Biology subjects

Corbit, L. H.

Publications and source records attributed to Corbit, L. H..

3 recordsLinked to original sources

bioRxiv2025

Beta-Blocking Pavlov's Bells: Propranolol Attenuates Compound Extinction in an Error-Dependent Manner

A significant limitation of extinction-based therapies is their failure to be expressed across time and different contexts. The re-emergence of the original behaviour provides evidence that extinction training does not erase the original learning but rather relies on new learning that suppresses the expression of the original behaviour. Thus, a strategy for reducing relapse phenomena is to enhance the inhibitory learning that occurs during extinction training so that extinction is more robust. One such strategy is compound extinction where a combination of previously reinforced stimuli are presented together for the first time during extinction training. This treatment has been shown to enhance extinction learning, evidenced by reduced future spontaneous recovery. However, the mechanisms are not fully understood. Experiment 1 assessed whether the compound extinction effect is the result of increased expectation of reward generated by the compound of stimuli that is then violated, driving further learning, or more simply, the novelty of the compound which reengages attention and thus promotes extinction without increasing prediction error. Experiment 2 tested whether the effects of the noradrenaline beta-receptor antagonist propranolol, shown elsewhere to reduce the compound extinction effect, relate to prediction error or novelty. We found that, when equating the novelty of the stimulus compound, larger prediction error resulted in better extinction evidenced as reduced spontaneous recovery. Further, we found that propranolol reduced this effect suggesting that prediction error rather than novelty is important for both the behavioural and pharmacological effects. Together our results point to behavioural and pharmacological strategies that can be used to improve the long-term expression of extinction. HighlightsO_LIIncreasing prediction error during extinction enhances extinction retention C_LIO_LIThis effect is not explained by stimulus novelty C_LIO_LIBlocking beta-noradrenergic signaling attenuates the compound stimulus effect C_LI

animal behavior and cognition↗

bioRxiv2024

Alpha-2 agonism of the locus coeruleus impairs learning driven by negative prediction error

Refining previous learning when environmental contingencies change is a critical adaptive function. Studies have shown that systemic noradrenaline (NA) manipulations, as well as optogenetic manipulations of the locus coeruleus (LC), the primary source of forebrain NA, can strengthen long-term retention of appetitive extinction. To determine whether the contribution of NA is specific to extinction or extends to other forms of learning where reward is less than expected, we suppressed LC activity with clonidine, an 2A-adrenergic receptor agonist, in two tasks: compound extinction, where two previously rewarded cues are paired and no longer rewarded, and overexpectation, where animals are presented with two previously rewarded cues but receive a single reward rather than the expected two. In compound extinction, we found no differences between groups in training, extinction, or a spontaneous recovery test. However, animals that received clonidine reacquired responding to the previously extinguished cue significantly faster than saline animals, suggesting weakened extinction learning. In overexpectation testing, the saline group responded significantly less to a stimulus that had undergone overexpectation relative to a control stimulus, indicating that they had recalibrated their estimation of reward magnitude following training where reward was less than expected. In contrast, clonidine-treated animals did not differ in responding to the overexpectation versus control stimuli, suggesting that clonidine impaired learning resulting from overexpectation. These results demonstrate that activity of the LC is important for learning to reduce responding in both extinction and overexpectation paradigms.

animal behavior and cognition↗

bioRxiv2023

Optogenetic Stimulation of the Locus Coeruleus Enhances Appetitive Extinction in Rats

Extinction is a specific example of learning where a previously reinforced stimulus or response is no longer reinforced, and the previously learned behaviour is no longer necessary and must be modified. Current theories suggest extinction is not the erasure of the original learning but involves new learning that acts to suppress the original behaviour. Evidence for this can be found when the original behaviour recovers following the passage of time (spontaneous recovery), or reintroduction of the reinforcement (i.e., reinstatement). Recent studies have shown that pharmacological manipulation of noradrenaline (NA) or its receptors can influence appetitive extinction, however, the role and source of endogenous NA in these effects is unknown. Here, we examined the role of the locus coeruleus (LC) in appetitive extinction. Specifically, we tested whether optogenetic stimulation of LC neurons during extinction of a food-seeking behaviour would enhance extinction evidenced by reduced spontaneous recovery in future tests. LC stimulation during extinction trials did not change the rate of extinction but did serve to reduce subsequent spontaneous recovery suggesting that stimulation of the LC can augment reward-related extinction. Optogenetic inhibition of the LC during extinction trials reduced responding during the trials where it was applied, but no long-lasting changes in the retention of extinction were observed. Since not all LC cells expressed halorhodopisn, is possible that more complete LC inhibition or pathway-specific targeting would be more effective at suppressing extinction learning. These results provide further insight into the neural basis of appetitive extinction, and in particular the role of the LC. A deeper understanding of the physiological bases of extinction can aid development of more effective extinction-based therapies.

animal behavior and cognition↗