Inflammatory bowel disease is a group of chronic dysregulated inflammatory conditions in the large and small intestine of humans, and it is well known that chronic inflammation in the colon can lead to cancer [9], [10] and [11]. An experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane (AOM)/dextran sodium sulfate (DSS), has been used often for colorectal cancer research [12] and [13]. AOM is a genotoxic colonic

carcinogen frequently used to induce colon tumors [14] and [15]. We previously evaluated the effects of American ginseng (AG) in colorectal cancer chemoprevention in the AOM/DSS mouse model using a high-fat diet (20% fat) to mimic Western food [16]. In the present study, this established animal colon learn more carcinogenesis model was used in mice fed with regular mouse chow (5% fat) reflecting an oriental diet, with or without AG supplement. To ensure the quality of the study botanical, high-performance Sorafenib clinical trial liquid chromatography (HPLC) analysis was performed on the herb, and the contents of a number of important ginseng saponins were quantified. To extend previous tumor-related protein regulator observations, in this

study, selected enzyme-linked immunosorbent assay (ELISA) for inflammatory cytokines and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to elucidate the IBD related mechanisms of action. Standards of ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, Rg2, 20(R)-Rg2, Rg3, and Rh1 were obtained from Indofine Chemical Company (Somerville, NJ, USA) and Delta Information Center for Natural Organic Compounds (Xuancheng, AH, China). All standards were of biochemical-reagent

grade and at least 95% pure. AOM was obtained from the NCI Chemical Dipeptidyl peptidase Carcinogen Reference Standard Repository, Midwest Research (Kansas City, MO, USA). DSS (molecular weight of 36–50 kDa) was obtained from MP Biomedicals (Solon, OH, USA). HPLC grade ethanol, n-butanol, acetonitrile, and dimethylsulfoxide were obtained from Fisher Scientific (Pittsburgh, PA, USA). Milli Q water was supplied by a water purification system (US Filter, Palm Desert, CA, USA). Hemoccult Sensa test strips were obtained from Beckman Coulter (Brea, CA, USA). Multi-Analyte ELISArray Kits for inflammatory cytokine analysis were obtained from Qiagen (Germantown, MD, USA). AG roots (4-year-old, Panax quinquefolius L.) were obtained from Roland Ginseng, LLC (Marathon, WI, USA). The voucher samples were authenticated by Dr Chong-Zhi Wang and deposited at the Tang Center for Herbal Medicine Research at the University of Chicago. AG extract was prepared with a slight modification from previous works [17], [18] and [19]. The air-dried roots of AG were pulverized into powder and sieved through an 80 mesh screen. One kilogram of the powder placed into 12 L flask was extracted three times by heat-reflux with 8 L of 75% (v/v) ethanol at 95°C for 4 h each time.

Delivery of sediment through such canal networks thus mimics and enhances the yearly flood sediment pulses (Day et al., 1995 and Day et al., 2011) at a rate that is similar to the fast growing juvenile stages of fluvial dominated deltas (e.g., Jerolmack, 2009) when channel density is at maximum. Careful design of the depth and cross-section for such canal networks should be able Natural Product Library ic50 to optimize the amount of fines trapped on the plain to counteract the upstream decline in sediment load and/or

changes in flood regime. However, the question is if enough sediment exists now in the Danube to counteract sea level rise? Based on our analysis, the 10% of the present Danube load (i.e., 2.5 MT/yr) transiting the interior of the delta needs to be increased 4–8 times to fully maintain accretion in the internal Danube delta (i.e., ∼2000 km2 without considering the polder regions and ignoring the coastal region) at rates higher or equal to the present sea level rise of 3 mm/yr (Cazenave et al., 2002). However, the effective need of fluvial sediment for the internal delta plain could be significantly lower when organic sedimentation is taken into account (Reed, 1995, Kirwan and Temmerman, 2009 and Lorenzo-Trueba et al., 2012). Some similar positive results come from channelization on the small agricultural BAY 73-4506 PDK4 delta of

the Ebro, where canals for rice cultivation have captured suspended sediments at rates keeping up or above the contemporary sea level rise (Ibáñez et al., 2010 and Day et al., 2011) or from localized experiments in large deltas such as the Ganges-Brahmaputra (Sengupta, 2009). Although we are not aware of comprehensive studies on this topic, dense channelization has occurred in many deltas around the world (e.g., Nile, Mekong,

