American scientists conducted a series of experiments and discovered that low-threshold mechanoreceptors with unmyelinated C-fibers are responsible for shaking mammals (such as dogs) after their fur gets wet. These fibers are activated when water or oil, for example, hits the receptors, and the signal is then transmitted to the parabrachial nucleus of the pons, which triggers rapid body movements. The results were published in the journal Science.
Shaking is an evolutionarily conserved behavior, widespread in furred mammals. It consists of rapid shaking of the head and upper body after water or other irritants are applied to the skin of the back. Despite the prevalence of this behavior, the neurobiological mechanisms underlying it remain largely unexplored.
Mammalian skin is innervated by more than 12 physiologically and morphologically distinct subtypes of primary somatosensory neurons. These cutaneous sensory neurons collectively detect and encode a range of environmental stimuli, with individual subtypes exhibiting distinct stimulus response profiles. Even simple mechanical stimuli (such as stroking the skin) can activate multiple subtypes of mechanosensory receptors with distinct response properties. The question of how stimuli encoded as somatosensory signals are converted into motor commands in the central nervous system remains open.
To address this issue, a research team led by David Ginty of Harvard Medical School conducted a series of genetic, physiological, and behavioral tests on mice, as shaking is common across all mammalian species in response to various stimuli. The scientists used a drop of oil as the primary stimulus due to its reliability, ease of application, and precise spatiotemporal control. Mice were more sensitive to oil drops applied to the back of the neck and exhibited greater shaking and scratching behavior compared to oil drops applied to the lower back. This behavior may reflect a response to mechanical or thermal stimuli.
To test the extent to which mechanosensory receptors might be responsible for the observed behavior, the scientists removed the mechanosensitive ion channel Piezo2 from all neurons in the dorsal root ganglion located beneath the upper cervical spine of mice. After this, mice without the ion channel did not shake when a drop of oil or water was applied, but cold stimuli still triggered shaking.
The researchers then sought to identify the primary mechanosensory neurons responsible for triggering this response. Calcium imaging experiments in dorsal root ganglia revealed three low-threshold mechanoreceptor neurons, including neurons with low-threshold mechanoreceptors and unmyelinated C fibers (C-LTMRs). To determine whether stimulating just one of the low-threshold mechanoreceptors was sufficient, the scientists expressed a light-activated cation channel in these neurons. Optogenetic stimulation of the neurons revealed that it was the C-LTMRs that triggered shaking. Genetic ablation of the C-LTMRs resulted in reduced shaking activity.
The scientists then hypothesized that signals from the C-LTMR are transmitted from the superficial dorsal horn of the spinal cord to the lateral parabrachial nucleus in the pons via spinoparabrachial neurons. The researchers confirmed that optogenetic stimulation of the C-LTMR elicited a postsynaptic response in the spinoparabrachial neurons. Inhibition of these neurons resulted in the abolition of shaking. Optogenetic stimulation of the parabrachial nucleus also resulted in shaking in mice, while its inactivation resulted in a decrease in shaking activity.
According to Ginty's team, these results convincingly demonstrate a neurosensory pathway for the shake reflex. However, this pathway needs to be further confirmed in other mammals, and the neural networks of the parabrachial nucleus also need to be characterized.
You can read about the role the parabrachial nucleus plays in the development of itching in our blog. And you can learn about the different types of itching recognized by science in the article "Why It Itches."
