Detectability and criterion measures in temporal generalization

Computer simulation of performance on “normal” and “episodic” temporal generalization tasks was used to examine the relations between the theoretical parameters of models which fit temporal generalization data (“timing sensitivity” and “threshold”), and the d′ (detectability) and beta (decision criterion) measures of signal-detection theory. In general, changes in timing sensitivity altered d′, whereas threshold changes affected beta, supporting the assertion that the two sorts of variables (“sensitivity/detectability” and “threshold/criterion”) were psychologically equivalent. Cases where temporal generalization gradients were apparently contaminated by “random responding” could be treated by changes in beta, but cases in which temporal generalization gradients were not peaked at the standard posed severe problems for a simple signal-detection account, although existing models of temporal generalization performance could deal with them.     

Interactive effects of elevation,species richness and extreme climatic events on plant–pollinator networks

Plant–pollinator interactions are essential for the functioning of terrestrial ecosystems, but are increasingly affected by global change. The risks to such mutualistic interactions from increasing temperature and more frequent extreme climatic events such as drought or advanced snow melt are assumed to depend on network specialization, species richness, local climate and associated parameters such as the amplitude of extreme events. Even though elevational gradients provide valuable model systems for climate change and are accompanied by changes in species richness, responses of plant–pollinator networks to climatic extreme events under different environmental and biotic conditions are currently unknown. Here, we show that elevational climatic gradients, species richness and experimentally simulated extreme events interactively change the structure of mutualistic networks in alpine grasslands. We found that the degree of specialization in plant–pollinator networks (H2′) decreased with elevation. Nonetheless, network specialization increased after advanced snow melt at high elevations, whereas changes in network specialization after drought were most pronounced at sites with low species richness. Thus, changes in network specialization after extreme climatic events depended on climatic context and were buffered by high species richness. In our experiment, only generalized plant–pollinator networks changed in their degree of specialization after climatic extreme events. This indicates that contrary to our assumptions, network generalization may not always foster stability of mutualistic interaction networks.     

Chemosensory processing in the fruit fly,Drosophila melanogaster: generalization of a feeding response reveals overlapping odour representations

Insects are capable of detecting, and discriminating between, a very large number of odours. The biological relevance of many of those odours, particularly those related to food, must first be learned. Given that the number of sensory receptors and antennal lobe (AL) glomeruli is limited relative to the number of odours that must be detectable, this ability implies that the olfactory system makes use of a combinatorial coding scheme whereby each sensory cell or AL projection neuron can participate in coding for several different odours. An important step in understanding this coding scheme is to behaviourally quantify the degree to which sets of odours are discriminable. Here we evaluate odour discriminability in the fruit fly,Drosophila melanogaster, by first conditioning individual flies to not respond to any of several odourants using a nonassociative conditioning protocol (habituation). We show that flies habituate unconditioned leg movement responses to both mechanosensory and olfactory stimulation over 25 unreinforceed trials. Habituation is retained for at least 2 h and is subject to dishabituation. Finally, we test the degree to which the conditioned response generalizes to other odourants based on molecular features of the odourants (e.g. carbon chain length and the presence of a target functional group). These tests reveal predictable generalization gradients across these molecular features. These data substantiate the claim that these features are relevant coding dimensions in the fruit fly olfactory system, as has been shown for other insect and vertebrate species.     

Effects of d-amphetamine on behavior maintained by signaled and unsignaled delays to reinforcement

Four pigeons responded under a progressive-delay procedure. In a signaled-delay condition, a chained variable interval (VI) 30-s progressive time (PT) 4-s schedule was arranged; in an unsignaled-delay condition, a tandem VI 30-s PT 4-s schedule was arranged. Two pigeons experienced a signaled-unsignaled-signaled sequence; whereas, two pigeons experienced an unsignaled-signaled-unsignaled sequence. Effects of saline and d-amphetamine were determined under each condition. At intermediate doses (1.0 and 1.78 m/kg) delay functions were shallower, area under the curve was increased, and, when possible, break points were increased compared to saline; these effects were not systematically related to signaling conditions. These effects on control by delay often were accompanied by decreased response rates at 0 s. These results suggest that stimulus conditions associated with the delay may not play a crucial role in effects of d-amphetamine and other stimulants on behavior controlled by reinforcement delay.     

