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Negative patterning tasks are a key tool to unveil the mechanisms by which stimulus representations are acquired-a central concern in Robert Rescorla's research. In these tasks, target stimuli are reinforced when presented individually (A+/B+) but not when presented in compound (AB-). The discrimination of single stimuli from their compound presentation is a challenge for theories of associative learning, because it cannot be explained by the simple accrual of associative strength. The present study examined the conditions under which mice learn this part-whole discrimination in olfactory stimuli using a novel instrumental methodology. In two experiments, reinforcement was contingent on distinct responses depending on whether a set of odor mixtures were presented in isolation or as a compound. Using C57BL/6 mice, Experiment 1 showed a mutual interference between learning a response to individual odors and learning a different response to those odors presented in compound. Using wild-type APP/PS1 mice (a control strain for a murine model of Alzheimer's disease), Experiment 2 replicated this interference and showed that it is stimulus-specific. These experiments show that the instrumental patterning task may not only complement Pavlovian negative patterning tasks but may also motivate its own questions on the representation of complex stimuli. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Few studies have considered how signal detection parameters evolve during acquisition periods. We addressed this gap by training mice with differential prior experience in a conditional discrimination, auditory signal detection task. Naïve mice, mice given separate experience with each of the later correct choice options (Correct Choice Response Transfer, CCRT), and mice experienced in conditional discriminations (Conditional Discrimination Transfer, CDT) were trained to detect the presence or absence of a tone in white-noise. We analyzed data assuming a two-period model of acquisition: a pre-solution and solution period (Heinemann, 1983). The pre-solution period was characterized by a selective sampling of biased response strategies until adoption of a conditional responding strategy in the solution period. Correspondingly, discriminability remained low until the solution period; criterion took excursions reflecting response-strategy sampling. Prior experience affected the length and composition of the pre-solution period. Whereas CCRT and CDT mice had shorter pre-solution periods than naïve mice, CDT and Naïve mice developed substantial criterion biases and acquired asymptotic discriminability faster than CCRT mice. To explain these data, we propose a learning model in which mice selectively sample and test different response-strategies and corresponding task structures until they exit the pre-solution period. Upon exit, mice adopt the conditional responding strategy and task structure, with action values updated via inference and generalization from the other task structures. Simulations of representative mouse data illustrate the viability of this model.

Many developmental syndromes have been linked to genetic mutations that cause abnormal ERK/MAPK activity; however, the neuropathological effects of hyperactive signaling are not fully understood. Here, we examined whether hyperactivation of MEK1 modifies the development of GABAergic cortical interneurons (CINs), a heterogeneous population of inhibitory neurons necessary for cortical function. We show that GABAergic-neuron specific MEK1 hyperactivation in vivo leads to increased cleaved caspase-3 labeling in a subpopulation of immature neurons in the embryonic subpallial mantle zone. Adult mutants displayed a significant loss of parvalbumin (PV), but not somatostatin, expressing CINs and a reduction in perisomatic inhibitory synapses on excitatory neurons. Surviving mutant PV-CINs maintained a typical fast-spiking phenotype but showed signs of decreased intrinsic excitability that coincided with an increased risk of seizure-like phenotypes. In contrast to other mouse models of PV-CIN loss, we discovered a robust increase in the accumulation of perineuronal nets, an extracellular structure thought to restrict plasticity. Indeed, we found that mutants exhibited a significant impairment in the acquisition of behavioral response inhibition capacity. Overall, our data suggest PV-CIN development is particularly sensitive to hyperactive MEK1 signaling, which may underlie certain neurological deficits frequently observed in ERK/MAPK-linked syndromes.

A common assumption in the study of fixed-interval (FI) timing is that FI performance is largely stable within sessions, once it is stable between sessions. Within-session changes in FI performance were examined in published data (Daniels and Sanabria, 2017), wherein some rats were trained on a FI 30-s schedule of food reinforcement (FI30) and others on a FI 90-s schedule (FI90). Following stability, FI90 rats were pre-fed for five sessions. Response rates declined as a function of trial, due more to latency lengthening than to run-rate reduction. Latencies were best described by a dynamic gamma-exponential mixture distribution, in which latency lengthening was driven by the growth of the criterion pulse count for a response and not by a reduction in the speed of an endogenous clock. The speed of the clock was selectively sensitive to the length of the FI; the prevalence and length of exponentially-distributed latencies were selectively sensitive to pre-feeding. These findings reveal (a) that parameters governing FI latencies are selectively sensitive to a range of manipulations, (b) a potential degradation of the criterion pulse count between consecutive sessions, and (c) a subsequent recovery of the criterion pulse count within sessions.

