How fast do mobile organisms respond to stimuli? Response times from bacteria to elephants and whales.

Quick responses to fast changes in the environment are crucial in animal behaviour and survival, for example to seize prey, escape predators, or negotiate obstacles. Here, we study the 'simple response time' that is the time elapsed between receptor stimulation and motor activation as typically shown in escape responses, for mobile organisms of various taxa ranging from bacteria to large vertebrates. We show that 95% of these simple response times lie within one order of magnitude of the overall geometric mean of about 25 ms, which is similar to that of a well-studied sensory time scale, the inverse of the critical flicker fusion frequency in vision, also lying within close bounds for all the organisms studied. We find that this time scale is a few times smaller than the minimum time to move by one body length, which is known to lie also within a relatively narrow range for all moving organisms. The remarkably small 102-fold range of the simple response time among so disparate life forms varying over 1020-fold in body mass suggests that it is determined by basic physicochemical constraints, independently on the structure and scale of the organism. We thus propose first-principle estimates of the simple response and sensory time scales in terms of physical constants and a few basic biological properties common to mobile organisms and constraining their responses.

Olfactory coding in the turbulent realm.

Long-distance olfactory search behaviors depend on odor detection dynamics. Due to turbulence, olfactory signals travel as bursts of variable concentration and spacing and are characterized by long-tail distributions of odor/no-odor events, challenging the computing capacities of olfactory systems. How animals encode complex olfactory scenes to track the plume far from the source remains unclear. Here we focus on the coding of the plume temporal dynamics in moths. We compare responses of olfactory receptor neurons (ORNs) and antennal lobe projection neurons (PNs) to sequences of pheromone stimuli either with white-noise patterns or with realistic turbulent temporal structures simulating a large range of distances (8 to 64 m) from the odor source. For the first time, we analyze what information is extracted by the olfactory system at large distances from the source. Neuronal responses are analyzed using linear-nonlinear models fitted with white-noise stimuli and used for predicting responses to turbulent stimuli. We found that neuronal firing rate is less correlated with the dynamic odor time course when distance to the source increases because of improper coding during long odor and no-odor events that characterize large distances. Rapid adaptation during long puffs does not preclude however the detection of puff transitions in PNs. Individual PNs but not individual ORNs encode the onset and offset of odor puffs for any temporal structure of stimuli. A higher spontaneous firing rate coupled to an inhibition phase at the end of PN responses contributes to this coding property. This allows PNs to decode the temporal structure of the odor plume at any distance to the source, an essential piece of information moths can use in their tracking behavior.

Maximum relative speeds of living organisms: Why do bacteria perform as fast as ostriches?

Self-locomotion is central to animal behaviour and survival. It is generally analysed by focusing on preferred speeds and gaits under particular biological and physical constraints. In the present paper we focus instead on the maximum speed and we study its order-of-magnitude scaling with body size, from bacteria to the largest terrestrial and aquatic organisms. Using data for about 460 species of various taxonomic groups, we find a maximum relative speed of the order of magnitude of ten body lengths per second over a 1020-fold mass range of running and swimming animals. This result implies a locomotor time scale of the order of one tenth of second, virtually independent on body size, anatomy and locomotion style, whose ubiquity requires an explanation building on basic properties of motile organisms. From first-principle estimates, we relate this generic time scale to other basic biological properties, using in particular the recent generalisation of the muscle specific tension to molecular motors. Finally, we go a step further by relating this time scale to still more basic quantities, as environmental conditions at Earth in addition to fundamental physical and chemical constants.

Force per cross-sectional area from molecules to muscles: a general property of biological motors.

