Training-Dependent Change in Content of Association in Appetitive Pavlovian Conditioning

In appetitive Pavlovian conditioning, experience with a conditional relationship between a cue [conditioned stimulus (CS)] and a reward [unconditioned stimulus (US)] bestows CS with the ability to promote adaptive behavior patterns. Different features of US (e.g., identity-specific sensory, general motivational) can be encoded by CS based on the nature of the CS-US relationship experienced (e.g., temporal factors such as training amount) and the content of association may determine the influence of CS over behavior (e.g., mediated learning, conditioned reinforcement). The content of association changed with varying conditioning factors, thereby altering behavioral consequences, however, has never been addressed in relevant brain signals evoked by CS. Our previous study found that phospholipase C β1-knockout (PLCβ1-KO) mice display persistent mediated learning over the extended course of odor-sugar conditioning, and that wild-type (WT) mice lose mediated learning sensitivity after extended training. In this study, in order to see whether this behavioral difference between these two genotypes comes from a difference in the course of association content, we examined whether odor CS can evoke the taste sensory representation of an absent sugar US after minimal- and extended training in these mice. In contrast to WT, which lost CS-evoked neural activation (c-Fos expression) in the gustatory cortex after extended training, KO mice displayed persistent association with the sensory feature of sugar, suggesting that sensory encoding is reliably linked to mediated learning sensitivity and there is a training-dependent change in the content of association in WT. PLCβ1 knockdown in the left medial prefrontal cortex (mPFC) resulted in mediated learning sensitivity and CS-evoked gustatory cortical activation after extended training, proposing a molecular component of the neural system underlying this Pavlovian conditioning process. We also discuss how disruption of this process is implicated for hallucination-like behaviors (impaired reality testing).

Higher-Order Conditioning With Simultaneous and Backward Conditioned Stimulus: Implications for Models of Pavlovian Conditioning

In a new environment, humans and animals can detect and learn that cues predict meaningful outcomes, and use this information to adapt their responses. This process is termed Pavlovian conditioning. Pavlovian conditioning is also observed for stimuli that predict outcome-associated cues; a second type of conditioning is termed higher-order Pavlovian conditioning. In this review, we will focus on higher-order conditioning studies with simultaneous and backward conditioned stimuli. We will examine how the results from these experiments pose a challenge to models of Pavlovian conditioning like the Temporal Difference (TD) models, in which learning is mainly driven by reward prediction errors. Contrasting with this view, the results suggest that humans and animals can form complex representations of the (temporal) structure of the task, and use this information to guide behavior, which seems consistent with model-based reinforcement learning. Future investigations involving these procedures could result in important new insights on the mechanisms that underlie Pavlovian conditioning.

Higher-Order Conditioning: What Is Learnt and How it Is Expressed

Pairing a neutral conditioned stimulus (CS) with a motivationally significant unconditioned stimulus (US) results in the CS coming to elicit conditioned responses (CRs). The widespread significance and translational value of Pavlovian conditioning are increased by the fact that pairing two neutral CSs (A and X) enables conditioning with X to affect behavior to A. There are two traditional informal accounts of such higher-order conditioning, which build on more formal associative analyses of Pavlovian conditioning. But, higher-order conditioning and Pavlovian conditioning have characteristics that are beyond these accounts: Notably, the two are influenced in different ways by the same experimental manipulations, and both generate conditioned responses that do not reflect the US per se. Here, we present a formal analysis that sought to address these characteristics.

Corticostriatal suppression of appetitive Pavlovian conditioned responding

ABSTRACTThe capacity to suppress learned responses is essential for animals to adapt in dynamic environments. Extinction is a process by which animals learn to suppress conditioned responding when an expected outcome is omitted. The infralimbic cortex (IL) to nucleus accumbens shell (NAcS) neural circuit is implicated in suppressing conditioned responding after extinction, especially in the context of operant cocaine-seeking behaviour. However, the role of the IL-to-NAcS neural circuit in the extinction of responding to appetitive Pavlovian cues is unknown and the psychological mechanisms involved in response suppression following extinction are unclear. We trained rats to associate a 10 s auditory conditioned stimulus (CS; 14 trials per session) with a sucrose unconditioned stimulus (US; 0.2 mL per CS) in a specific context and then, following extinction in a different context, precipitated a renewal of CS responding by presenting the CS alone in the original Pavlovian conditioning context. Unilateral, optogenetic stimulation of the IL-to-NAcS circuit selectively during CS trials suppressed renewal. In a separate experiment, IL-to-NAcS stimulation suppressed CS responding regardless of prior extinction and impaired extinction retrieval. Finally, IL-to-NAcS stimulation during the CS did not suppress the acquisition of Pavlovian conditioning but was required for the subsequent expression of CS responding. These results are consistent with multiple studies showing that the IL-to-NAcS neural circuit is involved in the suppression of operant cocaine-seeking, extending these findings to appetitive Pavlovian cues. The suppression of appetitive Pavlovian responding following IL-to-NAcS circuit stimulation does not, however, appear to require an extinction-dependent process.SIGNIFICANCE STATEMENTExtinction is a form of inhibitory learning through which animals learn to suppress conditioned responding in the face of non-reinforcement. We investigated the role of infralimbic (IL) cortex inputs to the nucleus accumbens shell (NAcS) in the extinction of responding to appetitive Pavlovian cues and the psychological mechanisms involved in response suppression following extinction. Using in vivo optogenetics, we found that stimulating the IL-to-NAcS neural circuit suppressed context-induced renewal of conditioned responding after extinction. In a separate experiment, stimulating the IL-to-NAcS circuit suppressed conditioned responding in an extinction-independent manner. These findings can be leveraged by future research aimed at understanding how corticostriatal circuits contribute to behavioural flexibility and mental disorders that involve the suppression of learned behaviours.

