Estrous cycle-dependent neural plasticity in the caudal brainstem in the female golden hamster: ultrastructural and immunocytochemical studies of axo-dendritic relationships and dynamic remodeling.

UNLABELLED: During the short four-day estrous cycle of the female hamster various behavioral (lordosis, vocalization and aggression) and autonomic adaptations occur. Presumably, these changes are under ovarian control. Recently, we described a distinct estrogen receptor-alpha immunoreactive (ER-alpha-IR) cell group, now called nucleus para-retroambiguus (NPRA), in the caudal ventrolateral medulla (Gerrits et al., 2008). Neurons of this group project to the ipsilateral intermediolateral cell column in the thoracic and upper lumbar cord. Clearly, the NPRA is part of an estrogen-sensitive neuronal network and the same applies to the region containing the commissural part of the solitary tract nucleus (NTScom) and the A2 group, here called NTScom/A2. Estrogen is known to modulate neuronal ultrastructure in various brain areas and spinal cord, but not in the caudal brainstem. Because we assumed that the NPRA plays a role in estrous cycle related adaptations, we hypothesized the occurrence of plasticity in this nucleus. In the present study we examined morphological changes of axo-dendritic relationships in NPRA and NTScom/A2 in estrous, diestrous and ovariectomized (OVX) hamsters, using immuno-electron microscopy and the 1D5 anti-ER-alpha antibody. Ultrastructural analysis revealed that the ratio "axon terminals surface/dendrite surface" was significantly increased in both the NPRA and NTScom/A2 during the estrous phase compared to the OVX and diestrous conditions. Remodeling of axon terminals due to axonal sprouting into large terminal fields filled up with pleomorphic vesicles resulted in contacts with more dendrites, and was the main cause for the "axonal terminal-dendritic-ratio" shift. IN CONCLUSION: Estrous cycle-induced axonal and dendritic plasticity is present in the NPRA, and in the NTScom/A2 group. Our findings support our hypothesis that estrogen-sensitive neuronal networks in the caudal brainstem display structural plasticity, probably to modulate steroid hormone dependent behaviors or autonomic adaptations.

The role of the nucleus basalis of Meynert and reticular thalamic nucleus in pathogenesis of genetically determined absence epilepsy in rats: a lesion study.

The role of cholinergic nucleus basalis (of Meynert) and the reticular thalamic nucleus in mechanisms of the generation spontaneous spike-and-wave discharges (SWDs) was investigated in the WAG/Rij rat model of absence epilepsy. Selective lesions were affected by local unilateral intraparenchymal infusions of immunotoxin 192 IgG-saporin and cholinotoxin AF64A to the nucleus basalis and the rostral pole of reticular thalamic nucleus. Injections of 192 IgG-saporin into the nucleus basalis increased the number of spontaneous SWDs, while injections in the reticular thalamic nucleus were not effective. Thereby, a loss of cholinergic activity in the nucleus basalis stimulates the appearance of SWDs. At the same time, AF64A infused into reticular thalamic nucleus, besides the reduction of choline acetyltransferase immunoreactive neurons within contralateral nucleus basalis, produced some unspecified lesion of adjacent neuronal tissue, resulted in decrease of number and duration of SWDs as well as in spectral changes in EEG. Considering that the nucleus basalis is an important source of cortical and thalamic cholinergic afferentation, we conclude that cholinergic excitatory input from this structure is important in the control of SWDs in the WAG/Rij rat model of absence epilepsy.

Localisation and physiological regulation of corticotrophin-releasing factor receptor 1 mRNA in the Xenopus laevis brain and pituitary gland.

