Modeling Human Cortical Microcircuits in Depression and Aging

Abstract:

This talk will present recent biophysically detailed modeling studies of human cortical microcircuits that examine how aging and depression alter both cortical function and EEG biomarkers. By leveraging human-specific electrophysiological, morphological, and transcriptomic data, these models reveal how changes in inhibitory interneuron function and neuronal excitability affect microcircuit dynamics. The work offers mechanistic insights into how these cellular changes may contribute to EEG biomarkers of aging and depression. It also demonstrates how these models can be used to simulate pharmacological interventions — such as α5-GABAA receptor–positive allosteric modulators — and estimate pharmacological efficacy from EEG signals.

Short Bio:

Alexandre Guet-McCreight earned his PhD in Computational Neuroscience from the University of Toronto, under the supervision of Dr. Frances Skinner, with a focus on biophysical modeling of inhibitory hippocampal cells. After a postdoctoral period at the Krembil Brain Institute, he joined Dr. Etay Hay’s lab at the Center for Addiction and Mental Health and KCNI, where he integrates biophysical modeling and computational approaches to uncover digital biomarkers of depression, cognitive aging, and related pathologies. His research is supported by a CIHR Fellowship. More details can be found at https://agmccrei.github.io/personal_website/