A Descriptive Case Study of Skilled Football Goalkeepers During 1 v 1 Dyads: A Case for Adaptive Variability in the Quiet Eye.

Evidence investigating skilled performers in sport suggests that a prominent component of skilled behavior is, in part, due to the development of more effective and efficient perception-action couplings. Further, the Quiet Eye has emerged as a useful tool in which to investigate how skilled performers regulate action through fixating on visual information within the immediate environment before the onset of a goal directed movement. However, only a few contributions to the literature have attempted to examine the individual variations within these Quiet Eye fixations in skilled participants. In this case study, we first asked how goalkeepers control their actions, via the Quiet Eye in a representative task. Second, we sought to examine whether inter- and intra- individual differences in the Quiet Eye are present in skilled goalkeepers as a functional component of skilled performance. Results were consistent with previous work on football goalkeepers, with QE fixations located at the ball and visual pivot. However, individual analysis reveals different Quiet Eye gaze patterning between (inter) and within (intra) the goalkeepers during saving actions. To conclude, we have provided a descriptive case study in attempt to understand the Quiet Eye behaviors of a skilled sample of professional goalkeepers. In doing so we have suggested how adaptive variability, founded upon an Ecological Dynamics framework, may provide further insight into the function of the Quiet Eye.

Mapping the potential for Payments for Ecosystem Services schemes to improve water quality in agricultural catchments: A multi-criteria approach based on the supply and demand concept.

Payments for Ecosystem Services (PES) schemes are an increasingly popular form of catchment management for improving surface water and groundwater quality. In these schemes, downstream water users who are impacted by agricultural diffuse pollution incentivise upstream farmers to adopt better practices. However, this type of scheme will not be successful in all situations, in part, due to a lack of potential for agriculture to improve the suuply of good water quality and/or a lack in demand from downstream users for good water quality. As such, this study aims to present a flexible approach to mapping the potential for PES schemes to improve water quality in agricultural catchments. The approach is based on multi-criteria analysis, with supply and demand as key criteria. It uses expert judgement or current guidance on PES to select supply and demand sub-criteria, expert judgement to weight all criteria through pairwise comparisons and readily available, national datasets to indicate criteria. Once indicator data are normalized, it combines them in a weighted sums analysis and presents results spatially at the national scale, all within a geographical information system. The approach can easily be applied to the country or region of interest by using locally relevant criteria, expert judgement and data. For example, when applied to the situation for river waterbodies in England, supply sub-criteria were the contribution of agriculture to loads of the major pollutants (nitrogen, phosphorus and sediments) and demand sub-criteria were the different downstream water users present (water companies and, tourist and local recreational users). Experts assigned equal weight to supply and demand criteria and the highest weights to sediments and water companies for sub-criteria, respectively. When national scale datasets to indicate these criteria were combined in a weighted sums analysis, it was possible to identify areas of high potential for PES. This would hopefully motivate more detailed research at the individual catchment level into the constraints in linking supply and demand. Three case-study schemes were also examined to show how some of these constraints are being identified and overcome. As such, the approach forms the first tier in a two-tier framework for establishing PES schemes to improve water quality in agricultural catchments.

Comparison of electrophysiological and motility assays to study anthelmintic effects in Caenorhabditis elegans.

Currently, only a few chemical drug classes are available to control the global burden of nematode infections in humans and animals. Most of these drugs exert their anthelmintic activity by interacting with proteins such as ion channels, and the nematode neuromuscular system remains a promising target for novel intervention strategies. Many commonly-used phenotypic readouts such as motility provide only indirect insight into neuromuscular function and the site(s) of action of chemical compounds. Electrophysiological recordings provide more specific information but are typically technically challenging and lack high throughput for drug discovery. Because drug discovery relies strongly on the evaluation and ranking of drug candidates, including closely related chemical derivatives, precise assays and assay combinations are needed for capturing and distinguishing subtle drug effects. Past studies show that nematode motility and pharyngeal pumping (feeding) are inhibited by most anthelmintic drugs. Here we compare two microfluidic devices ("chips") that record electrophysiological signals from the nematode pharynx (electropharyngeograms; EPGs) ─ the ScreenChip™ and the 8-channel EPG platform ─ to evaluate their respective utility for anthelmintic research. We additionally compared EPG data with whole-worm motility measurements obtained with the wMicroTracker instrument. As references, we used three macrocyclic lactones (ivermectin, moxidectin, and milbemycin oxime), and levamisole, which act on different ion channels. Drug potencies (IC50 and IC95 values) from concentration-response curves, and the time-course of drug effects, were compared across platforms and across drugs. Drug effects on pump timing and EPG waveforms were also investigated. These experiments confirmed drug-class specific effects of the tested anthelmintics and illustrated the relative strengths and limitations of the different assays for anthelmintic research.