We propose to formally extend the notion of specific tension, i.e. force per cross-sectional area-classically used for muscles, to quantify forces in molecular motors exerting various biological functions. In doing so, we review and compare the maximum tensions exerted by about 265 biological motors operated by about 150 species of different taxonomic groups. The motors considered range from single molecules and motile appendages of microorganisms to whole muscles of large animals. We show that specific tensions exerted by molecular and non-molecular motors follow similar statistical distributions, with in particular, similar medians and (logarithmic) means. Over the 10(19) mass (M) range of the cell or body from which the motors are extracted, their specific tensions vary as M(α) with α not significantly different from zero. The typical specific tension found in most motors is about 200 kPa, which generalizes to individual molecular motors and microorganisms a classical property of macroscopic muscles. We propose a basic order-of-magnitude interpretation of this result.

Firing and intrinsic properties of antennal lobe neurons in the Noctuid moth Agrotis ipsilon.

The antennal lobe (AL) of the Noctuid moth Agrotis ipsilon has emerged as an excellent model for studying olfactory processing and its plasticity in the central nervous system. Odor-evoked responses of AL neurons and input-to-output transformations involved in pheromone processing are well characterized in this species. However, the intrinsic electrical properties responsible of the firing of AL neurons are poorly known. To this end, patch-clamp recordings in current- and voltage-clamp mode from neurons located in the two main clusters of cell bodies in the ALs were combined with intracellular staining on A. ipsilon males. Staining indicated that the lateral cluster (LC) is composed of 85% of local neurons (LNs) and 15% of projection neurons (PNs). The medial cluster (MC) contains only PNs. Action potentials were readily recorded from the soma in LNs and PNs located in the LC but not from PNs in the MC where recordings showed small or no action potentials. In the LC, the spontaneous activity of about 20% of the LNs presented irregular bursts while being more regular in PNs. We also identified a small population of LNs lacking voltage-gated Na(+) currents and generating spikelets. We focused on the firing properties of LNs since in about 60% of LNs, but not in PNs, action potentials were followed by depolarizing afterpotentials (DAPs). These DAPs could generate a second action potential, so that the activity was composed of action potential doublets. DAPs depended on voltage, Ca(2+)-channels and possibly on Ca(2+)-activated non-specific cationic channels. During steady state current injection, DAPs occurred after each action potential and did not require high-frequency firing. The amplitude of DAPs increased when the interspike interval was small, typically within bursts, likely arising from a Ca(2+) build up. DAPs were more often found in bursting than in non-bursting LNs but do not support bursting activity. DAPs and spike doublets also occurred during odor-evoked activity suggesting that they can mediate olfactory integration in the AL.

Heterogeneity and convergence of olfactory first-order neurons account for the high speed and sensitivity of second-order neurons.

In the olfactory system of male moths, a specialized subset of neurons detects and processes the main component of the sex pheromone emitted by females. It is composed of several thousand first-order olfactory receptor neurons (ORNs), all expressing the same pheromone receptor, that contact synaptically a few tens of second-order projection neurons (PNs) within a single restricted brain area. The functional simplicity of this system makes it a favorable model for studying the factors that contribute to its exquisite sensitivity and speed. Sensory information--primarily the identity and intensity of the stimulus--is encoded as the firing rate of the action potentials, and possibly as the latency of the neuron response. We found that over all their dynamic range, PNs respond with a shorter latency and a higher firing rate than most ORNs. Modelling showed that the increased sensitivity of PNs can be explained by the ORN-to-PN convergent architecture alone, whereas their faster response also requires cell-to-cell heterogeneity of the ORN population. So, far from being detrimental to signal detection, the ORN heterogeneity is exploited by PNs, and results in two different schemes of population coding based either on the response of a few extreme neurons (latency) or on the average response of many (firing rate). Moreover, ORN-to-PN transformations are linear for latency and nonlinear for firing rate, suggesting that latency could be involved in concentration-invariant coding of the pheromone blend and that sensitivity at low concentrations is achieved at the expense of precise encoding at high concentrations.

Pheromone modulates plant odor responses in the antennal lobe of a moth.

