Amplifications were

done in a total volume of 25 μl containing Tris–HCl, KCl, (NH4)2SO4, 8.0 mM of MgCl2, and 1.25 U HotStar Taq Polymerase (Qiagen, Hilden), as well as 200 μM of each dNTP, 1 μM of each primer, 0.2 μM of each probe and 250 ng of DNA. For each PCR test, positive controls of genomic babesial DNA from each subspecies and negative controls containing DNA from uninfected dogs were included in every run. Amplifications of target genes were done using an iCycler (Biorad, Munich) with an initial Taq Polymerase activation step of 13 min at MS-275 concentration 95 °C, followed by 50 cycles at 95 °C for 30 s, annealing at 50 °C for 30 s and elongation at 72 °C for 30 s. Fluorescence was measured at each annealing step. Reactions were evaluated using the software version 3.1 (iCycler iQ Real Time PCR detection system, Biorad) and were regarded as positive if the amount of fluorescence exceeded a threshold value (basal emission

plus the 10 fold of its standard deviation) and followed a curve of a sigmoid shape. Blood samples were collected from dogs living in farms in three regions within the State of Minas Gerais, Brazil: Lavras (latitude – S 21°20′; longitude – W 45°00′), Belo Horizonte (latitude – S 19°55′; longitude – W 43°56′) and Nanuque (latitude – S 17°49′; longitude – W 40°20′). In these areas two seasons are well defined during the year: a dry season (from April to September) and a rainy season (from October to March). The climatic data, as referred in http://www.agritempo.gov.br/agroclima/pesquisaWeb?uf=MG, were obtained throughout the experimental HIF inhibitor period for each region. Blood samples were collected during a dry season of 2004 from 252 dogs living in the following locations: Lavras (n = 100), found Belo Horizonte (n = 50) and Nanuque (n = 102). In the subsequent rainy season, a total of 166 dogs were re-sampled, as followed: Lavras (n = 71), Belo Horizonte (n = 29) and Nanuque

(n = 66). From each sample, DNA was extracted using the Wizard Genomic DNA Purification (Promega, Madison, USA) and Giemsa stained smears were microscopically examined for direct detection of Babesia parasites. DNA concentration was determined using the spectrophotometer NanoDrop ND-1000 (NanoDrop, Wilmington, USA) and DNA samples were diluted using ultrapure water to reach a concentration of 50 ng/μl. The Chi-square test was used to evaluate associations between prevalence and incidence among municipalities and seasons. The Kappa test was performed to compare detection in blood smears and by the Real Time PCR. Although the Real Time PCR developed in this study had been designed to detect all subspecies of B. canis ( Fig. 1), only B. canis vogeli was found in all three regions analyzed. Prevalence rates by region and season are shown in Table 2. Direct examination of blood smears detected few positive animals (0.8% during dry season, and 0.0% during the rainy season), while the Real Time PCR detected 9.9% of positive animals during the dry season and 10.8% during the rainy season.

For this test rats received four reinstatement trials before each of which a single outcome was delivered. After each outcome, delivery responding during the next 2 min was recorded (i.e., the postoutcome period) recorded (Figure 3A). Performance in the final 2 min of extinction and prior to each of the reinstatement trials served as the pretest period. As is clear from Figure 3I, the Sham group reinstated performance of the action most recently associated with the delivered outcome (i.e., Post-reinst) relative to

the other action (Post-other). In contrast, both actions were reinstated in the Pf-lesioned Selleck Dorsomorphin group in an undifferentiated manner. Accordingly, although there was no effect of group, F (1, selleck products 10) = 0.8, p = 0.392, responding on the reinstated action relative to the other action differed between groups; in the sham group, the increase in responding was specific to the reinstated lever, F (1, 10) = 11.68, p = 0.007, whereas

in the Pf group, it was not and was similarly distributed between the two levers, F (1, 10) = 0.99, p = 0.343. Together, the contingency degradation, devaluation, and outcome-specific reinstatement tests confirm that Pf-lesioned rats were unable to use action-outcome information to guide instrumental performance after the initial contingencies were altered. Although our initial results imply that the effects of Pf lesions on action-outcome encoding and retrieval were secondary to their effects on cholinergic activity in striatum, we sought to confirm