Red River to name a few) and they may have had similar effects on delta plain accretion. For example, it is known that the intricate canal network for irrigation on the Nile delta captures almost all sediments coming down the Nile after the Aswan Dam (Stanley and Warne, 1998). And on the Mississippi, upstream diversions (e.g., Blum and Roberts, 2009) would be directed toward delta plain maintenance by augmenting accretion rather than primarily build land anew as proposed for the lower Mississippi delta plain. However, cutting of canals by the oil industry on the Mississippi delta plain without a regular infusion of suspended sediments from the river has had instead destructive effects on the marshes of that delta (e.g., Turner, 1997). While ecological analysis is beyond the scope of the present work, it is clear that the ecological effects of channelization must be carefully considered (Day et al., 2007).

The combination of ginsenosides in ginseng extracts may be important for providing more powerful therapeutic and pharmacological effects [15], [16] and [17]. Notably, ginsenoside Rg3

provides various protective effects, including anti-inflammatory [18] and antitumor effects [19], and it also enhances NO production and eNOS activity [20]. The aim of this study was to investigate whether Rg3-enriched Korean Red Ginseng (REKRG), a ginsenoside fraction enriched in Rg3, increases eNOS activity and NO production and exhibits anti-inflammatory effects. Dried Korean Red Ginseng (P. ginseng) root was purchased from Gumsan Nonghyup (Gumsan, Korea). Korean ginseng was extracted two times with 10 volumes of ethanol at 50°C for 7 hours (1st Saracatinib cell line 50%, 2nd 85%), and then concentrated under vacuum at 50°C. The crude extract was dissolved in water and enzyme-acid hydrolysis to maximize ginsenoside Rg3 was performed (raw ginsenoside was hydrolyzed to Rg3) in acidic (pH 2.5∼3.5) and thermophilic (65∼80°C) condition. The enzyme, which has β-glycosidase activity including cellulase, hemicellulose,

Enzalutamide cell line and glucosidase activity, was produced by Aspergillus niger. To remove acid solution and concentrate Rg3, the reactant was passed through DIAION HP20 resin (Mitsubishi Chemical Industries, Tokyo, Japan) packed column. The ginsenoside Rg3 was concentrated to powder under vacuum conditions. It was kindly provided by BTGin Corporation (Occheon, Korea). The powder was dissolved in 70% methanol, and ginsenosides including Rg3 was analyzed by high-performance liquid chromatography (HPLC). HPLC was carried out on an Liquid chromatography (LC) system equipped with a quaternary gradient pump (Spectra 4000) and UV detector (Spectra PRKD3 2000; Thermo Scientific, San Jose, CA, USA). A reversed-phase column (Hypersil gold C18,

100 mm 4.6 mm, internal diameter 5 μm; Thermo Scientific) was used for quantitative determination of ginsenosides Rg3. The mobile phase consisted of acetonitrile and water with a flow rate at 1.6–2.5 mL/min, and the column was kept at room temperature. The detection wavelength was set at 203 nm. Human umbilical vein endothelial cells (HUVECs) were purchased from Clonetics (San Diego, CA, USA) and cultured in Endothelial Growth Medium-2 from Lonza (Walkersville, MD, USA). Subconfluent, proliferating HUVECs were used between passages 2 and 8. The Animal Care Committee of Chungnam National University approved the animal care and all experimental procedures conducted in this study. All instrumentation was used under aseptic conditions. Male Wistar rats and spontaneously hypertensive rats (SHRs; 3 months old) were each divided into two groups (n = 5) randomly: a normal saline group and a REKRG group. REKRG (10 mg/kg) was orally administered to animals for 6 weeks. Anti-ICAM-1, anti-eNOS, and anti-COX-2 antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA).

