Individualistic reward-seeking strategies that predict response to nicotine emerge among isogenic male mice living in a micro-society.

Individual animals differ in their traits and preferences, which shape their social interactions, survival, and susceptibility to disease, including addiction. Nicotine use is highly heterogenous and has been linked to the expression of personality traits. Although these relationships are well documented, we have limited understanding of the neurophysiological mechanisms that give rise to distinct behavioral profiles and their connection to nicotine susceptibility.

Transient nicotine exposure in early adolescent male mice freezes their dopamine circuits in an immature state.

How nicotine acts on developing neurocircuitry in adolescence to promote later addiction vulnerability remains largely unknown, but may hold the key for informing more effective intervention efforts. We found transient nicotine exposure in early adolescent (PND 21-28) male mice was sufficient to produce a marked vulnerability to nicotine in adulthood (PND 60 + ), associated with disrupted functional connectivity in dopaminergic circuits. These mice showed persistent adolescent-like behavioral and physiological responses to nicotine, suggesting that nicotine exposure in adolescence prolongs an immature, imbalanced state in the function of these circuits.

Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment.

Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we use UK Biobank GWAS summary statistics of body mass index (BMI) and body fat percentage (BF%) to identify genes encoding proteins known to interact with postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and -methyl-d-aspartate (NMDA) receptors. Loci in/near discs large homolog 4 () and protein interacting with C kinase 1 () reached genome-wide significance ( < 5 × 10) for BF% and/or BMI.

Neural tube-associated boundary caps are a major source of mural cells in the skin.

In addition to their roles in protecting nerves and increasing conduction velocity, peripheral glia plays key functions in blood vessel development by secreting molecules governing arteries alignment and maturation with nerves. Here, we show in mice that a specific, nerve-attached cell population, derived from boundary caps (BCs), constitutes a major source of mural cells for the developing skin vasculature. Using Cre-based reporter cell tracing and single-cell transcriptomics, we show that BC derivatives migrate into the skin along the nerves, detach from them, and differentiate into pericytes and vascular smooth muscle cells.

Laminar organization of neocortical activities during systemic anoxia.

The neocortex is highly susceptible to metabolic dysfunction. When exposed to global ischemia or anoxia, it suffers a slowly propagating wave of collective neuronal depolarization that ultimately impairs its structure and function. While the molecular signature of anoxic depolarization (AD) is well documented, little is known about the brain states that precede and follow AD onset.

Pharmacological targeting of glutamatergic neurons within the brainstem for weight reduction.

Food intake and body weight are tightly regulated by neurons within specific brain regions, including the brainstem, where acute activation of dorsal raphe nucleus (DRN) glutamatergic neurons expressing the glutamate transporter Vglut3 (DRN) drive a robust suppression of food intake and enhance locomotion. Activating Vglut3 neurons in DRN suppresses food intake and increases locomotion, suggesting that modulating the activity of these neurons might alter body weight. Here, we show that DRN neurons project to the lateral hypothalamus (LHA), a canonical feeding center that also reduces food intake.

Edinger-Westphal peptidergic neurons enable maternal preparatory nesting.

Optimizing reproductive fitness in mammalians requires behavioral adaptations during pregnancy. Maternal preparatory nesting is an essential behavior for the survival of the upcoming litter. Brain-wide immediate early gene mapping in mice evoked by nesting sequences revealed that phases of nest construction strongly activate peptidergic neurons of the Edinger-Westphal nucleus in pregnant mice.

Mapping the Fine-Scale Organization and Plasticity of the Brain Vasculature.

The cerebral vasculature is a dense network of arteries, capillaries, and veins. Quantifying variations of the vascular organization across individuals, brain regions, or disease models is challenging. We used immunolabeling and tissue clearing to image the vascular network of adult mouse brains and developed a pipeline to segment terabyte-sized multichannel images from light sheet microscopy, enabling the construction, analysis, and visualization of vascular graphs composed of over 100 million vessel segments.

The mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue.

Light-sheet microscopy is an ideal technique for imaging large cleared samples; however, the community is still lacking instruments capable of producing volumetric images of centimeter-sized cleared samples with near-isotropic resolution within minutes. Here, we introduce the mesoscale selective plane-illumination microscopy initiative, an open-hardware project for building and operating a light-sheet microscope that addresses these challenges and is compatible with any type of cleared or expanded sample ( www.mesospim.

Regulation of Energy Expenditure by Brainstem GABA Neurons.

Homeostatic control of core body temperature is essential for survival. Temperature is sensed by specific neurons, in turn eliciting both behavioral (i.e.