PII S0361-9230(00)00442-1 Lamina I-periaqueductal gray (PAG) projections represent only a limited part of the total spinal and caudal medullary input to the PAG in the cat Leonora J. Mouton,* Esther-Marije Klop and Gert Holstege Department of Anatomy and Embryology, Faculty of Medical Sciences, Rijksuniversiteit Groningen, Groningen, The Netherlands [Received 29 May 2000; Revised 15 September 2000; Accepted 19 October 2000] ABSTRACT: The periaqueductal gray is well known for its involvement in nociception control, but it also plays an impor- tant role in the emotional motor system. To accomplish these functions the periaqueductal gray receives input from the limbic system and from the caudal brainstem and spinal cord. Earlier studies gave the impression that the majority of the periaque- ductal gray projecting cells in caudal brainstem and spinal cord are located in the contralateral lamina I, which is involved in nociception. The present study in the cat, however, demon- strates that of all periaqueductal gray projecting neurons in the contralateral caudal medulla less than 7% was located in lam- ina I. Of the spinal periaqueductal gray projecting neurons less than 29% was located in lamina I. However, within the spinal cord large segmental differences exist: in few segments of the enlargements the lamina I-periaqueductal gray projecting neu- rons represent a majority. In conclusion, although the lamina I-periaqueductal gray projection is a very important nociceptive pathway, it constitutes only a limited part of the total projection from the caudal medulla and spinal cord to the periaqueductal gray. These results suggest that a large portion of the medullo- and spino-periaqueductal gray pathways conveys information other than nociception. © 2001 Elsevier Science Inc. KEY WORDS: Spinomesencephalic, Trigeminal, Nucleus cau- dalis, Marginal layer, Nociception. INTRODUCTION The periaqueductal gray (PAG) is well known for its role in nociception control. Stimulation of the PAG results in a strong decrease of nociception in all parts of the body [5,23,29,35]. However, the PAG also plays an important role in the control of emotional motor behaviors necessary for the survival of the indi- vidual and species [16]. PAG-controlled emotional motor behav- iors are, e.g., defence behaviors, such as fight, threat display, flight, and immobility [1,2,3,10], but also mating behavior [17,37], mic- turition [7,8,17], vocalization [2,14,18,19], and maternal behavior [25,26]. To control nociception and the emotional motor behaviors, the PAG needs to be informed about the internal and external envi- ronment of the individual. Anatomical studies have shown that the PAG receives a major afferent input from more rostrally located limbic structures such as the hypothalamus, the central nucleus of the amygdala and the medial preoptic area [15,38]. Besides this, it has been demonstrated that the PAG receives direct input from the caudal medulla and spinal cord [13,27,30,32,43]. Concerning this spinal and medullary projections to the PAG, still no insight exists about its precise organization. Most attention until now has been given to the many cells located in lamina I of the caudal medulla [12] and lamina I of the spinal cord [36] that project to the ventral and ventrolateral PAG [6,11,21,24,25,28,32, 33,40 – 42]. This ascending lamina I-PAG projection is most likely involved in informing the PAG about the pain situation of the body, as lamina I is known for its almost exclusive involvement in nociceptive functions [5]. However, besides these many lamina I afferents probably involved in nociception, the PAG also receives other caudal medullary and spinal afferents; many cells located in other laminae than lamina I in both the caudal medulla [4,13,31] and spinal cord [20,21,28,32,34,39,43] were found to project to the PAG. It is most likely that these other afferents relay other infor- mation to the PAG than nociception and might be important for the PAG to control the emotional motor behaviors. Until now rela- tively little attention has been given to these other spinal and medullary projections to the PAG. The question is why so little attention has been paid to these other medullary and spinal PAG projecting cells. It might be that it derives from the fact that some well-known studies [6,41,42] on the caudal medullary and spinal afferents to the PAG in cat and monkey concluded that tracer injections in the dorsal part of the midbrain, including the PAG, resulted in an overwhelming major- ity of labeled spino-mesencephalic cells in lamina I. Such results might suggest a smaller importance of the other PAG projections. However, doubts have arisen as to whether the lamina I-PAG projections really form the majority of the medullary and spinal PAG projecting neurons, considering the results of some more recent studies [20,21]. Keay and Bandler [20], in a study on the upper cervical cord projections to the PAG in the cat, found that the majority of labeled neurons was located in lamina I, but only when the tracer injections were placed in the lateral PAG. When * Address for correspondence: Leonora J. Mouton, Department of Anatomy and Embryology, Faculty of Medical Sciences, Rijksuniversiteit Groningen, Groningen, The Netherlands. Fax: 31-50-3632461; E-mail: L.J.Mouton@med.rug.nl Brain Research Bulletin, Vol. 54, No. 2, pp. 167–174, 2001 Copyright © 2001 Elsevier Science Inc. Printed in the USA. All rights reserved 0361-9230/01/$–see front matter 167