Nature Neuroscience

High-frequency (~90Hz) ripple oscillations may promote integrative processing in mammalian brains. Previous work has demonstrated that the co-occurrence of these ripple oscillations is associated with enhanced temporal binding of neural activity between human cortical neurons separated by up to 12mm. However, it remains unclear whether co-ripple facilitation of neuronal coupling supports cognitiv…

Maternal immune activation (MIA) disrupts brain development and increases the risk of neurodevelopmental disorders, yet the mechanisms by which MIA impacts human cortical development remain poorly understood. Here we introduce a three-dimensional ex vivo culture system, termed 'cerebroids,' derived from the dorsolateral prefrontal cortex of human fetal brain tissue, which preserves the key develo…

One-shot learning-the ability to form memories after a single, brief salient event-is essential for behavioral flexibility in a dynamic world. However, how one-shot learning unfolds in the brain and whether it relies on distinct plasticity mechanisms remains unknown. Here we show that a nonclassical plasticity mechanism requiring only a few stimulations-endocannabinoid-mediated long-term potentia…

The insular cortex integrates interoceptive and exteroceptive information to mediate bodily homeostasis, emotion and learning. However, the cellular and circuit substrates governing insular functions are poorly understood compared to primary cortices. Here we quantify dendritic morphology together with projections, electrical properties and/or local inputs of 1,130 mouse insular pyramidal neurons…

Glioma pathophysiology is robustly regulated by interactions with neurons. Key to these interactions is the role of neuroligin-3 (NLGN3), a synaptic adhesion molecule shed in response to neuronal activity that functions as a paracrine factor crucial for glioma growth. Here we elucidate the mechanistic pathway whereby shed NLGN3 interacts with glioma and their normal glial counterparts. NLGN3 bind…

ABSTRACT Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin have emerged as potentially transformative therapeutics for many neuropsychiatric diseases, including depression, anxiety, post-traumatic stress disorder, migraine, and cluster headaches. LSD and psilocybin exert their psychedelic effects via activation of the 5-hydroxytryptamine 2A receptor (HTR2A). Here we provide a…

Recovering forgotten memories is a double-edged sword. While regaining access to forgotten information can be advantageous, targeted memory recovery carries the risk of generating false memories. The neuronal processes governing true memory recovery and false memory formation remain poorly understood. Here we show in Drosophila that reminder cues recover forgotten aversive memories. Forgotten mem…

Abstract Diverse risk genes have been identified for neurodevelopmental disorders (NDDs), but how these genes converge on similar biological pathways in neurons, and thus give rise to similar phenotypes, is unclear. Here we apply a pooled CRISPR approach to successfully target 23 NDD loss-of-function genes with roles in chromatin biology and examine convergent effects on gene expression across hu…

The entorhinal cortex is a critical brain area for memory formation, while also the region exhibiting the earliest histological and functional alterations in Alzheimer's disease (AD). The entorhinal cortex therefore has been long hypothesized as one of the originating brain areas of AD pathophysiology, although circuit mechanisms causing its selective vulnerability remain poorly understood. Here …