In nature, male moths are exposed to a complex plant odorant environment when they fly upwind to a sex pheromone source in their search for mates. Plant odors have been shown to affect responses to pheromone at various levels but how does pheromone affects plant odor perception? We recorded responses from neurons within the non-pheromonal "ordinary glome ruli" of the primary olfactory center, the antennal lobe (AL), to single and pulsed stimulations with the plant odorant heptanal, the pheromone, and their mixture in the male moth Agrotis ipsilon. We identified 3 physiological types of neurons according to their activity patterns combining excitatory and inhibitory phases. Both local and projection neurons were identified in each physiological type. Neurons with excitatory responses to heptanal responded also frequently to the pheromone and showed additive responses to the mixture. Moreover, the neuron's ability of resolving successive pulses generally improved with the mixture. Only some neurons with combined excitatory/inhibitory, or purely inhibitory responses to heptanal, also responded to the pheromone. Although individual mixture responses were not significantly different from heptanal responses in these neurons, pulse resolution was improved with the mixture as compared with heptanal alone. These results demonstrate that the pheromone and the general odorant subsystems interact more intensely in the moth AL than previously thought.

Machine learning for automatic prediction of the quality of electrophysiological recordings.

The quality of electrophysiological recordings varies a lot due to technical and biological variability and neuroscientists inevitably have to select "good" recordings for further analyses. This procedure is time-consuming and prone to selection biases. Here, we investigate replacing human decisions by a machine learning approach. We define 16 features, such as spike height and width, select the most informative ones using a wrapper method and train a classifier to reproduce the judgement of one of our expert electrophysiologists. Generalisation performance is then assessed on unseen data, classified by the same or by another expert. We observe that the learning machine can be equally, if not more, consistent in its judgements as individual experts amongst each other. Best performance is achieved for a limited number of informative features; the optimal feature set being different from one data set to another. With 80-90% of correct judgements, the performance of the system is very promising within the data sets of each expert but judgments are less reliable when it is used across sets of recordings from different experts. We conclude that the proposed approach is relevant to the selection of electrophysiological recordings, provided parameters are adjusted to different types of experiments and to individual experimenters.

Responses of single neurons and neuronal ensembles in frog first- and second-order olfactory neurons.

A major challenge in sensory neuroscience is to elucidate the coding and processing of stimulus representations in successive populations of neurons. Here we recorded the spiking activity of receptor neurons (RNs) and mitral/tufted cells (MCs) in the frog olfactory epithelium and olfactory bulb respectively, in response to four odorants applied at precisely controlled concentrations. We compared how RN responses are translated in MCs. We examined the time course of the instantaneous firing frequency before and after stimulation in neuron ensembles and the dependency on odorant concentration of the number of action potentials fired in a preselected 5-s time window (dose-response curves) in both single neurons and neuron ensembles. In RNs and MCs, the dose-response curves typically increase then decrease and are well described by alpha functions. We established the main quantitative properties of these curves, including the distributions of concentrations at threshold and maximum responses. We showed that the main transformations occurring in the transition from RNs to MCs is the lowering of the firing threshold and a large decrease in the total number of spikes fired. We also found that the number of action potentials fired by recorded neurons and hence their energy consumption is independent of odorant concentration, and that this is a consequence of their time- and concentration-dependent activities. This article is part of a Special Issue entitled Neural Coding 2012.

Multiphasic on/off pheromone signalling in moths as neural correlates of a search strategy.

Insects and robots searching for odour sources in turbulent plumes face the same problem: the random nature of mixing causes fluctuations and intermittency in perception. Pheromone-tracking male moths appear to deal with discontinuous flows of information by surging upwind, upon sensing a pheromone patch, and casting crosswind, upon losing the plume. Using a combination of neurophysiological recordings, computational modelling and experiments with a cyborg, we propose a neuronal mechanism that promotes a behavioural switch between surge and casting. We show how multiphasic On/Off pheromone-sensitive neurons may guide action selection based on signalling presence or loss of the pheromone. A Hodgkin-Huxley-type neuron model with a small-conductance calcium-activated potassium (SK) channel reproduces physiological On/Off responses. Using this model as a command neuron and the antennae of tethered moths as pheromone sensors, we demonstrate the efficiency of multiphasic patterning in driving a robotic searcher toward the source. Taken together, our results suggest that multiphasic On/Off responses may mediate olfactory navigation and that SK channels may account for these responses.

