, 2012) and toxoplasmosis in sheep and humans (Hide et al., 2009). Despite the efforts of previous studies to confirm this transmission route in horses (Duarte et al., 2004 and Locatelli-Dittrich et al., 2006), many points are still unclear, including the relationship between the level of antibodies in mares and the frequency of vertical transmission of

these agents in the Sarcocystidae family. Therefore, the aim of study was to correlation levels of antibodies in mares with pre colostral foals seropositive and assess the level and distribution of antibodies against Neospora spp., S. neurona and T. gondii, in mares and pre colostral foals an the parturition We obtained 181 samples from mares, without clinical history of neurological and reproductive Neratinib manufacturer diseases, and their newborns, in Rio

Grande do Sul, Brazil. The blood was drawn by jugular puncture from mares during parturition and from their newborns before colostrum intake. The whole blood was centrifuged at 250 × g for 10 min to separate serum, which was stored at −20 °C until tested. This research was licensed by the Ethics and Animal Experimentation Federal University of Santa Maria, with number 81/2009. Neospora caninum (NC-1 strain) and Erastin molecular weight S. neurona (SN-37R) tachyzoites were maintained under the same conditions by the continuous passage of HeLa cells and CV-1 cells, respectively, at 37 °C and 5% CO2 in RPMI medium supplemented with 25 mM HEPES, 2 mM of l-glutamine, 3 mM sodium bicarbonate and antibiotic/antimycotic solution (penicillin 100 IU/mL, streptomycin 100 μg/mL and amphotericin B 0.25 g/mL; Gibco). T. gondii (RH) tachyzoites were maintained in BALB/c mice by serial passage for 48–72 h ( Mineo et al., 1980). This maintained licensed by the Ethics and Animal Experimentation Federal University of Uberlandia, with number 029/2012. A parasite suspension was washed two times (720 × g, 10 min, 4 °C) in phosphate-buffered saline 0.01 M (PBS, pH 7.2), treated with protease inhibitors (Complete, Roche) and then subjected to ten freeze–thaw cycles and sonication Isotretinoin (60 Hz,

90% amplitude, in ice bath). After centrifugation (10,000 × g, 30 min, 4 °C), the supernatant was collected and filtered through 0.22 μm membrane (Millex, Millipore, USA). The supernatant, containing soluble antigens of N. caninum (NLA), S. neurona (SnLA) or T. gondii (STAg), was collected and the protein concentration was estimated using the Bradford assay. Aliquots were stored at −20 °C until use. Indirect ELISAs were carried out to detect IgG antibodies as described elsewhere Silva et al. (2007), with modifications. In summary, high-binding microtiter plates were coated with NLA, SnLA or STAg (10 μg/ml) in 0.06 M carbonate buffer (pH 9.6) overnight at 4 °C. The plates were then washed three times with PBS containing 0.

, 2010). Recent microarray approaches using tissue enriched for dendrites expanded the local transcriptome to ∼285 mRNAs (Poon et al., 2006 and Zhong et al., 2006) and the high-throughput in situ hybridization screen performed by the Allen Brain Project identified 68 mRNAs in the synaptic neuropil (Lein et al., 2007). Analysis of the overlap between the various studies, however, yields a surprisingly small number of mRNAs discovered by two or more studies (Figure 1A), suggesting that the identification of the local mRNA population is not near saturation. Here, we used deep RNA sequencing to identify the full complement of mRNAs present in synaptic regions (Figure 2). We focused our attention

on the CA1 area of the rat hippocampus because, as indicated above, synapses in this region express several forms of plasticity that require local translation. Following sequencing and bioinformatic analysis with other data sets, Vemurafenib order we identified 2,550 mRNAs that are associated with the dendrites and/or axons in the hippocampal Alpelisib research buy neuropil. High-resolution imaging allowed us to validate, independently, a subset of these mRNAs and to localize them specifically to the dendrites of hippocampal neurons. To discover the full local transcriptome, we first microdissected individual synaptic neuropil (stratum radiatum

and lacunosum moleculare) segments from area CA1 of the adult rat hippocampus (Figures 1B and 1C). This synaptic neuropil comprises dendrites, axons, glia, and a sparse population of interneurons, but lacks principal neuron cell bodies (Figures 1D and 1E). Microdissection of CA1 synaptic neuropil