In Xenopus laevis, corticotrophin-releasing factor (CRF) and urocortin 1 are present in the brain and they both are potent stimulators of alpha-melanophore stimulating hormone (MSH) secretion by melanotroph cells in the pituitary gland. Because both CRF and urocortin 1 bind with high affinity to CRF receptor type 1 (CRF1) in mammals and Xenopus laevis, one of the purposes of the present study was to identify the sites of action of CRF and urocortin 1 in the Xenopus brain and pituitary gland. Moreover, we raised the hypothesis that the external light intensity is a physiological condition controlling CRF1 expression in the pituitary melanotroph cells. By in situ hybridisation, the presence of CRF1 mRNA is demonstrated in the olfactory bulb, amygdala, nucleus accumbens, preoptic area, ventral habenular nuclei, ventromedial thalamic area, suprachiasmatic nucleus, ventral hypothalamic area, posterior tuberculum, tectum mesencephali and cerebellum. In the pituitary gland, CRF1 mRNA occurs in the intermediate and distal lobe. The optical density of the CRF1 mRNA hybridisation signal in the intermediate lobe of the pituitary gland is 59.4% stronger in white-adapted animals than in black-adapted ones, supporting the hypothesis that the environmental light condition controls CRF1 mRNA expression in melanotroph cells of X. laevis, a mechanism likely to be responsible for CRF- and/or urocortin 1-stimulated secretion of alpha-MSH.

Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions?

Most of our current understanding of the neurobiology, neuroanatomy and psychopharmacology of sexual behavior and ejaculatory function has been derived from preclinical studies in the rat. When a large population of male rats is tested on sexual activity during a number of successive tests, over time individual rats display a very stable sexual behavior that is either slow, normal or fast as characterized by the number of ejaculations performed. These sexual endophenotypes are postulated as rat counterparts of premature (fast rats) or retarded ejaculation (slow rats). Psychopharmacology in these endophenotypes helps to delineate the underlying mechanisms and pathology. This is illustrated by the effects of serotonergic antidepressants and serotonergic compounds on sexual and ejaculatory behavior of rats. These preclinical studies and models contribute to a better understanding of the neurobiology of ejaculation and boost the development of novel drug targets to treat ejaculatory disorders such as premature and retarded ejaculation.

Effects of chronic paroxetine pretreatment on (+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin induced c-fos expression following sexual behavior.

Chronic treatment with the selective serotonin reuptake inhibitor paroxetine impairs the functioning of 5-HT(1A) receptors involved in ejaculation. This could underlie the development of delayed ejaculation often reported by men treated with paroxetine. The neurobiological substrate linking the effects of selective serotonin reuptake inhibitor-treatment and 5-HT(1A) receptor activation with ejaculation was investigated. Male Wistar rats that were pretreated with paroxetine (20 mg/kg/day p.o.) or vehicle for 22 days and had received an additional injection with the 5-HT(1A) receptor agonist 8-OH-DPAT ((+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin; 0.4 mg/kg s.c.) or saline on day 22, 30 min prior to a sexual behavior test, were perfused 1 h after the sexual behavior test. Brains were processed for Fos-, and oxytocin immunohistochemistry. The drug treatments markedly changed both sexual behavior and the pattern and number of Fos-immunoreactive cells in the brain. Chronic pretreatment with paroxetine caused delayed ejaculation. Acute injection with 8-OH-DPAT facilitated ejaculation in vehicle-pretreated rats, notably evident in a strongly reduced intromission frequency, whereas 8-OH-DPAT had no effects in paroxetine-pretreated rats. Chronic treatment with paroxetine reduced Fos-immunoreactivity in the locus coeruleus, and prevented the increase in Fos-immunoreactive neurons induced by 8-OH-DPAT in the oxytocinergic magnocellular part of the paraventricular nucleus as well as in the locus coeruleus. Since oxytocin and noradrenalin facilitate ejaculation, the alterations in Fos-IR in these areas could connect selective serotonin reuptake inhibitor treatment and 5-HT(1A) receptor activation to ejaculation. Chronic paroxetine treatment and 8-OH-DPAT changed c-fos expression in a number of other brain areas, indicating that Fos-immunohistochemistry is a useful tool to find locations where selective serotonin reuptake inhibitors and 8-OH-DPAT exert their effects.

The role of oxytocin in male and female reproductive behavior.