Phosphorus leaching from riparian soils with differing management histories under three grass species.

Plants release carbon-based exudates from their roots into the rhizosphere to increase phosphorus (P) supply to the soil solution. However, if more P than required is brought into solution, additional P could be available for leaching from riparian soils. To investigate this further, soil columns containing a riparian arable and buffer strip soil, which differed in organic matter contents, were sown with three common agricultural and riparian grass species. The P loads in leachate were measured and compared with those from unplanted columns, which were 0.17 ± 0.01 and 0.89 ± 0.04 mg kg-1 for the arable and buffer strip soil, respectively. A mixture of ryegrass and red fescue significantly (p ≤ .05) increased dissolved inorganic P loads in leachate from the arable (0.23 ± 0.01 mg kg-1 ) and buffer strip soil (1.06 ± 0.05 mg kg-1 ), whereas barley significantly reduced P leaching from the buffer strip soil (0.53 ± 0.08 mg kg-1 ). This was dependent on the dissolved organic C released under different plant species and on interactions with soil management history and biogeochemical conditions, rather than on plant uptake of P and accumulation into biomass. This suggested that the amount and forms of P present in the soil and the ability of the plants to mobilize them could be key factors in determining how plants affect leaching of soil P. Selecting grass species for different stages of buffer strip development, basing species selection on root physiological traits, and correcting soil nutrient stoichiometry in riparian soils through vegetative mining could help to lower this contribution.

Spatial and temporal variability in costs and effectiveness in phosphorus loss mitigation at farm scale: A scenario analysis.

Current policy instruments under the EU Water Framework Directive (WFD) to mitigate phosphorus (P) loss require that P use on farms is managed through regulation of farm gate P balances. Regulation at farm scale does not account for spatial variability in nutrient use and soil fertility at field scale, affecting the costs and effectiveness of farm gate measures. This study simulated the implementation of a P loss mitigation measure coupled with improving soil fertility so that farm productivity would not be compromised. The measure was simulated at field scale and the costs and effectiveness assessed at farm scale. Effectiveness was expressed as the time taken for excessive soil P levels to decline to levels that matched off-takes and this varied temporally and spatially within and between farms ranging from 1 to 8 years. Sub-optimum soil fertility was corrected on all fields across both farms, with applications of other soil nutrients and lime to protect productivity. An increase in costs ranging from 1.5 to 116% was predicted in the first two years of the measure on both farms after-which savings of 15-31% were predicted for each subsequent year until the measure was effective in year 9. Despite initial cost increase, there was no statistically significant difference in costs over the time taken for the measure to be effective, when compared to baseline costs. Successful implementation of measures should consider the impact on farm costs and time taken for measures to environmentally effective. Adoption of measures could improve if demonstrating to farmers that costs will not vary significantly from current practice and in time may results in savings if measures are paired with correcting soil fertility and increasing yields. This 'win-win' approach could be used into the future to ensure successful implementation and uptake of measures within the farming community.

Anthelmintic drug actions in resistant and susceptible C. elegans revealed by electrophysiological recordings in a multichannel microfluidic device.

