Neuroscience

RNA abundance is a powerful indicator of the state of individual cells.

The mammalian nervous system executes complex behaviors controlled by specialized, precisely positioned, and interacting cell types. Here, we used RNA sequencing of half a million single cells to create a detailed census of cell types in the mouse nervous system. We mapped cell types spatially and derived a hierarchical, data-driven taxonomy. Neurons were the most diverse and were grouped by developmental anatomical units and by the expression of neurotransmitters and neuropeptides.

Stress adaptation is essential for neuronal health. While the fundamental role of mitochondria in neuronal development has been demonstrated, it is still not clear how adult neurons respond to alterations in mitochondrial function and how neurons sense, signal, and respond to dysfunction of mitochondria and their interacting organelles.

The latent sensitization model of chronic pain reveals that recovery from some types of long-term hyperalgesia is an altered state in which nociceptive sensitization persists but is suppressed by the ongoing activity of analgesic receptors such as μ-opioid receptors (MORs). To determine whether these MORs are the ones present in nociceptive afferents, we bred mice expressing Cre-recombinase under the Nav1.8 channel promoter (Nav1.8cre) with MOR-floxed mice (flMOR).

Shank2 is an abundant postsynaptic scaffolding protein implicated in neurodevelopmental and psychiatric disorders, including autism spectrum disorders (ASD).

Regulation of cerebral endothelial cell function plays an essential role in changes in blood-brain barrier permeability. Proteins that are important for establishment of endothelial tight junctions have emerged as critical molecules, and PDZ domain containing-molecules are among the most important. We have discovered that the PDZ-domain containing protein periaxin (PRX) is expressed in human cerebral endothelial cells.

In the auditory system, type I spiral ganglion neurons (SGNs) convey complex acoustic information from inner hair cells (IHCs) to the brainstem. Although SGNs exhibit variation in physiological and anatomical properties, it is unclear which features are endogenous and which reflect input from synaptic partners. Using single-cell RNA sequencing, we derived a molecular classification of mouse type I SGNs comprising three subtypes that express unique combinations of Ca 2+ binding proteins, ion channel regulators, guidance molecules, and transcription factors.

Hexanucleotide repeat expansion in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis, but the pathogenic mechanism of this mutation remains unresolved. Haploinsufficiency has been proposed as one potential mechanism.

The transcriptional programs that drive the generation of diverse GABAergic neuron populations from their common progenitor pools in the developing cerebellum remain unclear. Neurog1 is a pro-neural basic helix-loop-helix transcription factor expressed in GABAergic progenitor cells in the ventricular zone (VZ) of embryos and subsequently in the presumptive white matter (pWM) tracts of developing postnatal mice.

Orphan G-protein-coupled receptors (oGPCRs) possess untapped potential for drug discovery. In the brain, oGPCRs are generally expressed at low abundance and their function is understudied. Expression profiling is an essential step to position oGPCRs in brain function and disease, however public databases provide only partial information. Here, we fine-map expression of 78 brain-oGPCRs in the mouse, using customized probes in both standard and supersensitive in situ hybridization. Images are available at http://ogpcr-neuromap.douglas.qc.ca.