The present study examined how systemic low doses of nicotine affect the microstructure of reinforced food-seeking behavior in rats. Rats were first given an acute saline or nicotine treatment (0.1–0.6 mg/kg, with an inter-injection interval of at least 48 h), and then a chronic saline or nicotine treatment (0.3 mg/kg/day for 10 consecutive days). Immediately after each injection, rats were required to press a lever five times to obtain food that was available at unpredictable times (on average every 80 s) with constant probability. Acute nicotine dose-dependently suppressed behavior prior to the delivery of the first reinforcer, but enhanced food-reinforced behavior afterwards. These effects were primarily observed in the time it took rats to initiate food-seeking behavior. Enhancing effects were also observed in the microstructure of food-seeking behavior, with lower nicotine doses (0.1–0.3 mg/kg) increasing the rate at which response bouts were initiated, and higher doses (0.3–0.6 mg/kg) increasing within-bout response rates. A pre-feeding control suggests that changes in appetite alone cannot explain these effects. Over the course of chronic nicotine exposure, tolerance developed to the suppressive, but not to the enhancing effects of nicotine on food-seeking behavior. These results suggest that (a) lower doses of nicotine enhance the reward value of food and/or food-associated stimuli, (b) higher doses of nicotine enhance motoric activity, and (c) ostensive sensitization effects of nicotine on behavior partially reflect a tolerance to its transient suppressive motoric effects.

Data have accumulated suggesting that motivation and timing are correlated processes, yet few studies have tested whether motivation and timing are procedurally dissociable. This may be attributed to the fact that the most common framework in which to study timing, the pacemaker-accumulator model, does not readily suggest a route by which to dissociate motivation and timing. In contrast, the behavioral systems framework suggests that motivation and timing could be dissociated if subjects were trained in response-initiated (RI) interval-timing procedures rather than in common externally-initiated (EI) procedures. RI procedures were predicted to enhance temporal control and yield timing performance robust to fluctuations in motivation. Experiment 1 tested this hypothesis by training rats to either initiate switch-timing trials with a single press on the lever associated with the shorter FI schedule (SL-RI), or wait for switch-timing trials to be initiated (EI). Motivation was varied through pre-feeding. SL-RI and EI rats showed similar levels of temporal control and sensitivity to pre-feeding in their switch-timing performance. Experiment 2 tested a revised RI hypothesis, the discriminative-RI hypothesis, which predicts that as the trial-initiating response becomes progressively different from target responses, motivation and timing are increasingly dissociated. This experiment replicated Experiment 1 and added a trial-initiating condition in which a nose-poke into a nose port (NP-RI) initiated trials. As predicted, the sensitivity of switching-timing performance to pre-feeding scaled such that EI > SL-RI > NP-RI. These data suggest that it is possible to dissociate timing and motivation, challenging the notion that these processes are correlated.

The behavior systems framework suggests that motivated behavior—e.g., seeking food and mates, avoiding predators—consists of sequences of actions organized within nested behavioral states. This framework has bridged behavioral ecology and experimental psychology, providing key insights into critical behavioral processes. In particular, the behavior systems framework entails a particular organization of behavior over time. The present paper examines whether such organization emerges from a generic Markov process, where the current behavioral state determines the probability distribution of subsequent behavioral states. This proposition is developed as a systematic examination of increasingly complex Markov models, seeking a computational formulation that balances adherence to the behavior systems approach, parsimony, and conformity to data. As a result of this exercise, a nonstationary partially hidden Markov model is selected as a computational formulation of the predatory subsystem. It is noted that the temporal distribution of discrete responses may further unveil the structure and parameters of the model but, without proper mathematical modeling, these discrete responses may be misleading. Opportunities for further elaboration of the proposed computational formulation are identified, including developments in its architecture, extensions to defensive and reproductive subsystems, and methodological refinements.