Activation of Exchange Protein Activated by cAMP in the Rat Basolateral Amygdala Impairs Reconsolidation of a Memory Associated with Self-Administered Cocaine

The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT) impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA) following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side) rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior.     

The role of temporal generalization in a temporal discrimination task

Two experiments trained rats to discriminate two or three stimulus durations using a temporal discrimination task. A standard peak shift effect was observed when training was administered with short versus long signals in Experiment 1. Both discrimination accuracy scores and the generalization gradients revealed that shorter intervals were discriminated more accurately, which may be due to the scalar property of timing. In Experiment 2, three signals (short, medium, and long) were associated with three different responses, or two of the intervals were associated with one response (short and long or short and medium) and the other interval with a different response. Here, the short/medium versus long discrimination was learned most readily of the three tasks. The results of both experiments indicated a strong contribution of learning of individual durations combined with scalar generalization gradients, but Experiment 2 indicated that categorical encoding of durations may have also been operating.     

Choice behavior in spontaneously hypertensive rats: Variable vs. fixed schedules of reinforcement

Spontaneously hypertensive rats (SHR) and Wistar rats were evaluated in the successive-encounters procedure (an operant simulation of natural foraging) with the idea of assessing differences between them in their preference for variable schedules of reinforcement. In this procedure, after satisfying a schedule of reinforcement associated with search time, the subjects could “accept” or “reject” another schedule of reinforcement associated with handling time. Two schedules of reinforcement were available: a fixed interval (FI), and a variable interval (VI) with the same mean value. The results indicated preference for the variable schedule in both strains, as suggested by the observation that the VI was always accepted while the FI was often rejected. The difference in FI acceptability between strains was not statistically significant, a result which is relevant for the current debate of SHR as an adequate animal model of Attention Deficit Hyperactivity Disorder.     

Resistance to extinction, generalization decrement, and conditioned reinforcement

This study investigated generalization decrement during an extinction resistance-to-change test for pigeon key pecking using a two-component multiple schedule with equal variable-interval 3-min schedules and different reinforcer amounts (one component presented 2-s access to reinforcement and the other 8s). After establishing baseline responding, subjects were assigned to one of the two extinction conditions: hopper stimuli (hopper and hopper light were activated but no food was available) or Control (inactive hopper and hopper light). Responding in the 8-s component was more resistant to extinction than responding in the 2-s component, the hopper stimuli group was more resistant to extinction compared to the Control group, and an interaction between amount of reinforcement, extinction condition, and session block was present. This finding supports generalization decrement as a factor that influences resistance to extinction. Hopper-time data (the amount of time subjects spent with their heads in the hopper) were compared to resistance-to-change data in an investigation of the role of conditioned reinforcement on resistance to change.     

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e. 8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e. one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.     

Membrane-Associated Non-Receptors and Morphogen Gradients

A previously investigated basic model (System B) for the study of signaling morphogen gradient formation that allows for reversible binding of morphogens (aka ligands) with signaling receptors, degradation of bound morphogens and diffusion of unbound morphogens is extended to include the effects of membrane-bound non-signaling molecules (or non-receptors for short) such as proteoglycans that bind reversibly with the same morphogens and degrade them. Our main goal is to delineate the effects of the presence of non-receptors on the existence and properties of the steady-state concentration gradient of signaling ligand–receptor complexes. Stability of the steady-state morphogen gradients is established and the time to reach steady-state behavior after the onset of morphogen production will be analyzed. The theoretical findings offer explanations for observations reported in several previous experiments on Drosophila wing imaginal discs.     

Notch and PKC Are Involved in Formation of the Lateral Region of the Dorso-Ventral Axis in Drosophila Embryos

The Notch gene encodes an evolutionarily conserved cell surface receptor that generates regulatory signals based on interactions between neighboring cells. In Drosophila embryos it is normally expressed at a low level due to strong negative regulation. When this negative regulation is abrogated neurogenesis in the ventral region is suppressed, the development of lateral epidermis is severely disrupted, and the dorsal aminoserosa is expanded. Of these phenotypes only the anti-neurogenic phenotype could be linked to excess canonical Notch signaling. The other phenotypes were linked to high levels of Notch protein expression at the surface of cells in the lateral regions indicating that a non-canonical Notch signaling activity normally functions in these regions. Results of our studies reported here provide evidence. They show that Notch activities are inextricably linked to that of Pkc98E, the homolog of mammalian PKCδ. Notch and Pkc98E up-regulate the levels of the phosphorylated form of IκBCactus, a negative regulator of Toll signaling, and Mothers against dpp (MAD), an effector of Dpp signaling. Our data suggest that in the lateral regions of the Drosophila embryos Notch activity, in conjunction with Pkc98E activity, is used to form the slopes of the opposing gradients of Toll and Dpp signaling that specify cell fates along the dorso-ventral axis.     