this more directly in two further experiments in which we disconnected the Pf from the pDMS using (1) asymmetrical lesions and (2) pharmacological blockade of cholinergic activity. The logic behind disconnection experiments is straightforward (Everitt et al., 1991): if the Pf and pDMS are functionally connected, then, for example, combining a unilateral Pf lesion with a unilateral lesion of the pDMS in the contralateral hemisphere should disconnect these structures and disrupt this function. Hence, for this experiment, we compared a group that received contralateral (Contra) Pf and pDMS lesions with a group that received ipsilateral (Ipsi) lesions during of these structures, inducing the same degree of cell loss while preserving the Pf-DMS pathway in the one hemisphere. To evaluate any impairment in the Ipsi group, a Sham control was also included. Representative lesions are shown in Figure 4A and schematically in Figure 4I. After recovery from surgery, we conducted a direct replication of the behavioral procedures previously described, the results of which are presented in Figure 4. As is clear from this figure, the effect of the disconnection was similar to that induced by bilateral Pf lesions.

On day 1 mice were habituated to the training chamber for 12 min. Training occurred on day 2 as follows: mice were allowed to acclimate to the chamber for

4 min prior to the onset of six consecuative training blocks, each consisting of a 20 s baseline, followed by a 20 s, 2 KHz, 80 dB tone (conditioned stimulus, CS), followed by an 18 s trace interval of silence, followed by a 2 s scrambled 1 mA foot shock (unconditioned stimulus, US), followed by a 40 s intertrial interval (ITI). On day 3 mice were tested. Mice were first placed in the training chamber for 3 min to assess contextual fear conditioning, after which they were returned to their home cage for 3 min. Testing for trace fear conditioning took place in a novel chamber, which Ion Channel Ligand Library molecular weight was see more distinct from the training chamber. Mice were allowed to acclimate to the novel chamber for 3 min

prior to tone presentation to assess % freezing in the novel chamber. Next, mice were presented with four testing blocks consisting of a 20 s baseline followed by a 20 s 2 KHz, 80 dB tone followed by a 60 s ITI. Percentage of time freezing was quantified using automated motion detection software (CleverSys). Hippocampal neurons from E18 rat pups were plated onto poly-L-lysine coated dishes or coverslips in Neurobasal growth medium supplemented with 2% B27, 2 mM Glutamax, 50 U/mL penicillin, 50 μg/mL streptomycin, and 5% FBS. Neurons were switched to serum-free Neurobasal medium 24 hr postseeding and fed twice a week. Neurons were transfected at DIV 14–15 using lipofectamine 2000 (Invitrogen) and pH-GluA2 recycling live-imaging assays were performed 48 hr posttransfection as described previously (Lin and Huganir, 2007). Briefly, coverslips containing neurons were assembled onto a closed perfusion chamber and continuously perfused with recording

buffer (25 mM HEPES, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, 2 mM MgCl2, 30 mM D-glucose, 1 μM Digestive enzyme TTX, pH 7.4). After 10 min of baseline recording (F0), neurons were perfused with NMDA solution (25 mM HEPES, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, 0.3 mM MgCl2, 30 mM D-glucose, 1 μM TTX, 20 μM NMDA, 10 μM glycine, pH 7.4) for 5 min before the perfusion was switched back to recording buffer for the remainder of the session. All imaging experiments were performed at room temperature using a Zeiss LSM 510 Meta/NLO system (Carl Zeiss, Thornwood, NY). The pHluorin fluorescence was imaged at 488 nm excitation and collected through a 505–550 nm filter, while the mCherry signal was imaged at 561 nm excitation and 575–615 nm emission. Neurons were imaged through a 63× oil objective (N.A. = 1.40) at a 3 μm single optical section and collected at a rate of 1 image per min.

, 2010 and Rothschild et al., 2010) as well as from the mouse olfactory bulb (Wachowiak et al., 2004) and rat cerebellum (Sullivan et al., 2005). Various approaches can be used for extracting the action potential activity underlying such somatic calcium transients (Holekamp et al., 2008, Kerr et al., 2005, Sasaki et al., 2008, Vogelstein et al., 2010, Vogelstein et al., 2009 and Yaksi and Friedrich, 2006). For example, an effective approach is the “peeling algorithm” (Grewe et al., 2010), which is based on subtracting single action-potential-evoked calcium transients from the fluorescent trace until no additional event is present in the residual trace. Again, GECIs can be adapted as well for such studies of neuronal

network function in different animal models (see also Table 1). Meanwhile, they have been used in rodents, Drosophila, this website C. elegans, zebrafish, and even primates ( Díez-García et al., 2005, Heider et al., 2010, Higashijima Nintedanib et al., 2003, Horikawa et al., 2010, Li et al., 2005, Lütcke et al., 2010,