Interactions of odorants with olfactory receptors and other preprocessing mechanisms: how complex and difficult to predict?

In this issue of Chemical Senses, Münch et al. present a thorough analysis of how mixtures of odorants interact with olfactory receptors (ORs) borne by olfactory receptor neurons (ORNs). Using fruit fly ORNs expressing the receptor OR22a, they provide a clear example of mixture interaction and confirm that the response of an ORN to a binary mixture can be sometimes predicted quantitatively knowing the ORN responses to its components as shown previously in rat ORNs. The prediction is based on a nonlinear model that assumes a classical 2-step activation of the OR and competition of the 2 odorants in the mixture for the same binding site. Can this success be generalized to all odorant-receptor pairs? This would be an encouraging perspective, especially for the fragrance and flavor industries, as it would permit the prediction of all mixtures. To address this question, I outline its conceptual framework and discuss the variety of mixture interactions found so far. In accordance with the effects described in the study of other receptors, several kinds of mixture interactions have been found that are not easily predictable. The relative importance of the predictable and less predictable effects thus appears as a major issue for future developments.

Function and central projections of gustatory receptor neurons on the antenna of the noctuid moth Spodoptera littoralis.

Chemosensory information is crucial for most insects to feed and reproduce. Olfactory signals are mainly used at a distance, whereas gustatory stimuli play an important role when insects directly contact chemical substrates. In noctuid moths, although the antennae are the main olfactory organ, they also bear taste sensilla. These taste sensilla detect sugars and hence are involved in appetitive learning but could also play an important role in food evaluation by detecting salts and bitter substances. To investigate this, we measured the responses of individual taste sensilla on the antennae of Spodoptera littoralis to sugars and salts using tip recordings. We also traced the projections of their neuronal axons into the brain. In each sensillum, we found one or two neurons responding to sugars: one NaCl-responsive and one water-sensitive neuron. Responses of these neurons were dose-dependent and similar across different locations on the antenna. Responses were dependent on the sex for sucrose and on both sex and location for glucose and fructose. We did not observe a spatial map for the projections from specific regions of the antennae to the deutocerebrum or the tritocerebrum/suboesophageal ganglion complex. In accordance with physiological recordings, back-fills from individual sensilla revealed up to four axons, in most cases targeting different projection zones.

Plant odour stimuli reshape pheromonal representation in neurons of the antennal lobe macroglomerular complex of a male moth.

Male moths are confronted with complex odour mixtures in a natural environment when flying towards a female-emitted sex pheromone source. Whereas synergistic effects of sex pheromones and plant odours have been observed at the behavioural level, most investigations at the peripheral level have shown an inhibition of pheromone responses by plant volatiles, suggesting a potential role of the central nervous system in reshaping the peripheral information. We thus investigated the interactions between sex pheromone and a behaviourally active plant volatile, heptanal, and their effects on responses of neurons in the pheromone-processing centre of the antennal lobe, the macroglomerular complex, in the moth Agrotis ipsilon. Our results show that most of these pheromone-sensitive neurons responded to the plant odour. Most neurons responded to the pheromone with a multiphasic pattern and were anatomically identified as projection neurons. They responded either with excitation or pure inhibition to heptanal, and the response to the mixture pheromone + heptanal was generally weaker than to the pheromone alone, showing a suppressive effect of heptanal. However, these neurons responded with a better resolution to pulsed stimuli. The other neurons with either purely excitatory or inhibitory responses to all three stimuli did not exhibit significant differences in responses between stimuli. Although the suppression of the pheromone responses in AL neurons by the plant odour is counter-intuitive at first glance, the observed better resolution of pulsed stimuli is probably more important than high sensitivity to the localization of a calling female.

