Neural correlates of sensory gating in the rat: decreased Fos induction in the lateral septum.

In the P(50) gating or conditioning-testing paradigm in the rat, two identical click stimuli are presented with an inter-click interval of 500 ms. The reaction towards the second click, as measured with evoked potentials, is reduced in respect to that towards the first click; this phenomenon is called sensory gating. In the present experiments, the inter-click interval was varied systematically and auditory evoked potentials were measured. Sensory gating was found to occur only at intervals between 500 and 1000 ms, but not at longer intervals. Fos immunohistochemistry was then performed using two groups of rats exposed to double clicks: the inter-click interval was 500 ms in the experimental group and 2500 ms in the control group. Fos induction was analyzed in selected brain structures. In the auditory pathways, Fos-immunoreactive neurons were found in both groups of rats in the inferior colliculus and medial geniculate body. Fos-immunoreactive cells were also examined in the septum and hippocampus. In the ventral part of the lateral septal nucleus, the labeled neurons were significantly fewer in the experimental animals compared to the control group. Smaller and non-significant quantitative differences of Fos-positive neurons were documented in the medial septum and hippocampal CA1 region. These data point out a selective decrease in the lateral septum of Fos induced by auditory sensory gating, and suggest an involvement of this structure, and possibly of other parts of the septo-hippocampal system, in sensory gating mechanisms. The results might be relevant for theories on sensory gating deficits in schizophrenia.

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.

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.

Descending efferent connections of the sub-pallidal areas in the cat: projections to the subthalamic nucleus, the hypothalamus, and the midbrain.

The efferent connections of the sub-pallidal regions to the mediodorsal thalamic nucleus, the subthalamic nucleus, the lateral hypothalamic area, and the midbrain were investigated in the cat, using Phaseolus vulgaris--leucoagglutinin (PHA-L) as an anterograde label. The results indicate that the sub-pallidal regions of the cat project to the (dorso)medial tip of the subthalamic nucleus and the adjoining lateral hypothalamic area as well as to the ventral tegmental area and the greater extent of the dorsolateral tier of the substantia nigra pars compacta. Extensive projections were also found to the peripeduncular nucleus. The central gray as well as the mesencephalic locomotor region receive some input from the basal forebrain too. In contrast only very limited projections were found to the mediodorsal thalamic nucleus. The results are discussed in view of the possible role of these output regions in oro-facial dyskinesia.

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)

Behavioural responses of bicucculline methiodide injections into the ventral hypothalamus of freely moving, socially interacting rats.

Several studies, using electrical stimulation of parts of the hypothalamus, have shown, that different parts of the hypothalamus yield different behavioural responses upon stimulation. In order to differentiate between stimulation of neuronal cell bodies and passing fibres and to investigate the role of GABA in hypothalamically elicited behaviour, 25 local injections with bicucculline methiodide, a GABA antagonist, (35 ng/0.2 microliter) were performed in the ventral parts of the hypothalamus of 16 freely moving rats in a social environment. A cannula system was used that allowed injection without interruption of the ongoing social interactions. Digging, gnawing, drinking and attack behaviour were elicited in different animals. By plotting the behavioural responses of the animals into a detailed hypothalamic atlas, we assessed the hypothalamic distribution of the elicited behavioural responses. A number of injections elicited a combination of two or three different responses, probably due to diffusion of the substance, thus disinhibiting more than one behavioural system. Our results are in general agreement with previous electrical stimulation data and show that, in an overlapping pattern, different populations of neurons are involved in the elicitation of digging, gnawing, drinking and attack behaviour. In the hypothalamus, a tonic GABAergic inhibition of neurons involved in the display of these types of behaviour appears to exist.

Brain and behaviour: morphological and functional aspects of the hypothalamus in the rat.

In a short historical overview some developments in the behavioural research of the hypothalamus of the rat are introduced. Especially the ventromedial and the lateral hypothalamus have received much attention in the past. Numerous different behavioural effects have been described as the result of some kind of activation or inactivation of parts of the hypothalamus in the rat. Questions concerning the topographical distribution and the specificity of the effects observed, are addressed in the later parts. These behavioural observations were very important for the comparison with our anatomical observations concerning the hypothalamus, including the topographical organization of some afferent and efferent relationships. Non-synaptic or paracrine communication may play an important role in the hypothalamic effects on the organization of behaviour.

Grooming induced by intrahypothalamic injection of ACTH in the rat: comparison with grooming induced by intrahypothalamic electrical stimulation and i.c.v. injection of ACTH.

Intracerebroventricular (i.c.v.) injection of adrenocorticotropic hormone (ACTH) elicits grooming in the rat, but the neural organization of this response is still obscure. Electrical stimulation (EHS) in an area around the hypothalamic paraventricular nucleus (PVH) also elicits grooming. This hypothalamic area contains many ACTH-immunoreactive fibres. Injection of ACTH1-24 (0.3 microgram/0.3 microliters) in the same area elicits intense grooming responses in the rat. Latency, intensity and precise patterning of the grooming response are dependent upon the exact site of injection. Comparison of grooming responses elicited by EHS, ACTH injected i.c.v. and ACTH injected in the PVH reveals that these are slightly dissimilar. This may provide clues as to the brain mechanisms involved in the organization of the different components of grooming. EHS does not elicits scratching and even reduces 'spontaneous' scratching. Also, EHS-elicited grooming is characterized by short pauses. The time-course of appearance of yawning differs between ACTH-PVH and ACTH-i.c.v. injections. Excited locomotion elicited only by ACTH-i.c.v. is apparently caused by ACTH-sensitive systems outside the PVH. The results suggest that the ACTH-containing part of the hypothalamus around the PVH is crucially involved in the organization of grooming behaviour. We believe that at this level in the brain, the subroutines of grooming, scratching and yawning are integrated into one skin maintenance behaviour.

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 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.

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.