Tian et al., 2009, Wallace et al., 2008 and Wang et al., 2003). A promising application of in vivo two-photon calcium imaging is the investigation of neuronal network plasticity. For example, experimental paradigms of visual deprivation (e.g., stripe rearing to influence orientation selectivity or unilateral eyelid closure to influence ocular dominance plasticity) have been shown to impact significantly the functional properties of mouse visual

cortex neurons (Kreile et al., 2011 and Mrsic-Flogel et al., 2007). Similarly, calcium imaging has been used to study the plasticity of neuronal networks in mouse models of disease, for example after ischemic only damage of the somatosensory cortex (Winship and Murphy, 2008). There is a wide interest to examine brain circuits in relation to defined behaviors in awake animals. To achieve this, there are at present two major strategies involving calcium imaging as the central method for cellular functional analysis. One approach involves the use of head-mounted portable minimicroscopes (see section on imaging devices); the other concentrates on the study of head-fixed animals involving the use of standard two-photon microscopes. Figure 8A illustrates an experiment that was performed in the motor cortex of head-fixed mice that were engaged in an olfactory discrimination test (Komiyama et al., 2010). The animals were trained to lick in response to odor A and to stop licking in response to odor B (Figure 8Aa). The somatic calcium transients that were recorded in motor cortical neurons of the behaving mice had an excellent signal-to-noise ratio (Figures 8Ab–8Ac). Such experiments involving head fixation are possible because the mice have been gradually adapted to the experimental set-up, which includes the training in a tube-like construction which provides protection to the animal (in that particular study training lasted for 5 days on average).

, 2008 and Lee et al., 2006). MD increased turnover and led to a transient decrease in inhibitory tone (Chen et al., 2011). Consistent with the findings above, immunohistochemistry of VGAT revealed a loss of inhibitory synapses onto layer 5 apical dendrites, but not the neighboring dendrites of layer 2/3 pyramidal neurons (Chen et al., 2011). MD and recovery in adult mice each produce a

transient loss of Gephyrin-labeled inhibitory synapses on spine heads of excitatory neurons, but not on their dendritic shafts (Chen et al., 2012 and van Versendaal et al., 2012). The spine heads themselves showed little change, suggesting that excitatory connections were stable (Chen et al., 2012). Considering the events we discuss in the development of V1, there is a satisfying account of topographic map formation. The next major event, the formation of highly selective receptive fields, Veliparib clinical trial remains largely a mystery. We do not know the details of the neural circuitry that gives rise to selective responses, and we lack experimental confirmation of SNS-032 purchase the mechanisms responsible for its formation. The emergence of binocular responses in V1

seems to require no explanation beyond the convergence of eye-specific thalamocortical inputs, but the matching of preferred orientation in the two eyes suggest that experience dependent plasticity sculpts these circuits during normal development. A great deal is known about the mechanisms responsible for changes in binocular responses following MD in the critical period, and about some of the accompanying changes in the neural circuit, but it is not clear which of these mechanisms is responsible for the normal process of binocular matching. Finally, it is not yet clear how adult plasticity differs mechanistically and functionally from that of the critical period (Figure 7). These questions can now be addressed using

a number of new tools for tracking neural activity, structure, and biochemical from signaling pathways in individual cells over the course of development and plasticity. Observations can be targeted to specific cells in V1 using many novel brain region-, cortical layer-, and neuronal subtype-specific Cre-transgenic mice (Madisen et al., 2010) in combination with Cre-dependent structural or physiological markers (Bernard et al., 2009 and Luo et al., 2008). Activity can be measured in the targeted cells using chemical and protein-based fluorescent biosensors of intracellular calcium (Hasan et al., 2004, Mank et al., 2008 and Tian et al., 2009), vesicle release (Li and Tsien, 2012), or voltage (Miller et al., 2012). Structural rearrangements can be measured in targeted cells along with fluorescently tagged synaptic proteins, including those that are newly synthesized and those that may indicate the strength of synaptic connections (Lin et al., 2008).

