In many furry animalsWhat are the neurological mechanisms underlying snorting, this behavior that is manifested by the appearance of jerks of the whole body when leaving the water? How can we explain the appearance of the stereotypical movements that a dog makes when emerging from immersion in water? A behavior that has an evocative name in English (wet dog shakesliterally “wet dog shakes”). This is the question that concerned American researchers Howard Hughes from Harvard Medical School (Boston).
These neurobiologists used several sophisticated techniques to analyze and decipher, in mice, the mechanisms of this fascinating behavior. They used genetics, physiology, and optogenetics to discover the neural structures and neural pathways involved in conserved behavior in mice and rats, as well as other fur-bearing mammals, such as dogs, cats, bears, tigers, and lions, to name just a few. some. .
In these furry animals, this reflex behavior consists of the appearance of rapid oscillations of the head and upper part of the trunk, after exposure of the back to water or certain irritating and potentially harmful substances. It has lost its share of mystery in view of the results published on November 8, 2024 in the magazine Science.
To carry out their experiments, the researchers used various means to elicit a snort in mice, such as drops of sunflower seed oil, thin nylon filaments calibrated to flex with a known force when applied to the skin of the back, or even fine air currents. Observing that drops of sunflower oil caused a snort comparable to other methods, they opted for this type of stimuli to elucidate what type of neurons and what neuronal circuit were at the origin of this stereotyped behavior in these mammals.
In these mice, applying these oily drops to the skin of the back caused snorting, characterized by a series of jerks that lasted more than five minutes and were often accompanied by scratching and grooming movements. On average, the deposition of a single drop caused tremors after about ten seconds. The shaking was stronger during the first minute. Behavior was stereotyped among all rodents, with an average of 3 complete forward and backward movements during each series of shakes.
The mice responded more strongly when the researchers applied the oil drops to the back of the neck than to the lower back. Furthermore, no snorting was observed when the oil drops were applied to the thigh of the mice.
The researchers wanted to know what type of skin receptors were stimulated. To do this, they used genetically manipulated mice, which lack Piezo2 receptors in the s, located in the dorsal sensory root of the spinal nerve that emerges from the spinal cord. Piezo2 is a mechanoreceptor, that is, an ion channel that is activated during mechanical stimulation. It plays a crucial role in the perception of touch.
Let us note in passing that the discovery of piezomechanosensitive ion channels has allowed us to understand the fundamental mechanisms of tactile perception. She was honored when, in 2021, the Nobel Prize in Medicine or Physiology was awarded to David Julius and Ardem Patapoutian for their work on temperature and touch receptors.
Piezo2, main touch sensor
In the absence of the Piezo 2 mechanoreceptor in the dorsal spinal ganglion, mice did not snort when sunflower oil was applied to their lower back. Similarly, no twitching occurred in the mutant mice when water was placed on them. This absence of snorting is therefore due to the absence of mechanical stimuli in these rodents that lack piezo 2 receptors.
But what are the sensory neurons that transmit the tactile information perceived by the Piezo 2 mechanoreceptors? It appears that of all the types of sensory neurons present in the dorsal spinal ganglion, C low threshold mechanoreceptors (C-LTMR) respond most strongly to the application of oil droplets to the skin of the back. C-LTMR neurons are not myelinated. They form small diameter nerve fibers that end in a very specific region of the dorsal spinal cord, in this case in a superficial part called lamina II (or lamina II).
Therefore, it is these nerve fibers composed of specific sensory neurons, the C low-threshold mechanoreceptors (C-LTMR), that transmit the stimuli that cause snorting. They innervate the hair follicles of the shaggy skin and detect light touch. These C-LTMR neurons, whose cell body is located in the dorsal spinal ganglia, terminate in the skin at the level of the hair follicles.