When a category-cued final test was employed, individuals with ADHD exhibited the same amount of retrieval-induced forgetting as did individuals without ADHD. When a category-plus-stem final test was employed, however, individuals with ADHD exhibited significantly less retrieval-induced forgetting than did individuals without ADHD. In fact, individuals with ADHD failed to exhibit any evidence of retrieval-induced forgetting on the category-plus-stem final test, consistent with the proposal

that the test provides a better MK-8776 price estimate of the costs of inhibitory control. This prediction was also tested in research on inhibition deficits in schizophrenia and in development. Tests of the correlated costs and benefits account revealed that both young children (Aslan

& Bäuml, 2010) and schizophrenics (Soriano, Jiménez, Román, & Bajo, 2009) show significant retrieval-induced forgetting on category-cued recall tests, even though they show significantly impaired retrieval-induced forgetting on tests involving item specific cuing (i.e., an item-recognition final test in which participants must determine whether exemplars had been previously studied). Taken together, these findings indicate that controlling for the benefits of inhibition Enzalutamide supplier at test may reveal theoretically important relationships between retrieval-induced forgetting and inhibitory control ability. Although the findings concerning ADHD, schizophrenia, and development confirm important predictions of the correlated costs and benefits framework, a stronger and more direct test would seek to (a) relate retrieval-induced

forgetting to an independent measure of inhibition ability, and (b) show that this relationship varies by test type in the expected manner. Towards that end, the present study had two goals. First, we tested the relationship between retrieval-induced forgetting and performance on an established measure of inhibitory control: stop-signal reaction time (SSRT; Logan Reverse transcriptase & Cowan, 1984). If retrieval-induced forgetting truly is the consequence of an inhibitory process that suppresses inappropriate responses, then measures of response inhibition, such as SSRT, should predict this form of forgetting. Briefly, in the typical stop-signal task, participants are asked to respond as quickly as possible to each stimulus they see, except on a minority of trials, in which they hear a tone, signaling them to withhold their response. By measuring participants’ ability to stop their response (as reflected by their SSRT, to be explained in Methods), the stop-signal task has proven to be a robust and reliable measure of inhibitory control. For example, young children (e.g., Williams, Ponesse, Schachar, Logan, & Tannock, 1999), older adults (Kramer, Humphrey, Larish, Logan, & Strayer, 1994), impulsive individuals (Logan, Schachar, & Tannock, 1997), and children with ADHD (e.g.

This seasonal flow regulation largely favors water consumption in non-flood seasons, primarily for farming irrigation. In non-flood season, the difference between average daily water discharge at Huayuankou and Lijin

results mainly from water consumption loss. This value increased in a step-wise manner from 26 m3/s in 1950–1968 to 242 m3/s in 1969–1986 Selleck Z VAD FMK and 421 m3/s in 1987–1999, respectively, followed by a slight decrease of 384 m3/s in 2000–2011 (Table 2). This pattern can be explained by increasing water use favored by strengthening runoff regulations. The construction of large dams on the Huanghe has largely controlled the frequent floods on the lower reaches that are ded by monsoon rains. Long-term (1950–2011) Selleckchem LEE011 observations of daily water discharge at Lijin reveal that peak flow > 6000 m3/s decreased dramatically from a total 155 days during 1950–1968 to 17 days during 1969–1986, and vanish completely since 1987 (Table 3). Even smaller flood peaks (4000–6000 m3/s) could not be observed after the construction of Xiaolangdi reservoir in 1999. Since 2000, low flow (<2000 m3/s) dominates the discharge pattern of the lower reaches most of the year, and flow >2000 m3/s is mainly concentrated within the annual WSM (often less than 20 days) when the released floodwater

is confined to <4000 m3/s. Huayuankou station recorded a similar trend, as shown in Table eltoprazine 3. Here, we select representative years (1954, 1988, 2003) to show the stepwise

drops in the amplitude of flood peaks recorded at Lijin and Huayuankou over time (Fig. 2). Both the Lijin and Huayuankou records show a similar pattern, with the amplitudes of flood peaks dramatically decreasing. At Huayuankou station, pre-dam discharge levels (1950–1960) show several flood peaks during the flood season, with extreme peaks approaching ∼17,000 m3/s (e.g. 1954, Fig. 2A). In 1988 smaller flood peaks (<7000 m3/s) could be observed (Fig. 2B). In 2003 (after Xiaolangdi Reservoir was constructed), flood peaks >4000 m3/s become non-existent, e.g. in 2003 (Fig. 2C). Since 1950, no catastrophic flooding has occurred in the lower reaches of the Huanghe, owing to the effect of the dams. Sediment sequestration is a common problem in many large reservoirs. This problem is particularly severe for the Huanghe owing to the high suspended sediment concentration. Spatially, the Longyangxia and Liujiaxia reservoirs have a minor effect in trapping sediment, since only a small fraction of the Huanghe sediment is sourced from its upper reaches. The Liujiaxia and Longyangxia annually trap only 0.53 × 108 m3 (average 1968–1997 level) and 0.16 × 108 m3 (average 1986–1997 level) of sediment, respectively (Peng and Chen, 2009). The Sanmenxia and Xiaolangdi reservoirs in the lower middle reaches have trapped large amounts of sediment since their operation. The Sanmenxia Reservoir, in particular, had lost 45.

