Stimulus-Secretion Coupling in Isolated Adrenal Chromaffin Cells: Calcium Channel Activation and Possible Role of Cytoskeletal Elements

Abstract: The catecholamine secretory function of a preparation of isolated bovine adrenal chromaffin cells has been further characterized under conditions designed to elucidate the mechanism of calcium channel activation and the possible role of cytoskeletal elements in stimulus-secretion coupling. Three related sets of data were obtained: (1) Differences in kinetics, Ca dependence, strength, and additivity of the secretory response to acetylcholine (ACh) versus excess K; (2) the effects on secretion of the Ca channel-blocking agents, Ni, Mg, and verapamil; and (3) the Ca dependence of vinblastine action on ACh- and K-evoked secretion. The results suggest that a major portion of the Ca influx required for catecholamine release enters the cell via voltage-dependent Ca channels with some additional Ca influx via the ACh receptor channel. Comparison of the present secretion data with corresponding known electrophysiological properties of isolated chromaffin cells provides added evidence for a role of chromaffin cell action potentials in regulation of Ca influx and the secretory response. Elevated Ca concentrations enhanced K-evoked secretion to levels comparable to that of ACh but did not induce a vinblastine block of K-evoked release. This provides further evidence against a role of microtubules in the common exocytosis event per se. However, a role of cytoskeletal elements in directing the movement of secretory granules, or an action of vinblastine at cholinergic receptors, remain distinct possibilities.     

Stimulus enhancement and spread of a spontaneous tool use in a colony of long-tailed macaques

In a captive group of long-tailed macaques, tool-using behavior by a single competent individual had a significant effect on the synchronous manipulative behavior of naïve animals. Group members engaged in manipulations on the same object class more frequently during times when the model was working than when it was not. The form of their behavior, however, in no way resembled the technique used by the model. All three animals that later became successful tool users were among the few subjects that exhibited a significant increase in manipulations on the same object class while the model was working. Possible causal relationships between this stimulus enhancement and the transmission of the new behavior to other group members are analyzed and discussed.     

Discriminative predation: Simultaneous and sequential encounter experiments

There are many situations in which the ability of animals to distinguish between two similar looking objects can have significant selective consequences.For example,the objects that require discrimination may be edible versus defended prey,predators versus non-predators,or mates of varying quality.Working from the premise that there are situations in which discrimination may be more or less successful,we hypothesized that individuals find it more difficult to distinguish between stimuli when they encounter them sequentially rather than simultaneously.Our study has wide biological and psychological implications from the perspective of signal perception,signal evolution,and discrimination,and could apply to any system where individuals are making relative judgments or choices between two or more stimuli or signals.While this is a general principle that might seem intuitive,it has not been experimentally tested in this context,and is often not considered in the design of models or experiments,or in the interpretation of a wide range of studies.Our study is different from previous studies in psychology in that a) the level of similarity of stimuli are gradually varied to obtain selection gradients,and b) we discuss the implications of our study for specific areas in ecology,such as the level of perfection of mimicry in predator-prey systems.Our experiments provide evidence that it is indeed more difficult to distinguish between stimuli - and to learn to distinguish between stimuli - when they are encountered sequentially rather than simultaneously,even if the intervening time interval is short.     

The effects of stimulus type on consistency of responses to conflicting stimuli in Siamese fighting fish

Individuals must often decide among a range of behavioral responses in a given situation and individuals will likely vary from one another in the choices they make. A rarely explored example of this is when both a male and a female are present simultaneously and a male must decide to fight or court. Consistent individual differences have been found in decision-making in Siamese fighting fish; however, dummies were used to explore this question and it is possible that individuals respond differently in this situation when faced with live stimuli as a result of feedback. Therefore, this study investigated whether males behave similarly to dummy and live stimuli by exposing them to male and female conspecifics both simultaneously and separately. Subjects were tested first with dummies and then in the same situations using live conspecifics. It was hypothesized that males would respond in the same manner to both the dummy and live fish. The results indicated that individuals behaved similarly to the dummy fish and the live fish in corresponding conditions. In addition, repeatability levels suggest that individuals behaved similarly across trials of a given treatment type while differing from one another in their responses. This study demonstrates that males are consistent in their responses even when receiving feedback from conspecifics and supports the continued use of dummy stimuli as an effective tool.     

Effects of stimulus transformations on estimates of sensory neuron selectivity

Stimulus selectivity of sensory systems is often characterized by analyzing response-conditioned stimulus ensembles. However, in many cases these response-triggered stimulus sets have structure that is more complex than assumed. If not taken into account, when present it will bias the estimates of many simple statistics, and distort the estimated stimulus selectivity of a neural sensory system. We present an approach that mitigates these problems by modeling some of the response-conditioned stimulus structure as being generated by a set of transformations acting on a simple stimulus distribution. This approach corrects the estimates of key statistics and counters biases introduced by the transformations. In cases involving temporal spike jitter or spatial jitter of images, the main observed effects of transformations are blurring of the conditional mean and introduction of artefacts in the spectral decomposition of the conditional covariance matrix. We illustrate this approach by analyzing and correcting a set of model stimuli perturbed by temporal and spatial jitter. We apply the approach to neurophysiological data from the cricket cercal sensory system to correct the effects of temporal jitter. Action Editor: Matthew Wiener     

