Perceptual learning in an appetitive Pavlovian procedure: Analysis of the effectiveness of the common element

Non-reinforced preexposure to two stimuli often enhances discrimination between them. Analyses of this perceptual learning phenomenon have mainly focused on the role played by the distinctive stimulus features; this study examined the contribution of the non-distinctive common elements. A standard appetitive Pavlovian procedure was used. Rats received two different schedules of exposure - alternated or blocked - to two compound auditory stimuli, AX and BX. In Experiment 1 a generalization test to BX that followed conditioning to AX showed that animals responded less, and hence discriminated better, following alternated exposure, thus extending the generality of this perceptual learning effect to standard appetitive Pavlovian procedures. The degree to which the common element X was mediating this effect was explored in the next three experiments. Experiment 2 assessed the effectiveness of X following conditioning to AX. Experiment 3 explored X's effectiveness throughout extensive conditioning to X. Experiment 4 tested the ability of X to overshadow a novel stimulus Y. The results were consistent with the suggestion that alternated preexposure can reduce the relative effectiveness of the common element.     

Comparison of the instrumental reinforcer devaluation effect in two strains of rats (Wistar and Lister)

In this experiment, the effect of the reinforcer devaluation upon instrumental performance was analysed in two strains of rats (Wistar and Lister): Food deprived rats were trained to press a lever for sucrose pellets in a single session. Immediately after the fulfilment of this session, half of the Wistar and Lister rats received an injection of lithium chloride (LiCl), while the remaining animals were injected with a sodium chloride (NaCl) solution. A subsequent extinction test showed that the subjects who had received immediate LiCl did not press the lever as often as those injected with NaCl. No differences in response suppression were found between the two strains of rats. These results also show that a single devaluation experience is sufficient for an impact on instrumental performance.     

Cdh13 and AdipoQ gene knockout alter instrumental and Pavlovian drug conditioning

Genome‐wide association studies in humans have suggested that variants of the cadherin‐13 (CDH13) gene are associated with substance use disorder, subjective response to amphetamine, and attention deficit hyperactivity disorder. To examine the role of the Cdh13 and its peptide ligand adiponectin (AdipoQ) in addiction‐related behaviors, we assessed Cdh13 knockout (KO) rats and AdipoQ KO mice using intravenous cocaine self‐administration and conditioned place preference (CPP) paradigms. During intravenous cocaine self‐administration, male Cdh13 heterozygous (+/?) and KO (?/?) rats showed increased cue‐induced reinstatement compared with wild‐type (WT) rats when presented with a cocaine‐paired stimulus, whereas female Cdh13 rats showed no differences across genotype. Cdh13 ?/? rats showed higher responding for a saccharin reinforcer and learned the choice reaction time (RT) task more slowly than WTs. However, we found no differences between Cdh13 ?/? and +/+ rats in responding for sensory reinforcement, number of premature responses in the RT task, tendency to approach a Pavlovian food cue, CPP and locomotor activation to cocaine (10 or 20 mg/kg). In AdipoQ ?/? mice, there was a significant increase in CPP to methamphetamine (1 mg/kg) but not to a range of d‐amphetamine doses (0.5, 1, 2 and 4 mg/kg). Taken together, these data suggest that Cdh13 and AdipoQ regulate sensitivity to psychomotor stimulants and palatable rewards without producing major changes in other behaviors. In humans, these two genes may regulate sensitivity to natural and drug rewards, thus influencing susceptibility to the conditioned drug effects and relapse.     

Nicotine-evoked conditioned responding is dependent on concentration of sucrose unconditioned stimulus

Previous studies have shown that the interoceptive nicotine conditional stimulus (CS) functions similarly to exteroceptive CSs such as lights or environments. For instance, the appetitive conditioned response (CR) evoked when nicotine is repeatedly paired with sucrose presentations (the unconditioned stimulus; US) is sensitive to changes in training dose (CS salience) and the contiguity between the CS effects and sucrose. The current study was conducted to extend this research by examining the possible role of US intensity in CR acquisition and maintenance. Rats were trained using one of four sucrose concentrations: 0, 4, 16, or 32% (w/v). On nicotine sessions (0.4 mg base/kg), rats received 36 deliveries (4 s each) of their assigned concentration intermittently throughout the session; sucrose was withheld on saline sessions. In all groups, an appetitive goal-tracking CR was acquired at a similar rate. However, the asymptotic CR level varied with sucrose concentration. The magnitude of the CR was increased in rats trained with higher sucrose US concentrations. These findings are consistent with previous Pavlovian conditioning research, and extend the conditions under which the nicotine state functions as an interoceptive conditional stimulus.     