from 120 individual slices yielded sufficient RNA for a single deep sequencing run (Figure 1F; 454 Technology, Roche). To maximize coverage of the tuclazepam local mRNA population, poly(A) RNA was isolated and then normalized cDNA libraries were prepared (Patanjali et al., 1991) to enhance sensitivity to lower abundance transcripts. Two different neuropil sequencing runs (using starting material from two different dissections) yielded 550,442 and 571,554 reads for a total of 1,121,196 reads with a mean read length of ∼400 nucleotides (Figure S1 available online). Reads were annotated to identify the genes represented (see Experimental Procedures; Figure S1). We chose 50% coverage of the coding sequence (Table S1, Column F) as a threshold value for inclusion in our subsequent analysis of the neuropil data sets yielding 8,379 unique mRNAs (Table S1). We compared this data set with the three most recently published neuropil transcriptome data sets obtained from microarrays (Poon et al., 2006 and Zhong et al., 2006) and high-throughput in situ hybridization analysis (Lein et al., 2007). Using the above data set of 8,379 unique mRNAs we found substantial overlap between our data and the other three data sets (86%, 86%, and 91%, respectively, for Zhong et al.

, 2009). The hairpin maze enabled us to determine whether representations in PPC and MEC were expressed synchronously or independently since it elicited spatially discrete firing fields from cells in both areas. We hypothesized that running the rats in hairpin mazes in two different rooms would drive grid cells to realign their firing fields (Fyhn et al., 2007 and Hafting et al., 2005) and allow us to observe whether such a realignment extended to representations

in PPC as well (Figure 6A). We ran the rats in hairpin mazes in two different rooms and found that grid cells realigned their firing fields completely in the different rooms, selleck chemical while parietal cells maintained the same preferences (Figure 6A). Statistical analysis confirmed that the firing field locations of PPC cells were more correlated than those of grid cells in different rooms (mean r value of 0.47 for PPC cells versus 0.03 for grids cells; D = 0.54, find more p < 0.001, K-S test; Figure 6B), while cells from both areas expressed comparable stability

in the same-room condition (mean r value of 0.56 for PPC cells versus 0.59 for grid cells; D = 0.11, p > 0.3; Figure 6B). Thus, representations in PPC were unchanged despite a complete realignment of firing fields in MEC. The observation that cells in PPC maintain their firing preferences in different recording rooms does not mean that representations in PPC are disconnected from the Tryptophan synthase environment. Electrophysiological studies have shown that locomotor responses of PPC cells vary depending on where in a maze or along which route an action was made (McNaughton et al., 1989, Chen et al., 1994a, Nitz,

2006 and Sato et al., 2006). It has never been determined, however, whether PPC cells respond primarily to the structure of the animal’s behavior in the task, or to the structure of the environment in which the recording was made. To address this we compared firing properties of PPC cells in the hairpin maze and open field in several ways. First, we generated self-motion and acceleration rate maps from recordings in the hairpin maze and found that a large fraction of PPC cells showed tuning to discrete modes of movement and that these representations were stable across west- and eastbound traversals (Figures S6–S8). The independence of running direction implies that the firing was independent of major sensory cues in this task. At the same time, we found that running in the hairpin task expanded the tuning of PPC cells to path segments traversed more than 1 s before and after the animals’ actual position (Figure S9). This may reflect the stereotypic sequential ordering of the animal’s behavior in this particular task, suggesting that the firing may have been dependent on the particular actions performed by the animal.

, 2009 and Walton et al., 2010). In the present study, we found that signals related to actual and hypothetical outcomes resulting from specific actions are encoded in both DLPFC and OFC, although OFC neurons tend to encode such outcomes regardless of the animal’s actions more than DLPFC neurons. Three monkeys were trained to perform a computer-simulated

rock-paper-scissors game task (Figure 1A). In each trial, the animal was required to shift its gaze from the central this website fixation target toward one of three green peripheral targets. After the animal fixated its chosen target for 0.5 s, the colors of all three targets changed simultaneously and indicated the outcome of the animal’s choice as well as the hypothetical outcomes that the animal could have received from the other two unchosen targets. These outcomes were determined by the payoff matrix of a biased rock-paper-scissors game (Figure 1B). For example, the animal would receive three drops of juice when it beats the computer opponent by choosing the “paper” target (indicated by the red feedback stimulus in Figure 1A, top). The computer opponent simulated a competitive player trying to minimize the animal’s expected payoff by exploiting statistical biases in the animal’s choice and

