Just a few days ago, I wrote a post about a very unusual occurrence: a serious change in a fundamental piece of neuroanatomy. To recapitulate, Jean Francois Brunet and his colleagues, including lead author Isabel Espinosa–Medina, used a modern molecular approach to show that the autonomic motor neurons in the sacral cord share their characteristics with the sympathetic motor neurons in the thoracic cord and not with the parasympathetic motor neurons in the hindbrain.

[The authors did not study the autonomic motor neurons in the midbrain. While these neurons have hitherto been classified as parasympathetic, the jury remains out as to whether this classification is supported by molecular signatures. I hope that we will learn the answer to this question within the next few years.]

Upon further reflection, I amend my conclusion

In my original post, written within hours of my reading the report by Brunet and colleagues, I concluded that the findings support a cooperative relationship rather than an antagonistic one between parasympathetic and sympathetic outflows. Upon further reflection, I would like to amend that conclusion. The parasympathetic outflow from the hindbrain still supports rest and digest and is not appropriate during the three “f”-times of high arousal fight, flight, or freeze. Conversely, the sympathetic outflow from the thoracic cord still supports behaviors that require arousal and are counterproductive during periods such as sleep when rest and digest is the order of the day.

This is my mom and her dog, Woodie, having a nap. During this period of rest and digest (parasympathetic-dominated), voiding is not imminent.

The crux of the change implied by reclassifying sacral autonomic motor neurons as sympathetic is that two functions, hitherto classified as parasympathetic, are in fact sympathetically controlled:

• Voiding (both urine and feces)
• Sexual arousal (including erection in males)

This makes so much sense that it’s puzzling that there was no major pushback on the idea that voiding and sexual arousal were parasympathetic functions. [On my to-do list is to read Gaskell and others to better understand how that original classification was arrived at, what motivated it.]

Voiding is an active behavior

As any dog-walker knows, choosing a place to void is not a sleepy activity. My mother’s dog, Woodie, pees in two different styles:

• Trot, trot, trot, pee, trot, trot, trot
• Trot, stop, sniff, sniff, move a step, sniff, sniff, move back two steps, sniff, sniff, repeat for many iterations, pee, trot off

Both of these peeing patterns is performed by an awake, alert dog. Neither could be mistaken for a sleepy behavior. The attention paid to peeing, either quick or considered, is warranted because during the actual period of voiding, animals are highly vulnerable to attack and predation. They are well served by being alert to environmental clues. Throughout evolutionary time, the voiding animal that is vigilant survives to void on another day; the drowsy one eventually gets caught in the act and eaten. Cats (see Minnie in the act of pooping in the video below) are similarly alert when voiding.

The consideration that an animal gives to choosing the location for voiding is species-specific. For male dogs, the locations of urine mark the dog’s territory. For house cats, the location is kept constant. For rats and horses, voiding occurs while ambulating with no special attention paid to where. Regardless of its location, voiding is performed by an alert mammal. As far as sexual arousal goes, no additional words are needed.

Unified sympathetic functions

In sum, spinal autonomic outflow belongs to a single branch of the autonomic nervous system, that which we call sympathetic. The functions of this unified sympathetic aka spinal autonomic system are many “f”-s: fleeing , freezing, fighting, f-cking (excuse me), and two “p”-s: peeing and pooping.

The postganglionic autonomic neurons

I received an email that included a note from a great scientist of the autonomic nervous system, particularly the sacral outflow to the bladder, who wrote, “The TL [thoracolumbar] and S [sacral] pathways still are antagonistic in most organs and use different postganglionic transmitters. The functional similarities between cranial and sacral  support the continued use of the sympathetic/parasympathetic terminology.” In a similar vein, Steve Jacques commented on my original post, saying “Are we forgetting the postganglionics here? Presumably the postganglionics innervated by the sacral outflow can be considered sympathetic cholinergic and hence can still be ‘antagonistic’ to the ‘classic’ sympathetics.”

This is a valid concern. There are developmental differences that have no known functional consequences in the adult. One example is branchiomeric vs somatic motoneurons, a difference in developmental origin without a known function in the adult (and people have examined this question, actively looking for differences, and ultimately finding none).

Brunet and colleagues address the issue of postganglionic anatomy and pharmacology. First they point out that there are cholinergic ganglionic neurons in the sympathetic ganglia innervated by the thoracic cord. The targets of these cholinergic ganglionic neurons are sweat glands and possibly cutaneous blood vessels. [It is known that active vasodilation depends on cholinergic signaling but it is not completely certain where the acetylcholine in question arises from.] Second, the markers that mark sympathetic ganglia targeted by thoracic cord are also contained in the pelvic ganglia targeted by thoracic and sacral autonomic outflow. Third, within the pelvic ganglia are neurons that receive input from both thoracic and sacral preganglionic neurons. This makes their identity mixed even by old fashioned standards. Ganglionic neurons that receive input from both thorasic and sacral cord are heretical in the old formulation but no big deal in the new order.

Science is F-U-N

However the scientific community ends up judging Brunet’s re-classification of the sacral autonomics, this is living, breathing science. This exciting paper highlights that science is not a group of facts raining down upon us from on high. Rather, science is a continuous struggle to best approximate the truths of the natural world. In the end, it matters less to me whether textbooks in 2050 list sacral autonomics as sympathetics or parasympathetics than that the public is exposed to the joy and excitement of vibrant scientific inquiry. As illustrated by a conversation with my friend Aaron Freeman, aka The Excitable Ape, questioning scientific truths is F-U-N. So go science your day and question the “truths” in your life!