Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform

Abstract

Determining cell types is critical for understanding neural circuits but remains elusive in the living human brain. Current approaches discriminate units into putative cell classes using features of the extracellular action potential (EAP); in absence of ground truth data, this remains a problematic procedure. We find that EAPs in deep structures of the brain exhibit robust and systematic variability during the cardiac cycle. These cardiac-related features refine neural classification. We use these features to link bio-realistic models generated from in vitro human whole-cell recordings of morphologically classified neurons to in vivo recordings. We differentiate aspiny inhibitory and spiny excitatory human hippocampal neurons and, in a second stage, demonstrate that cardiac-motion features reveal two types of spiny neurons with distinct intrinsic electrophysiological properties and phase-locking characteristics to endogenous oscillations. This multi-modal approach markedly improves cell classification in humans, offers interpretable cell classes, and is applicable to other brain areas and species.