Odor discrimination in classical conditioning of proboscis extension in two stingless bee species in comparison to Africanized honeybees

Learning in insects has been extensively studied using different experimental approaches. One of them, the proboscis extension response (PER) paradigm, is particularly well suited for quantitative studies of cognitive abilities of honeybees under controlled conditions. The goal of this study was to analyze the capability of three eusocial bee species to be olfactory conditioned in the PER paradigm. We worked with two Brazilian stingless bees species, Melipona quadrifasciata and Scaptotrigona aff. depilis, and with the invasive Africanized honeybee, Apis mellifera. These three species present very different recruitment strategies, which could be related with different odor-learning abilities. We evaluated their gustatory responsiveness and learning capability to discriminate floral odors. Gustatory responsiveness was similar for the three species, although S. aff. depilis workers showed fluctuations along the experimental period. Results for the learning assays revealed that M. quadrifasciata workers can be conditioned to discriminate floral odors in a classical differential conditioning protocol and that this discrimination is maintained 15 min after training. During conditioning, Africanized honeybees presented the highest discrimination, for M. quadrifasciata it was intermediate, and S. aff. depilis bees presented no discrimination. The differences found are discussed considering the putative different learning abilities and procedure effect for each species.     

Recovery of Pavlovian sign-tracking (autoshaping) following the discontinuation of inter-trial interval food in rats

In pigeons, Pavlovian autoshaped keypecking produced by keylight-food pairings has been eliminated by introducing food during periods between CS presentations (i.e., during the inter-trial intervals). Keypecking eliminated in this manner reappears when the inter-trial USs are discontinued even though the CS is no longer paired with US. The present experiment investigated whether this recovery of responding produced by discontinuing unpaired inter-trial US presentations could be extended to another species, rats, within a Pavlovian sign-tracking paradigm. Rats were initially trained on a procedure where insertion of one retractable lever (CS(+)) was followed, response independently, with food, while insertion of another lever (CS(-)) was not paired with food. Rats quickly came to contact the CS(+) lever at high rates, but contacted the CS(-) lever infrequently. In the next phase, CS(+) was no longer followed by food. Explicitly unpaired food was presented only during the inter-trial intervals when both levers were absent. This treatment essentially eliminated the sign-tracking response. In the final phase, the unpaired inter-trial food presentations were discontinued while both CSs continued to be presented without food. This produced a significant recovery of the sign-tracking elicited by the CS(+) lever, extending the species generality of the Pavlovian resurgence phenomenon that has previously only been reported in pigeons, to rats.     

Habituation and associative learning during exploratory behavior of the crab Chasmagnathus

Summary Chasmagnathus crabs placed in a choice-chamber device (a dark compartment, DC, and a light one, LC, of identical size separated by a central partition with a sliding door) display an exploratory activity that declines over time (training session). Such decrement persists at the testing session, 24 h later, and meets the criterion of stimulus specificity, so that it is accounted for in terms of a long-term habituation. Alternative explanations involving far-reaching effects of handling, change of context or isolation during the training session, are excluded. If animals are allowed to find food in LC during training, no decrease in the exploratory activity is shown and the enhanced effect on exploring is retained for at least 24 h. This result is interpreted as an instance of associative learning, appetitively motivated. Performances are analysed measuring the latencies to pass from DC to LC, so that crabs given food in training show in testing shorter latencies than controls. In addition, unlike controls, trained crabs often display at testing a feeding behavior despite the absence of food or odor of food in the choice-chamber. The possible use of both exploratory habituation and appetitive learning in studies on memory modulation is discussed.     