Oxytocin (OT) is a nonapeptide with an impressive variety of physiological functions. Among them, the 'prosocial' effects have been discussed in several recent reviews, but the direct effects on male and female sexual behavior did receive much less attention so far. As our contribution to honor the lifelong interest of Berend Olivier in the control mechanisms of sexual behavior, we decided to explore the role of OT in the present review. In the successive sections, some physiological mechanisms and the 'pair-bonding' effects of OT will be discussed, followed by sections about desire, female appetitive and copulatory behavior, including lordosis and orgasm. At the male side, the effects on erection and ejaculation are reviewed, followed by a section about 'premature ejaculation' and a possible role of OT in its treatment. In addition to OT, serotonin receives some attention as one of the main mechanisms controlling the effects of OT. In the succeeding sections, the importance of OT for 'the fruits of labor' is discussed, as it plays an important role in both maternal and paternal behavior. Finally, we pay attention to an intriguing brain area, the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl), apparently functioning in both sexual and aggressive behavior, which are at first view completely opposite behavioral systems.

The medial forebrain bundle of the rat. I. General introduction.

This paper is the first of a projected series of studies on the structure and composition of the medial forebrain bundle (MFB) of the rat and the relations of this fiber system to its bed nucleus, the lateral hypothalamic area. The first part of the paper comprises an extensive review of literature on the MFB from its discovery by Ganser in 1882 to the present. This review serves as the basis for an evaluation of our present-day knowledge of the organization of the MFB, which is presented in the second part of this paper. Despite the wealth of information available on the origins and sites of termination of the axons that constitute the MFB, surprisingly little attention has been given to the bundle itself, to its topographic boundaries, its fiber composition, or to the spatial arrangement of its constituent components. These features of the MFB as it extends through the lateral preoptic and lateral hypothalamic areas have been analyzed in normal Klüver-Barrera- and Bodian-stained material. From this analysis, a detailed atlas of the MFB and some of the surrounding structures has been prepared. This atlas, which forms the third section of this paper, illustrates the appearance and organization of the MFB at ten equidistant levels through the lateral preoptic and lateral hypothalamic continuum.

Medial forebrain bundle of the rat: IV. Cytoarchitecture of the caudal (lateral hypothalamic) part of the medial forebrain bundle bed nucleus.

In the preceding study (Geeraedts et al.: J. Comp. Neurol. 294:507-536, '90), the rostral or telencephalic portion of the rat's bed nucleus of the medial forebrain bundle (MFB) has been parcellated into several cytoarchitectonically distinct cellular groups and subgroups. The purpose of the present investigation is to subject the caudal or lateral hypothalamic (LH) portion of the MFB bed nucleus to a detailed cytoarchitectonic analysis. This analysis is based on the same materials, methods, and cytoarchitectonic criteria that were also employed in the preceding study. In contrast to descriptions in the literature, it was found that the LH-region constitutes a very heterogeneous population of neurons with an evident arrangement into groups, several of which have not been identified previously. Many of these cellular groups are partly or entirely located within the boundary of the LH-trajectory of the MFB as previously established by Nieuwenhuys et al. (J. Comp. Neurol. 206:49-81, '82). These groups are designated here as the MFB-related cellular groups. They appear to be arranged into two longitudinal zones. Both zones are caudally replaced by the ventral tegmental area (VTA) and a part of the mesencephalic tegmentum (TEGM1). The lateral zone lies in close proximity to the internal capsule/cerebral peduncle and comprises the following cellular groups: the ventrolateral subarea of the lateral hypothalamic area (LHVL), the anterolateral subarea of the lateral hypothalamic area (LHAL), the lateral tuberal nucleus (TUL), the pre-subthalamic nucleus (PSUT), the retro-subthalamic nucleus (RSUT), the anterodorsal subarea of the lateral hypothalamic area (LHAD), and the lateral hypothalamic nucleus (LHN). The medial zone consists of the following cellular groups: the intermediate hypothalamic area (IHA), the medial tuberal nucleus (TUM), the perifornical nucleus (PFX), the lateral supramammillary nucleus (SUL), the submammillothalamic nucleus (SMT), and the nucleus geminus posterior (GEP). The cellular groups of the medial zone together with the tuberomammillary nucleus groups of the medial zone together with the tuberomammillary nucleus (TUMM) are positioned at the interface between the lateral and the medial hypothalamus, and form an array of cellular groups indicated in our study as the intermediate division of the hypothalamus. The MFB-related cellular groups are dorsally, medially, ventrally, and laterally surrounded by rather well-known brain structures. Both the MFB-related cellular groups and the surrounding structures have been identified and delimited. This resulted in a new, elaborate cytoarchitectonic atlas of the rat's lateral hypothalamic region.(ABSTRACT TRUNCATED AT 400 WORDS)

Medial forebrain bundle of the rat: III. Cytoarchitecture of the rostral (telencephalic) part of the medial forebrain bundle bed nucleus.

