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Dopamine D1–D2 signalling in hippocampus arbitrates approach and avoidance
Heterogeneous pericoerulear neurons tune arousal and exploratory behaviours
Striatum supports fast learning but not memory recall
Oncogene aberrations drive medulloblastoma progression, not initiation
Light-microscopy-based connectomic reconstruction of mammalian brain tissue
Intragrain 3D perovskite heterostructure for high-performance pure-red perovskite LEDs
Bioremediation of complex organic pollutants by engineered <i>Vibrio natriegens</i>
PLA2G15 is a BMP hydrolase and its targeting ameliorates lysosomal disease
Twist-programmable superconductivity in spin–orbit-coupled bilayer graphene
Global emergence of unprecedented lifetime exposure to climate extremes
‘Forever’ molecules arrange themselves into cell-like structures
How Korea’s female divers have adapted to cold plunges
Herring population loses migration 'memory' after heavy fishing
Publisher Correction: Stress dynamically modulates neuronal autophagy to gate depression onset
Controversial geoengineering projects to test Earth-cooling tech funded by UK agency
How protein-slayer drugs could beat some of the cruellest cancers
Ambitious project to revive Louisiana coastline runs aground
Politics and environmental concerns imperil plans to divert the Mississippi River to build new land
Development of a brain-penetrant G9a methylase inhibitor to target Alzheimer's disease-associated proteopathology
Current Aβ-targeting therapeutics for Alzheimer's disease (AD) only slow cognitive decline due to poor understanding of AD pathogenesis. Here we describe a mechanism of AD pathogenesis in which the histone methyltransferase G9a noncanonically regulates translation of hippocampal proteins associated with AD pathology. Correspondingly, we developed a brain-penetrant inhibitor of G9a, MS1262, which restored both age-related learning & memory and noncognitive functions in multiple AD mouse models....
Revealing the location and dynamics of a concealed binding site in the dopamine transporter
The dopamine transporter (DAT) is linked to neuropsychiatric disorders including ADHD, Parkinson's disease, and substance use disorders. Accordingly, DAT is the target of illicit drugs and clinically important medicines. However, the number and function of ligand binding sites in DAT is enigmatic due to conflicting data from available structures and molecular pharmacology. Herein, we design force sensors with DAT ligands and measure their interaction forces with wild-type and mutated DATs, from...
Phylogenetic divergence of GABA<sub>B</sub> receptor signaling in neocortical networks over adult life
Cortical circuit activity is controlled by GABA-mediated inhibition in a spatiotemporally restricted manner. GABA(B) receptor (GABA(B)R) signalling exerts powerful slow inhibition that controls synaptic, dendritic and neuronal activity. But, how GABA(B)Rs contribute to circuit-level inhibition over the lifespan of rodents and humans is poorly understood. In this study, we quantitatively determined the functional contribution of GABA(B)R signalling to pre- and postsynaptic domains in rat and...