Enucleation of protoplasts derived from suspension cultures of winged bean and from a crown gall cell line ofParthenocissus tricuspidata

Protoplasts derived from suspension cultures of the winged bean and a crown gall lineof Parthenocissus tricuspidata were enucleated by centrifugation on iso-osmotic discontinuous Percoli gradients and on discontinuous sucrose-mannitol density gradients. Enucleation was achieved according to the buoyant density of the protoplasts and preparations of both cytoplasts and miniprotoplasts were recovered. The Percoll gradients gave more satisfactory results than the sucrose-mannitol gradients. Enucleation was increased by raising the centrifugal force from 20 kg to 60 kg. The presence of nuclei was determined by the DNA specific probe 4′6-diamidino-2-phenylindole (DAPI). Membrane integrity, as measured by staining with fluorescein diacetate, showed that some 85 % of the cytoplasts were bounded by an intact plasma membrane.     

Influence of the reinforcement magnitude on omission effects

Reinforcement Omission Effects (ROEs), indicated by higher rate of responses after nonreinforced trials in a partial reinforcement schedule, have been interpreted as behavioral transient facilitation after nonreinforcement induced by primary frustration, and/or behavioral transient inhibition after reinforcement induced by demotivation or temporal control. The size of the ROEs should depend directly on the reinforcement magnitude. The present experiment aimed to clarify the relationship between reinforcement magnitude and the omission effects manipulating the magnitude linked to discriminative stimuli in a partial reinforcement FI schedule. The results showed that response rates were higher after omission than after reinforcement delivery. Besides, response rates were highest immediately after the reinforcement omission of a larger magnitude than of a smaller magnitude. These data are interpreted in terms of ROEs multiple process behavioral facilitation after nonreinforcement, and behavioral transient inhibition after reinforcement.     

Using light to shape chemical gradients for parallel and automated analysis of chemotaxis

Numerous molecular components have been identified that regulate the directed migration of eukaryotic cells toward sources of chemoattractant. However, how the components of this system are wired together to coordinate multiple aspects of the response, such as directionality, speed, and sensitivity to stimulus, remains poorly understood. Here we developed a method to shape chemoattractant gradients optically and analyze cellular chemotaxis responses of hundreds of living cells per well in 96‐well format by measuring speed changes and directional accuracy. We then systematically characterized migration and chemotaxis phenotypes for 285 siRNA perturbations. A key finding was that the G‐protein G_iα subunit selectively controls the direction of migration while the receptor and Gβ subunit proportionally control both speed and direction. Furthermore, we demonstrate that neutrophils chemotax persistently in response to gradients of fMLF but only transiently in response to gradients of ATP. The method we introduce is applicable for diverse chemical cues and systematic perturbations, can be used to measure multiple cell migration and signaling parameters, and is compatible with low‐ and high‐resolution fluorescence microscopy.     

Contextual determinants of temporal control: Behavioral contrast in a free-operant psychophysical procedure

The question of how temporal control of responding might be influenced by contingency changes in other contexts was investigated. Each of three pigeons first was exposed to a two-component multiple schedule in which a two-key free-operant psychophysical procedure operated in one component and a variable-interval schedule operated in the other component. The variable-interval schedule then was changed to extinction while the free-operant psychophysical procedure remained unchanged. Finally, the variable-interval schedule was reintroduced. Response rates on the left key and the estimated temporal threshold under the free-operant psychophysical procedure increased for each pigeon when the alternate component schedule was changed to extinction and then decreased again when the variable-interval schedule was reintroduced. The results suggest one way that temporal control is affected by its context, and may be interpreted through the direct effects of overall reinforcement rate on temporal control mechanisms or the disruptive effects of alternative sources of reinforcement on temporally controlled behavior.     