Many anthelmintic drugs used to treat parasitic nematode infections target proteins that regulate electrical activity of neurons and muscles: ion channels (ICs) and neurotransmitter receptors (NTRs). Perturbation of IC/NTR function disrupts worm behavior and can lead to paralysis, starvation, immune attack and expulsion. Limitations of current anthelmintics include a limited spectrum of activity across species and the threat of drug resistance, highlighting the need for new drugs for human and veterinary medicine. Although ICs/NTRs are valuable anthelmintic targets, electrophysiological recordings are not commonly included in drug development pipelines. We designed a medium-throughput platform for recording electropharyngeograms (EPGs)-the electrical signals emitted by muscles and neurons of the pharynx during pharyngeal pumping (feeding)-in Caenorhabditis elegans and parasitic nematodes. The current study in C. elegans expands previous work in several ways. Detecting anthelmintic bioactivity in drugs, compounds or natural products requires robust, sustained pharyngeal pumping under baseline conditions. We generated concentration-response curves for stimulating pumping by perfusing 8-channel microfluidic devices (chips) with the neuromodulator serotonin, or with E. coli bacteria (C. elegans' food in the laboratory). Worm orientation in the chip (head-first vs. tail-first) affected the response to E. coli but not to serotonin. Using a panel of anthelmintics-ivermectin, levamisole and piperazine-targeting different ICs/NTRs, we determined the effects of concentration and treatment duration on EPG activity, and successfully distinguished control (N2) and drug-resistant worms (avr-14; avr-15; glc-1, unc-38 and unc-49). EPG recordings detected anthelmintic activity of drugs that target ICs/NTRs located in the pharynx as well as at extra-pharyngeal sites. A bus-8 mutant with enhanced permeability was more sensitive than controls to drug treatment. These results provide a useful framework for investigators who would like to more easily incorporate electrophysiology as a routine component of their anthelmintic research workflow.

Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing.

Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching and development of Ancylostoma caninum hookworms and kill Schistosoma mansoni flatworms, three widely divergent parasitic helminth species. C. elegans mutants with resistance to known anthelmintic drugs such as ivermectin are equally or more susceptible to these three drugs, suggesting that they may act on novel targets to kill worms. Sertraline, paroxetine, and chlorpromazine have long histories of use clinically as antidepressant or antipsychotic medicines. They may represent new classes of anthelmintic drug that could be used in combination with existing front-line drugs to boost effectiveness of anti-parasite treatment as well as offset the development of parasite drug resistance.

Evaluating Weaknesses of "Perceptual-Cognitive Training" and "Brain Training" Methods in Sport: An Ecological Dynamics Critique.

The recent upsurge in "brain training and perceptual-cognitive training," proposing to improve isolated processes, such as brain function, visual perception, and decision-making, has created significant interest in elite sports practitioners, seeking to create an "edge" for athletes. The claims of these related "performance-enhancing industries" can be considered together as part of a process training approach proposing enhanced cognitive and perceptual skills and brain capacity to support performance in everyday life activities, including sport. For example, the "process training industry" promotes the idea that playing games not only makes you a better player but also makes you smarter, more alert, and a faster learner. In this position paper, we critically evaluate the effectiveness of both types of process training programmes in generalizing transfer to sport performance. These issues are addressed in three stages. First, we evaluate empirical evidence in support of perceptual-cognitive process training and its application to enhancing sport performance. Second, we critically review putative modularized mechanisms underpinning this kind of training, addressing limitations and subsequent problems. Specifically, we consider merits of this highly specific form of training, which focuses on training of isolated processes such as cognitive processes (attention, memory, thinking) and visual perception processes, separately from performance behaviors and actions. We conclude that these approaches may, at best, provide some "general transfer" of underlying processes to specific sport environments, but lack "specificity of transfer" to contextualize actual performance behaviors. A major weakness of process training methods is their focus on enhancing the performance in body "modules" (e.g., eye, brain, memory, anticipatory sub-systems). What is lacking is evidence on how these isolated components are modified and subsequently interact with other process "modules," which are considered to underlie sport performance. Finally, we propose how an ecological dynamics approach, aligned with an embodied framework of cognition undermines the rationale that modularized processes can enhance performance in competitive sport. An ecological dynamics perspective proposes that the body is a complex adaptive system, interacting with performance environments in a functionally integrated manner, emphasizing that the inter-relation between motor processes, cognitive and perceptual functions, and the constraints of a sport task is best understood at the performer-environment scale of analysis.

