R E V I E W Eur J Anat, 6 (1): 47-57 (2002) Neuropeptides in the cat diencephalon: II. Hypohalamus R. Coveñas 1, M. de León 1, M. Belda 1,P. Marcos 2, J.A. Narváez 3, J.A. Aguirre 3, G. Tramu4 and S. González-Barón 3 1 - Instituto de Neurociencias de Castilla y León (INCYL), Laboratorio de Neuroanatomía de los Sistemas Pep- tidérgicos, Salamanca, Spain 2- Un i v e r sidad de Castilla-La Mancha, Facultad de Medicina, De p a r tamento de Ciencias de la Salud, Al b a c e t e , Sp a i n 3 - Universidad de Málaga, Facultad de Medicina, Departamento de Fisiología, Málaga, Spain 4- Un i v e r sité de Bordeaux I, Laboratoire de Neurocytochimie Fon c t i o n e l l e , C. N . R . S . , U.R.A. 339, Tal e n c e , Fra n c e SUMMARY INTRODUCTION We have reviewed the distribution and func- The hypothalamus is part of the dien- tions of neuropeptides in the cat hypothalamus. cephalon. Along the animal scale, it is one of the Our review focuses in the cat hypothalamus on most preserved zones of the central nervous sys- the following points: 1) the distribution and tem (CNS). This shows that the findings coexistence of neuropeptides; 2) the anatomical observed in the hypothalamus of animals used relationships among the different neuropeptides; for experimental research can be extrapolated to 3) the peptidergic pathways (afferences and humans. It is a centre that is connected with the efferences); 4) comparison of the distribution of limbic system, which is involved in autonomic neuropeptides in the mammalian hypothalamus; and homeostasis functions. In this sense, the and 5) the physiological functions of neuropep- hypothalamus has been considered as the “great tides. Although at present the distribution of ganglion” of the autonomic nervous system, many neuropeptides in the hypothalamus of the since it integrates autonomic function at central cat is known, there is little information about level (Kupfermann, 1981). In addition, the hypo- other aspects of neuropeptides in the same dien- thalamus has been implicated in a large number cephalic region. Thus, in order to know more of very important functions, such as drinking, the distribution and functions of neuropeptides food intake, thermoregulation, neuroendocrine in the cat hypothalamus in detail, in the future control of the hypophysis (by means of releasing appropriate methodologies must be applied in and inhibiting factors), defence (immunoregula- order to determine, for example, the distribution tion), circadian rhythms, blood pressure, emo- of the neuropeptide receptors, the distribution of tions, stress, reproduction, aggressive behaviour, neuropeptidases, the peptidergic synaptic con- sexual orientation, as well as in the production nections, the coexistence of neuropeptides and of neurohormones (vasopressin, oxytocin,…) the physiological actions of the neuropeptides in (see Swaab, 1997). In sum, it is a small centre in the cat hypothalamus. the CNS, but is involved in very important func- tions. Thus, it has been indicated that lesions in Key Words: Neuropeptides – Hypothalamus – the hypothalamus could elicit several diseases/ Diencephalon – Cat alterations: depression, anorexia nervosa, bulim- Correspondence to: Dr. R. Coveñas. Instituto de Neurociencias de Castilla y León (INCYL), Laboratorio de Neu- roanatomía de los Sistemas Peptidérgicos, Facultad de Medicina, c/ Alfonso X El Sabio Submitted: November 23, 2001 s/n, 37007-Salamanca, Spain. Phone: 923-294400 ext. 1856; Fax: 923-294549. E-mail: Accepted: February 15, 2002 [email protected] 47 R. Coveñas, M. de León, M. Belda, P. Marcos, J.A. Narváez, J.A. Aguirre, G. Tramu and S. González-Barón ia, changes in sexual orientation, diabetes neuropeptides studied showed a widespread dis- insipidus, Cushing’s disease, alterations in sleep tribution throughout the cat hypothalamus. At and temperature, sudden-infant-death-syndrome, present, the distribution of thirteen neuropep- Wolfram’s syndrome, Prader-Willi’s syndrome, tides has been fully studied in the cat hypothal- malignant syndrome, aggressive behaviour, alter- amus. In this sense, the distribution has been ations in the emotions, as well as alterations in studied of methionine-enkephalin (Micevych the release of hormones into the hypophysis. and Elde, 1980; Coveñas et al., 1988; Yoshimoto M o re o v e r, hypothalamic modifications have et al., 1989), substance P (Burgos et al., 1988; been reported in neurodegenerative diseases, Yoshimoto et al., 1989), neurotensin (Hu et al., such as Alzheimer’s, Parkinson’s, Huntington’s, 1988; Yoshimoto et al., 1989; de León et al., multiple sclerosis,… (see Swaab, 1997). 