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Activity in a set of parabranchial neurons in the mouse brain is increased during chronic pain, predicts coping behaviour, and can be modulated by circuits activated by survival threats.

A fresh approach to protein design that incorporates excited intermediate states enables precise control over the lifetime of protein interactions, with potential applications in cell-signalling modulation and in biosensors and synthetic circuits.

This study reveals that graded expression of the transcription factor BRN3B fine-tunes the identity and function of melanopsin-expressing ipRGC subtypes in the retina. Altering BRN3B levels disrupts subtype-specific features and visual behaviour.

Mass spectrometry (MS) is a powerful tool for the structural characterization of protein complexes. Here the authors offer a path for direct integration of MS and electron microscopy with a MS approach that enables grid deposition and structural preservation of gaseous protein complex ions.

A mechanism of mechanosensation and transduction in the presynaptic boutons is identified, in which sensing of fine pressure leads to enhanced neurotransmitter release.

Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity drives proliferation of small lung cell cancer via paracrine interactions and through synapses formed with tumour cells.

This study shows that, rather than causing inhibition, axonal GABA_A receptors often facilitate sodium channel activation and prevent spike propagation failure at branch points of myelinated spinal cord sensory neuron axons.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

The roles of distinct dopaminergic neuron subpopulations and the circuit projections driving their activity during threat behaviors remain incompletely understood. Here, the authors demonstrate that substantia nigra pars lateralis dopamine neurons receive selective, robust excitation from auditory and temporal association cortices, which, combined with rapid action potential firing, contributes to auditory threat conditioning.

Single-cell transcriptomic analysis of mouse hypothalamus and behavioural experiments show that specific hypothalamic networks regulate conflicting feeding versus parenting behaviours of female mice.

The role of TRPV1 in the CNS is not fully understood. Here the authors show that TRPV1 is expressed specifically in somatostatin-positive OLM interneurons of the hippocampus, where it promotes excitatory innervation of these cells.

In conical nanopores, the transient current generated by disturbing the ionic flux equilibrium is slow to respond to changes in the ionic state due to Warburg-like impedance, producing ‘ionic filters’ and negative capacitance with memory.

Across species, how aging leads to progressive spatial memory decline is not fully understood. This study reports dysfunctional spatial coding by aged entorhinal grid cells and networks related to impaired spatial memory and identifies implicated neuronal gene expression changes.

Intracellular, intercellular and extracellular silicon interfaces enable light-controlled non-genetic modulation of intracellular calcium dynamics, of cellular excitability, of neurotransmitter release from brain slices, and of brain activity in vivo.

Many animals, including mammals and insects, like slightly acidic yet dislike highly acidic foods, but how animals discriminate low from high acidity is unclear. Here the authors demonstrate that the fruit fly uses an evolutionarily conserved taste receptor to distinguish low from high concentrations of acid.

Controlling the crystallographic registry of layered materials through interlayer twist angles has introduced a distinctive degree of freedom for tuning their electronic behaviour. Now, the interfacial electrochemical kinetics of solution-phase redox complexes at twisted bilayer graphene electrodes have been modulated by the angle-dependent tuning of moiré-derived flat bands.

Using their unique bioadhesives, barnacles can adhere to a great variety of surfaces. Here, Gohad et al.show that the barnacle larval bioadhesive contains lipids and phosphoproteins that are organized in a complex structure and work together to maximize adhesion.

The accessory β2 subunit was proposed to inactivate BK channels via the ball-and-chain model, but structural evidence was missing. Here, using cryo-EM, the authors captured the occlusion of the BK channel pore by the N-terminus of the β2 subunit.

Traditional systematic anti-seizure treatments alter brain-wide activity and often carry significant side effects. The authors engineered an inhibitory, acetylcholine receptor-based, chemogenetic tool to suppress targeted neurons, enabling control of chronic seizures in mice.

A connectome analysis identifies, and experiments confirm, three state-dependent circuit motifs that modify the response of an aggressive female Drosophila or a courting male to fly-sized visual objects.

G-protein-gated inward rectifying potassium channels (GIRKs) require G_βγ subunits and phosphorylated phosphatidylinositides (PIPs) for gating. Here authors use native ion mobility mass spectrometry to monitor small molecule binding events to GIRK2 and shed light on the selectivity of GIRK2 towards PIPs.

Juvenile male zebra finches learn their songs from adult male tutors, but the role of females in this process is less clear. Here the authors show that the presence of adult females enhances song imitation in young males, with female calls influencing both the behavior and neural activity linked to vocal learning.

Psychophysical studies predict that retinal cone-opponent mechanisms interact in specific combinations to generate color perception. Here, the authors show that the predicted interactions are implemented by organized circuits in primary visual cortex.

Chopra and colleagues show that the hormone asprosin, independent of its effects on hypothalamic AgRP neurons, activates its cell surface receptor Ptprd on cerebellar Purkinje neurons to enhance thirst for maintenance of fluid homeostasis.

A disease model using cardiomyocytes derived from induced pluripotent stem cells of patients with mutated LMNA-related dilated cardiomyopathy reveals that the abnormal activation of the PDGF pathway is associated with the arrhythmic phenotypes of patients.

