Structure and function of the brain serotonin system.

The differential projections from the dorsal raphe and median raphe nuclei of the midbrain were autoradiographically traced in the rat brain after 3H-proline micro-injections. Six ascending fiber tracts were identified, the dorsal raphe nucleus being the sole source of four tracts and sharing one with the median raphe nucleus. The tracts can be classified as those lying within the medial forebrain bundle (dorsal raphe forebrain tract and the median raphe forebrain tract) and those lying entirely outside (dorsal raphe arcuate tract, dorsal raphe periventricular tract, dorsal raphe cortical tract, and raphe medial tract). The dorsal raphe forebrain tract lies in the ventrolateral aspect of the medial forebrain bundle (MFB) and projects mainly to lateral forebrain areas (e.g., basal ganglion, amygdala, and the pyriform cortex). The median raphe forebrain tract lies in the ventromedial aspect of the MFB and projects to medial forebrain areas (e.g., cingulate cortex, medial septum, and hippocampus). The dorsal raphe cortical tract lies ventrolaterally to the medial longitudinal fasciculus and projects to the caudate-putamen and the parieto-temporal cortex. The dorsal raphe periventricular tract lies immediately below the midbrain aqueduct and projects rostrally to the periventricular region of the thalamus and hypothalamus. The dorsal raphe arcuate tract curves laterally from the dorsal raphe nucleus to reach the ventrolateral edge of the midbrain and projects to ventrolateral geniculate body nuclei and the hypothalamic suprachiasmatic nuclei. Finally, the raphe medial tract receives fibers from both the median and dorsal raphe nuclei and runs ventrally between the fasciculus retroflexus and projects to the interpeduncular nucleus and the midline mammillary body.



Further studies were done to test whether the fiber tracts travelling in the MFB contained 5-HT. Unilateral (left) injections of 5,7-dihydroxytryptamine (5 μgm/400 nl) 18 days before midbrain raphe microinjections of 3H-proline produced a reduction in the grain concentrations in all the ascending fibers within the MFB. Furthermore, pharmacological and behavioural evidence was obtained to show that the 5-HT system had been unilaterally damaged; these animals displayed preferential ipsilateral turning in a rotameter which was strongly reversed to contralateral turning after 5-hydroxytryptophan administration.



The results show that DR and MR nuclei have numerous ascending projections whose axons contain the transmitter 5-HT. The results agree with the neuroanatomical distribution of the 5-HT system previously determined biochemically, histochemically, and neurophysiologically. The midbrain serotonin system seems to be organized by a series of fiber pathways. The fast transport rate in these fibers was found to be about 108 mm/day.

An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat

Hypothalamic Integration: Organization of the Paraventricular and Supraoptic Nuclei

Nucleus locus ceruleus: new evidence of anatomical and physiological specificity

Preface .............................................................. 649

The functional states of the thalamus and the associated neuronal interplay.

The adrenergic innervation of the thalamus, epithalamus, metathalamus, and subthalamus in the rat has been investigated by means of the recently introduced glyoxylic acid fluorescence method. Many areas of the thalamus and adjoining regions, that appear sparsely innervated by catecholamine (CA) fibers in specimens processed according to the standard Falck-Hillarp formaldehyde method, were found to be richly supplied with such fibres in the glyoxylic acid-treated specimens. Moreover, the glyoxylic acid method allows the tracing of the CA axons from the cell bodies up to the terminals, and in combination with stereotaxic lesions the following CA systems to the thalamus could be established: 

1
The locus coeruleus system. Most of these axons ascend in the so-called dorsal tegmental bundle through the mesencephalon and the zona incerta into the medial forebrain bundle. From this bundle branches were traced along several routes, giving rise to extensive terminal systems in many thalamic, metathalamic and pretectal areas, most notably the anterior, ventral and lateral nuclear complexes, and the medial and lateral geniculate bodies.

2
The dorsal periventricular bundle, which constitutes a previously not described adrenergic component of the dorsal longitudinal fasciculus. This system originates in cell bodies (defined as the A11 cell group) in the dorsal raphe region, the central gray of the mesencephalon, and in the periventricular gray of the caudal thalamus. The axons ascend within the dorsal longitudinal fasciculus and give rise to a thalamic and hypothalamic periventricular system, projecting to medial and midline thalamic, epithalamic and pretectal regions.

3
Part of the terminals in the paraventricular thalamic nucleus was identified with a non-locus projection from cell bodies in the pontine or medullary reticular formation.

4
A system of delicate, probably dopamine-containing axons was revealed in the caudal thalamus, the zona incerta and the dorsal and anterior hypothalamus. This system probably originates in the dopamine cell bodies of the diencephalic A11 and A13 cell groups, forming a hitherto unknown intradiencephalic dopaminergic system.





The adrenergic afferent systems to the thalamus can, to a large extent, be regarded as adrenergic components of known ascending reticular projections. The information on the adrenergic systems obtained with the glyoxylic acid method revealed new features of the organization of the thalamic projections from the brain stem reticular formation.

The adrenergic innervation of the rat thalamus as revealed by the glyoxylic acid fluorescence method

Evidence of an incerto-hypothalamic dopamine neurone system in the rat.

Fluorescence histochemical and microspectrofluorometric mapping of dopamine and noradrenaline cell groups in the rat diencephalon.

Autologous adrenal medullary tissue was transplanted unilaterally to the putamen in two patients with severe Parkinson's disease. The first patient exhibited a transient, two-day improvement of motor performance in the limbs contralateral to the implantation site. He also had significantly longer episodes of normal function for about two months. The second patient reported a minor improvement of balance and gait, again lasting for two months. Electrophysiological studies of the motor readiness and auditory evoked potentials were consistent with increased catecholaminergic activity in the basal ganglia after transplantation in both patients. Positron emission tomography showed no postoperative alteration of receptor density in the putamen. No significant adverse effects of the transplantation were observed in the patients' performance on neurological and psychological tests or in their quantitative electroencephalogram and cerebral blood flow recordings. Immediately after the grafting, one patient showed transient signs of sympathetic hyperactivity, probably caused by release of catecholamines from the implanted tissue into the peripheral circulation. We conclude that catecholamine-rich cellular implants in the basal ganglia have transient beneficial effects in patients with severe Parkinson's disease.

Transplantation in Parkinson's disease: two cases of adrenal medullary grafts to the putamen.

The usefulness of three neurotoxic dihydroxytryptamines — 5,6-dihydroxytryptamine, 5,7-dihydroxytryptamine and 4,5-dihydroxytryptamine — for fluorescence microscopical tracing and localized lesioning of central indolamine-containing axon bundles has been studied in the rat brain. The lesions produced by intraventricularly or intracerebrally administered dihydroxytryptamines were found to be much superior to mechanical or electrolytic lesions in producing extensive accumulations of fluorescence in the indolamine axon pathways. This greatly improves the possibilities for tracing of the normally non-fluorescent or weakly fluorescent indolamine axons from their cells of origin for long distances through the main fibre bundles and their branches. Much new information concerning the anatomy of the indolamine neuron systems is obtained with this technique, and some preliminary observations are presented.

Anders Nobin

Papers

The adrenergic innervation of the rat thalamus as revealed by the glyoxylic acid fluorescence method

Evidence of an incerto-hypothalamic dopamine neurone system in the rat.

Fluorescence histochemical and microspectrofluorometric mapping of dopamine and noradrenaline cell groups in the rat diencephalon.

Transplantation in Parkinson's disease: two cases of adrenal medullary grafts to the putamen.

The use of neurotoxic dihydroxytryptamines as tools for morphological studies and localized lesioning of central indolamine neurons