The boundaries of the medial forebrain bundle (MFB) of the rat have been presented in previous work on the structure of this fiber system (Nieuwenhuys et al.: J. Comp. Neurol. 206:49-81, '82). Neuronal cell bodies within these outlines constitute the bed nucleus of the MFB. Many fiber components of the MFB appeared to be spatially arranged within the bundle and featured an orderly topography (Veening et al.: J. Comp. Neurol. 206:82-108, '82). As the fibers of the MFB are thought to be a major source of afferents to the bed nucleus (Millhouse: In P.J. Morgane and J. Panksepp (eds): Anatomy of the Hypothalamus, Vol. 1. New York: Marcel Dekker, pp. 221-265, '79), the latter has been subjected in this and the companion study (Geeraedts et al.: J. Comp. Neurol. 294:537-568, '90) to a detailed cytoarchitectonic analysis. This analysis is based on continuous series sectioned in the three conventional planes. On the basis of cytoarchitectonic characteristics, including size and shape, staining intensity, packing density, and spatial orientation of the cell bodies, it was found that the bed nucleus of the MFB as described in the literature is by no means a cytoarchitectonic unit per se. Rather, the neuronal cell population located within the telencephalic stream of the MFB can be parcellated into a number of cellular groups, which partly or entirely belong to more-or-less known basal telencephalic structures. These structures are designated here as the MFB-related areas. They correspond largely to the subcommissural substantia innominata (SIC), the sublenticular substantia innominata (SIL), the nucleus of the diagonal band of Broca, the olfactory tubercle, the magnocellular preoptic nucleus (POMA), the lateral preoptic area (LPOA), and the interstitial nucleus of the stria medullaris (ISM). The complex of the MFB-related areas is surrounded by the following cellular entities: the nucleus accumbens (ACB), the caudatus-putamen region (CPU), the globus pallidus (GP), the bed nucleus of the stria terminalis (BST), the anterior amygdaloid area (AAA), the amygdaloid nuclear complex (A), the medial preoptic area (MPOA) and the anterior hypothalamic area (AHA). Both MFB-related areas and their surroundings have been identified and delimited in this study. This resulted in a new cytoarchitectonic atlas of the rat's basal telencephalon. Our atlas does not only show the relative positions of the above mentioned cellular groups, but also those of their subdivisions.(ABSTRACT TRUNCATED AT 400 WORDS)

Anatomical interrelationships of the medial preoptic area and other brain regions activated following male sexual behavior: a combined fos and tract-tracing study.

The medial preoptic nucleus (MPN) is an essential site for the regulation of male sexual behavior. Previous studies using c-fos as a marker for neural activation have shown that copulation increased c-fos expression in the MPN. Neural activation was also present in brain regions that are connected with the MPN and are involved in male sexual behavior, including the posteromedial bed nucleus of the stria terminalis (BNSTpm), posterodorsal preoptic nucleus (PD), posterodorsal medial amygdala (MEApd), and parvocellular subparafascicular thalamic nucleus (SPFp). The present study investigated whether the copulation-induced, activated neurons in these brain regions are involved in the bidirectional connections with the MPN. Therefore, mating-induced Fos expression was combined with application of anterograde (biotinylated dextran amine) or retrograde (cholera toxin B subunit) tracers in the MPN. The results demonstrated that neurons in the BNSTpm, PD, MEApd, and SPFp that project to the MPN were activated following copulation. However, in males that displayed sexual behavior but did not achieve ejaculation, few double-labeled neurons were evident, although both retrogradely labeled neurons and Fos-immunoreactive cells were present. In addition, retrograde neurons that expressed Fos were located in discrete subdivisions within the brain regions studied, where Fos is induced after ejaculation. Likewise, anterogradely labeled fibers originating from the MPN were not distributed homogeneously but were particularly dense in these discrete subdivisions. These results demonstrate that copulation-induced Fos-positive neurons in specific subdivisions of the BNSTpm, PD, MEApd, and SPFp have bidirectional connections with the MPN. Taken together with previous findings, this supports the existence of a discrete subcircuit within a larger neural network underlying male sexual behavior.

