In this review, Braun et al. propose that psychotic symptoms across psychiatric and neurological disorders arise from disturbances in neuromodulatory systems that alter neural gain and precision weighting, destabilizing cortico-striato-thalamo-cortical circuits and large-scale brain networks, offering a transdiagnostic, testable framework for future research.

This article discusses research providing renewed reasons to revisit the utility of glutamatergic drugs for treating schizophrenia.

A quantification artifact confounds CRISPR-mediated RNA knockdown.

Dorsal and ventral noradrenergic neurons in the locus coeruleus form topographic subpopulations whose projection patterns and activity encode choice switching, reward-prediction errors and disregard o...

The ciliary transition zone (TZ) regulates ciliary proteome composition, yet its molecular architecture, protein content, and contribution to motile ciliopathies remain poorly defined. We applied in situ cryo-electron tomography and subtomogram averaging ...

Nature Structural & Molecular Biology, Published online: 09 September 2026; doi:10.1038/s41594-026-01882-9AMPA receptor (AMPAR) gating proceeds through an intermediate pre-active state that has structurally remained an enigma. Here, Newton et al. use full and partial agonists and time-resolved cryo-electron microscopy to resolve this state and reveal the complete gating pathway of AMPARs.

How ligands with different efficacies regulate G protein-coupled receptor signaling remains incompletely understood. Here, we combine Markov state modeling of nearly one millisecond of aggregate all-a...

Neural mechanisms underlying sensory-guided learning are not fully understood. Here authors show that salient visual stimuli elicit striatal dopamine partly through a local cholinergic mechanism and i...

Dong et al. identify a descending brainstem-to-spinal-cord circuit that drives widespread, opioid-resistant pain in mice. They show that glycine from this pathway acts as an excitatory signal by activating a specific type of NMDA receptor in the spinal cord, revealing a previously unknown mechanism for refractory tactile pain.

The integration of synaptic inputs is a fundamental function of neurons. In the traditional model, excitatory inputs are summed at the soma to generate action potentials. However, how synaptic inputs ...

Dopamine acts at D2-NMDA receptor heteromers to control glutamatergic transmission and aversive learning.

Developing therapies and vaccines against integral membrane proteins is hindered by their extensive hydrophobic surfaces, which complicate production and structural analysis. Here, we describe a gener...

β-Arrestins 1 and 2 are multifunctional adaptor proteins1 that regulate the signalling of G-protein-coupled receptors (GPCRs), the largest class of receptors, which impact nearly all aspects of physiology and are one of the most common drug targets2. Although β-arrestins interact with a wide array of signalling effectors at many GPCRs, it is unclear how β-arrestins promote such varied functions. Here we show that β-arrestins undergo liquid–liquid phase separation, forming condensates that regulate GPCR function. We show that condensation is specific to visual arrestins and β-arrestins, and demonstrate that β-arrestin oligomerization occurs in proximity to the GPCR to regulate GPCR functions such as internalization and signalling. Our work provides a paradigm for β-arrestin condensates as regulators of GPCR function, with liquid–liquid phase separation serving as an important promoter of signalling compartmentalization at GPCRs. β-Arrestins, multifunctional adaptor proteins that re

The Howard Hughes Medical Institute’s Janelia Research Campus is banking on whole-brain imaging in the Danionella fish to advance neuroscience, but some scientists forced to close their labs say that…

Cannabidiol (CBD), a nonpsychoactive phytocannabinoid from Cannabis sativa, modulates the α7 nicotinic acetylcholine receptor (α7 nAChR), a key tar...

Phase contrast enables structures of smaller proteins, could drive in-cell proteomics

Nature Structural & Molecular Biology, Published online: 09 June 2026; doi:10.1038/s41594-026-01818-3Hu et al. show that physiological temperature and intrinsic Ca2+ reprogram TRPM4 pharmacology, revealing hidden ligand activities missed under simplified assay conditions—even at structurally stable sites—and highlighting the need for environment-aware drug discovery.

Microglia-mediated neuroinflammation drives Alzheimer’s disease progression. In this article, Liu et al. show that the histone acetyltransferase KAT7 promotes mitochondrial DNA-dependent inflammation in microglia. Inhibiting KAT7 reduces β-amyloid accumulation, neuroinflammation, and cognitive deficits in Alzheimer’s mouse models, revealing a potential epigenetic target to counteract disease-associated inflammation.

Williams et al. report structures of the MMM complex, a membrane-spanning E3 ligase. A single α helix suspends an activated RING domain below the plasma membrane to ubiquitylate the GPCR Smoothened and attenuate Hedgehog signaling. This work establishes a structural and mechanistic blueprint for how transmembrane E3s search and destroy key receptors in development, immunity, and metabolism.

The roles of water molecules in transcription have long been overlooked due to resolution limitations. Li et al. resolve high-resolution cryo-EM structures of RNA polymerase II and visualize previously undetected water molecules. These waters play essential roles in RNA polymerase II catalysis and in mediating interactions within the transcription machinery.

The axon initial segment was known to receive GABAergic synaptic inputs. Yang et al. show that it can be excited directly via specialized ‘axonic spines’. These spines thus boost neuronal firing and a...