outcome sequences (see Experimental Procedures). The optimal strategy for this game (Nash, 1950) is for the animal to choose “rock” with Onalespib clinical trial the

probability of 0.5 and each of the remaining targets with the probability of 0.25 (see Supplemental Experimental Procedures available online). In this study, the positions of the targets corresponding to rock, paper, and scissors were fixed in a block of trials and changed unpredictably across blocks (Figure S1). The animal’s choice behaviors gradually approached the optimal strategies after each block transition, indicating that the animals adjusted their behaviors flexibly (Figure S2A). Theoretically, learning during an iterative game can rely on two different types of feedback. First, decision makers can adjust their for choices entirely based on the actual outcomes of their previous choices. Learning algorithms exclusively relying on experienced outcomes are referred to as simple or model-free reinforcement learning (RL) models (Sutton and Barto, 1998). Second, behavioral changes can be also driven by the simulated or hypothetical outcomes that could have resulted from unchosen actions. For example, during social interactions, hypothetical outcomes can be inferred from the choices of other players, and in game theory, this is referred to as belief learning (BL; Camerer, 2003, Gallagher and Frith, 2003 and Lee et al., 2005).

Increased muscle glycogen utilisation following HGI breakfast consumption was reported previously,130 but not consistently.124 Contrasting findings may have been due to major differences in study design and, in particular, differences in the timing of the muscle biopsy, which was obtained 30 min114 or 2 h124 after exercise. Differences in FAT/CD36 gene expression following HGI and LGI CHO consumption may be another underlying mechanism controlling differences in fat oxidation. In men, FAT/CD36 mRNA and protein levels

were down-regulated 3 h after the consumption of an HGI post-exercise meal, but were unchanged when an isoenergetic LGI meal with similar macronutrient content was consumed. 131 Conversely, muscle glucose transporter type 4 (GLUT-4) expression was reduced similarly following both meals, suggesting that this is not implicated in the relationship between FK228 in vivo GI and substrate oxidation. The effect of GI on FAT/CD36 expression may also be mediated through differences in the insulin Akt inhibitor response to meals differing in GI. 132 and 133 Regular breakfast consumption

is associated with a variety of nutritional and lifestyle-related health outcomes in large diverse samples of young people, which may prevent weight gain, nutrient deficiency, and the development of chronic disease risk factors. Health benefits of breakfast consumption may be enhanced with the inclusion of RTEBC, particularly those containing LGI carbohydrates. Substituting an HGI breakfast for an LGI breakfast

may be particularly beneficial for overweight young people through increased glycaemic control, fat oxidation and satiety. Overall, the potential benefits Rolziracetam of LGI breakfasts seem to indicate that this could represent a positive factor supplementary to regular breakfast consumption. Breakfast consumption and composition, therefore, represent an important area of research that may have broad public health applications in obesity prevention and health. However, it is noteworthy that breakfast comprises just one component of a healthy lifestyle and those involved in breakfast promotion should highlight this to the target audience. Research on breakfast consumption and health has typically taken the form of cross-sectional and descriptive prospective studies; controlled, systematic experimental studies are required to infer causality and the mechanisms controlling these relationships require further investigation. However, randomised controlled trials involving the intentional manipulation of breakfast omission over a period of time may be challenging for ethical reasons. Conversely, evidence surrounding breakfast GI and health is most often based on experimental research. There is a notable gap in the literature that has recognised the integrative effect of regular breakfast consumption and breakfast GI.

0% versus 58.5%), while the mEC-5xmyc truncated protein led to an intermediate reduction (25.5%; Figure 7A). However, significant but modest rescue of CNS defects was observed

in embryos carrying either mICD or Fc/mICD mutant Sema-1a proteins, which lack forward signaling activity ( Figure 7A). These results demonstrate that multimerization of the Sema-1a extracellular domain is largely sufficient to mediate Sema-1a functions in CNS axon guidance. Furthermore, we found that neuronal expression NVP-BKM120 price of either of these signaling mutant transgenes partially rescued Sema-1a null ISNb pathway phenotypes ( Figure 7A). In particular, neuronal expression of mEC/Fc-5xmyc, which should allow forward but not reverse signaling, resulted in only modest rescue of ISNb defects but significant rescue of CNS defects, suggesting an essential role for Sema-1a-mediated reverse signaling in peripheral axon guidance. Next, we performed additional rescue experiments in order to examine whether the introduction of both forward (mEC/Fc-5xmyc) Selleck GW-572016 and reverse (mICD or Fc/mICD) signaling mutant transgenes together can further rescue Sema-1a ISNb phenotypes. However, simultaneous expression of these transgenes did not lead to additional rescue of Sema-1a null PNS phenotypes, as compared to neuronal expression of either single transgene (