Expression of c-fos in the rat brainstem after exposure to hypoxia and to normoxic and hyperoxic hypercapnia.

In this study, Fos immunohistochemistry was used to map brainstem neuronal pathways activated during hypercapnia and hypoxia. Conscious rats were exposed to six different gas mixtures: (a) air; (b) 8% CO2 in air; (c) 10% CO2 in air; (d) 15% CO2 in air; (e) 15% CO2 + 60% O2, balance N2; (f) 9% O2, balance N2. Double-staining was performed to show the presence of tyrosine hydroxylase. Hypercapnia, in a dose-dependent way caused Fos expression in the following areas: caudal nucleus tractus solitarius (NTS), with few labeled A2 noradrenergic neurons; noradrenergic A1 cells and noncatecholaminergic neurons in the caudal ventrolateral medulla; raphe magnus and gigantocellular nucleus pars alpha (GiA); many noncatecholaminergic (and relatively few C1) neurons in the lateral paragigantocellular nucleus (PGCl), and in the retrotrapezoid nucleus (RTN); locus coeruleus (LC), external lateral parabrachial and Kölliker-Fuse nuclei, and A5 noradrenergic neurons at pontine level; and in caudal mesencephalon, the ventrolateral column of the periaqueductal gray (vlPAG). In most of these nuclei, hypoxia also induced Fos expression, albeit generally less than after hypercapnia. However, hypoxia did not cause labeling in RTN, juxtafacial PGCl, GiA, LC, or vlPAG. After normoxic hypercapnia, more labeled cells were present in NTS and PGCl than after hyperoxic hypercapnia. Part of the observed labeling could be caused by stress- or cardiovascular-related sequelae of hypoxia and hypercapnia. Possible implications for the neural control of breathing are also discussed, particularly with regard to the finding that several nuclei, not belonging to the classical brainstem respiratory centres, contained labeled cells.

The medial forebrain bundle of the rat. II. An autoradiographic study of the topography of the major descending and ascending components.

The medial forebrain bundle (MFB) is a complex fiber system that courses through and partly arises and partly terminates within the lateral preoptic and lateral hypothalamic areas. It consists mainly of thin fibers and may be comprised of as many as 50 descending and ascending components of varying lengths and of different origins and/or destinations (Nieuwenhuys et al., '82). With the aid of an an atlas of the MFB and the surrounding brain areas in the rat presented in the preceding paper (Nieuwenhuys et al., '82), the position and topographic relationships of some 21 components of the bundle have been analyzed in detail, in brains that had been prepared for autoradiography following injections of tritiated amino acids into a number of structures that are known to contribute fibers to the MFB. From this analysis it is clear that most of the labeled components occupy specific and rather constant positions within the MFB. For example, the ascending components are largely confined to the dorsal half of the bundle; those arising from the medial preoptic area and the various hypothalamic nuclei are distributed rather diffusely over much of the MFB; and the descending components that arise from the olfactory tubercle and the magnocellular preoptic nucleus are confined to restricted parts of the bundle. These findings indicate that the neurons which occupy different parts of the lateral hypothalamic area probably receive distinctive inputs, and to a first approximation these are likely to be determined principally by their position within the MFB.

Distribution of Fos immunoreactivity following mating versus anogenital investigation in the male rat brain.

