American scientists conducted a series of experiments and found that low-threshold mechanoreceptors with unmyelinated C-fibers are responsible for shaking mammals (for example, dogs) after their fur gets wet. These fibers are activated when, for example, water or oil hits the receptors, and then the signal from them is transmitted to the parabrachial nucleus of the pons, which triggers rapid body movements. The results are published in the journal Science.
Shaking is an evolutionarily conserved behavior common in furred mammals. It consists of rapid head and upper body shaking after exposure to water and other irritants on the skin of the back. Despite the prevalence of this behavior, the neurobiological mechanisms underlying it remain largely unknown.
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 (e.g., stroking the skin) can activate multiple mechanosensory receptor subtypes with different response properties. And how stimulus input encoded into somatosensory signals is translated into motor commands in the central nervous system remains an open question.
To investigate this issue, a research team led by David Ginty of Harvard Medical School conducted a series of genetic, physiological, and behavioral tests on mice, since shaking is common across mammalian species in response to a variety of stimuli. The scientists used a drop of oil as the primary stimulus because of its reliability, ease of application, and precise spatiotemporal control. Mice were more sensitive to oil drops applied to the back of the neck, and shook and scratched more than when oil drops were 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, under the upper neck of mice. The mice without the ion channels then did not shake when a drop of oil or water was applied, but a cold sham 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 that three low-threshold mechanoreceptor neurons, including neurons with low-threshold mechanoreceptors and unmyelinated C fibers (C-LTMRs), were involved. 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 led to shaking. Genetic deletion of the C-LTMRs resulted in reduced shaking activity.
The scientists then hypothesized that signals from the C-LTMR were transmitted from the superficial dorsal horn of the spinal cord to the lateral parabrachial nucleus in the pons via spinoparabrachial neurons. The researchers found that optogenetic stimulation of the C-LTMR induced 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, further confirmation of this pathway in other mammals and characterization of the neural networks of the parabrachial nucleus are needed.
You can read about the role the parabrachial nucleus plays in the formation of itching in our blog. And you can find out how many itches science distinguishes from the material “Why It Itches.”