Poepplau, J. A. | Search bioRxiv

bioRxiv2018

Identifying neurophysiological features associated with anesthetic state in newborn mice and humans

One Sentence SummaryMachine learning reveals consistent features of anesthetic states assessed by intracranial recordings in newborn mice and multichannel EEG in human neonates and infants.\n\nAbstractMonitoring the hypnotic component of anesthesia during surgeries is critical to prevent intraoperative awareness and reduce adverse side effects. For this purpose, electroencephalographic methods complementing measures of autonomic functions and behavioral responses are in use in clinical practice. However, in human neonates and infants existing methods may be unreliable and the correlation between brain activity and anesthetic depth is still poorly understood. Here, we characterize the effects of different anesthetics on activity of several brain areas in neonatal mice and develop machine learning approaches to identify electrophysiological features predicting inspired or end-tidal anesthetic concentration as a proxy for anesthetic depth. We show that similar features from electroencephalographic recordings can be applied to predict anesthetic concentration in neonatal mice, and human neonates and infants. These results might support a novel strategy to monitor anesthetic depth in human newborns.

neuroscience↗

bioRxiv2018

Microglia inhibition rescues developmental hypofrontality in a mouse model of mental illness

Cognitive deficits, core features of mental illness, largely result from dysfunction of prefrontal-hippocampal networks. This dysfunction emerges already during early development, before a detectable behavioral readout, yet the cellular elements controlling the abnormal maturation are still unknown. Combining in vivo electrophysiology and optogenetics with neuroanatomy and pharmacology in neonatal mice mimicking the dual genetic - environmental etiology of psychiatric disorders, we identified pyramidal neurons in layer II/III of the prefrontal cortex as key elements causing disorganized oscillatory entrainment of local circuits in beta-gamma frequencies. Their abnormal firing rate and timing result from sparser dendritic arborization and lower spine density. Pharmacological modulation of aberrantly hyper-mature microglia rescues morphological, synaptic and functional neuronal deficits and restores the early circuit function. Elucidation of the cellular substrate of developmental miswiring related to later cognitive deficits opens new perspectives for identification of neurobiological targets, amenable to therapies.\n\nHighlightsO_LIMice mimicking the etiology of mental illness have dysregulated prefrontal network\nC_LIO_LIStructural and synaptic deficits cause abnormal rate and timing of pyramidal firing\nC_LIO_LIWeaker activation of prefrontal circuits results from deficits of pyramidal neurons\nC_LIO_LIRescue of microglial function restores developing prefrontal circuits\nC_LI

neuroscience↗