In the present study a detailed quantitative analysis was made using Fos as a marker for neural activation to define which subregions in the neural circuitry underlying male sexual behavior are involved in display of anogenital investigation versus copulation. Neural activity was differentially distributed following anogenital investigation versus mating and was restricted to specific subdivisions that form a heavily interconnected network. Chemosensory investigation increased neural activity in the posteromedial subdivision of the bed nucleus of the stria terminalis and the posterodorsal subdivision of the medial amygdala, brain regions that receive chemosensory signals processed through the olfactory bulbs, presumably reflecting the acquisition of chemosensory signals or the display of anogenital investigation. However, other sensory signals or sexual experience may also have contributed to the induction of neural activation in these brain areas. Moreover, consummatory behavior increased neural activity in the subparafascicular nucleus, a brain region that receives genital sensory inputs. In turn, this brain region projects to the medial preoptic nucleus and posterior nucleus of the amygdala, where neural activity was also abundant only following copulation. In addition, clusters of neurons were activated in the posteromedial subdivision of the bed nucleus of the stria terminalis and posterodorsal subdivision of the medial amygdala following consummatory behavior. The present study provides an anatomically detailed picture about the distribution of neural activation following sexual behavior in the rat, specifically in relation to differences following anogenital investigation versus mating.

Efferent connections of the hypothalamic "grooming area" in the rat.

The efferent connections of the hypothalamic area, where grooming can be elicited by local electrical stimulation or injection of various substances, were studied using iontophoretic injections of Phaseolus vulgaris leucoagglutinin. This hypothalamic "grooming area" consists of parts of the hypothalamic paraventricular nucleus and of the dorsal hypothalamic area. The specificity of these efferents for the hypothalamic "grooming area" was investigated by comparison with efferents of hypothalamic sites adjacent to this area. In addition, the distribution of oxytocinergic fibres was studied, since oxytocinergic neurons are present in the hypothalamic "grooming area" and oxytocin is possibly involved in grooming behaviour. The efferents of the hypothalamic "grooming area" as well as of hypothalamic sites surrounding this area and the oxytocinergic fibres studied do not form well determined bundles, but rather spread out throughout the hypothalamus. Clusters of fibres could be traced rostrally and caudally, forming diffuse fibre "streams". Three rostral, two thalamic and three caudal fibre "streams" have been distinguished along which efferent fibres innervate different brain areas. The many varicosities on labelled fibres "en passant" suggest that hypothalamic fibres are able to influence many parts of the brain along their way. The anterior periventricular area, the median preoptic nucleus, the ventral tegmental area and nucleus of the solitary tract were found to be more or less specifically innervated by hypothalamic "grooming area" fibres and oxytocinergic fibres. Other brain areas, like the septum, the medial amygdaloid nucleus, the central gray and the paraventricular nucleus of the thalamus were found to receive efferent projections from the hypothalamic "grooming area" and hypothalamic loci outside this area, as well as from the oxytocinergic system. Within the septum and the mesencephalic central gray, differences in the spatial organization of terminating fibres from the hypothalamic "grooming area" and hypothalamic "non-grooming" sites have been found. Fibres from the grooming area clustered in the ventral part of the lateral septal nucleus, while fibres from surrounding hypothalamic loci innervated other parts of that brain area. In the central gray, fibres from the hypothalamic "grooming area" clustered in rostrodorsal and caudoventral parts. A number of brain areas, that are innervated by hypothalamic "grooming area" fibres and oxytocinergic fibres, like central gray, ventral tegmental area and the noradrenergic A5 area, have been reported previously to be involved in grooming behaviour. It is concluded from the present findings, that the hypothalamic "grooming area" has preferential connections with a number of brain sites, not shared with hypothalamic projections from outside the "grooming area".(ABSTRACT TRUNCATED AT 400 WORDS)

Efferent connections of the striatopallidal and amygdaloid components of the substantia innominata in the cat: projections to the nucleus accumbens and caudate nucleus.

