Student Theses and Dissertations
Date of Award
2023
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Abstract
Interval timing, the ability to accurately measure elapsed time between events, is critical for generating appropriate behavioral responses. Research conducted over the past decades has implicated the cortico-striatal-thalamic loop in time encoding,suggesting that the cortex utilizes high-dimensional dynamics to represent time. The dorsal lateral region of the striatum (d1St) is a key structure involved in interval timing,where neurons exhibit dynamic firing rate patterns that encode elapsed time, enabling animals to make perceptual judgments about time intervals. However, it is unlikely that this striatal activity is self-generated, pointing towards cortical afferent inputs as the driving force behind it. This thesis aims to investigate cortical activity responsible for time encoding that can drive striatal activity. To achieve this, we developed a 2-alternative force choice head-fixed sensory timing task in mice. The mice were trained to perceive and categorize two different time intervals by licking the corresponding waterspout, demonstrating their ability to learn the task. Challenge sessions introduced two additional time intervals within each category to assess generalization of the learned task. Initially, we explored the necessity of d1St activity in perceiving and accurately categorizing time intervals. Using bilateral activation of the inhibitory opsin GtACR to suppress d1St activity during time perception, we observed impaired performance of the sensory timing task. Subsequently inhibiting d1St activity after the delivery of time interval stimuli resulted in more variable effects on the animals’ performance. These experiments confirmed the crucial role of d1St neural activity in executing the sensory timing task accurately. To investigate the cortical inputs to the d1St, we employed a calcium indicator (GCaMP) to label cortical neurons projecting directly to the d1St. Under two-photon microscopy, we recorded their neural activity while the animals performed the sensory timing task. Most of the labeled neurons were found in the secondary motor cortex (sMO-d1St). We discovered that this cortical neuron population carries relevant information about perceived time intervals by forming coordinated neuronal ensembles, referred to as timing ensembles. Importantly, these neuronal ensembles exhibited dynamic engagement in neuronal activity on a trial-by-trial basis, rendering the timing ensembles as more reliable time encoders than individual neurons alone. Notably, timing ensembles exhibited linear adjustments in activity according to the timed interval, while individual neurons contributed to both linear and non-linear changes in their activity patterns. In conclusion, this thesis advances our understanding of interval timing by highlighting the essential role of cortical activity, particularly within the sMO-d1St circuit, in driving striatal encoding. The involvement of d1St neural activity in accurate time perception underscores its significance within the cortico-striatal circuit. Furthermore, the discovery of dynamic timing ensembles within the sMO-d1St population provides valuable insights into the coordinated and flexible nature of time encoding. These findings contribute to our understanding of how the brain tracks elapsed time and lay the groundwork for future research exploring the integration of timing information into complex cognitive processes and behavioral responses.
Recommended Citation
Traub, Francisca Martínez, "Neural Population Dynamics Underlying Encoding of Time in the Cortico-Striatal Circuit" (2023). Student Theses and Dissertations. 768.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/768
Comments
A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy