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The dorsomedial striatum mediates Pavlovian appetitive conditioning and food consumption.

ABSTRACT: The dorsomedial striatum (DMS) is an important sensorimotor region mediating the acquisition of goal-directed instrumental reward learning and behavioral flexibility. However, whether the DMS also regulates Pavlovian cue-food learning is less clear. The current study used excitotoxic lesions to determine whether the DMS is critical in Pavlovian appetitive learning and behavior, using discriminative conditioning and reversal paradigms. The results showed that DMS lesions transiently retarded cue-food learning and subsequent reversal of this learning. Rats with DMS lesions selectively attenuated responding to a food cue but not a control cue, early in training, suggesting the DMS is involved when initial associations are formed. Similarly, initial reversal learning was attenuated in rats with DMS lesions, which suggests impaired flexibility to adjust behavior when the cue meaning is reversed. We also examined the effect of DMS lesions on food intake during tests with access to a highly palatable food along with standard chow diet. Rats with DMS lesions showed an altered pattern of intake, with an initial reduction in high-fat diet followed by an increase in chow consumption. These results demonstrate that the DMS has a role in mediating cue-food learning and its subsequent reversal, as well as changes in food intake when a choice is provided. Together, these results demonstrate the DMS is involved in reward associative learning and reward consumption, when behavioral flexibility is needed to adjust responding or consumption to match the current value. (PsycINFO Database Record

SUBMITTER: Cole S

PROVIDER: S-EPMC5726437 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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The dorsomedial striatum mediates Pavlovian appetitive conditioning and food consumption.

Cole Sindy S Stone Andrew D AD Petrovich Gorica D GD

Behavioral neuroscience 20171201 6

The dorsomedial striatum (DMS) is an important sensorimotor region mediating the acquisition of goal-directed instrumental reward learning and behavioral flexibility. However, whether the DMS also regulates Pavlovian cue-food learning is less clear. The current study used excitotoxic lesions to determine whether the DMS is critical in Pavlovian appetitive learning and behavior, using discriminative conditioning and reversal paradigms. The results showed that DMS lesions transiently retarded cue- ...[more]

PMID: 29189017

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Project description: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).

Project description:Excessive alcohol intake leads to mesostriatal neuroadaptations, and to addiction phenotypes. We recently found in rodents that alcohol increases fibroblast growth factor 2 (FGF2) expression in the dorsomedial striatum (DMS), which promotes alcohol consumption. Here, we show that systemic or intra-DMS blockade of the FGF2 receptor, FGF receptor-1 (FGFR1), suppresses alcohol consumption, and that the effects of FGF2-FGFR1 on alcohol drinking are mediated via the phosphoinositide 3 kinase (PI3K) signaling pathway. Specifically, we found that sub-chronic alcohol treatment (7 d × 2.5 g/kg, i.p.) increased Fgfr1 mRNA expression in the dorsal hippocampus and dorsal striatum. However, prolonged and excessive voluntary alcohol consumption in a two-bottle choice procedure increased Fgfr1 expression selectively in DMS. Importantly, systemic administration of the FGFR1 inhibitor PD173074 to mice, as well as its infusion into the DMS of rats, decreased alcohol consumption and preference, with no effects on natural reward consumption. Finally, inhibition of the PI3K, but not of the mitogen-activated protein kinase (MAPK) signaling pathway, blocked the effects of FGF2 on alcohol intake and preference. Our results suggest that activation of FGFR1 by FGF2 in the DMS leads to activation of the PI3K signaling pathway, which promotes excessive alcohol consumption, and that inhibition of FGFR1 may provide a novel therapeutic target for alcohol use disorder.SIGNIFICANCE STATEMENT Long-term alcohol consumption causes neuroadaptations in the mesostriatal reward system, leading to addiction-related behaviors. We recently showed that alcohol upregulates the expression of fibroblast growth factor 2 (FGF2) in dorsomedial striatum (DMS) or rats and mice, and in turn, FGF2 increases alcohol consumption. Here, we show that long-term alcohol intake also increases the expression of the FGF2 receptor, FGFR1 in the DMS. Importantly, inhibition of FGFR1 activity by a selective receptor antagonist reduces alcohol drinking, when given systemically or directly into the DMS. We further show that the effects of FGF2-FGFR1 on alcohol drinking are mediated via activation of the PI3K intracellular signaling pathway, providing an insight on the mechanism for this effect.

Project description:Threat conditioning is a common associative learning model with translational relevance. How threat-conditioned cues impact on formally unrelated instrumental behavior in humans is not well known. Such an effect is known as Pavlovian-to-instrumental transfer (PIT). While PIT with aversive primary Pavlovian reinforcers is established in nonhuman animals, this is less clear in humans, where secondary reinforcers or instructed instrumental responses are most often investigated. We modified an existing human PIT procedure to include primary reinforcers. Participants first learned to obtain (or avoid losing) appetitive instrumental reinforcement (chocolate) by appropriate approach or avoidance actions. They either had to act (Go) or to withhold an action (NoGo), and in the Go condition either to approach a reward target to collect it or to withdraw from the reward target to avoid losing it. Then they learned to associate screen color (CS) with aversive Pavlovian reinforcement (electric shock US). In the transfer phase, we conducted the instrumental task during the presence of Pavlovian CS. In a first experiment, we show that the aversive Pavlovian CS+, compared to CS-, increased response rate in Go-Withdraw trials, i.e., induce conditioned facilitation of avoidance responses. This finding was confirmed in a second and independent experiment with an increased number of Go-Withdraw trials. Notably, we observed no appreciable conditioned suppression of approach responses. Effect size to distinguish CS+/CS- in Go-Withdraw trials was d = 0.42 in the confirmation sample. This would require n = 37 participants to demonstrate threat learning with 80% power. Thus, the effect size is on a practically useful scale although smaller than for model-based analysis of autonomic measures. In summary, our results indicate conditioned facilitation of formally unrelated instrumental avoidance behavior in humans and provide a novel behavioral threat learning measure that requires only key presses.

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The dorsomedial striatum mediates Pavlovian appetitive conditioning and food consumption.

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The dorsomedial striatum mediates Pavlovian appetitive conditioning and food consumption.

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