Assessing the risk of phosphorus transfer to high ecological status rivers: Integration of nutrient management with soil geochemical and hydrological conditions.

Agriculture has been implicated in the loss of pristine conditions and ecology at river sites classified as at 'high ecological status' across Europe. Although the exact causes remain unclear, diffuse phosphorus (P) transfer warrants consideration because of its wider importance for the ecological quality of rivers. This study assessed the risk of P loss at field scale from farms under contrasting soil conditions within three case-study catchments upstream of near-pristine river sites. Data from 39 farms showed P surpluses were common on extensive farm enterprises despite a lower P requirement and level of intensity. At field scale, data from 520 fields showed that Histic topsoils with elevated organic matter contents had low P reserves due to poor sorption capacities, and received applications of P in excess of recommended rates. On this soil type 67% of fields recorded a field P surplus of between 1 and 31kgha-1, accounting for 46% of fields surveyed across 10 farms in a pressured high status catchment. A P risk assessment combined nutrient management, soil biogeochemical and hydrological data at field scale, across 3 catchments and the relative risks of P transfer were highest when fertilizer quantities that exceeded current recommendations on soils with a high risk of mobilization and high risk of transport as indicated by topographic wetness index values. This situation occurred on 21% of fields surveyed in the least intensively managed catchment with no on-farm nutrient management planning and soil testing. In contrast, the two intensively managed catchments presented a risk of P transfer in only 3% and 1% of fields surveyed across 29 farms. Future agri-environmental measures should be administered at field scale, not farm scale, and based on soil analysis that is inclusive of OM values on a field-by-field basis.

Microfluidic platform for electrophysiological recordings from host-stage hookworm and Ascaris suum larvae: A new tool for anthelmintic research.

The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device ('chip') that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels. Microfluidic technologies have transformed C. elegans research and the goal of the current study was to validate hookworm and Ascaris suum host-stage larvae in the microfluidic EPG platform. Ancylostoma ceylanicum and A. caninum infective L3s (iL3s) that had been activated in vitro generally produced erratic EPG activity under the conditions tested. In contrast, A. ceylanicum L4s recovered from hamsters exhibited robust, sustained EPG activity, consisting of three waveforms: (1) conventional pumps as seen in other nematodes; (2) rapid voltage deflections, associated with irregular contractions of the esophagus and openings of the esophogeal-intestinal valve (termed a 'flutter'); and (3) hybrid waveforms, which we classified as pumps. For data analysis, pumps and flutters were combined and termed EPG 'events.' EPG waveform identification and analysis were performed semi-automatically using custom-designed software. The neuromodulator serotonin (5-hydroxytryptamine; 5HT) increased EPG event frequency in A. ceylanicum L4s at an optimal concentration of 0.5 mM. The anthelmintic drug ivermectin (IVM) inhibited EPG activity in a concentration-dependent manner. EPGs from A. suum L3s recovered from pig lungs exhibited robust pharyngeal pumping in 1 mM 5HT, which was inhibited by IVM. These experiments validate the use of A. ceylanicum L4s and A. suum L3s with the microfluidic EPG platform, providing a new tool for screening anthelmintic candidates or investigating parasitic nematode feeding behavior.

Estimating the effects of land use at different scales on high ecological status in Irish rivers.

