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Authors requiring further information regarding Elsevier’s archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright Author's personal copy Journal of Chemical Neuroanatomy 43 (2012) 112–119 Contents lists available at SciVerse ScienceDirect Journal of Chemical Neuroanatomy jo urnal homepage: www.elsevier.com/locate/jchemneu Nuclear organization of the serotonergic system in the brain of the rock cavy (Kerodon rupestris) a,b a,b a,b a,b Joacil G. Soares , Jose´ R.L.P. Cavalcanti , Francisco G. Oliveira , Andre´ L.B. Pontes , a,b a,b a,b a,b Twyla B. Sousa , Leandro M. Freitas , Jeferson S. Cavalcante , Expedito S. Nascimento Jr , a,b a,b, Judney C. Cavalcante , Miriam S.M.O. Costa * a Departments of Morphology, Laboratory of Neuroanatomy, Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil b Department of Physiology, Laboratory of Neuroanatomy, Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil A R T I C L E I N F O A B S T R A C T Article history: Serotonin, or 5-hydroxytryptamine (5-HT), is a substance found in many tissues of the body, including as Received 23 August 2011 a neurotransmitter in the nervous system, where it can exert different post-synaptic actions. Inside the Received in revised form 12 March 2012 neuro-axis, 5-HT neurons are almost entirely restricted to the raphe nuclei of the brainstem. As such, 5- Accepted 12 March 2012 HT-immunoreactivity has been considered a marker of the raphe nuclei, which are located in the Available online 20 March 2012 brainstem, at or near the midline. The present study investigated distribution of serotonergic neurons in the brain of the rock cavy (Kerodon rupestris), a rodent species inhabiting the Brazilian Northeast. The Keywords: cytoarchitectonic location of serotonergic neurons was established through a series of 5-HT Brainstem immunostained sections, compared with diagrams obtained from adjacent coronal and sagittal sections Immunohistochemistry stained by the Nissl method. The following nuclei were defined: the rostral group, consisting of rostral Raphe nuclei Rock cavy linear raphe, caudal linear raphe, median and paramedian raphe, dorsal raphe, and pontine raphe nuclei, Rodent and the caudal group composed of raphe magnus, raphe pallidus and raphe obscurus nuclei. Other Serotonin serotonergic neuronal clusters, such as the supralemniscal group and the rostral and caudal ventrolateral medulla oblongata clusters, were found outside the midline. Rare 5-HT-producing neurons were identified in the lateral parabrachial nucleus and in the pontine reticular formation, mostly along fibers of the lateral lemniscus. Despite exhibiting some specializations, the picture outlined for serotonergic groups in the rock cavy brain is comparable to that described for other mammalian species. ß 2012 Elsevier B.V. All rights reserved. 1. Introduction Abbreviations: 3N, oculomotor nerve nucleus; 4N, trochlear nerve nucleus; 4V, 4th ventricle; 7N, facial nerve nucleus; 10N, vagal nerve nucleus; 12N, hypoglossal Interest in the morphology and functions of raphe nuclei was nerve nucleus; AP, area postrema; Aq, cerebral aqueduct; cp, cerebral peduncle; Cu, cuneatus nucleus; DTg, dorsal tegmental nucleus; ECu, external cuneate nucleus; triggered following the description of a system of monoaminergic g7, genu of the facial nerve; Gi, gigantocellular reticular nucleus; Gr, gracilis neurons in the rat brainstem, using formaldehyde-induced fluores- nucleus; IC, inferior colliculus; IO, inferior olive; IP, interpeduncular nucleus; LC, cence (Falck et al., 1962; Dahlstrom and Fuxe, 1964). Although a locus coeruleus; lfp, longitudinal fibers pons; ll, lateral lemniscus; LL, lateral large overlap was observed between putatively producing serotonin lemniscus nuclei; LPB, lateral parabrachial nucleus; M5, motor trigeminal nucleus; (5-HT) neurons and the raphe nuclei, serotonergic groups were mcp, middle cerebelar peduncle; MdD, medullary reticular nucleus dorsal; MdV, medullary reticular nucleus ventral; MG, medial geniculate nucleus; ml, medial designated as B1–B9 groups in a caudal to rostral direction, given lemniscus; mlf, medial longitudinal fasciculus; MPB, medial parabrachial nucleus; that the overlap is imprecise (Dahlstrom and Fuxe, 1964). With the PAG, periaqueductal gray; Pn, pontine nuclei; PnC, pontine reticular nucleus caudal; introduction of immunohistochemical techniques, this classification PnO, pontine reticular nucleus