Deconditioning the Mind for Better Learning: The Gift of Reasoning

This paper discusses classical or Pavlovian conditioning, deconditioning, and critical thinking within the context of the human condition and relevant literature. The practical goal of this analysis is to demonstrate how to ‘reprogram’ our thinking from previous, somewhat dysfunctional learning to improve our responsiveness to others and our joy. Becker (2020) defined deconditioning as a systematic self-training process to free oneself from “undesirable desires”–urges and emotions that pop up when we would prefer they did not, thereby making life more stressful. By training oneself to ‘tune out’ these undesirable or distracting desires, one becomes more capable of making and adhering to intentional decisions. Such purposefulness can lead to increased experiences of the pleasures of life emanating from a sense of freedom rather than compulsion (Becker, 2020,p.1). To achieve that goal, this paper explores the important distinctions between conditioning and deconditioning, examining their roles and usefulness in learning generally. In this pursuit, several pertinent articles and books describing conditioning and deconditioning, combined with critical reflection on the researcher’s relevant experiences, are examined to illustrate how people can ‘decondition’ their thinking to stimulate appropriate reasoning for improved learning and memory. Briefly, deconditioning can lead to superior reasoning, resulting in benefits for learning, character development and beyond.

Temporal Factors Modulate Haloperidol-Induced Conditioned Catalepsy

Repeated pairings of a neutral context and the effects of haloperidol give rise to conditioned catalepsy when the context is subsequently presented in a drug-free test. In order to confirm whether this response is based on Pavlovian processes, we conducted two experiments involving two manipulations that affect conditioning intensity in classical conditioning procedures: time of joint exposure to the conditioned and the unconditioned stimulus, and the length of the inter-stimulus interval (ISI). The results revealed that both an increase in the length of context-drug pairings during conditioning and a reduced ISI between drug administration and context exposure increased conditioned catalepsy. These results are discussed in terms of the temporal peculiarities of those procedures that involve drugs as the unconditioned stimulus along with the role of Pavlovian conditioning in context-dependent catalepsy.

What Is Learned in Pavlovian Conditioning in Crickets? Revisiting the S-S and S-R Learning Theories

In Pavlovian conditioning in mammals, two theories have been proposed for associations underlying conditioned responses (CRs). One theory, called S-S theory, assumes an association between a conditioned stimulus (CS) and internal representation of an unconditioned stimulus (US), allowing the animal to adjust the CR depending on the current value of the US. The other theory, called S-R theory, assumes an association or connection between the CS center and the CR center, allowing the CS to elicit the CR. Whether these theories account for Pavlovian conditioning in invertebrates has remained unclear. In this article, results of our studies in the cricket Gryllus bimaculatus are reviewed. We showed that after a standard amount of Pavlovian training, crickets exhibited no response to odor CS when water US was devalued by providing it until satiation, whereas after extended training, they exhibited a CR after US devaluation. An increase of behavioral automaticity by extended training has not been reported in Pavlovian conditioning in any other animals, but it has been documented in instrumental conditioning in mammals. Our pharmacological analysis suggested that octopamine neurons mediate US (water) value signals and control execution of the CR after standard training. The control, however, diminishes with extension of training and hence the CR becomes insensitive to the US value. We also found that the nature of the habitual response after extended Pavlovian training in crickets is not the same as that after extended instrumental training in mammals concerning the context specificity. Adaptive significance and evolutionary implications for our findings are discussed.

Inferring spikes from calcium imaging in dopamine neurons

Calcium imaging has led to discoveries about neural correlates of behavior in subcortical neurons, including dopamine (DA) neurons. However, spike inference methods have not been tested in most populations of subcortical neurons. To address this gap, we simultaneously performed calcium imaging and electrophysiology in DA neurons in brain slices and applied a recently developed spike inference algorithm to the GCaMP fluorescence. This revealed that individual spikes can be inferred accurately in this population. Next, we inferred spikes in vivo from calcium imaging from these neurons during Pavlovian conditioning, as well as during navigation in virtual reality. In both cases, we quantitatively recapitulated previous in vivo electrophysiological observations. Our work provides a validated approach to infer spikes from calcium imaging in DA neurons and implies that aspects of both tonic and phasic spike patterns can be recovered.