yrs BC) the human presence in the Alpine region was too sparse to influence the natural climate- and vegetation-driven fire regime (Carcaillet et al., 2009; Fig. 2). During this first fire epoch buy S3I-201 sensu Pyne (2001), fires were ignited by lightning, as volcanoes in the Alps were already inactive, and the fire regime was characterized by long fire return intervals, e.g., 300–1000 yrs ( Tinner et al., 2005, Stähli et al., 2006 and Carcaillet et al., 2009). The shift to the second fire epoch sensu Pyne (2001) took place with the Mesolithic-Neolithic transition (6500–5500 cal. yrs BC; Fig.

2) when fire activity increased markedly throughout the Alps ( Tinner et al., 1999, Ali et al., 2005, Favilli et al., 2010, Kaltenrieder et al., 2010 and Colombaroli et al., 2013) as a consequence of an increase in the sedentary population and a corresponding use of fire for hunting and to clear vegetation for establishing settlements, pastures and crops ( Tinner et al., 2005 and Carcaillet et al., 2009). The anthropogenic signature of the second fire epoch is documented in the Alps from the Neolithic to the Iron age (5500–100 cal. yrs BC) by the positive correlation HER2 inhibitor between charcoal particles and peaks in pollen

types indicative of human activities ( Tinner et al., 1999, Tinner et al., 2005, Kaltenrieder et al., 2010, Berthel et al., 2012 and Colombaroli et al., 2013). Despite the anthropogenic origin, the general level of fire activity highly depended on the climate conditions. Areas on the northern slopes of the Alps experienced charcoal influx values one order of magnitude lower than the fire-prone environments of the southern slopes ( Tinner et al., 2005). Similarly, phases of cold-humid climate coincided with periods of low fire activity in these areas ( Vannière et al., 2011). In the Alps, the human approach to fire use for land management has changed continuously according to the evolution

of the population and the resources and fires set by the dominant cultures alternating in the last 2000 years (Fig. 3). Consequently, the shift from the second to the third fire epoch sensu Pyne (2001) is not definite as they have coexisted up to the present, similarly to other European regions, e.g., Seijo and Gray (2012), and differently from other areas Resminostat where it coincides with the advent of European colonization ( Russell-Smith et al., 2013 and Ryan et al., 2013). For example, the extensive use of fire that characterizes the second fire epoch completely changed in the Alpine areas conquered by the Romans starting at around 2000 cal. yrs BC. Under Roman control the territory and most forest resources were actively managed and also partially newly introduced (i.e., chestnut cultivation) and hence the use of fire was reduced proportionally ( Tinner et al., 1999, Conedera et al., 2004a and Favilli et al., 2010; Fig. 2). Consequently, during Roman Times, studies report a corresponding decrease in fire load throughout the Alps ( Blarquez et al.

19 Data collectors recorded lesson activities every 15 s on the instrument. A lesson focus was determined when one activity category exceeded 50% of lesson time. All data were collected by data collectors who were specifically trained for this study. Each data collector was assigned to two schools. A detailed data collection protocol for each variable was developed for the data collectors to follow during data collection. Students’ height and weight data were collected first for calculating BMI and programming

the accelerometers. Gender and age information was collected at the same time. In each data collection lesson, data collectors arrived at their assigned schools approximately 15 min before the bell. They calibrated equipment such as the stopwatch, weight and height scale, and laptop selleck chemical computer. Caloric expenditure data were collected in three to four lessons from each of the 87 classes. Thus, the data represented a total of 270 lessons of various lengths and content. Before each lesson began, the data collector identified the data providing students and secured individually-programmed accelerometers on their waistband above the right knee. After the lesson, the data collector took down the accelerometer and uploaded the accelerometer data into a laptop computer. Two sets of accelerometers were available

for collecting data from back-to-back lessons. Otherwise the data collector re-programmed accelerometers using a laptop LDN-193189 purchase computer between lessons. But data from 27 lessons were deemed unusable due to either equipment

