Inferring pattern-driving intercellular flows from single-cell and spatial transcriptomics.

From single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST), one can extract high-dimensional gene expression patterns that can be described by intercellular communication networks or decoupled gene modules. These two descriptions of information flow are often assumed to occur independently. However, intercellular communication drives directed flows of information that are mediated by intracellular gene modules, in turn triggering outflows of other signals.

Modulation of sleep/wake patterns by gephyrin phosphorylation status.

Sleep/wake cycles intricately shape physiological activities including cognitive brain functions, yet the precise molecular orchestrators of sleep remain elusive. Notably, the clinical impact of benzodiazepine drugs underscores the pivotal role of GABAergic neurotransmission in sleep regulation. However, the specific contributions of distinct GABA receptor subtypes and their principal scaffolding protein, gephyrin, in sleep dynamics remain unclear.

The gephyrin scaffold modulates cortical layer 2/3 pyramidal neuron responsiveness to single whisker stimulation.

Gephyrin is the main scaffolding protein at inhibitory postsynaptic sites, and its clusters are the signaling hubs where several molecular pathways converge. Post-translational modifications (PTMs) of gephyrin alter GABA receptor clustering at the synapse, but it is unclear how this affects neuronal activity at the circuit level. We assessed the contribution of gephyrin PTMs to microcircuit activity in the mouse barrel cortex by slice electrophysiology and in vivo two-photon calcium imaging of layer 2/3 (L2/3) pyramidal cells during single-whisker stimulation.

Brain organoid-on-a-chip to create multiple domains in forebrain organoids.

Brain organoids are three-dimensionally reconstructed brain tissue derived from pluripotent stem cells in vitro. 3D tissue cultures have opened new avenues for exploring development and disease modeling. However, some physiological conditions, including signaling gradients in 3D cultures, have not yet been easily achieved.

Adamtsl3 mediates DCC signaling to selectively promote GABAergic synapse function.

The molecular code that controls synapse formation and maintenance in vivo has remained quite sparse. Here, we identify that the secreted protein Adamtsl3 functions as critical hippocampal synapse organizer acting through the transmembrane receptor DCC (deleted in colorectal cancer). Traditionally, DCC function has been associated with glutamatergic synaptogenesis and plasticity in response to Netrin-1 signaling.

Suprachiasmatic to paraventricular nuclei interaction generates normal food searching rhythms in mice.

Searching for food follows a well-organized decision process in mammals to take up food only if necessary. Moreover, scavenging is preferred during their activity phase. Various time-dependent regulatory processes have been identified originating from the suprachiasmatic nuclei (SCN), which convert external light information into synchronizing output signals.

A genetically encoded sensor for in vivo imaging of orexin neuropeptides.

Orexins (also called hypocretins) are hypothalamic neuropeptides that carry out essential functions in the central nervous system; however, little is known about their release and range of action in vivo owing to the limited resolution of current detection technologies. Here we developed a genetically encoded orexin sensor (OxLight1) based on the engineering of circularly permutated green fluorescent protein into the human type-2 orexin receptor. In mice OxLight1 detects optogenetically evoked release of endogenous orexins in vivo with high sensitivity.

The behavioural response of mice lacking NK₁ receptors to guanfacine resembles its clinical profile in treatment of ADHD.

Background And Purpose: Mice with functional ablation of substance P-preferring neurokinin-1 receptors (NK1R-/- mice) display behavioural abnormalities resembling those in attention deficit hyperactivity disorder (ADHD). Here, we investigated whether the ADHD treatment, guanfacine, alleviated the hyperactivity and impulsivity/inattention displayed by NK1R-/- mice in the light/dark exploration box (LDEB) and 5-choice serial reaction-time task (5-CSRTT), respectively. Following reports of co-morbid anxiety in ADHD, we also investigated effects of guanfacine on anxiety-like behaviour displayed by NK1R-/- and wild-type (WT) mice in the elevated plus maze (EPM).