Emerging role of the lateral habenula in conditioned inhibition and depression.

Associating a neutral conditioned stimulus (CS) with the absence of a biologically significant unconditioned stimulus (US) confers conditioned inhibitory properties upon the CS, referred to as conditioned inhibition. Conditioned inhibition and conditioned excitation, an association of a CS with the presence of the US, are fundamental components of associative learning. While the neural substrates of conditioned excitation are well established, those of conditioned inhibition remain poorly understood. Recent research has shed light on the lateral habenula (LHb) engagement in conditioned inhibition, along with the midbrain dopaminergic neurons. This article reviews behavioral tasks conducted to assess conditioned inhibition and how experimental LHb manipulations affect performance in these tasks. These results underscore the critical role of the LHb in conditioned inhibition. Intriguingly, stress increases LHb reactivity and impairs performances in tasks consisting of a component of conditioned inhibition in animals. Dysfunction of the LHb is observed in patients with depression. The ability of an organism to perform conditioned inhibition is closely linked to altered neuronal activity in the LHb, which has implications for mental disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Lateral habenula lesions impair the association of a conditioned stimulus with the absence of an unconditioned stimulus: Retardation task.

Recent studies have indicated that the lateral habenula (LHb) mediates the association of a conditioned stimulus (CS) with the absence of an unconditioned stimulus (US). We generated a CS-no US association using an explicit unpaired training procedure and evaluated the conditioned inhibitory properties using the modified version of the retardation-of-acquisition procedure, one of the procedures for assessing conditioned inhibition. First, rats in the unpaired group received explicit unpaired light (CS) and food (US) presentations, followed by light-food pairings. Rats in the comparison group received paired training alone. The rats in the two groups showed increased food-cup responses to light over paired training. However, rats in the unpaired group showed a slower acquisition of light and food excitatory conditioning than those in the comparison group. Light acquired conditioned inhibitory properties through explicitly unpaired training, as evidenced by its slowness. Second, we examined the effects of the LHb lesions on the decremental effects of unpaired learning on subsequent excitatory learning. Sham-operated rats exhibited decremental effects of unpaired learning on subsequent excitatory learning, while rats with LHb neurotoxic lesions did not. Third, we tested whether preexposure to the same number of lights presented in the unpaired training retarded the acquisition of subsequent excitatory conditioning. Preexposure to light did not significantly retard the acquisition of subsequent excitatory associations, with no LHb lesion effects. These findings indicate that LHb is critically involved in the association between CS and the absence of US.

Chemogenetic activation of lateral habenula accelerates the extinction of the appetitive conditioned responses.

A previous study reported lateral habenula (LHb) lesions decelerated appetitive extinction. Therefore, we examined whether LHb activation accelerated appetitive extinction. In this study, rats received appetitive Pavlovian conditioning, pairing a conditioned stimulus (CS, light) with an unconditioned stimulus (food pellets), followed by CS-alone presentations. Chemogenetic LHb activation accelerated the decline in conditioned food-cup responses during extinction. The present results and the reports of previous LHb lesion studies suggest that LHb mediates appetitive extinction. (PsycInfo Database Record (c) 2023 APA, all rights reserved).