Sounds were presented through Sensimetric MRI Compatible Insert Earphones (www.sens.com/s14/index.htm). To set the volume levels in the scanner, a functional run Metabolism inhibitor was started and the volume of the stimuli was slowly increased until the participant pressed a button indicating they could hear the stimuli clearly. Before the experiment,

observers were given detailed instructions that they should imagine only isolated objects, and that “giant” versions of small objects should be imagined “as having the same size as a car or piano” while tiny versions of large objects should be imagined “as having the same size as a matchbox or something that could fit in your hand.” Observers then were given a short practice

run outside the scanner in which they heard the names of small objects, big objects, tiny versions of big objects, and giant versions of small objects, following the same timing as in the experimental runs. None of these practice object stimuli were used in the main experiment. Functional data were preprocessed using Brain Voyager QX software (Brain Innovation, Maastricht, Netherlands). Preprocessing included slice scan-time correction, 3D motion correction, linear trend removal, temporal high-pass filtering (0.01 Hz cutoff), spatial smoothing (4 mm FWHM kernel), and transformation into Talairach coordinates. For the ROI overlap computations, analyses were performed on unsmoothed functional data in ACPC space (no Talairach transform). Statistical analyses were based Raf phosphorylation on the general linear model. All GLM analyses included regressors for each experimental condition, defined as square-wave regressors for each stimulus presentation time convolved with a gamma-function to approximate the idealized hemodynamic response. A whole-brain, random-effects group average analysis was conducted on data from the Big versus Small Object Experiment (E1). A contrast was performed at an uncorrected threshold of p < 0.001 (with an additional cluster threshold of 10 mm3 applied) to test for regions more active to small

versus big objects and vice-versa. To obtain Farnesyltransferase size-preference maps for each subject, an object-responsive mask was computed by taking all voxels posterior to Y = −19 (to isolate the occipital-temporal lobes) that were active in either the Small > Rest or the Big > Rest contrast at T > 2.0. The preference map shows the t values of the small object versus big object contrast, within this object-responsive mask. To compute the group size-preference map, the time series of each subject was concatenated and a fixed-effects GLM analysis was run on the group data (see Hasson et al., 2003 and Levy et al., 2001), and the same procedure as in the single subject case was subsequently followed. To obtain regions-of-interest from the Big and Small Object experiment, whole-brain GLMs were conducted for each individual.

We found that we could reconstitute glutamate-gated currents in Xenopus oocytes or C. elegans muscle cells when s-SOL-1 was coexpressed with SOL-2, STG-1, and GLR-1 ( Figures 1E and 1F), but not in the absence of SOL-2 ( Figure 1B). Thus, s-SOL-1 function was dependent on SOL-2. Furthermore, SOL-2 cannot simply replace SOL-1 given that we were unable to reconstitute

glutamate-gated current in either oocytes or muscle cells by co-expressing GLR-1, STG-1 and SOL-2 ( Figures GSK-3 inhibitor 1E and 1F). Our reconstitution studies demonstrated that SOL-2 and SOL-1 contribute to the function of the GLR-1 signaling complex. In addition, our finding that mutations in sol-2 disrupt the behavior of transgenic lurcher mutants ( Figure 1C) predicts that glutamatergic neurotransmission is disrupted in sol-2 mutants. Thus, we Ceritinib research buy evaluated the behavior of sol-2 mutants using two standard assays that depend on GLR-1 function ( Hart et al., 1995; Maricq et al., 1995; Mellem et al., 2002). When tested in an osmotic avoidance assay the sol-2 mutants were as slow to recoil from the hyperosmotic stimuli as glr-1 or sol-1 mutants ( Figure 2A).