The researchers then used optogenetics to identify and confirm that these sensory neurons, which respond to very low-threshold stimuli, are indeed involved in inhalation in mice. Optogenetics consists of introducing a gene that encodes a photosensitive protein into a cell. This technique allows neurons to become sensitive to light. It allows you to activate and deactivate populations of genetically modified neurons, thus allowing you to study the functioning of neuronal circuits.
Low threshold C mechanoreceptors
The experiments consisted of illuminating the skin on the neck or back of mice, while observing whether or not they showed twitches. It appears that optogenetic stimulation of C low-threshold mechanoreceptors (C-LTMR), whose extensions terminate in the skin of the neck, caused very pronounced snorting. These were of lesser magnitude when stimulation concerned low-threshold mechanoreceptor C fibers located in the lower back. Finally, optogenetic stimulation of C-LTMR neurons located in the thigh did not elicit any snorting.
The researchers then showed that ablation of C-LTMR neurons had the effect of approximately halving the snoring normally caused by the application of oily drops.
It remained to know which neuronal pathway reached the brain through the tactile information generated by the stimulation of C-LTMR neurons. Optogenetic experiments have shown that these low-threshold C mechanoreceptors contact neurons located in the brain at the level of the lateral parabrachial nucleus, a small area of the brain stem that integrates much information from the spinal cord*.
By silencing the lateral parabrachial nucleus using optogenetics, the researchers abolished the mice’s ability to snort when drops of sunflower oil were applied to them or when C neurons in the skin were stimulated. However, these animals were still able to scratch, groom, and move normally, indicating that this neural circuit is specific to snorting.
Spinoparabrachial route
Therefore, these results show that the spinoparabrachial pathway (connecting the spinal cord to the lateral parabrachial nucleus) is involved in inhalation. Therefore, it is this that transmits to the brain the signals initially transmitted to the hairy skin by the low-threshold C mechanoreceptor neurons.
A mystery that dates back to research published in 1939
Thus, this study allowed us to identify the nature of sensory neurons, as well as the neuronal pathways that participate in animal behavior conserved in many animal species. These results appear almost 80 years after a Swedish researcher, Yngve Zotterman, suggested, in 1939, that low-threshold C mechanoreceptors are involved in light tactile stimuli on hairy skin.
Since these C-LTMR neuronal fibers have a lanceolate-shaped peripheral end that innervates the base of hair follicles, the researchers hypothesize that these mechanoreceptors detect the smallest forces acting on hairy skin, such as water, movements of insects and parasites and other stimuli that divert hair. The animal’s brain then triggers a motor response, the famous snort, which allows it to get rid of the irritating substance or a potential threat.
Marc Gozlan (Follow me on unknownFacebook, LinkedIn, Mastodon, blue skyand on my other blog ‘Diabetes in all its forms’dedicated to the thousand and one facets of diabetes (it already has 73 posts).
*The parabrachial nuclei are symmetrical paired nuclei that include the ventral parabrachial nucleus, the lateral parabrachial nucleus, and the medial parabrachial nucleus. They are found in the reticular formation (relay between the spinal cord and the brain), at the junction of the midbrain and the dorsolateral part of the pons. Neurons in the parabrachial nuclei are particularly involved in pain. The parabrachial area receives most of the contingent of fibers from specific neurons of the superficial layer of the medulla. This area maintains connections with the hypothalamus.
To know more:
Zhang D, Turecek J, Choi S, et al. C-LTMRs mediate wet shakes in dogs via the spinoparachial pathway. Science. 2024 Nov;386(6722):686-692. doi: 10.1126/ciencia.adq8834
Li L, Rutlin M, Abraira VE, et al. The functional organization of low-threshold cutaneous mechanosensory neurons. Cell. December 23, 2011; 147 (7): 1615-27. doi:10.1016/j.cell.2011.11.027
Zotterman Y. Touch, pain, and tickling: an electrophysiological investigation of cutaneous sensory nerves. J Physiol. February 14, 1939; 95 (1): 1-28. doi: 10.1113/jphysiol.1939.sp003707
