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Jung et al. show that shelter experience boosts dopamine release in the nucleus accumbens, generating a goal-location memory. Reactivating a neuronal ensemble developed from shelter experience enables memory-guided navigation to the goal during escape.

In this study using an adult-onset mouse model of Alzheimer’s pathology, we uncovered a neuron-type-specific mechanism responsible for region-specific circuit dysfunction. Short-term expression of human amyloid precursor protein (hAPP) led to hyperexcitability in the entorhinal cortex, but not in isocortex, due to a distinct vulnerability of PV interneurons in the entorhinal region.

Neurons in the dorsal motor nucleus of vagus are involved in the absorption of fat in the intestine, and the natural compound puerarin shows utility in modulating this brain–gut axis to reduce fat absorption.

Long-chain acyl-Coenzyme-A is a metabolic intermediate with important signaling functions. Here the authors show that it activates the Ca²⁺ selective ion channels TRPV5 and TRPV6 and elucidate the structural basis of TRPV5 activation using CryoEM.

This study reveals neuronal targets of Lac-Phe in the hypothalamus that mediate its suppression of food intake.

One challenge in drug screening for neurological disorders is how to accurately capture disease pathology and side effects. Here, the authors developed a multi-channel recording platform based on a zebrafish genetic model of epilepsy to screen for antiepileptic drugs.

Men are often more willing to compete compared to women, which may contribute to gender differences in wages and career advancement. Here, the authors show that ‘power priming’ - encouraging people to imagine themselves in a situation of power - can close the gender gap in competitiveness.

Na_V1.3 is involved in neuronal development, hormone secretion and pain perception. Here, the authors elucidate the molecular mechanism for modulation of Na_V1.3 by a site-2 neurotoxin bulleyaconitine A and a subtype selective antagonist ICA121431.

Seegren et al. demonstrate that the mitochondrial calcium uptake complex is a key molecular apparatus that links age-related changes in mitochondrial physiology to systemic macrophage-mediated age-associated inflammation.

The orphan enzyme phosphotriesterase-related (PTER) is identified as a mammalian N-acetyltaurine hydrolase that has roles in regulating body weight and energy balance.

Chen et al. show that transitions to innate behaviors, such as feeding and social interaction, rely on their encoding during beta oscillations by neuron populations in the lateral hypothalamus, coordinated with the medial prefrontal cortex and ventral tegmental area.

Gouwens et al. established a morpho-electrical taxonomy of cell types for the mouse visual cortex via unsupervised clustering analysis of multiple quantitative features from 1,938 neurons available online at the Allen Cell Types Database.

Generating and characterizing human telencephalic brain organoids from stem cell-derived single neural rosettes for studying the specification and organization of different neural cells, as well as modeling of neurodevelopmental disorders.

We have limited knowledge of how aging affects brain vascular structure and function. Here, the authors show that aging induces selective reduction of vasculature and related cell types in key cognitive brain areas and reduces blood oxygenation.

pH sensation is critical for survival of vertebrates. Here, authors found six vertebrate OTOP1 channels that were highly conserved and directly activated by extracellular alkali. Key mutations of OTOP1 reduced alkali affinity without affecting acid activation.

The P2X₇ receptor is an ATP-gated ion channel that mediates inflammasome activation. Here, authors report the structure of P2X₇ bound to high-affinity agonist, BzATP, providing a framework to develop small molecules applicable to cancer biology.

Light-driven sodium-pumping rhodopsins are unique ion transporters. Here, authors present a characterization of such rhodopsins with a modified active center allowing for efficient sodium transport under various environmental conditions.

TPC2 is a lysosomal ion channel permeable to both calcium and sodium ions. Here, the authors show that TPC2 can selectively increase its calcium permeability when simultaneously challenged by both its natural activators- NAADP and PI(3,5)P₂.

Fan et al. report a potent and subtype-selective TRPV3 antagonist, Trpvicin, and reveal its binding sites and mode of action for TRPV3 inhibition via high-resolution cryogenic electron microscopy structures.

Perineuronal nets stabilize synapses inhibiting synaptic plasticity. Here, the authors show that perineuronal nets act as a diffusion barrier facilitating astrocytic clearance of synaptically released ions and neurotransmitters.

Studying GnRH neuroendocrine cells in the mouse olfactory bulb (GnRH^OB neurons), Decoster et al. show that these cells respond to female odors and their activation regulates males’ female-odor preference and mating behavior.

The P2X1 receptor is an ATP-gated ion channel that is a target for anti-platelet therapy. Here, authors resolve cryo-EM structures of human P2X1 in multiple states, revealing subtype-specific features and supramolecular competitive antagonism.

Human Eag2 is a voltage-gated potassium channel with unique delayed rectifying gating kinetics. Here, authors show how voltage opens the channel and illuminate a mechanism of delayed rectifier gating.

Copy number alterations in stem cells impair neural crest differentiation and set the stage for neuroblastoma-like traits and tumours. This study hints at early tumourigenesis mechanisms and finds developmental gene signatures linked to prognosis.

Synaptic exocytosis depends on formation of the SNARE complex but its assembly mechanism is still under debate. Here, the authors identify an interaction between Munc13-1 and synaptobrevin-2 that is critical for the transition of the Munc18-1/syntaxin-1 complex to the SNARE complex.