Figure 7A). Given that Sema-1a functions as a ligand for PlexA in the PNS (forward signaling; Winberg et al., 1998), these complementation analyses strongly suggest that both the extracellular and intracellular Sema-1a domains, Phosphoprotein phosphatase and therefore the coordinated action of bidirectional

signaling, are necessary for Sema-1a-mediated motor axon guidance. Since overexpression of wild-type Sema-1a synergistically enhances pbl misexpression phenotypes in both the PNS and CNS ( Figures 6B–6F), we reasoned that if this synergistic enhancement occurs through the potentiation of reverse signaling, the Sema-1a intracellular domain alone should recapitulate the synergistic enhancement we see when wild-type Sema-1a is coexpressed with HA-pbl. We found in our GOF analysis that expression of mICD or Fc/mICD did indeed increase pbl GOF ISNb phenotypes to a similar level as wild-type Sema-1a, but produced only mild defects in CNS patterning ( Figures 6E and 6F). However, overexpression of the Sema-1a extracellular domain (mEC-5xmyc or mEC/Fc-5xmyc) did not affect pbl GOF phenotypes in either ISNb or CNS axon guidance. These in vivo GOF data strongly suggest that Pbl mediates Sema-1a reverse signaling. To address further Sema-1a receptor function and its regulation by Pbl, we performed additional GOF experiments utilizing apterous-GAL4 (apGAL4), which drives expression of GAL4 in only three neurons per hemisegment; these neurons extend axons longitudinally and do not cross the CNS midline ( O’Keefe et al.

To identify functional roles for the γ-Pcdhs in cortical development, we crossed Pcdh-γfcon3 conditional mutant mice ( Prasad et al., 2008) with a line expressing Cre from the Emx1 locus (see Figures GABA inhibitor drugs S1A–S1G available online). The Emx1-Cre line has been used extensively to excise floxed alleles in progenitors that give rise to primary glutamatergic neurons as well as astrocytes in the cortex, while sparing ganglionic eminence-derived GABAergic cortical interneurons ( Gorski et al., 2002). We confirmed that Emx1-Cre efficiently recombined the Pcdhγfcon3 allele

by immunostaining in neonatal Emx1-Cre; Pcdh-γfcon3/+ brains ( Figures S1A–S1G). Emx1-Cre; Pcdh-γfcon3/fcon3 mutants were born in Mendelian ratios and were viable and fertile. Gross examination of the brain revealed no obvious abnormalities or changes in overall size. Comparison

of sections through the primary somatosensory cortex (S1), however, revealed that the mutant cortex was thinner than that of controls. Close examination showed that this was due entirely to a reduction of the superficial, cell-sparse layer I: layers II–VI were remarkably similar in side-by-side micrographs of controls and mutants ( Figures Vorinostat mouse 1A and 1B), and quantitative analysis of a variety of cortical layer markers indicated no difference in cell number or in lamination ( Figures S1H–S1M). Layer I thinning occurred between postnatal day 18 (P18) and P28, with the distance between layer II and the pia reduced by 42% (n = 48 total measurements before from three animals per genotype; Figure 1C). Apoptosis was similarly low in control and mutant cortex throughout the postnatal period ( Figures S1N and S1O), and loss of the γ-Pcdhs in the primary neurons of the cortex also did not affect the numbers of cortical interneurons ( Figures S1P and S1Q; data not shown). Because cortical layer I is composed mainly

of apical dendritic tufts of deep-layer pyramidal neurons, loss of layer I in the mutants could be due to defects in dendrite arborization. To investigate this, we crossed Emx1-Cre; Pcdh-γfcon3 mice with the Thy1-YFPH transgenic line ( Feng et al., 2000), in which a population of layer V neurons throughout the cortex strongly expresses yellow fluorescent protein (YFP). We analyzed confocal stacks from 100 μm vibratome sections of Emx1-Cre; Pcdh-γfcon3/fcon3; Thy1-YFPH mutants and littermate controls between P18 and 3 months of age. As in controls, mutant layer V pyramidal neurons extended apical dendrites into layer I ( Figures 1D and 1E), and their axons correctly exited the cortex through the internal capsule to form the corticospinal tract (data not shown). Individual neurons were reconstructed through confocal stacks by using a program (Neuromantic) to disambiguate processes from those of any neighboring YFP+ cells.