1991a), somatostatin-28 (1-12) (de León et al., Moreover, the hypothalamus is connected to 1991b), neuropeptide Y (Ueda et al., 1986; Hu et a large number of other CNS centres (Carpenter, al., 1987; Léger et al., 1987), endorphin (1-27) 1980; Saper, 1990). Thus, the hypothalamus (Coveñas et al., 1996a), -endorphin (1-31) receives inputs from the hippocampus, the (Micevych and Elde, 1982), -melanocyte-stimu- amygdala, the cerebral cortex, the retina, the lating hormone (Micevych and Elde, 1982; Rao et spinal cord, the ventrolateral medulla, the nucle- al., 1987; Coveñas et al., 1996b), adrenocorti- us of the solitary tract, the parabrachial nucleus, cotropin hormone (Kitahama et al., 1984, 1986; the locus coeruleus and the raphe, whereas Rao et al., 1986; Coveñas et al., 1996c), luteiniz- hypothalamic neurons send projections into the ing horm o n e - releasing hormone (Barry and amygdala, the periaqueductal gray, the reticular Dubois, 1975; Belda et al., 2000), neurokinin A formation of the mesencephalon, the thalamus, (Velasco et al., 1993), delta sleep-inducing pep- the hypophysis, the nucleus of the solitary tract, tide (Charnay et al., 1990) and vasoactive intesti- the parabrachial nucleus, the locus coeruleus, nal polypeptide (Obata-Tsuto et al., 1983, 1984) the nucleus ambiguus, the area postrema, the (see Figure 1). Also, there are very few data con- spinal cord, the nucleus accumbens and the cerning the distribution of another seven neu- median eminence. ropeptides (not shown in Table 1): galanin, cor- As mentioned in a previous article (Part I: t i c o t ro p i n - releasing factor, somatostatin-14, Thalamus) (Coveñas et al., 2001), a large number vasopressin, oxytocin, cholecystokinin octapep- of neuroanatomical, neurophysiological, neu- tide and thyro t ro p i n - releasing horm o n e ropharmacological and behavioural data have (Micevych and Elde, 1980; Kawata et al., 1982; been reported for the cat. However, until the Graybiel and Elde, 1983; Wahle and Albus, 1985; eighties research on the distribution of neu- Caverson et al., 1987; Yoshimoto et al., 1989). ropeptides in the cat diencephalon has received Thus, immunoreactive cell bodies containing little attention. Here, our aim is to review, in the galanin were observed in the hypothalamus ven- cat, currently available morphological and phys- tromedialis and in the regio praeoptica; those iological data concerning neuropeptides that containing corticotropin-releasing factor in the have emerged over the past eighteen-twenty hypothalamus posterior, hypothalamus lateralis, years concerning one of the most important nucleus supraopticus, nucleus periventricularis functional areas of the CNS: the hypothalamus. hypothalami and in the regio praeoptica; those We also compare the results obtained on neu- containing thyrotropin-releasing hormone in the ropeptides in the cat hypothalamus with those regio praeoptica and around the anterior hypo- found in the same diencephalic area of others thalamic nucleus; those containing vasopressin mammalian species (e.g., rat, monkey, human). in the nuclei periventricularis hypothalami, suprachiasmaticus and supraopticus, hypothala- mus lateralis and in the regio praeoptica; those NEUROPEPTIDES IN THE CAT HYPOTHALAMUS containing oxytocin in the hypothalamus dorso- medialis, hypothalamus lateralis, regio praeopti- The hypothalamus can be divided according ca and in the nuclei periventricularis hypothala- to topographic criteria into several re g i o n s mi and supraopticus, and those containing (Kupfermann, 1981): mamillar, periventricular, cholecystokinin in the nuclei arcuatus and medial, lateral and preoptic (see Table 1). In this periventricularis hypothalami, as well as in the review, we use the terminology of the hypothal- hypothalamus lateralis. In addition, somatostatin- amic nuclei according to the stereotaxic atlas of 14-, galanin-, corticotropin-releasing factor-, and the diencephalon of the cat carried out by Jasper t h y ro t ro p i n - releasing horm o n e - i m m u n o re a c t i v e and Ajmone-Marsan (1966). Table 1 shows the fibers were observed in the hypothalamus pos- distribution of fibers and cell bodies containing terior, whereas fibers containing vasopressin and neuropeptides in the cat hypothalamus, using oxytocin have been described in the nuclei immunocytochemical methods. In general, as periventricularis hypothalami and supraopticus. can be seen in the table, the immunoreactive Furthermore, using a microdissection tech- structures (fibers and cell bodies) containing the nique combined with radioimmunoassay the 48 Neuropeptides in the cat diencephalon: II. Hypothalamus Table 1.- Distribution of neuropeptides in the nuclei of the cat hypothalamus. MET-E SP NT SOM NPY b-END a -MSH ACTH LH-RH NKA b-END DSIP VIP (1-31) F CB F CB F CB F CB F CB F CB F CB F CB F CB F CB F CB F CB F CB MAMILLAR REGION Ml ++-+----+-+-+---+-++ +- Mm -+ -+----+-+- RIA + - - - + - -