This study investigated the role of the dorsal hippocampus (dHPC) in the temporal entrainment of behavior, while addressing limitations of previous evidence from peak procedure experiments. Rats were first trained on a switch-timing task in which food was obtained from one of two concurrently available levers; one lever was effective after 8 s and the other after 16 s. After performance stabilized, rats underwent either bilateral NMDA lesions of the dHPC or sham lesions. After recovery, switch-timing training resumed. In a subsequent condition, the switch-timing task was modified such that food was available after either 8 or 32 s. Although dHPC lesions had subtle and complex effects on when rats stopped seeking for food at the 8-s lever (departures), it more systematically reduced the time when rats started seeking for food at the 16-s and 32-s lever (switches). No systematic effect of dHPC lesions were observed on the coefficient of quartile variation (normalized dispersion) of latencies to switch. Within the context of the pacemaker-accumulator framework of interval timing, these findings suggest that partially or wholly independent mechanisms control the initiation and termination of timed responses, and that the dHPC is primarily involved in encoding the time to start responding.

There is evidence that impulsive decision-making is associated with errors in timing. However, there has been little attempt to identify the putative mechanism responsible for impulsive animals' timing errors. One means of manipulating impulsivity in non-human animals is providing different levels of access to conspecifics. These preclinical models have revealed that social isolation increases impulsive responding across a wide range of tasks. The goal of the present study was to determine whether social isolation modulates time perception in pigeons by inducing more variability or a bias to underestimate the passage of time in temporal judgments. A temporal bisection task was used to characterize time perception. One group of pigeons performed the bisection following social enrichment, and the remaining half of the pigeons were tested following social isolation. Results revealed pigeons in the social isolation condition categorized a temporal stimulus sample as "long" at shorter durations than pigeons in the social enrichment condition. These data highlight the mechanism(s) thought to underlie timing-based interventions aimed at reducing impulsivity in humans. Future work should consider whether impulsivity is produced by misperceptions of time or a reduced threshold for a response.

The distribution of latencies and interresponse times (IRTs) of rats was compared between two fixed-interval (FI) schedules of food reinforcement (FI 30 s and FI 90 s), and between two levels of food deprivation. Computational modeling revealed that latencies and IRTs were well described by mixture probability distributions embodying two-state Markov chains. Analysis of these models revealed that only a subset of latencies is sensitive to the periodicity of reinforcement, and prefeeding only reduces the size of this subset. The distribution of IRTs suggests that behavior in FI schedules is organized in bouts that lengthen and ramp up in frequency with proximity to reinforcement. Prefeeding slowed down the lengthening of bouts and increased the time between bouts. When concatenated, latency and IRT models adequately reproduced sigmoidal FI response functions. These findings suggest that behavior in FI schedules fluctuates in and out of schedule control; an account of such fluctuation suggests that timing and motivation are dissociable components of FI performance. These mixture-distribution models also provide novel insights on the motivational, associative, and timing processes expressed in FI performance. These processes may be obscured, however, when performance in timing tasks is analyzed in terms of mean response rates.

Paradoxical choices in human and nonhuman animals represent substantial deviations from rational models of behavior; such deviations often demand models that incorporate multiple perspectives, including psychology, biology, and economics. The past couple of decades have seen an increased interest in the paradoxical choice of pigeons in 2-armed bandit tasks (2ABT) developed by Zentall and colleagues. In these 2ABTs, pigeons, but not rats, systematically choose an alternative that yields less reward over multiple trials but provides more information on events within a trial, over an alternative that yields more reward over trials but provides less information on events within a trial. Although current computational models account for much of the extant data generated in studies on 2ABT choice, they do not explain, in a trial-by-trial basis, how pigeons learn to ignore some stimuli and not others in 2ABTs. To address the provenance of this differential allocation of attention, a simple model composed of Bush-Mosteller linear operators and a Pearce-Hall-like associability mechanism is proposed. This model, referred to as the Associability Decay Model (ADM) of paradoxical choice, adequately accounts for the performance of pigeons and rats in 2ABTs. The ADM yields an untested prediction that is inconsistent with other computational models of 2ABT performance, and offers potential explanations for why differences in motivation, social enrichment, and impulsivity alter the degree to which pigeons systematically choose information despite earning fewer rewards. The success of the ADM shows that a relatively simple dynamic trial-by-trial model can account for much of the extant paradoxical-choice data while identifying opportunities for further study and refinement of models of 2ABT performance. (PsycINFO Database Record