Modelling the signal delivered by a population of first-order neurons in a moth olfactory system.

A statistical model of the population of first-order olfactory receptor neurons (ORNs) is proposed and analysed. It describes the relationship between stimulus intensity (odour concentration) and coding variables such as rate and latency of the population of several thousand sex-pheromone sensitive ORNs in male moths. Although these neurons likely express the same olfactory receptor, they exhibit, at any concentration, a relatively large heterogeneity of responses in both peak firing frequency and latency of the first action potential fired after stimulus onset. The stochastic model is defined by a multivariate distribution of six model parameters that describe the dependence of the peak firing rate and the latency on the stimulus dose. These six parameters and their mutual linear correlations were estimated from experiments in single ORNs and included in the multidimensional model distribution. The model is utilized to reconstruct the peak firing rate and latency of the message sent to the brain by the whole ORN population at different stimulus intensities and to establish their main qualitative and quantitative properties. Finally, these properties are shown to be in agreement with those found previously in a vertebrate ORN population. This article is part of a Special Issue entitled: Neural Coding.

Interaction of cellular and network mechanisms for efficient pheromone coding in moths.

Sensory systems, both in the living and in machines, have to be optimized with respect to their environmental conditions. The pheromone subsystem of the olfactory system of moths is a particularly well-defined example in which rapid variations of odor content in turbulent plumes require fast, concentration-invariant neural representations. It is not clear how cellular and network mechanisms in the moth antennal lobe contribute to coding efficiency. Using computational modeling, we show that intrinsic potassium currents (I(A) and I(SK)) in projection neurons may combine with extrinsic inhibition from local interneurons to implement a dual latency code for both pheromone identity and intensity. The mean latency reflects stimulus intensity, whereas latency differences carry concentration-invariant information about stimulus identity. In accordance with physiological results, the projection neurons exhibit a multiphasic response of inhibition-excitation-inhibition. Together with synaptic inhibition, intrinsic currents I(A) and I(SK) account for the first and second inhibitory phases and contribute to a rapid encoding of pheromone information. The first inhibition plays the role of a reset to limit variability in the time to first spike. The second inhibition prevents responses of excessive duration to allow tracking of intermittent stimuli.

Dynamical modeling of the moth pheromone-sensitive olfactory receptor neuron within its sensillar environment.

In insects, olfactory receptor neurons (ORNs), surrounded with auxiliary cells and protected by a cuticular wall, form small discrete sensory organs--the sensilla. The moth pheromone-sensitive sensillum is a well studied example of hair-like sensillum that is favorable to both experimental and modeling investigations. The model presented takes into account both the molecular processes of ORNs, i.e. the biochemical reactions and ionic currents giving rise to the receptor potential, and the cellular organization and compartmentalization of the organ represented by an electrical circuit. The number of isopotential compartments needed to describe the long dendrite bearing pheromone receptors was determined. The transduction parameters that must be modified when the number of compartments is increased were identified. This model reproduces the amplitude and time course of the experimentally recorded receptor potential. A first complete version of the model was analyzed in response to pheromone pulses of various strengths. It provided a quantitative description of the spatial and temporal evolution of the pheromone-dependent conductances, currents and potentials along the outer dendrite and served to determine the contribution of the various steps in the cascade to its global sensitivity. A second simplified version of the model, utilizing a single depolarizing conductance and leak conductances for repolarizing the ORN, was derived from the first version. It served to analyze the effects on the sensory properties of varying the electrical parameters and the size of the main sensillum parts. The consequences of the results obtained on the still uncertain mechanisms of olfactory transduction in moth ORNs--involvement or not of G-proteins, role of chloride and potassium currents--are discussed as well as the optimality of the sensillum organization, the dependence of biochemical parameters on the neuron spatial extension and the respective contributions of the biochemical and electrical parameters to the overall neuron response.

