2023 Theses Doctoral

Flexible Temporal Processing and Its Neural Bases

Akdogan, Basak

Temporal information-processing is critical for adaptive behavior and goal-directed action. It has a crucial role in various cognitive and behavioral processes that are of vital biological significance. Therefore, it is important to characterize the behavioral and neural mechanisms of adaptive timing behavior. To this end, in this dissertation we first demonstrate the behavioral properties of flexible timing ability in humans and mice, and then investigate the neural substrates of temporal processing.

After providing a brief introduction to theoretical and methodological approaches to interval timing in Chapter 1, we first examined the nature of temporal representations in Chapter 2, with the aim of understanding how the temporal distance between behaviorally relevant events is encoded to guide behavior. Our findings demonstrate that mice can represent experienced durations both as having a certain magnitude (absolute representation) and as being shorter or longer of the two durations (an ordinal relation to other cue durations), with relational control having a more enduring influence in temporal discriminations.

After showing that animals are capable of representing event durations in various ways (i.e., in relation to one another or in absolute time units), in Chapter 3 we investigated if humans can mentally manipulate time intervals and perform arithmetic operations on durations. Our results indicated that participants’ time estimates were highly accurate and similar across conditions that required them estimate either single durations or the sum of two durations, further providing evidence for the flexible timing ability. After presenting two behavioral studies on adaptive timing behavior in humans and mice, we then investigated the neural bases of adaptive temporal processing, with a particular focus on the serotonergic and dopaminergic systems. We first examined the effects of serotonin (5-HT) 2A receptor activation on temporal discriminations by systemic administration of a 5-HT2A agonist, DOI, prior to testing in a duration discrimination task in Chapter 4. Our findings consistently revealed that a higher dose of DOI led to the relative shortening of longer durations, possibly due to parallel changes in attention and memory processes which are highly related to temporal cognition.

Finally, in Chapter 5, we focused on the dopaminergic modulation of timed actions and investigated the effects of chemogenetic inactivation of dopamine D1 and D2 receptor-expressing striatal neurons in a waiting task. Our results shed light on the distinct contributions of direct and indirect pathways to timing, and provide evidence for a significant role of the striatopallidal pathway in modulating time-dependent behaviors. Taken together, these studies not only help elucidate how organisms represent and mentally manipulate time intervals, but also illustrate the modulation of flexible timing behavior by serotonergic and dopaminergic systems.