Insular cortex inactivation generalizes fear-induced underestimation of interval timing in a temporal bisection task.

In this study, we investigated: (1) the effect of fear on interval timing-time perception in the seconds-to-minutes range-and (2) the role of the insular cortex in the modulation of this effect. Rats were first trained on a temporal bisection task in which their response to a lever A was reinforced following a 2.00-s tone, whereas their response to a lever B was reinforced following an 8.00-s tone. After acquisition, the rats were also presented with intermediate-duration tones and pressed one of two levers to indicate whether tone duration was closer to 2.00 or 8.00s. Subsequently, the rats underwent differential fear conditioning in which one pitch tone (conditioned stimulus; CS+) was paired with an electric foot shock, while the other pitch tone (CS-) was presented alone. Either artificial cerebrospinal fluid (aCSF) or the GABA agonist muscimol was then infused into the rats' bilateral insular cortex before the animals were tested on the bisection task using the CS+and CS- tones. We found that in the rats infused with aCSF, the point of subjective equality (PSE) of the CS+ was higher than that for CS-, suggesting that the duration for CS+ was perceived to be shorter than that of CS-. However, muscimol eliminated the difference in PSE between CS+ and CS- by generalizing of the effect from CS+to the CS-. Taken together, our results show that normal activity in the insular cortex is involved in fear-induced modulation of interval timing.