We show that simple assumptions about neural processing lead to a model of interval timing as a temporal integration process, in which a noisy firing-rate representation of time rises linearly on average toward a response threshold over the course of an interval. Our assumptions include: that neural spike trains are approximately independent Poisson processes, that correlations among them can be largely cancelled by balancing excitation and inhibition, that neural populations can act as integrators, and that the objective of timed behavior is maximal accuracy and minimal variance. The model accounts for a variety of physiological and behavioral findings in rodents, monkeys, and humans, including ramping firing rates between the onset of reward-predicting cues and the receipt of delayed rewards, and universally scale-invariant response time distributions in interval timing tasks. It furthermore makes specific, well-supported predictions about the skewness of these distributions, a feature of timing data that is usually ignored. The model also incorporates a rapid (potentially one-shot) duration-learning procedure. Human behavioral data support the learning rule9s predictions regarding learning speed in sequences of timed responses. These results suggest that simple, integration-based models should play as prominent a role in interval timing theory as they do in theories of perceptual decision making, and that a common neural mechanism may underlie both types of behavior.

Pro‐inflammatory cytokines have been proposed to be associated with the pathogenesis of depression. Consistent with this notion, several clinical observations have suggested the antidepressant efficacy of TNF‐α inhibitors in patients with chronic inflammatory diseases. In this study, we evaluated the antidepressant and anxiolytic effects of chronic TNF‐α inhibitor (infliximab, 5 mg/kg, i.p., weekly) administration in the chronic mild stress (CMS) model of depression. Rats were divided into three groups: saline‐control (no stress), saline‐CMS, and infliximab‐CMS. Rats in the latter two groups were exposed to CMS for 8 weeks. Saline (former two groups) or infliximab was injected weekly during this period. After CMS, total locomotor activity, anxiety‐like behaviour and depression‐like behaviours were evaluated using automated locomotor activity cage, elevated plus maze (EPM), and sucrose preference (SPT) and forced swimming (FS) tests, respectively. As expected, the saline‐CMS group exhibited higher depression‐like behaviours in FS and SPT tests compared with the saline‐control group. There were no differences between these two groups in terms of the anxiety‐like behaviour or total locomotor activity. Infliximab reduced the depression‐like behaviour of CMS rats compared with saline‐CMS group, and anxiety‐like behaviour of CMS rats compared with saline‐CMS and saline‐control groups. Our findings suggest that chronic and systemic TNF‐α inhibition reduced depression and anxiety‐like behaviour in the CMS model of depression in rats.

Human and mouse subjects tried to anticipate at which of 2 locations a reward would appear. On a randomly scheduled fraction of the trials, it appeared with a short latency at one location; on the complementary fraction, it appeared after a longer latency at the other location. Subjects of both species accurately assessed the exogenous uncertainty (the probability of a short versus a long trial) and the endogenous uncertainty (from the scalar variability in their estimates of an elapsed duration) to compute the optimal target latency for a switch from the short- to the long-latency location. The optimal latency was arrived at so rapidly that there was no reliably discernible improvement over trials. Under these nonverbal conditions, humans and mice accurately assess risks and behave nearly optimally. That this capacity is well-developed in the mouse opens up the possibility of a genetic approach to the neurobiological mechanisms underlying risk assessment.