Associative symmetry and stimulus-class formation by pigeons: The role of non-reinforced baseline relations

Two experiments tested the assumption of Urcuioli's (2008) theory of pigeons’ equivalence-class formation that consistent non-reinforcement of certain stimulus combinations in successive matching juxtaposed with consistent reinforcement of other combinations generates stimulus classes containing the elements of the reinforced combinations. In Experiment 1, pigeons were concurrently trained on symbolic (AB) and two identity (AA and BB) successive tasks in which half of all identity trials ended in non-reinforcement but all AB trials were reinforced, contingent upon either responding or not responding to the comparisons. Subsequent symmetry (BA) probe trials showed evidence of symmetry in one of four pigeons. In Experiment 2, pigeons learned three pair-comparison tasks in which left versus right spatial choices were reinforced after the various sample-comparison combinations comprising AB, AA, and BB conditional discriminations. Non-differentially reinforced BA probe trials following acquisition showed some indication of symmetrical choice responding. The overall results contradict the theoretical predictions derived from Urcuioli (2008) and those from Experiment 2 challenge other stimulus-class analyses as well.     

Absolute and relational control of a sequential auditory discrimination by pigeons (Columba livia)

Recent evidence indicates that pigeons can readily learn visual discriminations based on both absolute and relational stimulus factors. To examine how these two types of control function in their non-dominant auditory modality, we tested four pigeons in a go/no-go sequential auditory discrimination in which both absolute and relational cues were redundantly available. In this task, sequences of different sounds created from one set of pitches were reinforced, while different sequences created from another set of pitches and any same sequences made from either set of pitches were not. Across three experiments, we independently varied the relative discriminability of the absolute and relational components. The pigeons were consistently and primarily controlled by the absolute fundamental pitch of our notes in all of the experiments, although this was influenced by the range and arrangement of the pitches used in each set. A majority of the pigeons also demonstrated relational control when this component was made more salient. The more robust control exhibited by absolute factors is consistent with the comparative hypothesis that birds in general may have a well-developed aptitude for processing absolute pitch in many auditory settings. The relational control is consistent with our recent evidence of same/different auditory learning by pigeons.     

Biased competition through variations in amplitude of <Emphasis Type="Italic">γ</Emphasis>-oscillations

Experiments in visual cortex have shown that the firing rate of a neuron in response to the simultaneous presentation of a preferred and non-preferred stimulus within the receptive field is intermediate between that for the two stimuli alone (stimulus competition). Attention directed to one of the stimuli drives the response towards the response induced by the attended stimulus alone (selective attention). This study shows that a simple feedforward model with fixed synaptic conductance values can reproduce these two phenomena using synchronization in the gamma-frequency range to increase the effective synaptic gain for the responses to the attended stimulus. The performance of the model is robust to changes in the parameter values. The model predicts that the phase locking between presynaptic input and output spikes increases with attention.     

The local enhancement conundrum: In search of the adaptive value of a social learning mechanism

Social learning mechanisms are widely thought to vary in their degree of complexity as well as in their prevalence in the natural world. While learning the properties of a stimulus that generalize to similar stimuli at other locations (stimulus enhancement) prima facie appears more useful to an animal than learning about a specific stimulus at a specific location (local enhancement), empirical evidence suggests that the latter is much more widespread in nature. Simulating populations engaged in a producer–scrounger game, we sought to deploy mathematical models to identify the adaptive benefits of reliance on local enhancement and/or stimulus enhancement, and the alternative conditions favoring their evolution. Surprisingly, we found that while stimulus enhancement readily evolves, local enhancement is advantageous only under highly restricted conditions: when generalization of information was made unreliable or when error in social learning was high. Our results generate a conundrum over how seemingly conflicting empirical and theoretical findings can be reconciled. Perhaps the prevalence of local enhancement in nature is due to stimulus enhancement costs independent of the learning task itself (e.g. predation risk), perhaps natural habitats are often characterized by unreliable yet highly rewarding payoffs, or perhaps local enhancement occurs less frequently, and stimulus enhancement more frequently, than widely believed.     

Robust identification of metabolic control for microbial l-methionine production following an easy-to-use puristic approach

The identification of promising metabolic engineering targets is a key issue in metabolic control analysis (MCA). Conventional approaches make intensive use of model-based studies, such as exploiting post-pulse metabolic dynamics after proper perturbation of the microbial system. Here, we present an easy-to-use, purely data-driven approach, defining pool efflux capacities (PEC) for identifying reactions that exert the highest flux control in linear pathways. Comparisons with linlog-based MCA and data-driven substrate elasticities (DDSE) showed that similar key control steps were identified using PEC. Using the example of l-methionine production with recombinant Escherichia coli, PEC consistently and robustly identified main flux controls using perturbation data after a non-labeled ¹²C-l-serine stimulus. Furthermore, the application of full-labeled ¹³C-l-serine stimuli yielded additional insights into stimulus propagation to l-methionine. PEC analysis performed on the ¹³C data set revealed the same targets as the ¹²C data set. Notably, the typical drawback of metabolome analysis, namely, the omnipresent leakage of metabolites, was excluded using the ¹³C PEC approach.