Competition-based model of pheromone component ratio detection in the moth.

For some moth species, especially those closely interrelated and sympatric, recognizing a specific pheromone component concentration ratio is essential for males to successfully locate conspecific females. We propose and determine the properties of a minimalist competition-based feed-forward neuronal model capable of detecting a certain ratio of pheromone components independently of overall concentration. This model represents an elementary recognition unit for the ratio of binary mixtures which we propose is entirely contained in the macroglomerular complex (MGC) of the male moth. A set of such units, along with projection neurons (PNs), can provide the input to higher brain centres. We found that (1) accuracy is mainly achieved by maintaining a certain ratio of connection strengths between olfactory receptor neurons (ORN) and local neurons (LN), much less by properties of the interconnections between the competing LNs proper. An exception to this rule is that it is beneficial if connections between generalist LNs (i.e. excited by either pheromone component) and specialist LNs (i.e. excited by one component only) have the same strength as the reciprocal specialist to generalist connections. (2) successful ratio recognition is achieved using latency-to-first-spike in the LN populations which, in contrast to expectations with a population rate code, leads to a broadening of responses for higher overall concentrations consistent with experimental observations. (3) when longer durations of the competition between LNs were observed it did not lead to higher recognition accuracy.

Transformation of the sex pheromone signal in the noctuid moth Agrotis ipsilon: from peripheral input to antennal lobe output.

How information is transformed along synaptic processing stages is critically important to understand the neural basis of behavior in any sensory system. In moths, males rely on sex pheromone to find their mating partner. It is essential for a male to recognize the components present in a pheromone blend, their ratio, and the temporal pattern of the signal. To examine pheromone processing mechanisms at different levels of the olfactory pathway, we performed single-cell recordings of olfactory receptor neurons (ORNs) in the antenna and intracellular recordings of central neurons in the macroglomerular complex (MGC) of the antennal lobe of sexually mature Agrotis ipsilon male moths, using the same pheromone stimuli, stimulation protocol, and response analyses. Detailed characteristics of the ORN and MGC-neuron responses were compared to describe the transformation of the neuronal responses that takes place in the MGC. Although the excitatory period of the response is similar in both neuron populations, the addition of an inhibitory phase following the MGC neuron excitatory phase indicates participation of local interneurons (LN), which remodel the ORN input. Moreover, MGC neurons showed a wider tuning and a higher sensitivity to single pheromone components than ORNs.

Calcium activates a chloride conductance likely involved in olfactory receptor neuron repolarization in the moth Spodoptera littoralis.

The response of insect olfactory receptor neurons (ORNs) to odorants involves the opening of Ca(2+)-permeable channels, generating an increase in intracellular Ca(2+) concentration. Here, we studied the downstream effect of this Ca(2+) rise in cultured ORNs of the moth Spodoptera littoralis. Intracellular dialysis of Ca(2+) from the patch pipette in whole-cell patch-clamp configuration activated a conductance with a K(1/2) of 2.8 microm. Intracellular and extracellular anionic and cationic substitutions demonstrated that Cl(-) carries this current. The anion permeability sequence I(-) > NO(3)(-) > Br(-) > Cl(-) > CH(3)SO(3)(-) >> gluconate(-) of the Ca(2+)-activated Cl(-) channel suggests a weak electrical field pore of the channel. The Ca(2+)-activated current partly inactivated over time and did not depend on protein kinase C (PKC) and CaMKII activity or on calmodulin. Application of Cl(-) channel blockers, flufenamic acid, 5-nitro-2-(3-phenylpropylamino) benzoic acid, or niflumic acid reversibly blocked the Ca(2+)-activated current. In addition, lowering Cl(-) concentration in the sensillar lymph bathing the ORN outer dendrites caused a significant delay in pheromone response termination in vivo. The present work identifies a new Cl(-) conductance activated by Ca(2+) in insect ORNs presumably required for ORN repolarization.