oral; Pr5, principal sensory 5 nucleus; Pr, prepositus was integrated with the cytoarchitectonic nomenclature of the nucleus; py, pyramid; R, red nucleus; SC, superior colliculus; scp, superior cerebelar raphe system (Steinbusch et al., 1978; Steinbusch, 1981; To¨rk, peduncle; scpx, superior cerebelar peduncle decussation; SN, substantia nigra; Sol, solitary tract nucleus; Sp5, spinal trigeminal nucleus; sp5, spinal trigeminal tract; 1985). Even though the main cell groups in the serotonin system SubB, subbrachial nucleus; VTA, ventral tegmental area; vtgx, ventral tegmental follow cytoarchitectonic divisions of the raphe nuclei, many 5-HT- decussation. immunoreactive (5-HT-IR) neurons are present in other areas of the * Corresponding author at: Department of Morphology/Laboratory of Neuro- brainstem beyond raphe nuclei boundaries, for example in the anatomy, Biosciences Center, Federal University of Rio Grande do Norte, 59072-970, Natal, RN, Brazil. Tel.: +55 84 32153431; fax: +55 84 32119207. vicinity of the medial lemniscus or sectors of the reticular formation E-mail address: [email protected] (Miriam S.M.O. Costa). (Jacobs and Azmitia, 1992; Vertes and Crane, 1997). On the other 0891-0618/$ – see front matter ß 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.jchemneu.2012.03.001 Author's personal copy J.G. Soares et al. / Journal of Chemical Neuroanatomy 43 (2012) 112–119 113 hand, other neurotransmitters are also found in the neurons of raphe et al., 2008), nociceptive sensory processing (Bardin et al., 2000; nuclei, including substance P, thyrotropin-releasing hormone (TRH), Zeitz et al., 2002), circadian regulation (Pontes et al., 2010; norepinephrine and gamma-aminobutyric acid (GABA), co-localized Cavalcante et al., 2011), among others. Moreover, 5-HT dysfunction or not with 5-HT (To¨rk, 1985; Jacobs and Azmitia, 1992; Charara and has been associated with several neuropathological processes, such Parent, 1998; Harding et al., 2004). Nevertheless, the long ascending as sleep disturbances (Neylan et al., 2001), anxiety, aggression (Van and descending projections from raphe neurons are recognized as Praag, 1996; Ramboz et al., 1998; Lowry et al., 2008b), depression serotonergic (Jacobs and Azmitia, 1992; Charara and Parent, 1998; (Jacobs, 2002; Michelsen et al., 2007; Lowry et al., 2008b), anorexia Halberstadt and Balaban, 2006). and bulimia (Kaye et al., 2005), as well as neurodegenerative Thus, serotonergic groups originally classified as B1–B9 from the disorders such as Alzheimer’s (Meltzer et al., 1998), Parkinson’s medulla to the midbrain in the rat (Dahlstrom and Fuxe, 1964), may (Nicholson and Brotchie, 2002) and Huntington’s (Waeber and be approximately correlated with raphe nuclei, generally divided Palacios, 1989) diseases (see also Verge´ and Calas, 2000). into superior or rostral, and inferior or caudal, groups. In a classical The present study provides a foundation for future research on description, the superior group consists of five main nuclei: the the hodological and functional aspects of these neuronal groups in caudal linear raphe nucleus (CLi, B8); median raphe nucleus (MnR, this species, broadening the basis for understanding evolutionary B8 and B5, previously referred to as the central superior nucleus); processes associated with the nuclear organization of this neuronal dorsal raphe nucleus (DR, B7 and B6), pontine raphe nucleus (caudal system. end of B5, sometimes included in the median raphe nucleus), and lateral neurons of the B9 group located just dorsal to the medial 2. Materials and methods lemniscus and laterally displaced cells in the pontine nucleus centralis oralis. The most rostral of the raphe nuclei, as cytoarch- Four young adult rock cavies (1 male and 3 females), weighing between 300 and 400 g, from rural municipalities in Rio Grande do Norte state, Brazil, were used. itectonically defined (Taber et al., 1960), is the rostral linear raphe Animal capture was authorized by the Brazilian Environmental Agency (IBAMA, nucleus, which contains only rare serotonergic neurons and is licenses 21440-1). Approval for the experiments was obtained from the local Animal predominantly a dopaminergic nucleus (To¨rk, 1985). Experimentation Ethics Committee in compliance with National Institute of Health The inferior group consists of four main nuclei: the raphe (NIH) guidelines. All efforts were made to minimize the number of animals and their obscurus nucleus (ROb, B2), raphe pallidus nucleus (RPa,