Cell Type Specific Biophysical Changes in the Aging Human Brain

On behalf of Molecular Mechanisms of Neuronal Connectivity: From Membranes to Synapses' Group, Christiaan de Kock from CNCR, Amsterdam will give a talk titled "Cell Type Specific Biophysical Changes in the Aging Human Brain" as part of the ongoing Student/Postdoc-Run Speaker Series (SPRSS).

Abstract:

Normal human brain aging is typically associated with cognitive decline. The structural and functional changes in individual neurons leading to cognitive decline remain enigmatic. Here, we utilize a large cohort of donors undergoing brain surgery (age-range 18-83 years) to perform patch-seq and patchclamp electrophysiology on acute cortical resection tissue. We profiled morphology, electrophysiology, and gene transcription for all major excitatory and inhibitory subclasses across all cortical layers. For patch-clamp data, we developed a robust machine learning platform to predict transcriptomic identity, which results in annotating both datasets to the same transcriptomics taxonomy. In the combined dataset, we find that normal aging of the human brain leads to gradual changes in biophysical features of excitatory pyramidal neurons. In contrast, inhibitory neurons are robust and remain stable for the full age range. We conclude that excitatory neurons in human neocortex are vulnerable to aging and may drive age-related cognitive decline.