Neural Correlates of Anesthesia in Newborn Mice and Humans

Monitoring the hypnotic component of anesthesia during surgeries is critical to prevent intraoperative awareness and reduce adverse side effects. For this purpose, electroencephalographic (EEG) 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 characterized the effects of different anesthetics on brain activity in neonatal mice and developed 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 EEG recordings can be applied to predict anesthetic concentration in neonatal mice and humans. These results might support a novel strategy to monitor anesthetic depth in human newborns

Neonatal hypoxia-ischemia impairs juvenile recognition memory by disrupting the maturation of prefrontal-hippocampal networks.

High-prevalence/low-severity cognitive deficits represent the life-long burden of a perinatal hypoxic–ischemic (HI) insult. They have been proposed to result from dysmaturation of prelimbic-hippocampal networks, which account for mnemonic and executive performance. Already at neonatal age the communication within these networks is largely reduced after an early HI insult with mild/moderate structural outcome. However, the longlasting consequences of the neonatal network dysfunction remain unknown. Here,we combine MRI and electrophysiology in vivo with behavioral testing to assess the effects of an early HI insult on the structure and function of prelimbic-hippocampal networks and on related cognitive abilities of juvenile rats. Despite the absence of lesions over the prelimbic cortex (PL) and hippocampus (HP), juvenile rats experiencing an early HI have lower performance in item and temporal order recognition memory. These cognitive deficits do not result from delayed somatic development or increased locomotion or anxiety. More likely, abnormal activity patterns and interactions within prelimbic-hippocampal networks account for behavioral impairment. The early HI insult causes power reduction of the fast (12–48 Hz) network activity and diminishment of neuronal firing in the PL and HP. This weaker entrainment of local circuits at juvenile age emerges in the absence of sufficiently strong directed interactions within neonatal prelimbic-hippocampal networks. Similar developmental mechanisms may account for poorer academic achievements of HI-injured infants

Coordinated electrical activity in the olfactory bulb gates the oscillatory entrainment of entorhinal networks in neonatal mice.

Although the developmental principles of sensory and cognitive processing have been extensively investigated, their synergy has been largely neglected. During early life, most sensory systems are still largely immature. As a notable exception, the olfactory system is functional at birth, controlling mother-offspring interactions and neonatal survival. Here, we elucidate the structural and functional principles underlying the communication between olfactory bulb (OB) and lateral entorhinal cortex (LEC)-the gatekeeper of limbic circuitry-during neonatal development. Combining optogenetics, pharmacology, and electrophysiology in vivo with axonal tracing, we show that mitral cell-dependent discontinuous theta bursts in OB drive network oscillations and time the firing in LEC of anesthetized mice via axonal projections confined to upper cortical layers. Acute pharmacological silencing of OB activity diminishes entorhinal oscillations, whereas odor exposure boosts OB-entorhinal coupling at fast frequencies. Chronic impairment of olfactory sensory neurons disrupts OB-entorhinal activity. Thus, OB activity shapes the maturation of entorhinal circuits