When tested in a touch-avoidance assay (nose touch response) sol-2 mutants were significantly impaired, but not to the extent of glr-1 or sol-1 mutants ( Figure 2B). In both assays, sol-1; sol-2 double mutants were no more impaired than sol-1 mutants alone, suggesting that the two gene products act in the same pathway. The peak amplitude of the glutamate-gated current in AVA was considerably diminished in sol-2 mutants, and we could only measure a small, rapidly activating and desensitizing current ( Figures 2C and 2D). These currents are distinct from those recorded in sol-1

mutants where we could not detect a rapidly activating inward current under the same recording conditions ( Figures 1A and 2D). Only the GLR-1-mediated current was decreased in sol-2 mutants; the slower, outwardly rectifying current is mediated by NMDA receptors ( Brockie et al., 2001b) and did not appear appreciably Urease different than wild-type current ( Figure 2C). Glutamate-gated currents in the AVA neurons of transgenic sol-2 mutants were rescued by a functional SOL-2::GFP fusion protein that was specifically expressed in AVA using the rig-3 promoter ( Feinberg et al., 2008; Figures 2C and 2D). We were also able to rescue current in transgenic sol-2 mutants that expressed GFP fused to the extracellular N terminus of full-length SOL-2 (GFP::SOL-2; Figure S2). These results demonstrate that GFP-tagged SOL-2 is functional and acts cell autonomously. However, unlike the case for SOL-1, we did not observe rescue of transgenic sol-2 mutants that expressed a secreted variant of the fusion protein that lacked the transmembrane domain (GFP::s-SOL-2) ( Figure S2).

Although not as pathogenic as Ancylostoma caninum, heavy infections in young dogs may result in blood loss ( Rep, 1980) and hypoproteinemia ( Miller, 1968). However, the most significant concern with A. braziliense is its ability to cause cutaneous larva migrans in both dogs ( Vetter and Leegwater-vd Linden, 1977, Vetter and van der Linden, 1977a, Vetter and van der Linden, 1977b and Bowman et al., 2010) and humans ( Brenner and Patel, Talazoparib molecular weight 2003, Patel et al., 2008 and Purdy et al., 2011). Of the hookworm larvae,

A. braziliense tends to be more invasive by cutaneous penetration and shows the greatest enzyme activity for breaking down structures of the skin ( Hotez et al., 1992), thus allowing the larvae to enter by direct contact with intact skin and mucous membranes. Not only has A. braziliense been associated with cutaneous Dinaciclib chemical structure larva migrans in humans, but also migration to the lungs ( Butland and Coulson, 1985) and oral mucosa ( Damante et al., 2011). Even though the parasite is more common in the tropical regions of the world, it has also been reported in non tropical settings ( Herbener and Borak, 1988), suggesting the need for control outside the areas typically considered endemic. Therefore, effective control of A. braziliense in dogs is important because

of its potential pathogenicity in dogs and zoonotic potential for cutaneous larva migrans in humans. Milbemycin oxime is a macrocyclic lactone that is efficacious against infections of A. caninum ( Blagburn et al., 1992 and Niamatali et al., 1992), but no studies have been done specifically investigating effectiveness against A. braziliense. We hypothesized that milbemycin oxime would be over 90% efficacious when administered as a single treatment to dogs infected with A. braziliense. The study was a randomized, blinded, placebo controlled laboratory study using

naturally infected dogs conducted in compliance with GCP (VICH GL9), South African animal welfare regulations, as stipulated in the “National Code for Animal Use in Research, Education, Phosphoprotein phosphatase Diagnosis and Testing of Drugs and Related Substances in South Africa”. The protocol was submitted to the ClinVet Animal Ethics Committee (CAEC), the composition of which was in compliance with the National Code, for approval. In addition, the protocol was reviewed and approved by the Novartis Animal Health US, Inc. Institutional Animal Care and Use Committee. Thirty-six hookworm infected dogs (21 males and 15 females), a minimum of 10 weeks of age and of any pure or mixed breed were randomly assigned to cages at the beginning of acclimation. Animals were purchased from owners who were fully informed of the nature of the study. Each dog was identified by a unique number on a collar tag. All purchase contracts indicated each animal’s origin and procurement records traceable to each animal by identification number.

g., between hemispheres (Engel et al., 1991, Engel et al., 2001 and Buzsáki et al., 2003), between entorhinal cortex and hippocampus (Chrobak and Buzsáki, 1998), and between remote regions of the cerebral cortex (Gregoriou et al., 2009 and Melloni

www.selleckchem.com/products/SP600125.html et al., 2007). Candidates for the mediation of these synchronization phenomena are (1) reciprocal fast-conducting glutamatergic projections that originate from pyramidal cells and impinge on both inhibitory and excitatory neurons in the respective target structure and (2) long-range inhibitory projections that directly link the inhibitory network in one region with that in another (Buzsáki et al., 2004, Jinno et al., 2007 and Caputi et al., 2013). In addition to implementing fast-conducting synchronizing connections, nature seems to rely also on counter-intuitive properties of nonlinear dynamical systems that permit such Autophagy Compound Library screening synchronization by reciprocal coupling despite conduction

