Barrington's nucleus: Neuroanatomic landscape of the mouse “pontine micturition center”

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A small region of the upper brainstem, within the lateral pontine tegmentum, is critical for normal voiding behavior in cats (Barrington, 1921), rats (Satoh, Shimizu, Tohyama, & Maeda, 1978), and humans (Fowler, 1999; Sakakibara, 2015; Ueki, 1960). This region is located between the locus coeruleus (LC) and laterodorsal tegmental nucleus (LDT) and contains a small number of neurons that increase their activity in response to bladder distention (Rouzade‐Dominguez, Pernar, Beck, & Valentino, 2003). Immediately before the bladder contracts, these neurons begin firing, and they sustain this activity throughout the contraction and in close correspondence to bladder pressure (Hou et al., 2016; Tanaka et al., 2003). Injecting electric current or glutamate in this region triggers micturition (Kruse, Mallory, Noto, Roppolo, & de Groat, 1991; Mallory, Roppolo, & de Groat, 1991; Mallory & Steers, 1989; Nishizawa, Sugaya, Noto, Harada, & Tsuchida, 1988; Sugaya, Matsuyama, Takakusaki, & Mori, 1987), while inhibition of or injury to this region prevents voiding, causing urinary retention in rats, cats, and humans (Barrington, 1925; Komiyama, Kubota, & Hidai, 1998; Mallory et al., 1991; Satoh, Shimizu, et al., 1978).
These findings gave rise to the concept in rats that the pontine tegmentum contains a “pontine micturition center,” or PMC (Loewy, Saper, & Baker, 1979; Sugaya et al., 1987), which in cats was called the “pontine detrusor nucleus” (Kuru & Yamamoto, 1964) or “M‐region” (Holstege, Griffiths, de Wall, & Dalm, 1986). Each term conveys the notion that a population of neurons integrates a stretch signal from the bladder with other contextual information and, via long axonal projections to the spinal cord, coordinates bladder contraction with relaxation of the urethral sphincter (Kruse et al., 1991; Mallory et al., 1991).
Very few tegmental neurons have bladder‐related activity, and they are surrounded by and intermingle with much larger populations of unrelated neurons (Tanaka et al., 2003; Yamao, Koyama, Akihiro, Yukihiko, & Tsuneharu, 2001). Due to a paucity of markers for these diverse neuron populations, conflicting opinions arose about which features distinguish the PMC. More than one population of neurons was said to function as the PMC based on sites where electrical stimulation, lesions, or drug injection alter voiding. However, the anatomic resolution of these techniques cannot distinguish among the myriad, intermingled populations of neurons in this region of the brainstem, which form sub‐millimeter, overlapping distributions. Nonetheless, with limited histochemical markers, some investigators proposed that the PMC consists of catecholaminergic neurons in the LC or subcoeruleus (Kuru & Yamamoto, 1964; Mallory et al., 1991; Nishizawa et al., 1988; Sugaya et al., 1987), or cholinergic neurons in the LDT (Noto, Roppolo, Steers, & de Groat, 1991; Satoh, Shimizu, et al., 1978).
Axonal tracing in rats identified a third, unmarked, cluster of neurons centered between the LC and LDT. Like catecholamine neurons in the ventral LC and subcoeruleus, these neurons send long axonal projections to lumbosacral levels of the spinal cord, yet they survived chemical toxins that destroy catecholamine neurons (Loewy et al., 1979; Satoh, Tohyama, Sakumoto, Yamamoto, & Shimizu, 1978; Tohyama et al., 1978). Further, lesions in the LC had no effect on micturition, while lesions targeting this newly identified cluster caused urinary retention in rats (Satoh, Shimizu, et al., 1978). Thus, many investigators concluded that PMC function, at least in rats, relied on noncatecholamine neurons located just rostral and medial to the LC.
In honor of F.J.F.
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