Specific ssDNA binding proteins promote the annealing of complementary strands. Here the authors reveal an intermediate of annealing in which a duplex DNA is bound in an unusual conformation that is highly extended and unwound for the ssDNA binding protein Redβ from bacteriophage λ.

Although cortical GABAergic interneuron (CIN) dysfunction is implicated in several neuropsychiatric disorders, we still know very little about how they attain their unique properties or how their dysfunction impacts neuropsychiatric disorders. In this study, authors show that conditional loss of Tsc1, causes SST+ CINs, which are distinct from PV+ CINs, to express PV and adopt fast-spiking properties, via MTOR activity

Kodo et al. show that patient-specific iPSC-derived cardiomyocytes recapitulate the proliferative defects associated with the disease, which are a result of TBX20 mutations and abnormal TGF-β signalling.

Adapter proteins assist clathrin coated pit assembly. Here, the authors combine native mass spectrometry, crystallography and SAXS measurements and show that the membrane–proximal domains of the adaptor proteins epsin and Sla2 form complexes mediated through phosphatidylinositol 4,5-bisphosphate interfaces leading to assembly formation.

The authors show that mitochondria can chronically hyperpolarize under normal or disease conditions and be induced by environmental exposures. This triggers phospholipid remodeling, which in turn affects the epigenome to regulate transcription.

The role of astrocyte NMDA receptor signaling in cortical circuits is unclear. Here, the authors show that NMDA receptors contribute to astrocyte calcium events and support neuronal processing of sensory information that maintains sensory activity in mice.

BATTLES enables high-throughput analysis of TCR–pMHC interactions in a physiological force-dependent manner.

PXo bodies, non-canonical multilamellar organelles, serve as a reservoir for intracellular inorganic phosphate and are a critical regulator of both cytosolic phosphate levels and tissue homeostasis.

Reliable measuring the voltage dynamics of individual neurons in the intact brain is significantly challenging. Here authors developed an all-optical method combining two-photon voltage imaging and optogenetics to measure and induce synaptic plasticity in vivo, revealing LTP of inhibition in cerebellar circuits and providing a blueprint to link synaptic changes to learning.

Visceral pain and anxiety in mice are found to be associated with gut enterochromaffin cells, and genetic models for eliciting visceral hypersensitivity and studying the sex bias of gut pain are proposed.

16p11.2 CNVs are associated with neurodevelopmental disorders. Here, the authors show that 16p11.2 deletion is associated with hyperactivation of human iPSC-derived dopaminergic neuron networks and is rescued by RHOA inhibition in vitro.

Neural probes mimicking the size and mechanical properties of neurons interpenetrate the brain tissue, allowing stable single-unit recordings from implantation up to at least three months, and acting as scaffolds for the migration of new-born neurons.

Mesoaccumbal terminals within the VTA are known to co-release both GABA and dopamine, although the functional role of the former has yet to be determined. Here, the authors find that non-canonical GABA release is regulated by the E3-ubiquitin ligase, UBE3A, and enhances optogenetic self-stimulation.

The essential role of ORAI1 channels in receptor-evoked Ca²⁺ signaling is well understood, but the roles of ORAI2 and ORAI3 remained obscure. Here authors show that ORAI2 and ORAI3 channels multimerize with ORAI1 to expand the range of sensitivity of receptor-activated Ca²⁺ signals, reflecting their enhanced basal STIM1-binding and heightened Ca²⁺-dependent inactivation.

The Cousa objective is an ultra-long working distance air objective optimized for two- and three-photon imaging. Bypassing challenges caused by water immersion and short working distances, the Cousa enables and improves imaging of diverse specimens.

How systemic inflammation impairs brain functions remains elusive. Here, the authors identified adenosine as an immune signal mediator that was rapidly increased in the blood and brain in sepsis, triggering astrocytic adenosine A1 receptors to exacerbate brain dysfunction.

A cell-surface fragment complementation strategy is used to identify the proteome at the junction of astrocytes and synapses in vivo, and shows that NRCAM expressed in astrocytes has a key role in regulating inhibitory synapse function.

This protocol describes how to fabricate and apply silicon-based structures for optically controlled neuromodulation. The structures can be used for nongenetic neuronal excitation in cultured neurons, brain slices, and in vivo applications.

The authors show human embryo lineage specification in the blastocyst is driven by differential FGF/ERK signaling, which segregates yolk sac-fated hypoblast and embryonic epiblast. They establish naïve embryonic stem cells based on these insights.

The ASAP4 family of genetically encoded voltage indicators allows recording of action potentials and subthreshold activity with either one- or two-photon microscopy over extended periods of time.

Discovering that nociceptive sensory neurons express the receptor for anthrax toxin, Yang et al. show that anthrax toxin can induce potent analgesia in mice and facilitate the delivery of potentially analgesic cargo proteins into nociceptive neurons.

This paper describes a single-vector strategy for flexible intersectional expression of genetically encoded reporters and tools in precisely defined cell types in the mouse.

BRCA2 plays a central role in facilitating DNA repair by homologous recombination (HR). Here the authors describe how BRCA2 forms a complex with the protein phosphatase PP2A-B56 in response to DNA damage, which is required for HR.