Biology subjects

Bitzenhofer, S. H.

Publications and source records attributed to Bitzenhofer, S. H..

3 recordsLinked to original sources

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↗

bioRxiv2017

Glutamatergic drive along the septo-temporal axis of hippocampus boosts prelimbic oscillations in the neonatal mouse

The long-range coupling within prefrontal-hippocampal networks that account for cognitive performance emerges early in life. The discontinuous hippocampal theta bursts have been proposed to drive the generation of neonatal prefrontal oscillations, yet the cellular substrate of these early interactions is still unresolved. Here, we selectively target optogenetic manipulation of glutamatergic projection neurons in the CA1 area of either dorsal or intermediate/ventral hippocampus at neonatal age to elucidate their contribution to the emergence of prefrontal oscillatory entrainment. We show that despite stronger theta and ripples power in dorsal hippocampus, the prefrontal cortex is mainly coupled with intermediate/ventral hippocampus by phase-locking of neuronal firing via dense direct axonal projections. Theta band-confined activation by light of pyramidal neurons in intermediate/ventral but not dorsal CA1 that were transfected by in utero electroporation with high-efficiency channelrhodopsin boosts prefrontal oscillations. Our data causally elucidates the cellular origin of the long-range coupling in the developing brain.\n\nHighlightsO_LINeonatal theta bursts, sharp waves and ripples vary along septo-temporal axis\nC_LIO_LIHippocampal activity times prefrontal oscillations via direct axonal projections\nC_LIO_LISelective hippocampal targeting along septo-temporal axis causes precise firing\nC_LIO_LILight stimulation of hippocampal neurons at 8 Hz boosts prefrontal oscillations\nC_LI

neuroscience↗