PdCO is a switchable optogenetic tool for inhibiting synaptic transmission in neuronal terminals in vivo, as demonstrated in a variety of contexts mainly in the mouse.

In mouse brain, neurotensin released into the basolateral amygdala by neurons in the paraventricular nucleus of the thalamus assigns positive or negative valence during associative learning.

Cell and tissue polarity mechanisms organize functional domains at the surface of many cells. Here, authors reveal that a Wnt-Ror-Dvl signalling cascade forms planar-polarized membrane compartments in C. elegans muscle cells.

Georgiou et al. found that the sex of the person performing experiments affects mouse behavior, including responses to stress and ketamine. This effect was mediated by corticotropin-releasing factor neurons in the entorhinal cortex that project to CA1.

The voltage-gated sodium channel Na_V1.7 plays essential roles in pain sensation. The authors report cryo-EM structures of Na_V1.7 in complexes with three pore blockers, elucidating distinct mechanisms of action of their modulation on Na_V1.7.

Using two-photon (2P) optogenetics and computational modeling, the authors find that neither space-based nor feature-based rules are sufficient to describe cell–cell interactions within the primary visual cortex (V1). Instead, models must include interactions between these cardinal axes.

The degradation of inner autophagosomal membranes remains poorly understood. Here, Makar et al. show that RNAseK is involved in a lysosomal hydrolase delivery pathway that contributes to autophagosomal membrane degradation.

Ouzounov et al. report calcium imaging with three-photon microscopy in the mouse brain. The approach enabled noninvasive recording of activity with high spatial and temporal resolution from GCaMP6-labeled neurons located as deep as the hippocampus.

Ancient Mars may have had an active sulfur cycle. In situ analyses by the Curiosity rover reveal large variations in the current sulfur isotopic composition of Martian sediments that can be explained by geologic and atmospheric processes.

Brain region-specific oligodendrocyte population dynamics are unclear. Here the authors implement long-term in vivo three-photon imaging to determine those dynamics in the cortical and subcortical areas in the living intact and demyelinated adult mouse brain.

In mice, a population of astrocytes in the central striatum, characterized by expression of μ-crystallin, has a role in perseveration phenotypes that are often associated with human neuropsychiatric disorders.

In this work, the authors investigated on the interaction of biomolecular condensates with membranes and report that they can exhibit two wetting transitions modulated by membrane or milieu composition. Condensate adhesion can trigger intriguing ruffling of the membrane interface into complex finger-like structures.

The mechanisms underlying the zebrafish spinal cord’s impressive innate ability to regenerate after traumatic insults remain largely unknown. Here, the authors show that spinal neurons enact an essential neuron-to-neuron neuroprotective strategy to safeguard cell survival and support the zebrafish’s regeneration process.

The nucleus connects to the actin cytoskeleton for nuclear movement in migrating cells. Here, the authors show that the endoplasmic reticulum shields actin cables to generate asymmetric nucleo-cytoskeleton connections for nuclear positioning.

How do cells regulate their migration speed and direction? Here, authors discover that keratocyte cells can reversibly switch between different migration modes, by changing the 3D lamellipodium shape and intracellular diffusion.

This study presents an extensive molecular characterization of the reprograming process by analysis of transcriptomic, epigenomic and proteomic data sets describing the routes to pluripotency; it finds distinct routes towards two stable pluripotent states characterized by distinct epigenetic events.

Mammalians rely on brown adipocytes to generate heat under cold exposure, this thermogenic function requires dynamic remodeling of the mitochondria. Here the authors identify a protein called FAM210A as a key regulator of cold-induced mitochondrial remodeling in brown adipocytes.

Emission levels useful for applications from upconversion nanoparticles require high laser irradiance. Here, Liang et al. exploit the superlensing effect from dielectric microbeads to enhance the luminescence efficiency of upconversion nanoparticles and show its application for optogenetics.

The Ca_V2.3 channel is involved in synaptic plasticity and neurological disorders. Here, authors resolve the human Ca_V2.3 structure to explore functional heterogeneity of VSDs and elucidated the closed- and open-state inactivation mechanisms of the channel.

A method for measuring oxygen abundances using optical and far-infrared emission lines provides absolute metallicities of the interstellar gas in Markarian 71 and could be applied across cosmic history.

Autophagy is essential for cellular homeostasis which decreases with age. Here, the authors identify aging-induced reduction of DHHC5-mediated beclin 1 palmitoylation as an underlying mechanism by which aging induces autophagy decline in the brain.

The TRPV3 ion channel has been reported to contribute to thermosensation. Here, the authors use electrophysiology and a thermal gradient ring method to show a transmembrane protein TMEM79 negatively regulates TRPV3-mediate currents and changed thermal preference.

A light-activated chloride pump that occurs naturally in bacteria can be transfected into neurons, thereby permitting inhibition of neural activity on a millisecond timescale. This complements an existing tool for activating neurons through a photoactivatable algal channel.

The neural basis underlying fear of heights is not well understood. Here the authors identify, in mice, a subcortical route for innate fear of heights, bypassing the primary visual cortex.