An insula-central amygdala circuit for behavioral inhibition

Predicting which substances are suitable for consumption during foraging is critical for animals to survive. While food-seeking behavior is extensively studied, the neural circuit mechanisms underlying avoidance of potentially poisonous substances remain poorly understood. Here we examined the role of the insular cortex (IC) to central amygdala (CeA) circuit in the establishment of such avoidance behavior. Using anatomic tracing approaches combined with optogenetics-assisted circuit mapping, we found that the gustatory region of the IC sends direct excitatory projections to the lateral division of the CeA (CeL), making monosynaptic excitatory connections with distinct populations of CeL neurons. Specific inhibition of neurotransmitter release from the CeL-projecting IC neurons prevented mice from acquiring the “no-go” response, while leaving the “go” response largely unaffected in a tastant (sucrose/quinine)-reinforced “go/no-go” task. Furthermore, selective activation of the IC-CeL pathway with optogenetics drove unconditioned lick suppression in thirsty animals, induced aversive responses, and was sufficient to instruct conditioned action suppression in response to a cue predicting the optogenetic activation. These results indicate that activity in the IC-CeL circuit is necessary for establishing anticipatory avoidance responses to an aversive tastant, and is also sufficient to drive learning of such anticipatory avoidance. This function of the IC-CeL circuit is likely important for guiding avoidance of substances with unpleasant tastes during foraging in order to minimize the chance of being poisoned.Significance StatementThe ability to predict which substances are suitable for consumption is critical for survival. Here we found that activity in the insular cortex (IC) to central amygdala (CeA) circuit is necessary for establishing avoidance responses to an unpleasant tastant, and is also sufficient to drive learning of such avoidance responses. These results suggest that the IC-CeA circuit is critical for behavioral inhibition in anticipation of potentially poisonous substances during foraging.

The Effects of Acute Stress-Induced Sleep Disturbance on Acoustic Trauma-Induced Tinnitus in Rats

Chronic tinnitus is a debilitating condition and often accompanied by anxiety, depression, and sleep disturbance. It has been suggested that sleep disturbance, such as insomnia, may be a risk factor/predictor for tinnitus-related distress and the two conditions may share common neurobiological mechanisms. This study investigated whether acute stress-induced sleep disturbance could increase the susceptibility to acoustic trauma-induced tinnitus in rats. The animals were exposed to unilateral acoustic trauma 24 h before sleep disturbance being induced using the cage exchange method. Tinnitus perception was assessed behaviourally using a conditioned lick suppression paradigm 3 weeks after the acoustic trauma. Changes in the orexin system in the hypothalamus, which plays an important role in maintaining long-lasting arousal, were also examined using immunohistochemistry. Cage exchange resulted in a significant reduction in the number of sleep episodes and acoustic trauma-induced tinnitus with acoustic features similar to a 32 kHz tone at 100 dB. However, sleep disturbance did not exacerbate the perception of tinnitus in rats. Neither tinnitus alone nor tinnitus plus sleep disturbance altered the number of orexin-expressing neurons. The results suggest that acute sleep disturbance does not cause long-term changes in the number of orexin neurons and does not change the perception of tinnitus induced by acoustic trauma in rats.

Overshadowing of subsequent events and recovery thereafter

Four experiments using a conditioned lick suppression preparation with rats were conducted to examine whether overshadowing of subsequent events could be obtained in Pavlovian backward conditioning (i.e. unconditioned stimulus [US] before conditioned stimulus [CS]), and to determine whether such overshadowing could be reversed without further training with the overshadowed CS, as has been reported in overshadowing of antecedent events. In Experiment 1, a backward-conditioned CS overshadowed a second backward-conditioned CS. Two posttraining manipulations, extinction of the overshadowing CS (Experiment 2) and shifting of the temporal relationship of the overshadowing CS to the US (Experiment 3), increased responding to the overshadowed CS. These results constitute the first unambiguous demonstration of stimulus competition between subsequent events using first-order conditioning, and they show that, like overshadowing with forward conditioning, such overshadowing is due, at least in part if not completely, to a failure to express information that had been acquired.