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

Hea-Jin Kim,Hae-Young Koh

doi:10.3389/fnbeh.2021.750131

Abstract

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).

Highlights

Pavlovian conditioning is the process whereby experience with a conditional relationship between a neutral cue [conditioned stimulus (CS)] and an outcome [unconditioned stimulus (US)] enables CS to promote behaviors toward obtaining or avoiding US [conditioned response (CR)]
According to the hypothesis by Holland, it is expected that the nature of the CS-evoked US representation changes from strongly perceptual to less perceptual one over the extended course of training in WT, and that it stays strongly perceptual in Phospholipase C β1 (PLCβ1)-KO mice
This study traced the content of association by assessing CS-evoked neural activation in the gustatory cortex (GC) for the sensory feature of sugar US, the nucleus accumbens (Nacc) for its incentive motivational value (Saunders et al, 2018), and the olfactory cortex (OC) as a control for associative learning (Figure 1C), after minimal or extended training, by using c-Fos immunohistochemistry, in the WT and PLCβ1-KO mice

Summary

Introduction

Pavlovian conditioning is the process whereby experience with a conditional relationship between a neutral cue [conditioned stimulus (CS)] and an outcome [unconditioned stimulus (US)] enables CS to promote behaviors toward obtaining or avoiding US [conditioned response (CR)]. After the presentation of a tone CS followed by an eye shock, specific eye blink and heart rate CRs are measured: CS elicits both the CRs when it predicts the eye shock with short latency, but does only heart rate CR when the latency is longer. These results suggest that the specific somatosensory location information is not encoded by CS with a longer ISI. The content of association changing with varying conditioning factors, has not yet been addressed in relevant brain area signals evoked by CS

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