Yi Juin Liew
BME PhD Defense Presentation

Date:2022-06-30
Time: 8 - 10 AM Eastern Time (8 – 10PM Beijing Time)
Location / Meeting Link: IBB Suddath Seminar Room #1128 and https://gatech.zoom.us/j/95139839097?pwd=bm1ZU0FzS3FmSHlvRllKb2pTNWJadz09

Committee Members:
Prof. Garrett Stanley, Biomedical Engineering, Georgia Tech/Emory (Advisor) Prof. Bilal Haider, Biomedical Engineering, Georgia Tech/Emory Prof. Annabelle Singer, Biomedical Engineering, Georgia Tech/Emory Prof. Michael Borich, Emory Rehabilitation Medicine, Biomedical Engineering, Georgia Tech/Emory Prof. Yong Zhang, IDG/McGovern Institute for Brain Research, PKU Health Science Center Prof. Xiaojie Duan, Biomedical Engineering, Georgia Tech/Emory/PKU


Title: The timescales of transformation across brain structures in the thalamocortical circuit

Abstract:
Sensory processing requires reliable transmission of sensory information across multiple brain regions, from peripheral sensors, through sub-cortical structures, to sensory cortex, ultimately producing the sensory representations that drive perception and behavior. Despite decades of research, we do not yet have a mechanistic understanding of how neural representations are transformed across these critical brain structures. This is primarily due to the fact that what we know at the circuit level has been mainly derived from electrophysiological recordings targeted at single regions and upon gross anatomical connection patterns across brain regions without specific, precise knowledge of synaptic connectivity. To fill this gap in knowledge and to uncover how signaling changes across brain regions in response to changes in the sensory environment, this thesis work has two primary contributions. First, we developed a work-flow of topographic mapping and histological validation for extracellular multi-electrode recordings of neurons in the thalamocortical circuit in rodents, followed by a novel statistical approach for inferring synaptic connectivity across the brain regions. Specifically, we developed a signal-detection based classification of synaptic connectivity of simultaneously recorded neurons in thalamus and S1 cortex, with an assessment of classification confidence that is scalable to the large-scale recording approaches that are emerging in the field. Utilizing this experimental and computational framework, we next investigated the neural mechanisms that underlie an important sensory phenomenon that emerges in this early sensory circuit: rapid sensory adaptation. While this phenomenon has been well-studied over very rapid timescales of hundreds of milliseconds, other studies suggest that longer time scales of 10’s of seconds may also be relevant. Here, we demonstrated that the thalamus and the thalamorecipient layer 4 excitatory and inhibitory neurons in S1 exhibit differential adaptation dynamics, and that the neuronal dynamics across these different regions and cell types show common signatures of multiple timescales in response to sensory adaptation. We characterized the adaptation profiles at the TC junction and further identified several mechanisms that potentially underlie the adaptation effects on the circuit dynamics, including synaptic depression of the TC synapse in identified mono-synaptically connected thalamic and cortical neurons, and changes in spike timing and synchronization in the thalamic population. These mechanisms together mediate a dynamic trade-off in the theoretical detectability and discriminability of stimulus inputs. These results suggest that adaptation of the thalamocortical circuit across timescales results from a complex interaction between distinct mechanisms, and the engagement of different mechanisms can shift depending on the timescale of environmental changes.