malfunctioning or incomplete data sets. The final lesson sample included 116 lessons Selleck Temsirolimus from the elementary schools and 127 lessons from the middle schools. Both total and activity calories were recorded on the accelerometers. Total calories were the sum of resting (basal metabolic) calorie expenditure and activity calories due to physical activity participation in class. Only activity calories were used in analyses to reflect lesson-induced caloric expenditure. In data reduction, caloric values were also converted to MET for each individual student. The conversion allowed meaningful interpretation of the caloric expenditure in relation to activity intensity. For example, a MET = 3.0 can be interpreted as the caloric expenditure resulted from moderate physical activity, indicating the individual is receiving health benefit.20 Preliminary statistical analysis included calculating descriptive statistics to determine data normality and variance homogeneity. Analysis of variance (ANOVA) on individual student means were used to determine the effects by the personal factors. ANOVA on class means were conducted to determine the effects by the lesson context factors. A hierarchical linear modeling (HLM) analysis was conducted to detect any impact from lesson length and content types on personal level caloric expenditure slope (rate of change) due to lesson factor variations.

However, in many neurons IPSPs are rather small because ECl may be less negative than EK or, as in the immature brainstem, may be positive to the resting membrane potential. Experimental evidence supports the idea that SPN neurons have a powerful outwardly directed chloride transporter and therefore large IPSPs. First, in an elegant study that employed gramicidin-perforated see more patch recording, the endogenous ECl in rat SPON neurons was shown to be around −100mV and this was associated with high membrane immunolabeling of the K+Cl− cotransporter, KCC2 ( Löhrke et al., 2005).

In the current study EIPSC was around −96 ± 4.2mV (n = 11) when a low chloride

concentration (6 mM) was chosen for the patch pipette ( Figure 3D). We tested the idea for an outwardly directed chloride pump, by setting an artificially high ECl and observing the change in EIPSP while perfusing the chloride transporter antagonist, furosemide. A high chloride pipette solution (34.5 mM) gave a predicted ECl of −36mV, but EIPSC remained negative at −88 ± 4.8mV (n = 9, Figure 3D). Perfusion of furosemide (0.5 mM) caused a gradual shift in EIPSC toward the ECl ( Figures 3B and 3C) predicted by the Nernst equation. We conclude that mouse SPN neurons also possess the powerful outwardly directed chloride transporter KCC2 ( Figure 2Gii), and that this maintains ECl at very negative levels. If this is true then physiological offset firing in response to synaptic MAPK Inhibitor high throughput screening input should also be blocked/suppressed by furosemide. Furosemide indeed caused the IPSPs to decline in amplitude and now the inhibitory input was insufficient to hyperpolarize the membrane to rebound-firing threshold

(−81.13 ± 1.3mV, Janus kinase (JAK) n = 71; blue shaded area in Figure 3D) and so failed to trigger offset APs ( Figures 3E and 3F). As expected, direct hyperpolarizing current injections could still trigger offset APs after furosemide application ( Figures 3G and 3H). The control EIPSC is sufficiently negative for the IPSPs to activate IH and trigger offset APs. Furosemide (0.5 mM) did not block either IH currents or glycinergic IPSCs directly ( Figure S4). In addition to IH, the IPSP, and ECl, contributions from other conductances were implied because the current-voltage relationship showed a region of negative slope conductance at around −50 to −30mV, suggesting large voltage-gated calcium currents in the SPN (see also Figure S1F). To measure calcium currents we used a Cs+ based patch solution that blocked the majority of K+ currents and combined this with use of appropriate voltage protocols and pharmacology under voltage clamp.

However, genetic inactivations of the murine homologs of genes mutated in human neuronal

migration disorders so far have failed to reproduce these malformations, prompting the suggestion that mutations at other as-yet-unrecognized loci may result in SBH (Bilasy et al., 2009, Croquelois et al., 2009 and Lee et al., 1997). These discrepancies highlight the complexity of human cerebral cortex in comparison to rodents. Not only do migrating neurons have to cover a much longer distance to their final destination, they also need to change radial guides more often due to the increase in pial surface compared to the ventricular surface with additional radial glia (RG) in the outer SVZ (Fietz et al., 2010, Hansen et al., 2010 and Reillo et al., 2010). Thus, migrating neurons in human cerebral cortex http://www.selleckchem.com/products/s-gsk1349572.html may require other pathways as they face additional challenges during their journey. Moreover, radial glial cells may need specific pathways, which are yet ill-understood in the mouse model. Indeed, so far only mutation of MEKK4 has been suggested to affect migrating neurons and radial glial cells, causing disruption of the ventricular surface and protrusions

