NMDA receptors regulate the firing rate set point of hippocampal circuits without altering single-cell dynamics.

Understanding how neuronal circuits stabilize their activity is a fundamental yet poorly understood aspect of neuroscience. Here, we show that hippocampal network properties, such as firing rate distribution and dimensionality, are actively regulated, despite perturbations and single-cell drift. Continuous inhibition of N-methyl-D-aspartate receptors (NMDARs) ex vivo lowers the excitation/inhibition ratio and network firing rates while preserving resilience to perturbations.

Linking activity dyshomeostasis and sleep disturbances in Alzheimer disease.

The presymptomatic phase of Alzheimer disease (AD) starts with the deposition of amyloid-β in the cortex and begins a decade or more before the emergence of cognitive decline. The trajectory towards dementia and neurodegeneration is shaped by the pathological load and the resilience of neural circuits to the effects of this pathology. In this Perspective, I focus on recent advances that have uncovered the vulnerability of neural circuits at early stages of AD to hyperexcitability, particularly when the brain is in a low-arousal states (such as sleep and anaesthesia).

Deep brain stimulation of thalamic nucleus reuniens promotes neuronal and cognitive resilience in an Alzheimer's disease mouse model.

The mechanisms that confer cognitive resilience to Alzheimer's Disease (AD) are not fully understood. Here, we describe a neural circuit mechanism underlying this resilience in a familial AD mouse model. In the prodromal disease stage, interictal epileptiform spikes (IESs) emerge during anesthesia in the CA1 and mPFC regions, leading to working memory disruptions.

Early alterations in the MCH system link aberrant neuronal activity and sleep disturbances in a mouse model of Alzheimer's disease.

Early Alzheimer's disease (AD) is associated with hippocampal hyperactivity and decreased sleep quality. Here we show that homeostatic mechanisms transiently counteract the increased excitatory drive to CA1 neurons in App mice, but that this mechanism fails in older mice. Spatial transcriptomics analysis identifies Pmch as part of the adaptive response in App mice.