Attention deficit/hyperactivity disorder (ADHD) is a risk factor for tobacco use and dependence. This study examines the responsiveness to nicotine of an adolescent model of ADHD, the spontaneously hypertensive rat (SHR). The conditioned place preference (CPP) procedure was used to assess nicotine-induced locomotion and conditioned reward in SHR and the Wistar Kyoto (WKY) control strain over a range of nicotine doses (0.0, 0.1, 0.3 and 0.6 mg/kg). Prior to conditioning, SHRs were more active and less biased towards one side of the CPP chamber than WKY rats. Following conditioning, SHRs developed CPP to the highest dose of nicotine (0.6 mg/kg), whereas WKYs did not develop CPP to any nicotine dose tested. During conditioning, SHRs displayed greater locomotor activity in the Nicotine-Paired compartment than in the Saline-Paired compartment across conditioning trials. SHRs that received nicotine (0.1, 0.3, 0.6 mg/kg) in the Nicotine-Paired compartment showed an increase in locomotor activity between conditioning trials. Nicotine did not significantly affect WKY locomotor activity. These findings suggest that the SHR strain is a suitable model for studying ADHD-related nicotine use and dependence, but highlights potential limitations of the WKY control strain and the CPP procedure for modeling ADHD-related nicotine reward.

This paper reviews the evidence for nicotine-induced acceleration of the internal clock when timing in the seconds-to-minutes timescale, and proposes an alternative explanation to this evidence: that nicotine reduces the threshold for responses that result in more reinforcement. These two hypotheses were tested in male Wistar rats using a novel timing task. In this task, rats were trained to seek food at one location after 8 s since trial onset and at a different location after 16 s. Some rats received the same reward at both times (group SAME); some received a larger reward at 16 s (group DIFF). Steady baseline performance was followed by 3 days of subcutaneous nicotine administration (0.3 mg/kg), baseline recovery, and an antagonist challenge (mecamylamine, 1.0 mg/kg). Nicotine induced a larger, immediate reduction in latencies to switch (LTS) in group DIFF than in group SAME. This effect was sustained throughout nicotine administration. Mecamylamine pretreatment and nicotine discontinuation rapidly recovered baseline performance. These results support a response-threshold account of nicotinic disruption of timing performance, possibly mediated by nicotinic acetylcholine receptors. A detailed analysis of the distribution of LTSs suggests that anomalous effects of nicotine on LTS dispersion may be due to loss of temporal control of behavior.

Schedule-induced polydipsia (SIP) was established in spontaneously hypertensive rats (SHR), Wistar Kyoto rats (WKY), and Wistar rats, using a multiple fixed-time (FT) schedule of food delivery, with 30- and 90-s components. Thereafter, animals were exposed to methylphenidate (MPH; 2.5mg/kg/d) for six consecutive SIP sessions. A test to assess possible sensitization effects was also conducted four days after termination of the drug treatment. At baseline, FT 90-s produced longer and more frequent drinking episodes in SHR than in WKY. An analysis of the distribution of inter-lick intervals revealed that drinking was organized in bouts, which were shorter in SHR than in WKY. Across strains and schedules, MPH shifted drinking episodes towards the beginning of inter-food intervals, which may reflect a stimulant effect on SIP. MPH transiently reduced the frequency of drinking episodes in WKY in FT 30-s, and more permanently reduced the frequency of licking bouts in Wistar rats. MPH also increased the length of licking bouts in Wistar rats. Overall, SHR displayed a hyperactive-like pattern of drinking (frequent but short bouts), which 2.5mg/kg MPH appears to reduce in WKY and Wistar but not in SHR rats. It appears that therapeutic effects of MPH on hyperactive-like SIP require higher doses in SHR relative to control strains.

When humans are asked to judge the value of a set of objects of excellent quality, they often give this set higher value than those same objects with the addition of some of lesser quality. This is an example of the affect heuristic, often referred to as the less-is-more effect. Monkeys and dogs, too, have shown this suboptimal effect. But in the present experiments, normally hungry pigeons chose optimally: a preferred food plus a less--preferred food over a more-preferred food alone. In Experiment 2, however, pigeons on a less-restricted diet showed the suboptimal less-is-more effect. Choice on control trials indicated that the effect did not result from the novelty of two food items versus one. The effect in the less-food-restricted pigeons appears to result from the devaluation of the combination of the food items by the presence of the less-preferred food item. The reversal of the effect under greater food restriction may occur because, as motivation increases, the value of the less-preferred food increases faster than the value of the more-preferred food, thus decreasing the difference in value between the two foods.