High ecological status at river sites is an indicator of minimal disturbance from anthropogenic activities and the presence of ecologically important species and communities. However, a lack of clarity on what factors cause sites to lose high ecological status is limiting the ability to maintain the quality of these sites. Examination of ecological status records at 508 high status river sites throughout the Republic of Ireland revealed that 337 had fallen below high status at some point between 2001 and 2012 due to changes in invertebrate communities. A geographical information system was used to characterise land use and environmental variables in the catchment, riparian and reach areas upstream of the sites. The relationships between these variables at the three spatial scales and whether or not river sites had maintained high ecological status were then estimated by multiple logistic regression and propensity modelling. The results indicated that grassland at either catchment or riparian scales had a greater negative impact on high ecological status than at the reach scale. This effect appeared to be strongest for upland, steeply sloping rivers that are subject to high rainfall, possibly due to the presence of sensitive biota and/or a greater potential for erosion. These results highlighted the need for better management of grassland upstream of the high status sites, with a focus on river alterations and critical source areas of nutrients, sediments and pesticides that are hydrologically connected to the river. Sustainable management practices and land use planning in those areas will need to be considered carefully if the aim of maintaining high ecological status at river sites is to be achieved.

A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans.

Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms.

A microfluidic device for whole-animal drug screening using electrophysiological measures in the nematode C. elegans.

This paper describes the fabrication and use of a microfluidic device for performing whole-animal chemical screens using non-invasive electrophysiological readouts of neuromuscular function in the nematode worm, C. elegans. The device consists of an array of microchannels to which electrodes are attached to form recording modules capable of detecting the electrical activity of the pharynx, a heart-like neuromuscular organ involved in feeding. The array is coupled to a tree-like arrangement of distribution channels that automatically delivers one nematode to each recording module. The same channels are then used to perfuse the recording modules with test solutions while recording the electropharyngeogram (EPG) from each worm with sufficient sensitivity to detect each pharyngeal contraction. The device accurately reported the acute effects of known anthelmintics (anti-nematode drugs) and also correctly distinguished a specific drug-resistant mutant strain of C. elegans from wild type. The approach described here is readily adaptable to parasitic species for the identification of novel anthelmintics. It is also applicable in toxicology and drug discovery programs for human metabolic and degenerative diseases for which C. elegans is used as a model.

Phosphorus retention and remobilization in vegetated buffer strips: a review.

Diffuse pollution remains a major threat to surface waters due to eutrophication caused by phosphorus (P) transfer from agricultural land. Vegetated buffer strips (VBSs) are increasingly used to mitigate diffuse P losses from agricultural land, having been shown to reduce particulate P transfer. However, retention of dissolved P (DP) has been lower, and in some cases VBSs have increased delivery to surface waters. The aims of this review were (i) to develop a conceptual model to enhance the understanding of VBS functioning in terms of DP, (ii) to identify key processes within the model that affect DP retention and delivery, and (iii) to explore evidence for the controls on these processes. A greater understanding in these areas will allow the development of management strategies that enhance DP retention. We found evidence of a surface layer in buffer strip soils that is enriched in soluble P compared with adjacent agricultural land and may be responsible for the reported increased DP delivery. Through increased biological activity in VBSs, plants and microorganisms may assimilate P from particulates retained in the VBSs or native soil P and remobilize this P in a more soluble form. These conclusions are based on a limited amount of research, and a better understanding of biogeochemical cycling of P in buffer strip soils is required.

An image-free opto-mechanical system for creating virtual environments and imaging neuronal activity in freely moving Caenorhabditis elegans.

Non-invasive recording in untethered animals is arguably the ultimate step in the analysis of neuronal function, but such recordings remain elusive. To address this problem, we devised a system that tracks neuron-sized fluorescent targets in real time. The system can be used to create virtual environments by optogenetic activation of sensory neurons, or to image activity in identified neurons at high magnification. By recording activity in neurons of freely moving C. elegans, we tested the long-standing hypothesis that forward and reverse locomotion are generated by distinct neuronal circuits. Surprisingly, we found motor neurons that are active during both types of locomotion, suggesting a new model of locomotion control in C. elegans. These results emphasize the importance of recording neuronal activity in freely moving animals and significantly expand the potential of imaging techniques by providing a mean to stabilize fluorescent targets.

Spikes and membrane potential oscillations in hair cells generate periodic afferent activity in the frog sacculus.