, 2002). Therefore, in our efforts to understand how CaV2.2 is regulated at the presynaptic terminal, we examined the regulation of CaV2.2 in the context of endogenous Cdk5 activity in neurons and inhibited Cdk5 with a dominant-negative Cdk5 virus rather than using roscovitine. Our findings also revealed a role

for Cdk5-mediated phosphorylation of CaV2.2 Selleck EGFR inhibitor in modulating the interactions of CaV2.2 with various active-zone proteins, including RIM1, to regulate neurotransmission and presynaptic plasticity. It was previously reported that RIM1 binds the auxiliary β subunit of both N-type and P/Q-type calcium channels to facilitate calcium influx and tether vesicles to the presynaptic terminal (Kiyonaka et al., 2007). Intriguingly, RIM1 also further reduces the G-protein-mediated inhibition of CaV2.2, which subsequently contributes to a prolonged increase in calcium influx (Weiss et al., 2011). As RIM1 is required for calcium-channel density and vesicle docking at the active zone of calyx of Held synapses and central synapses (Han et al., 2011; Kaeser et al., 2011), our results are PD-0332991 purchase consistent with the notion that the CaV2.2 interaction with RIM1 allows for coordinated transmitter release, and we propose that this interaction is regulated in part by Cdk5-mediated phosphorylation of CaV2.2. CaV2.2 and RIM1 are both closely associated with other active-zone proteins

and SNARE complexes. In this study, we examined the binding of CaV2.2 to a number of presynaptic proteins, and showed that RIM binding increased in neurons

expressing WT CaV2.2 HSV. Several groups previously reported a direct interaction between RIM1, or the RIM1 binding protein (RIMBP), and CaV2.2 (Coppola et al., 2001; Hibino et al., 2002; Kaeser et al., 2011). However, our results differ from other reports that RIM1 does not bind CaV2.2, even though both localize to the presynaptic terminal (Khanna Phosphatidylinositol diacylglycerol-lyase et al., 2006 and Khanna et al., 2007b). A possible explanation might be the previous use of an antibody targeting the synprint region of chicken CaV2.2 (Li et al., 2004), even though one study was conducted on rat brain preparations (Khanna et al., 2007a). The chicken synprint region shares only about 59% homology to the mouse and rat synprint regions, which share 88% homology with each other. Therefore, the different antibodies that were used might explain the discrepancies between our findings and those published previously. Although we did not observe a decrease in CaV2.2 binding to Syntaxin1A in primary neurons, in contrast to our Cdk5 cKO samples, we hypothesize that acute manipulations differ from chronic Cdk5 knockdown in vivo, which may in turn directly or indirectly affect the interaction of CaV2.2 with various SNARE proteins to alter neurotransmission. We also cannot exclude the possibility that other kinases, such as PKA, may phosphorylate CaV2.

ACh tone in the striatum is in http://www.selleckchem.com/screening/inhibitor-library.html part regulated by muscarinic autoreceptors M2 and M4 whose functions in turn are negatively modulated by the GTPase accelerator RGS4 ( Ding et al., 2006). Thus, the observed upregulation of M2 and downregulation of RGS4 gene expression indicate an enhancement of cholinergic autoreceptor function in surviving ACh neurons in the striatum of Shh-nLZC/C/Dat-Cre mice consistent with the observed reduction in striatal cholinergic tone. In contrast to the situation in ACh neurons, parvalbumin gene expression was strongly reduced at 5 weeks of age, but reached normal levels at 12 months

suggesting a compensatory upregulation by surviving FS neurons (Figure 5M(2)). General GABAergic marker and DA receptor gene expression were not affected at 5 weeks but DA receptors D1–D4, DARP32, and Gad1 were downregulated, while DA receptor interacting protein (D-IP) was upregulated at 12 months of age (Figure 5M(2)) Selleckchem PF-2341066 suggesting that GABAergic neuronal subtypes in addition to FS neurons in the striatum become phenotypically