of neuronal ectopia into the ventricle (Sarkisian et al., 2006). Here we set out to examine the role of the small GTPase RhoA for neuronal migration in the developing cerebral cortex, as RhoA had been suggested to play key roles in directed cell migration in various tissues and organs (Govek et al., 2005 and Heasman and Ridley, 2008). By using pharmacological means and dominant-negative or constitutively active constructs, Z-VAD-FMK in vivo several studies suggested that RhoA is crucial for neuronal migration (Besson et al., 2004, Heng et al., 2008, Kholmanskikh et al., 2003, Nguyen et al., 2006 and Pacary et al., 2011). However, the direct role of RhoA in neuronal migration has never been tested in the developing nervous system in vivo. Recently,

conditional deletion of RhoA has revealed insights into its role at early stages of central nervous system (CNS) development Parvulin in the spinal cord and midbrain, highlighting common functions in the maintenance of adherens junction coupling, as previously shown for other members of this family, such as Cdc42 and Rac1 (Cappello et al., 2006, Chen et al., 2009 and Leone et al., 2010), but an opposite role in regulating cell proliferation in spinal cord versus midbrain (Herzog et al., 2011 and Katayama et al., 2011). Moreover, neuronal migration or positioning of neurons was not examined in these mice at later embryonic or postnatal stages. We therefore set out here to delete RhoA in the brain region mostly affected by migrational disorders, namely, the cerebral cortex. In order to determine the role of RhoA in neuronal migration during the development of the cerebral cortex, the Emx1::Cre mouse line driving recombination at early stages selectively in this region (Cappello et al., 2006 and Iwasato et al.

Despite the fact that glutamate this website receptor antagonists caused map expansion and increased overlap between Mab and Mad, movement topography was not abolished. The Mab and Mad maps could still be distinguished in the presence of glutamate receptor antagonists (Figure 6B), with no significant reduction in the separation between their centers of gravity (Figure 6D). Application

of glutamate receptor antagonists did not cause a significantly greater shift in map centers from their baseline positions than application of saline for Mab (0.5 ± 0.09 versus 0.5 ± 0.1 mm, respectively, p = 0.96, n = 9 versus n = 5, t test) or Mad (0.5 ± 0.09 versus 0.2 ± 0.04 mm, respectively, p = 0.06). Although the increased movement durations (Figure 5C) and expansion of motor maps (Figure 6C) caused by disruption of excitatory synaptic transmission were unexpected, this may be explained

by PD-1/PD-L1 assay a loss of disynaptic inhibition (Helmstaedter et al., 2009, Murayama et al., 2009, Adesnik and Scanziani, 2010, Silberberg and Markram, 2007 and Kapfer et al., 2007). To test this hypothesis, we repeated these experiments with GABAA receptor antagonists (gabazine 1 μM n = 4 or picrotoxin 100 μM n = 2, Figure S6). GABA receptor antagonists diminished differences between Mab and Mad movement trajectories, but had no significant effect on movement kinematics (Figure S6), and generally did not degrade functional subdivisions of the motor cortex. Disrupting GABAergic transmission

did reproduce the increases in map amplitude (Figure S7C) and area (Figure S7D) seen during blockade of excitatory transmission. As with the delayed increase in movement speeds (Figure 5C), this effect was restricted to Mad. These effects are consistent with disinhibition causing the selective expansion of the Mad subregion. The separation between Mab and Mad and the region of overlap between them was unchanged (Figure S7E). Like glutamate receptor antagonists, GABA receptor antagonists did not cause greater displacement of map centers than saline treatment for Mab (0.6 ± 0.1 versus 0.5 ± 0.1 mm, p = 0.37, n = 6 versus n = 5, t test) or Mad Axenfeld syndrome (0.4 ± 0.1 versus 0.2 ± 0.04 mm, p = 0.24). The observation that disrupting intracortical synaptic transmission can impair the expression of diverse complex movements without abolishing the topography of movement maps was initially surprising, but may be explained by differences between the roles of intracortical and corticofugal circuits. It is possible that cortical application of receptor antagonists interferes with local circuit function and the generation of complex movements by prolonged stimulation, but does not alter the movement maps generated by the output of corticofugal cells directly activated by brief pulses of optogenetic excitation.