To look for membrane potential oscillations that may contribute to sensory coding or amplification in the ear, we made whole-cell and perforated-patch recordings from hair cells and postsynaptic afferent neurites in the explanted frog sacculus, with mechanoelectrical transduction (MET) blocked. Small depolarizing holding currents, which may serve to replace the in vivo resting MET current, evoked all-or-none calcium spikes (39-75 mV amplitude) in 37% of hair cells tested, and continuous membrane potential oscillations (14-28 mV; 15-130 Hz) in an additional 14% of cells. Spiking hair cells were on average taller and thinner than nonspiking hair cells, and had smaller outward currents through delayed rectifier channels (I(KV)) and noninactivating calcium-activated potassium channels (I(BK,steady)), and larger inward rectifier currents (I(K1)). Some spiking hair cells fired only a brief train at the onset of a current step, but others could sustain repetitive firing (3-70 Hz). Partial blockade of I(BK) changed the amplitude and frequency of oscillations and spikes, and converted some nonspiking cells into spiking cells. Oscillatory hair cells preferentially amplified sinusoidal stimuli at frequencies near their natural oscillation frequency. Postsynaptic recordings revealed regularly timed bursts of EPSPs in some afferent neurites. EPSP bursts were able to trigger afferent spikes, which may be initiated at the sodium channel cluster located adjacent to the afferent axon's most peripheral myelin segment. These results show that some frog saccular hair cells can generate spontaneous rhythmic activity that may drive periodic background activity in afferent axons.

Linear and nonlinear processing in hair cells.

Mechanosensory hair cells in the ear are exquisitely responsive to minute sensory inputs, nearly to the point of instability. Active mechanisms bias the transduction apparatus and subsequent electrical amplification away from saturation in either the negative or positive direction, to an operating point where the response to small signals is approximately linear. An active force generator coupled directly to the transducer enhances sensitivity and frequency selectivity, and counteracts energy loss to viscous drag. Active electrical amplification further enhances gain and frequency selectivity. In both cases, nonlinear properties may maintain the system close to instability, as evidenced by small spontaneous oscillations, while providing a compressive nonlinearity that increases the cell's operating range. Transmitter release also appears to be frequency selective and biased to operate most effectively near the resting potential. This brief overview will consider the resting stability of hair cells, and their responses to small perturbations that correspond to soft sounds or small accelerations.

Snaring otoferlin's role in deafness.

Mutations in the gene encoding otoferlin are known to cause deafness, but the mechanism is unclear. In this issue, Roux et al. (2006) demonstrate that otoferlin interacts with SNARE molecules at the afferent synapses of cochlear inner hair cells to trigger exocytosis of neurotransmitter.

Frequency selectivity of synaptic exocytosis in frog saccular hair cells.

The ability to respond selectively to particular frequency components of sensory inputs is fundamental to signal processing in the ear. The frog (Rana pipiens) sacculus, which is used for social communication and escape behaviors, is an exquisitely sensitive detector of sounds and ground-borne vibrations in the 5- to 200-Hz range, with most afferent axons having best frequencies between 40 and 60 Hz. We monitored the synaptic output of saccular sensory receptors (hair cells) by measuring the increase in membrane capacitance (deltaC(m)) that occurs when synaptic vesicles fuse with the plasmalemma. Strong stepwise depolarization evoked an exocytic burst that lasted 10 ms and corresponded to the predicted capacitance of all docked vesicles at synapses, followed by a 20-ms delay before additional vesicle fusion. Experiments using weak stimuli, within the normal physiological range for these cells, revealed a sensitivity to the temporal pattern of membrane potential changes. Interrupting a weak depolarization with a properly timed hyperpolarization increased deltaC(m). Small sinusoidal voltage oscillations (+/-5 mV centered at -60 mV) evoked a deltaC(m) that corresponded to 95 vesicles per s at each synapse at 50 Hz but only 26 vesicles per s at 5 Hz and 27 vesicles per s at 200 Hz (perforated patch recordings). This frequency selectivity was absent for larger sinusoidal oscillations (+/-10 mV centered at -55 mV) and was largest for hair cells with the smallest sinusoidal-stimuli-evoked Ca2+ currents. We conclude that frog saccular hair cells possess an intrinsic synaptic frequency selectivity that is saturated by strong stimuli.