Macroecology and macroevolution of body size in Anolis lizards

Body size is one of the most influential traits affecting many ecological and physiological processes across animal and plant taxa. Studies of the environmental factors shaping body size patterns may evaluate either temporal or spatial dimensions. Here, we analyzed body size evolution in the radiation of Anolis lizards across both geographical and temporal dimensions. We used a set of macroecological and macroevolutionary methods to test current and past environmental effects on geographical gradients of body size and its evolutionary rates. First, we test whether a set of current ecological/physiological hypotheses (heat balance, productivity and seasonality) explains spatial body size gradients. Second, we evaluate how tempo (i.e. evolutionary rates) and mode (i.e. evolutionary process) of body size evolution changed through time and the role of paleo-temperatures on rates of body size evolution during the Cenozoic. We did not find a signature of current environmental variables driving spatial body size gradients. By contrast, we found strong support for a correlation between temperature changes (i.e. climate cooling) during the Cenozoic and rates of body size evolution (i.e. body size diversification). We suggest that patterns of body size evolution in Anolis lizards might be influenced by thermoregulatory behavior across clades and regions.     

EMG Biofeedback: The Effects of CRF, FR, VR, FI, and VI Schedules of Reinforcement on the Acquisition and Extinction of Increases in Forearm Muscle Tension

Biofeedback was used to increase forearm-muscle tension. Feedback was delivered under continuous reinforcement (CRF), variable interval (VI), fixed interval (FI), variable ratio (VR), and fixed ratio (FR) schedules of reinforcement when college students increased their muscle tension (electromyograph, EMG) above a high threshold. There were three daily sessions of feedback, and Session 3 was immediately followed by a session without feedback (extinction). The CRF schedule resulted in the highest EMG, closely followed by the FR and VR schedules, and the lowest EMG scores were produced by the FI and VI schedules. Similarly, the CRF schedule resulted in the greatest amount of time-above-threshold and the VI and FI schedules produced the lowest time-above-threshold. The highest response rates were generated by the FR schedule, followed by the VR schedule. The CRF schedule produced relatively low response rates, comparable to the rates under the VI and FI schedules. Some of the data are consistent with the partial-reinforcement-extinction effect. The present data suggest that different schedules of feedback should be considered in muscle-strengthening contexts such as during the rehabilitation of muscles following brain damage or peripheral nervous-system injury.     

Influence of immobilized quaternary ammonium group surface density on antimicrobial efficacy and cytotoxicity

Bacterial colonization of medical devices causes infections and is a significant problem in healthcare. The use of antibacterial coatings is considered as a potential solution to this problem and has attracted a great deal of attention. Using concentration density gradients of immobilized quaternary ammonium compounds it was demonstrated that a specific threshold of surface concentration is required to induce significant bacterial death. It was determined that this threshold was 4.18% NR₄⁺ bonded nitrogen with a surface potential of + 120.4 mV. Furthermore, it is shown for the first time that adhesion of constituents of the culture medium to the quaternary ammonium modified surface eliminated any cytotoxicity towards eukaryotic cells such as primary human fibroblasts. The implications of this type of surface fouling on the antimicrobial efficacy of surface coatings are also discussed.     

Responses of the Smooth Muscle Membrane of Guinea Pig Jejunum Elicited by Field Stimulation

Field stimulation of the jejunum elicited successively an action potential of spike form, a slow excitatory depolarization, a slow inhibitory hyperpolarization, and a postinhibitory depolarization as a rebound excitation. The slow depolarization often triggered the spike. The inhibitory potential showed lower threshold than did the excitatory potential. Both the excitatory potentials were abolished by atropine and tetrodotoxin. Effective membrane resistance measured by the intracellular polarizing method was reduced during the peak of the excitatory potential, but the degree of reduction was smaller than that evoked by iontophoretic application of acetylcholine. Conditioning hyperpolarization of the muscle membrane modified the amplitude of the excitatory potential. The estimated reversal potential level for the excitatory potenialt was about 0 mv. No changes could be observed in the amplitude of the inhibitory potential when hyperpolarization was induced with intracellularly applied current. Low [K]_o and [Ca]_o blocked the generation of the excitatory potential but the amplitude of the inhibitory potential was enhanced in low [K]_o. Low [Ca]_o and high [Mg]_o had no effect on the inhibitory potential.