Relapse processes after the extinction of instrumental learning: renewal, resurgence, and reacquisition

It is widely recognized that extinction (the procedure in which a Pavlovian conditioned stimulus or an instrumental action is repeatedly presented without its reinforcer) weakens behavior without erasing the original learning. Most of the experiments that support this claim have focused on several "relapse" effects that occur after Pavlovian extinction, which collectively suggest that the original learning is saved through extinction. However, although such effects do occur after instrumental extinction, they have not been explored there in as much detail. This article reviews recent research in our laboratory that has investigated three relapse effects that occur after the extinction of instrumental (operant) learning. In renewal, responding returns after extinction when the behavior is tested in a different context; in resurgence, responding recovers when a second response that has been reinforced during extinction of the first is itself put on extinction; and in rapid reacquisition, extinguished responding returns rapidly when the response is reinforced again. The results provide new insights into extinction and relapse, and are consistent with principles that have been developed to explain extinction and relapse as they occur after Pavlovian conditioning. Extinction of instrumental learning, like Pavlovian learning, involves new learning that is relatively dependent on the context for expression.     

A Quantitative Study of the Ca2+/Calmodulin Sensitivity of Adenylyl Cyclase in Aplysia, Drosophila, and Rat

Studies in Aplysia and Drosophila have suggested that Ca2+/calmodulin-sensitive adenylyl cyclase may act as a site of convergence for the cellular representations of the conditioned stimulus (Ca2+ influx) and unconditioned stimulus (facilitatory transmitter) during elementary associative learning. This hypothesis predicts that the rise in intracellular free Ca2+ concentration produced by spike activity during the conditioned stimulus will cause an increase in the activity of adenylyl cyclase. However, published values for the Ca2+ sensitivity of Ca2+/calmodulin-sensitive adenylyl cyclase in mammals and in Drosophila vary widely. The difficulty in evaluating whether adenylyl cyclase would be activated by physiological elevations in intracellular Ca2+ levels is in part a consequence of the use of Ca2+/EGTA buffers, which are prone to several types of errors. Using a procedure that minimizes these errors, we have quantified the Ca2+ sensitivity of adenylyl cyclase in membranes from Aplysia, Drosophila, and rat brain with purified species-specific calmodulins. In all three species, adenylyl cyclase was activated by an increase in free Ca2+ concentration in the range caused by spike activity. Ca2+ sensitivity was dependent on both calmodulin concentration and Mg2+ concentration. Mg2+ raised the threshold for adenylyl cyclase activation by Ca2+ but also acted synergistically with Ca2+ to activate maximally adenylyl cyclase.     

Stimulus comparison in perceptual learning: roles of sensory preconditioning and latent inhibition

Rats were given exposure to a compound flavour (AX) and to one element of that compound (X). Two drinking tubes were made available to the rat on each exposure trial. For group concurrent (CNC) one tube contained AX and the other X. For groups alternating (ALT) and blocked (BLK), however, both tubes contained the same flavour (AX or X). Group ALT received AX and X on alternate trials; group BLK received AX in the first block of trials and X on the second, or vice versa. After an aversion had been established to X the groups were tested with AX. It was found that group ALT showed less generalization from X to AX than did group BLK. This difference was not accompanied by a parallel difference in the level of conditioning to X. However, group CNC showed both stronger conditioning to X and greater generalization from X to AX than groups ALT and BLK. Implications for the role of stimulus comparison in the perceptual learning effect are discussed.     

A comparison of the effects of social rearing and social training on approach responding of Gallus chicks

It has been shown in an earlier paper that chicks that were housed and trained in pairs demonstrated a greater resistance to extinction of the neonatal approach response than did chicks that were housed and trained in isolation. The purpose of the present study was to attempt to replicate these results and to determine whether housing or training is the more important factor in generating the previous finding. Eighty-three, white Leghorn chicks were tested in an experiment employing a 2 × 2 factorial design comparing social vs isolate housing and social vs isolate imprinting training on resistance to extinction of a socially-reinforced running response. The data were consistent with the earlier findings and also revealed that the housing condition is more important in producing subsequent social searching than is the training condition.     

