Convergence of type 1 spiral ganglion neuron subtypes onto principal neurons of the anteroventral cochlear nucleus.

The mammalian auditory system encodes sounds with subtypes of spiral ganglion neurons (SGNs) that differ in sound level sensitivity, permitting discrimination across a wide range of levels. Recent work suggests the physiologically-defined SGN subtypes correspond to at least three molecular subtypes. It is not known how information from the different subtypes converges within the cochlear nucleus.

Direct reprogramming of fibroblasts into spiral ganglion neurons by defined transcription factors.

Degeneration of the cochlear spiral ganglion neurons (SGNs) is one of the major causes of sensorineural hearing loss and significantly impacts the outcomes of cochlear implantation. Functional regeneration of SGNs holds great promise for treating sensorineural hearing loss. In this study, we systematically screened 33 transcriptional regulators implicated in neuronal and SGN fate.

Molecular signatures define subtypes of auditory afferents with distinct peripheral projection patterns and physiological properties.

Type I spiral ganglion neurons (SGNs) are the auditory afferents that transmit sound information from cochlear inner hair cells (IHCs) to the brainstem. These afferents consist of physiological subtypes that differ in their spontaneous firing rate (SR), activation threshold, and dynamic range and have been described as low, medium, and high SR fibers. Lately, single-cell RNA sequencing experiments have revealed three molecularly defined type I SGN subtypes.

Subtype maturation of spiral ganglion neurons.

Purpose Of Review: We review recent progress in the characterization of spiral ganglion neurons (SGNs), the afferent neurons that transmit sound information from mechanosensory hair cells in the inner ear to the central nervous system.

Recent Findings: Single-cell ribonucleic acid sequencing studies of murine SGNs have demonstrated that SGNs consist of molecularly distinct subtypes. The molecularly defined SGN subtypes likely correspond to SGN subtypes previously identified on the basis of physiological properties, although this has not been experimentally demonstrated.

Hair Cell Mechanotransduction Regulates Spontaneous Activity and Spiral Ganglion Subtype Specification in the Auditory System.

Type I spiral ganglion neurons (SGNs) transmit sound information from cochlear hair cells to the CNS. Using transcriptome analysis of thousands of single neurons, we demonstrate that murine type I SGNs consist of subclasses that are defined by the expression of subsets of transcription factors, cell adhesion molecules, ion channels, and neurotransmitter receptors. Subtype specification is initiated prior to the onset of hearing during the time period when auditory circuits mature.

Leaky Gate Model: Intensity-Dependent Coding of Pain and Itch in the Spinal Cord.

Coding of itch versus pain has been heatedly debated for decades. However, the current coding theories (labeled line, intensity, and selectivity theory) cannot accommodate all experimental observations. Here we identified a subset of spinal interneurons, labeled by gastrin-releasing peptide (Grp), that receive direct synaptic input from both pain and itch primary sensory neurons.

Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain.

Human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain inhibition, mainly because of its restricted expression in nociceptors within the peripheral nervous system. However, constrained by species differences across , drug candidates that activate MRGPRX1 do not activate rodent receptors, leaving no responsive animal model to test the effect on pain in vivo. Here, we generated a transgenic mouse line in which we replaced mouse with human This humanized mouse allowed us to characterize an agonist [bovine adrenal medulla 8-22 (BAM8-22)] and a positive allosteric modulator (PAM), ML382, of MRGPRX1.

Trp channels and itch.

Itch is a unique sensation associated with the scratch reflex. Although the scratch reflex plays a protective role in daily life by removing irritants, chronic itch remains a clinical challenge. Despite urgent clinical need, itch has received relatively little research attention and its mechanisms have remained poorly understood until recently.

Redefining the concept of protease-activated receptors: cathepsin S evokes itch via activation of Mrgprs.

Sensory neurons expressing Mas-related G-protein-coupled receptors (Mrgprs) mediate histamine-independent itch. We show that the cysteine protease cathepsin S activates MrgprC11 and evokes receptor-dependent scratching in mice. In contrast to its activation of conventional protease-activated receptors, cathepsin S-mediated activation of MrgprC11 did not involve the generation of a tethered ligand.

Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain.

The peripheral terminals of primary nociceptive neurons play an essential role in pain detection mediated by membrane receptors like TRPV1, a molecular sensor of heat and capsaicin. However, the contribution of central terminal TRPV1 in the dorsal horn to chronic pain has not been investigated directly. Combining primary sensory neuron-specific GCaMP3 imaging with a trigeminal neuropathic pain model, we detected robust neuronal hyperactivity in injured and uninjured nerves in the skin, soma in trigeminal ganglion, and central terminals in the spinal trigeminal nucleus.

Mechanisms of itch evoked by β-alanine.

β-Alanine, a popular supplement for muscle building, induces itch and tingling after consumption, but the underlying molecular and neural mechanisms are obscure. Here we show that, in mice, β-alanine elicited itch-associated behavior that requires MrgprD, a G-protein-coupled receptor expressed by a subpopulation of primary sensory neurons. These neurons exclusively innervate the skin, respond to β-alanine, heat, and mechanical noxious stimuli but do not respond to histamine.