulates attention by enhancing the firing rates of attended regions in the cortex (Fig. 7).