Enkephalin immunoreactivity is used to divide the feline substantia innominata into circumscript subregions, i.e. the "striatopallidal system" and the "extended amygdala". In addition, enkephalin immunoreactivity is used to subdivide the striatopallidal system into two distinct areas, i.e. the subcommissural part of the globus pallidus displaying high enkephalin immunoreactivity and the ventral pallidum displaying moderate enkephalin immunoreactivity. The anterograde axonal transport of Phaseolus vulgaris-leucoagglutinin is used to study the efferents of these areas innervating the caudate nucleus and the nucleus accumbens. It is found that the enkephalin-immunoreactive subcommissural part of the globus pallidus as well as the dorsal enkephalin-immunoreactive regions of the extended amygdala project topographically along a rostrocaudal and mediolateral dimension to the nucleus accumbens. The far rostral parts of the caudate nucleus are found to be innervated by the subcommissural part of the globus pallidus whereas the extended amygdala has no such connection. This pathway is also found to be topographically organized along a mediolateral dimension. The non-enkephalin-immunoreactive area ventral and lateral to the subcommissural part of the globus pallidus is found to have no projections to the nucleus accumbens and caudate nucleus. This region rather innervates the olfactory tubercle. In contrast to the striatopallidal system the sublenticular part of the extended amygdala preferentially projects to the adjoining part of the extended amygdala, i.e. the bed nucleus of the stria terminalis. However, the ventral regions preferentially innervate the medial division of the bed nucleus of the stria terminalis whereas the dorsal regions preferentially innervate the lateral division of the bed nucleus of the stria terminalis. These data indicate that the differential forebrain systems represented in the feline substantia innominata, i.e. the striatopallidal system and extended amygdala have differential output stations. The results are discussed in view of the role of the subcommissural part of the globus pallidus and the nucleus accumbens in orofacial dyskinesia and schizophrenia, respectively.

A topographical analysis of the origin of some efferent projections from the lateral hypothalamic area in the rat.

Some projections from the lateral hypothalamic area in the rat have been investigated, using combinations of fluorescent tracers, injected into several different parts of the central nervous system. Projections appear to arise from loosely organized assemblies of neurons, called sets and from more densely packed assemblies, called clusters. The sets and clusters vary considerably in position and in distinctness of their borderlines. Even within extensive and vaguely defined sets, however, high concentrations of labeled neurons may be present at specified sites in the lateral hypothalamus. Such concentrations are observed in the transitional area of the zona incerta and the dorsal part of the lateral hypothalamus, and in the ventrolateral part of the hypothalamus, bordering the cerebral peduncle and the subthalamic nucleus, in both cases after injections into some "autonomic centers" in the brainstem, such as the parabrachial nuclei and the dorsal vagal complex. Sets and clusters may overlap considerably. Within the fields of overlap the number of double labeled neurons may vary from almost zero up to more than 50%, depending on the injection sites. The results show that different parts of the lateral hypothalamus in the rat have different efferent relationships. Combination of the results of the present study with known data concerning the afferent relationships, the cytoarchitecture and behavioral functions of the lateral hypothalamic area, suggests that different parts of this entity are involved in different regulatory and behavioral functions.

The substantia innominata complex and the peripeduncular nucleus in orofacial dyskinesia: a pharmacological and anatomical study in cats.

It has been shown that orofacial dyskinesia, i.e. a syndrome of abnormal involuntary movements of the facial muscles, can be elicited from the sub-commissural part of the globus pallidus and the adjoining dorsal parts of the extended amygdala in cats. Until now it is unknown whether the peripeduncular nucleus, which receives input from these structures according to anterograde tracing studies, plays a role in the funneling of orofacial dyskinesia to lower output stations. In the present study the connection of the subcommissural part of the globus pallidus and dorsal parts of the extended amygdala with the peripeduncular nucleus was investigated anatomically, using cholera toxin subunit B as a retrograde tracer, and functionally, using intracerebral injections of GABAergic compounds. The anatomical data show that the sub-commissural part of the globus pallidus and dorsal parts of the extended amygdala were marked by cholera toxin sub-unit B-immunoreactive cells following injections of this retrograde tracer into the peripeduncular nucleus. Thus, it could be confirmed that the peripeduncular nucleus receives input from the sub-commissural part of the globus pallidus and dorsal parts of the extended amygdala. Still, the orofacial dyskinesia elicited by local injections of the GABA antagonist picrotoxin (500 ng/0.5 microliters) into the sub-commissural part of the globus pallidus and dorsal extended amygdala was only in part attenuated by local injections of the GABA agonist muscimol (100 ng/l microliters) into the peripeduncular nucleus. Only the number of tongue protrusions was significantly attenuated, but not that of the ear and cheek movements. Furthermore, tongue protrusions, but no additional oral movements, were elicited by picrotoxin injections (375-500 ng) into the peripeduncular nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Efferent connections of the hypothalamic "aggression area" in the rat.