Locomotor activity in a novel environment predicts both responding for a visual stimulus and self-administration of a low dose of methamphetamine in rats

There is evidence that visual stimuli used to signal drug delivery in self-administration procedures have primary reinforcing properties, and that drugs of abuse enhance the reinforcing properties of such stimuli. Here, we explored the relationships between locomotor activity, responding for a visual stimulus, and self-administration of methamphetamine (METH). Rats were classified as high or low responders based on activity levels in a novel locomotor chamber and were subsequently tested for responding to produce a visual stimulus followed by self-administration of a low dose of METH (0.025 mg/kg/infusion) paired with the visual stimulus. High responder rats responded more for the visual stimulus than low responder rats indicating that the visual stimulus was reinforcing and that operant responding for a visual stimulus has commonalities with locomotor activity in a novel environment. Similarly, high responder rats responded more for METH paired with a visual stimulus than low responder rats. Because of the reinforcing properties of the visual stimulus, it was not possible to determine if the rats were responding to produce the visual stimulus, METH or the combination. We speculate that responding to produce sensory reinforcers may be a measure of sensation seeking. These results indicate that visual stimuli have unconditioned reinforcing effects which may have a significant role in acquisition of drug self-administration, a role that is not yet well understood.     

A generally applicable assay for the quantification of inhibitory effects on PCR

PCR amplification of target genes from environmental DNA extracts can suffer from PCR inhibition, caused by co-extracted substances. No simple assay has been available to quantify this inhibition. Therefore, a generally applicable PCR inhibition-assay was developed, which allows determination of statistically significant inhibition of PCR. This information is important when documenting quality of DNA in environmental extracts used as template for PCR.     

Reduction of instrumental discrimination performance by post-conditioning devaluation of discriminative stimulus: the effects of novelty in reinforcing outcome and extended training

In three experiments the effects of post-conditioning pairings of a discriminative stimulus (Sd) with an illness-inducing agent (lithium chloride, LiCl) on subsequent discrimination performance in extinction and consumption of reinforcing outcome were investigated. Rats were trained to choose a correct lever to obtain food pellets, with a light presented on a bulb just above the correct lever serving for the Sd on each trial. After achievement of a criterion of the discrimination, animals received paired or unpaired presentations of the Sds and LiCl injection. In Experiment 1, in which a familiar outcome was given throughout the discrimination training, Sd-LiCl pairings did not reduce either lever-press performance during presentation of the Sds or amount of consumption of outcomes. On the other hand, in Experiment 2 where a novel outcome was introduced in the final two sessions of the discrimination training, subsequent Sd devaluation reduced lever-press performance during presentations of the Sds. Similar findings were obtained in Experiment 3, in which animals were given extended discrimination training with introduction of novel outcomes in the final two sessions. These findings suggest that a representation of the outcome, evoked by presentation of the Sd, and illness were associated in the course of Sd-LiCl pairings but only when a novel outcome was used.     

A comparison of the effects of metabolic inhibitors upon direct and antibody-dependent lymphocyte mediated cytotoxicity

The effect of metabolic inhibitors upon the lysis of allogeneic lymphocyte target cells by cytotoxic T lymphocytes and nonimmune lymphocyte K cells were studied by using identical culture conditions. Inhibition of lysis in both systems was induced by cycloheximide, puromycin, actinomycin D, diisopropylfluorophosphate, 2-deoxyglucose, antimycin A, oligomycin, and cytochalasins A and B, whereas ouabain and mitomycin C did not diminish lysis in either system. The strikingly parallel responses to a variety of agents that alter cellular processes suggest that both forms of lysis utilize similar mechanisms.     

Early Pavlovian studies on the effects of starvation. A contribution to the history of neurodietetics

This communication is based on the pioneering studies performed by I. P. Pavlov's associates, Yu. P. Frolov (in 1918) and I. S. Rozental' (in 1918/1919) at the Institute of Experimental Medicine, in Petrograd. The changes in the "independent variable"--the dogs' diet--were not planned but were the consequences of severe shortages of food for man and beast. The principal generalization concerns the order in which different forms of "complex nervous activity" were impaired: the order is opposite to the order in which they emerge in the process of ontogenesis. First to suffer was "internal inhibition," as documented by the failure of stimulus differentiation. This was followed by the decrease in the magnitude of well-established conditional responses (CRs). As a result of a more severe impairment of the excitatory processes, it became difficult or impossible to establish new CRs. In time, previously established CRs to artificial stimuli, visual and acoustic, disappeared totally. The CRs to natural conditional stimuli (CSs) were maintained fairly well but, eventually, they too decreased markedly. In the terminal phase of starvation, the unconditional salivary reflexes continued to function, although their magnitude was depressed.     

