Search

Drugs of abuse exert both motivational and emotional effects. Here, the authors show that nicotine and ethanol activate a VTA–NAc loop that inhibits dopamine neurons projecting to the amygdala, thereby inducing anxiety-like behavior and linking the reward and emotional circuits.

A set of neurons in the peri-locus coeruleus region controls arousal and avoidance states, providing an understanding of the neurobiological basis of arousal and exploratory behaviours.

Single-cell transcriptomics and protein expression analyses of salivary glands and gingiva, along with the detection of infectious virus and virus-specific antibodies in saliva from SARS-CoV-2-infected individuals, support a potential role for the oral cavity in COVID-19 pathogenesis.

How NRXN1 variants affect multiple neuropsychiatric disorders is explored.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Upon stimulation of receptors, NAADP is formed as calcium-mobilizing second messenger in many cells. Here, the authors develop MASTER-NAADP, a membrane-permeant precursor of NAADP, and characterize its biological activity.

In mice, learning and performance on an auditory task is driven by higher-order signals in the auditory cortex that are no longer required when the mouse has achieved expert-level performance.

Innovative technology is being used to unlock the world of precision medicine — but experts warn clinicians to tread lightly.

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.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The antidepressant vortioxetine affects rodent and human 5-HT₃ receptors differently. López-Sánchez et al. use a variety of methods, including structure determination of vortioxetine-bound human and mouse 5-HT₃ receptors, to reveal the basis of these differences.

Single-cell intracellular recordings have been used as the primary tool for estimating driving forces across inhibitory receptors within the nervous system. Here, the authors present ORCHID as an all-optical method to measure inhibitory receptor driving forces in targeted brain cell types.

Axons have always been assumed to be cylindrical. Using in silico modeling and cryopreservation of tissues, Griswold et al. demonstrate that unmyelinated axons of the mammalian central nervous system exhibit pearls-on-a-string morphology through their entire length.

Vast networks of capillaries feed the brain. Hartmann et al. show that pericyte contractility is critical for maintenance of enduring capillary tone, which sets an optimized rate and distribution of blood flow through brain capillary networks.

The reason why manipulating dopamine (DA) activity can affect both action latency, action direction, and movement vigor, but only in certain animal states and behavioral settings is not fully understood. Here, the authors propose that DA signaling builds and reveals latent attractors representing potential goals. They validate their model predictions: activation of dopamine neurons exerts context- and state-dependent effects on mouse movements.

The median eminence (ME) at the base of the brain controls body homeostasis. Here, the authors describe a functional tanycyte subpopulation at the ME which tastes the surrounding milieu, responds to metabolic signals and regulates glucose homeostasis.

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.

GnRH neurons control their own connectivity and function as well as the sexual maturation of the individual by using prostaglandin D₂ DP1 signaling to recruit and stably associate with newborn astrocytes in the preoptic region during infancy in rodents.

Warner et al. analyze tumor tissue and ctDNA from patients with de novo metastatic castrate-sensitive prostate cancer and find high intratumoral heterogeneity, suggesting that genomic profiling of multiple samples per patient is needed for accurate outcome prediction.

Andre Berndt and colleagues introduce a machine learning approach to enhance the biophysical characteristics of genetically encoded fluorescent indicators, deriving and testing in vitro new GCaMP mutations that surpass the performance of existing fast GCaMP indicators.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

During brain development, neuronal excitability controls the laminar migration of cortical interneurons from the caudal ganglionic eminences (CGEs). Here the authors identify the 5-HT_3Areceptor as a specific marker of CGE-derived cortical interneurons (cINs), and as a stimulator of cIN migration.

Experiments in human cortical organoid and mouse models of SYNGAP1 haploinsufficiency, which is associated with autism spectrum disorder (ASD), reveal altered cortical neurogenesis, suggesting that a non-synaptic mechanism contributes to the disorder.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Zhu et al. found that cholinergic signals from the basal forebrain relay auditory information to the auditory cortex. These signals are modulated by brain and behavioral states and provide repeated auditory representations across the cortical tonotopy.

While depression and chronic pain are frequently comorbid, underlying neuronal circuits and their psychopathological relevance remain poorly defined. Here, authors show the critical role of the BLA-ACC pathway in pain and emotional processing, and their comorbidity.

A new cluster randomized controlled trial conducted in 13 American states demonstrates that a social media advertising campaign using videos of healthcare professionals to encourage users to stay at home over the holiday season was effective in reducing travel and subsequent spread of COVID-19.

To model hepatocyte function accurately in vitro, it is necessary to generate and maintain a polarized epithelium. Here, the authors describe a protocol to generate polarized human pluripotent stem cell-derived hepatocyte-like cells (HLCs) to model enteric virus production and drug secretion in vitro.

Here, Easter et al. generate a single-cell atlas of human periodontium including sulcular and junctional keratinocytes. Cell-cell communication analysis is used to predict keratinocyte-specific immune cell interactions.

Chronic nicotine exposure impacts various components of decision-making processes, such as exploratory behaviors. Here, the authors identify the cellular mechanism and show that chronic nicotine exposure increases the tonic activity of VTA dopaminergic neurons and reduces exploration in mice.

Altering the community of bacteria that live in the gut might help infants to thrive or even avoid conditions such as asthma and diabetes.

A new protocol describes the synthesis and application of single-walled carbon nanotube-based catecholamine nanosensors, which can be used for near-IR imaging of dopamine signaling in acute brain slices at high spatiotemporal resolution.

Type VI secretion systems (T6SSs) are used by bacteria to inject toxic effector proteins into neighbouring cells. Here, Mariano et al. show that an antibacterial effector from Serratia marcescens forms cation-selective pores that lead to inner-membrane depolarisation and increased outer-membrane permeability.

Here, in a cohort of mother-child dyads, the authors show that maternal prenatal social disadvantage and psychosocial stressors associate with distinct gut microbiome taxonomic and functional diversity in both the mothers and their four-month children.

The lateral entorhinal cortex computes and transfers olfactory information from the olfactory bulb to the hippocampus and supports associative multimodal memories. Leitner et al. characterize the activity of odor-responsive cell types in this brain area and identify upstream and downstream brain areas to which olfactory information is conveyed.

Migrating cells display dynamic morphologies that are coordinated by signalling pathways. Here the authors identify a lateral signalling pathway, comprised of the planar cell polarity protein Pk1 and Arhgap21/23, that regulates fluctuations in cell shape during productive cell migration.

Synaptic vesicle fusion involves a multi-protein assembly called the SNARE complex that is tightly regulated both spatially and temporally. Here Kavanagh et al. show that after vesicle fusion and SNARE complex disassembly in the synapse, the SNARE protein syntaxin1a is sequestered in a monomeric form by munc18-1, preventing ectopic SNARE complex assembly.

Statin therapy is associated with numerous cellular effects. Here, the authors show that statin treatment increases post-translational modifications on fatty acid synthase in the active site, revealing communication between the cholesterol and lipid biosynthetic pathways.

Huntington disease (HD) is considered to be a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, enabling the entire disease course to be studied. Ross et al. describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments. Building on this information, they review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials.