ErbB4+ spinal cord dorsal horn neurons process heat pain.

How the spinal cord transmits heat signals from the periphery to the brain remains unclear. In this issue of Neuron, Wang et al. (2022) identify a population of spinal cord neurons functioning in this pathway.

Glutamate in primary afferents is required for itch transmission.

Whether glutamate or itch-selective neurotransmitters are used to confer itch specificity is still under debate. We focused on an itch-selective population of primary afferents expressing MRGPRA3, which highly expresses Vglut2 and the neuropeptide neuromedin B (Nmb), to investigate this question. Optogenetic stimulation of MRGPRA3+ afferents triggers scratching and other itch-related avoidance behaviors. Using a combination of optogenetics, spinal cord slice recordings, Vglut2 conditional knockout mice, and behavior assays, we showed that glutamate is essential for MRGPRA3+ afferents to transmit itch. We further demonstrated that MRGPRA3+ afferents form monosynaptic connections with both NMBR+ and NMBR- neurons and that NMB and glutamate together can enhance the activity of NMBR+ spinal DH neurons. Moreover, Nmb in MRGPRA3+ afferents and NMBR+ DH neurons are required for chloroquine-induced scratching. Together, our results establish a new model in which glutamate is an essential neurotransmitter in primary afferents for itch transmission, whereas NMB signaling enhances its activities.

Ventral striatal islands of Calleja neurons control grooming in mice.

The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely packed granule cells situated in the ventral striatum, predominantly in the olfactory tubercle (OT). Characterized by expression of the D3 dopamine receptor, the IC are evolutionally conserved, but have undefined functions. Here, we show that optogenetic activation of OT D3 neurons robustly initiates self-grooming in mice while suppressing other ongoing behaviors. Conversely, optogenetic inhibition of these neurons halts ongoing grooming, and genetic ablation reduces spontaneous grooming. Furthermore, OT D3 neurons show increased activity before and during grooming and influence local striatal output via synaptic connections with neighboring OT neurons (primarily spiny projection neurons), whose firing rates display grooming-related modulation. Our study uncovers a new role of the ventral striatum's IC in regulating motor output and has important implications for the neural control of grooming.

The development of somatosensory neurons: Insights into pain and itch.

Primary nociceptors are a heterogeneous class of peripheral somatosensory neurons, responsible for detecting noxious, pruriceptive, and thermal stimuli. These neurons are further divided into several molecularly defined subtypes that correlate with their functional sensory modalities and morphological features. During development, all nociceptors arise from a common pool of embryonic precursors, and then segregate progressively into their mature specialized phenotypes. In this review, we summarize the intrinsic transcriptional programs and extrinsic trophic factor signaling mechanisms that interact to control nociceptor diversification. We also discuss how recent transcriptome profiling studies have significantly advanced the field of sensory neuron development.