The efferent connections of the hypothalamic area of the rat, where attack behaviour can be elicited by electrical stimulation, were studied using iontophoretic injections of Phaseolus vulgaris-leucoagglutinin. Specificity for the hypothalamic "attack area" was investigated by comparison with efferents of hypothalamic sites outside the attack area. The hypothalamic attack area consists of the intermediate hypothalamic area and the ventrolateral pole of the ventromedial hypothalamic nucleus. Fibres from the hypothalamic attack area, as well as fibres from several other hypothalamic sites, form diffuse fibre "streams" running rostrally or caudally. Many varicosities that are found on the fibres suggest, that these fibres are capable of influencing many brain sites along their way. Projection sites were found throughout the brain. In the comparison between attack area efferents and controls, many overlapping brain sites were found. Hypothalamic efferents preferentially originating in the largest part of the attack area, i.e. the intermediate hypothalamic area, were found in the mediodorsal and parataenial thalamic nuclei. Within the septum, a spatial organization of hypothalamic innervation was found. Fibres from the attack area formed specialized "pericellular baskets" in the dorsolateral aspect of the intermediate part of the lateral septal nucleus. Fibres from other hypothalamic sites were found in other septal areas and did not form these septal baskets. Within the mesencephalic central gray, fibres from the attack area were found specifically in the dorsal part and dorsal aspect of the lateral part of the central gray. Physiological and pharmacological studies have shown that several brain sites are involved in different aspects of aggressive behaviour. Some of these areas, as for instance the dorsomedial thalamic nucleus, septum and central gray, are innervated by efferents from the hypothalamic attack area, whereas other sites, like ventral premammillary nucleus and ventral tegmental area, are not. It is concluded from the present findings, that a number of brain sites, that are known to be involved in agonistic behaviour, receive hypothalamic information preferentially from the hypothalamic attack area through diffusely arranged varicose fibres. The function of each connection in the regulation of specific behaviours remains to be further investigated.

Intravenous administration of interleukin-1 beta induces Fos-like immunoreactivity in corticotropin-releasing hormone neurons in the paraventricular hypothalamic nucleus of the rat.

It has been shown that acute administration of recombinant human interleukin 1 beta (IL-1) to rats elicits an activation of the pituitary-adrenal axis. In the present study we investigated immunohistochemically the expression of Fos-like immunoreactivity (Fos-LI) in the hypothalamus of rats following intravenous injection of IL-1. One, 2 and 4 h after IL-1 or physiological saline injections, rats were killed and perfused, and the brains processed for Fos-immunohistochemistry. Dense populations of neurons containing Fos-LI-positive nuclei were found in the paraventricular hypothalamic nuclei (PVH) of IL-1-treated rats. In particular, the dorsal medial parvocellular part, but also some of the other parvocellular subdivisions contained many Fos-LI neurons. Maximal induction of staining was found at a dose of 5 micrograms/rat after 1 or 2 h survival, while immunostaining had decreased to almost control levels after 4 h. No Fos-LI was found in the PVH of control animals. Double immunocytochemical staining for Fos and corticotropin-releasing hormone (CRH) revealed that Fos-LI was predominantly present in parvocellular CRH-containing neurons of the PVH. The finding that peripherally injected IL-1 induces Fos-LI in hypothalamic CRH neurons strengthens the hypothesis that these neurons are part of the circuitry mediating IL-1-induced activation of the pituitary-adrenal axis.

Descending efferent connections of the sub-pallidal areas in the cat: projections to the lateral habenula.

The descending efferent connections of the sub-pallidal areas to the lateral habenula were investigated in the cat using Phaseolus vulgaris leucoagglutinin (PHA-L) as an anterograde tracer. Several injections of PHA-L were made in various regions of the feline sub-pallidal regions. Subsequently, the distribution of anterogradely labelled fibres in the lateral habenula was charted. PHA-L injections into the rostral part of the sub-pallidal regions resulted in a limited number of labelled fibres in the lateral habenula, while PHA-L injections into the caudal regions of the sub-pallidum resulted in an extensive distribution of anterogradely labelled fibres in this area. Thus, the lateral habenula is an important output structure of the sub-pallidal areas in the cat.