involved subsequently to ACh and FS neurons. In support of a direct control of gene expression by Shh signaling in the striatum, we found that the transcription factor Gli3, whose expression is inhibited by Shh signaling (Ulloa and Briscoe, 2007), is upregulated by the Smo antagonist cyclopamine (Chen et al., 2002) and downregulated by the Smo Amisulpride agonist “SAG” (Frank-Kamenetsky et al., 2002) when injected into the adult striatum of C57Bl/6 wt mice (Figure 5M(3)). M2 expression was also acutely and dose-dependently increased by cyclopamine and decreased by SAG injection into the striatum, indicating that Shh signaling impinges directly on the regulation of cholinergic tone in the healthy striatum (Figure 5M(3)). Thus, the absence of Shh signaling originating from DA neurons elicits a sequential structural and functional corruption of the striatum which begins with cell physiological alterations in ACh and FS neurons and culminates in a progressive, adult-onset

degeneration of ACh and FS neurons without compensatory adaptations of surviving ACh neurons. GDNF is expressed by ACh and FS interneurons (Hidalgo-Figueroa et al., 2012). Consistent with the Shh-dependent maintenance of ACh and FS neurons, we found a progressive reduction in GDNF mRNA and protein expression, and an upregulation of the canonical receptor Ret and its coreceptor Gfrα1, which bind all members of the GDNF family of ligands, in the striatum of Shh-nLZC/C/Dat-Cre mice compared to controls ( Figures 6A and 6B). The progressive reduction in striatal GDNF tissue content correlated with the progressive degeneration of ACh neurons in Shh-nLZC/C/Dat-Cre mice ( Figures 6B and 2D; R2 = 0.95, p < 0.02 for ACh neurons).

The slope values were calculated in such a way that zero corresponds to complete rectification

whereas a value of unity corresponds to linear summation of s1s1 and s2s2. Details of these quantifications can be found in Supplemental Experimental Procedures. To obtain the nonlinearities for the subunit model (insets in Figures 3A–3C), we calculated the ganglion cell response as a weighted sum of two inputs. The two inputs were selleck screening library generated from the respective stimulus components s1s1 and s2s2 by the same nonlinear function N(si)N(si). This function is parameterized as a power law for preferred stimuli with potentially incomplete rectification of nonpreferred stimuli. We determined the parameters of the nonlinear function for individual iso-response curves by a maximum-likelihood fit. To investigate the effect of subunit size on rectification in the iso-response curves for stimuli arranged in a checkerboard fashion (Figure 4C), we modeled a ganglion cell with 600 μm receptive field diameter, composed of circular subunits with varying sizes. Each subunit integrated the visual signal linearly and transmitted the result through a threshold-quadratic nonlinearity with incomplete rectification to the ganglion cell. The ganglion cell’s response was computed as a weighted sum over all subunit inputs, with weights determined

by a Gaussian curve, centered Selleck PCI-32765 on the midpoint of the ganglion cell receptive field. These responses were used to compute the slope of the iso-response curve in the same way as for the experimentally measured data. To quantitatively test the hypothesized circuit for homogeneity detectors based

on local inhibition (Figure 7C), we set up a model with two subunits that correspond to the inputs from each half of the receptive field. Each subunit comprises a bipolar cell and an amacrine cell. The bipolar cell transmits the contrast signal of its respective receptive field half as excitatory input to the homogeneity detector through a threshold-quadratic synaptic Terminal deoxynucleotidyl transferase nonlinearity. The amacrine cell receives the same excitatory input from the bipolar cell and provides inhibition through another threshold-quadratic nonlinearity. In addition, the amacrine cell signal is low-pass filtered to account for the temporal delay. From the integrated input to the homogeneity detector, we calculated iso-rate and iso-latency curves (Figures 7D and 7E). Details of the models are provided in Supplemental Experimental Procedures. We thank A. Borst for comments on the manuscript and the members of the Gollisch Lab for helpful discussions. This work was supported by the Max Planck Society, the German Initiative of Excellence, the International Human Frontier Science Program Organization, the German Ministry for Education and Research through the Bernstein Center for Computational Neuroscience Munich, and the Deutsche Forschungsgemeinschaft (DFG) through the Collaborative Research Center 889.