The brain's capacity to sense and produce time intervals flexibly is an essential building block of many cognitive functions and sensorimotor skills. Yet, the neural mechanisms for measuring and producing an interval of time are unknown. We will take advantage of the foundational work on the anatomy and physiology of the primate oculomotor system to assess the mechanisms of interval timing in the oculomotor circuits of the brain. First, we will focus on the lateral intraparietal area (LIP) of the associaton cortex, where correlates of elapsed time have been reported previously. We will record from LIP neurons in an oculomotor time reproduction task to test the hypothesis that LIP response dynamics track the animal's estimate of elapsed time during both measurement and production of time intervals. Second, we will use optogenetics to excite and suppress neural activity in LIP at high temporal resolution to ask whether and how LIP plays a causal role in the perception and production of time intervals. Third, we will examine the neural signals at the output node of the lateral cerebellum (i.e., the dentate nucleus, DN), which is thought to play an important role in timing and temporal coordination. Based on previous work suggesting a role for the lateral cerebellum in non-motor timing, we will test the hypothesis that DN signals encode elapsed time during measurement of time intervals. These experiments combine multiple innovations including a novel behavioral paradigm and cutting-edge technology and have the potential to make a significant contribution to our understanding of the neural mechanisms of interval timing in the primate brain.
Timing is crucial for such complex behaviors as inferring causes, predicting effects, and sequencing thoughts and actions. These capabilities appear to be compromised in many neurological disorders such as ataxia, autism and schizophrenia. Our research on neural mechanisms of timing could expose common modes of failure in these disease states and help lay a foundation for developing new strategies for their treatment.