Neural encoding of timing in the rat striatum

The striatum forms a major input structure for the basal ganglia, and is a site of degeneration in diseases such as Parkinson’s and Huntington’s disease. It receives input broadly from cortex and thalamus, as well as from neuromodulatory systems, and funnels the resulting activity into a successively decreasing number of neurons before transmitting its output to the thalamus. This architecture is thought the facilitate selection of representations of actions, events, thoughts and relationships between them, from its various input patterns. Interestingly, perturbing normal function there through lesions or pharmacology can cause deficits in timing behavior, and, depending on site and type of manipulation, different aspects of learning. By parametrically varying a time interval that a rat estimates, while simultaneously recording action potentials from single neurons in the striatum, we aim to identify neurons whose activity is correlated with a change in estimated interval. The signals we identify will provide a starting point for modeling efforts as well as perturbation studies, wherein specific neural signals can be manipulated. We have begun by recording from neurons in the striatum of the rat. We will test the hypothesis that some of these neurons will shift their response rate and/or latency as we shift the time interval that rats estimate. By identifying neurons with such “tuning” for a temporal interval, we hope to identify a neural substrate for the time-based computations that may underlie learning.

In the past year, we have succeeded in training rats to press a lever in order to gain rewards at defined intervals, classically called operant conditioning on a Fixed Interval (FI) reinforcement schedule. We have adapted the classical FI schedule such that in blocks of 30 trials, on average, we shift the fixed interval over a range of about one minute. We call this schedule a Serial Fixed Interval (SFI) schedule of reinforcement and have analyzed rats’ behavior and initiated neurophysiological recordings during this task. Rats normally start responding just after the midpoint of the reinforcement interval, peaking around the time of reinforcement. We then shift the interval of reinforcement in blocks of trials to a different interval and animals shift the time at which they begin to respond, thus giving us a behavioural readout that reflects the animals changing knowledge about time until reward. Animals learn the interval associated with each block quickly, usually adapting their response times within five or fewer cycles of reward. This allows us to test animals on as many as ten distinct intervals that vary in duration over a range of about one minute during single sessions. This wide range of variation in estimated interval gives us statistical power when searching for neural correlates of timing behavior.

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