A reexamination of the effects of high rearing temperature on the nonolfactory turbinates of rats

The nasoturbinates and maxilloturbinates have previously been reported to be completely resorbed in Wistar rats reared at 32–33°C from 3 weeks to 6 months of age. The phenomenon was reinvestigated for the first time in the experiments reported here, with dramatically different results. Rats reared at 33°C and 53% relative humidity proved to have naso- and maxilloturbinates of almost the same size as rats reared at 21°C. After effects of skull and rostral size on turbinate size had been statistically removed, rearing temperature proved not to be important in explaining differences in turbinate widths or turbinate separation, but temperature and sex had significant interactive effects on turbinate lengths. Reasons why the turbinates were completely lost in the previous study but largely retained in the present study are unclear and probably subtle, given that procedures in the two studies were closely similar. Loss of the nonolfactory turbinates is demonstrably not a consistent response—adaptive or otherwise—to rearing under hot conditions, and probably factors in addition to temperature are critical to turbinate development.     

Behavioural Pharmacology in Classical Conditioning of the Proboscis Extension Response in Honeybees (Apis mellifera)

Honeybees (Apis mellifera) are well known for their communication and orientation skills and for their impressive learning capability^1,2. Because the survival of a honeybee colony depends on the exploitation of food sources, forager bees learn and memorize variable flower sites as well as their profitability. Forager bees can be easily trained in natural settings where they forage at a feeding site and learn the related signals such as odor or color. Appetitive associative learning can also be studied under controlled conditions in the laboratory by conditioning the proboscis extension response (PER) of individually harnessed honeybees^3,4. This learning paradigm enables the study of the neuronal and molecular mechanisms that underlie learning and memory formation in a simple and highly reliable way^5-12. A behavioral pharmacology approach is used to study molecular mechanisms. Drugs are injected systemically to interfere with the function of specific molecules during or after learning and memory formation^13-16.Here we demonstrate how to train harnessed honeybees in PER conditioning and how to apply drugs systemically by injection into the bee flight muscle.     

A comparison of the effects of decarboxylase inhibitors on L-dopa-induced circling behavior and the conversion of dopa to dopamine in the brain

The conversion in the brain of intravenously administered ³H-dopa to ³H-dopamine was determined in mice at various times after the administration of several inhibitors of aromatic L-amino acid decarboxylase. The effects of these same decarboxylase inhibitors were determined on the L-dopa-induced circling in mice with unilateral 6-hydroxydopamine lesions of striatum. Pretreatment with hydrazinomethyldopa (25 mg/kg), which blocks only peripheral decarboxylase activity, increased the brain concentrations of ³H-dopa and ³H-dopamine and enhanced L-dopa-induced circling behavior. Drugs which block both peripheral and central decarboxylase activity, NSD 1015 (100 mg/kg) and a high dose of Ro44602 (800 mg/kg), blocked L-dopa-induced circling and the conversion of ³H-dopa to ³H-dopamine in the brain. Pretreatment with NSD 1055 (100 mg/kg) or α-methyl-dopa (500 mg/kg) did not block the conversion of ³H-dopa to ³H-dopamine in the brain. L-Dopa-induced contralateral circling is correlated temporally with the conversion of this amino acid to dopamine in the brain. The specific inhibitor administered and the pretreatment interval time chosen are critical factors to consider when inhibitors of cerebral decarboxylase are being employed.     

A direct comparison of exogenous and endogenous inhibition of return and selective attention mechanisms in the somatosensory system

The interaction of excitation and inhibition in responses due to attentional mechanisms in the visual system has been investigated. The studies reported herein use the tactile system of humans to test a specific hypothesis about the processes of attention that have never been directly addressed. Both exogenous and endogenous Inhibition of Return (IOR) reaction-time paradigms with a 100?Hz, 35?µm of peak displacement amplitude were used. In these experiments multiple Stimulus Onset Asynchronies were tested which made it difficult for subjects to learn timing patterns. We tested whether a detection time to a target which is to be attended to is a composite of at least two underlying mechanisms. These mechanisms were explored using exogenous and endogenous IOR experiments. It is hypothesized that these mechanisms work in a push–pull fashion: one deploying attention when new events occur, and the other withdrawing attention (“Disengagement”) after it has been deployed. Based on the results, a new hypothesis is proposed stating that one form of attention (selective attention) competes with IOR in determining the time taken to detect a target in the tactile system.