delays (Vicente et al., 2008). The most precisely synchronized cortical rhythm is the fast “ripple” oscillation of the hippocampus (130–160 Hz in rats; Buzsáki et al., 1992 and O’Keefe and Nadel, 1978). The frequency of the ripple decreases somewhat from approximately 160–180 Hz in mice (Buzsáki et al., 2003) to 110 Hz in humans (Bragin et al., 1999; Supplementary Note 2); ripples can arise at any site along the septo-temporal axis of the hippocampus and can remain either localized or spread to the septal or temporal direction (Patel et al., 2013). isothipendyl The ripple-related synchronous hippocampal output can exert a powerful influence on widespread cortical and subcortical structures in both rats and monkeys (Siapas

et al., 2005 and Logothetis et al., 2012), and appropriate timing of these widespread regions demands structural support. It is not known though whether hippocampal ripples activate their different cortical and subcortical targets by delays, in which case their synchrony would not be guaranteed, or whether their target “hot spots” are coactivated to form a specific engram. Under the latter scenario, one might expect special constraints on the transmission pathways and mechanisms, both of which should scale with brain size. In summary, the preservation of temporal constants that govern brain operations across several orders of magnitude of time scales suggests that the brain’s architectural aspects, such as scaling of the ratios of neuron types, modular growth, system size, inter-system connectivity, synaptic path lengths, and axon caliber, are subordinated to a temporal organizational priority. Of these components, the changing features of axons across species are best documented.

Thus, a noise stimulus circumvents the threshold nonlinearity, resulting in a spiking receptive field map that is comparable to that recorded directly from Vm responses (Mohanty et al., 2012). Threshold is also likely to provide the explanation for why pharmacological blockade of GABAA-mediated inhibition broadens orientation tuning in cortical cells (Sillito, 1975). Blocking inhibition appears to increase the overall excitability of cortical neurons such that previously ineffective stimuli on the edges of the spike-rate tuning curve become suprathreshold (Katzner et al., 2011). Up to now, we have considered receptive field properties in the spatial

Ferroptosis inhibitor cancer domain—that two stimuli of different orientations suppress one another, that orientation tuning is contrast invariant, selleck kinase inhibitor and that the width of orientation tuning is narrower than predictions based on the receptive field map. Here we consider three temporal aspects of simple cell responses that also fail to emerge from the simplest forms of the feedforward model. First, simple cells do not respond well to rapidly changing stimuli. Compared to LGN cells, the preferred temporal frequencies (TFs) of simple cells are lower by a factor of

2 (Hawken et al., 1996 and Orban et al., 1985). Here, temporal frequency refers to the number of bars of the drifting grating that pass over the receptive field in each second. Compare, for example, the TF tuning of the LGN cell in Figure 6A (black) and the simple cell in Figure 6C (black). The peaks of the tuning curves are shifted relative to one another, as are the TF50 values Oxygenase (arrows; the frequency at which

the response amplitude falls to 50% of its peak). Note that the simple cell’s Vm responses (Figure 6B) fall somewhere between the LGN and the simple cell’s spike responses (Figures 6A and 6C). This mismatch in preferred TF between LGN and cortex does not represent a nonlinearity; a linear, low-pass RC filter could shift the peak frequency of a simple cell’s output relative to its input. The second temporal feature of simple cells is that the preferred TF in simple cells decreases almost 2-fold with decreasing stimulus contrast (Albrecht, 1995, Carandini et al., 1997, Hawken et al., 1996, Holub and Morton-Gibson, 1981 and Reid et al., 1992). Compare, for example, the black and gray tuning curves in Figure 6C. This property does represent a nonlinearity: the transformation between stimulus and response changes with stimulus strength (contrast). One element that surely contributes to the mismatch in preferred TF between simple cells and their synaptic input from the LGN is the membrane time constant, τ. Together, the membrane input resistance R and membrane capacitance C form a linear low-pass filter with a time constant τ = RC, which lies near 15 ms for most simple cells ( Anderson et al., 2000). The frequency at which such a filter attenuates its input by a factor of 2 (f3dB = 1/2πτ) is about 11 Hz.