In studies of transitive inference (TI), nonhuman animals are typically trained with the following 5-term task: A+B−, B+C−, C+D−, D+E− where the letters stand for arbitrary stimuli and [+] indicates that choice is reinforced and [−] indicates that choice is not reinforced. A TI effect is found when, given the untrained test pair BD, subjects choose B. TI effects have been found in many nonhuman species. Although reinforcement history has been posited as an account of the TI effect, it has failed to account for a variety of conditions under which TI effects have been found. A more cognitive account of TI is that organisms are able to form a representation of the series (A > B > C > D > E). In support of this hypothesis, Roberts and Phelps (Psychol Sci 5:368–374, 1994) found that presentation of the pairs of stimuli in a linear arrangement facilitated TI performance by rats, whereas presentation of the pairs of stimuli in a circular arrangement did not. Using methods adapted from Roberts and Phelps, we trained pigeons on either a linear or a circular arrangement of stimuli with the 5-term task. Results indicated that on the BD test pair, pigeons trained with a circular arrangement did not differ from those trained with a linear arrangement. Furthermore, we found that memory for training pairs was variable and was highly correlated with degree of TI. The results suggest that regardless of how pigeons are able to represent the stimuli, choice was not affected by the spatial arrangement of the stimuli during training.

Author(s): Daniels, Carter W; Fox, Adam E; Kyonka, Elizabeth G. E.; Sanabria, Federico | Abstract: Models of interval timing typically include a response threshold to account for temporal production. The present study sought to evaluate the dependent concurrent fixed-interval fixed-interval schedule of reinforcement as a tool for selectively isolating the response threshold in rats, pigeons, and humans. In this task, reinforcement is available either at one location after a short delay or at another location at a longer delay. Because the reinforced location is not signaled, subjects normally respond on the first location and, if reinforcement is not delivered, then switch to the second location. The latency to switch between locations served as the primary dependent measure. After training rats, pigeons, and humans with equal reinforcement magnitudes in the short and long delays, the magnitude of reinforcement was increased threefold on the long-delay location. Consistent with model predictions, this biasing procedure decreased estimates of the response threshold of rats and pigeons, but also reduced temporal control in these species and increased response-threshold estimates in humans. Human and pigeon performance also suggested a magnitude-induced increase in the speed of the internal clock. Collectively, these results suggest that differences in reinforcement magnitude between response alternatives appear to modulate the response threshold, but not selectively, and may provide guidance for better isolating response-threshold effects in humans.

In nonhuman animals, the transitive inference (TI) task typically involves training a series of four simultaneous discriminations involving, for example, arbitrary colors in which choice of one stimulus in each pair is reinforced [+] and choice of the other color is nonreinforced [−]. This can be represented as A+B−, B+C−, C+D−, D+E− and can be conceptualized as a series of linear relationships: A>B>C>D>E. After training, animals are tested on the untrained non endpoint pair, BD. Preference for B over D is taken as evidence of TI and occurs because B is greater than D in the implied series. In the present study we trained pigeons using a novel training procedure—a hybrid of successive pair training (training one pair at a time) and mixed pair training (training all pairs at once)—designed to overcome some of the limitations of earlier procedures. Using this hybrid procedure, we trained five premise pairs (A+B−, B+C−, C+D−, D+E−, and E+F−) which allowed us to test three untrained non endpoint pairs (BD, CE, and BE). A significant TI effect was found for most subjects on at least two out of three test pairs. Different theories of TI are discussed. The results suggest that this hybrid training is an efficient procedure for establishing mixed pair acquisition and a TI effect.

Pigeons prefer a low-probability, high-payoff but suboptimal alternative over a reliable low-payoff optimal alternative (i.e., one that results in more food). This finding is analogous to suboptimal human monetary gambling because in both cases there appears to be an overemphasis of the occurrence of the winning event (a jackpot) and an underemphasis of losing events. In the present research we found that pigeons chose suboptimally to the degree that they were impulsive as indexed by the steeper slope of the hyperbolic delay-discounting function (i.e., the shorter the delay they would accept in a smaller-sooner/larger-later procedure). These correlational findings have implications for the mechanisms underlying suboptimal choice by humans (e.g., problem gamblers) and they suggest that high baseline levels of impulsivity can enhance acquisition of a gambling habit.