Morphology of neurons and axon terminals associated with descending and ascending pathways of the lateral forebrain bundle in Rana esculenta

Summary The cells of origin of afferent and efferent pathways of the lateral forebrain bundle were studied with the aid of the cobalt-filling technique. Ascending afferents originated from the lateral thalamic nucleus, central thalamic nucleus, posterior tuberculum and the cerebellar nucleus. They terminated in the anterior entopeduncular nucleus, amygdala and the striatum. Telencephalic projection neurons, which are related to the lateral forebrain bundle, were located mainly in the ventral striatum and the anterior entopeduncular nucleus, but were not so numerous in the dorsal striatum. Irrespective of their location, most of the neurons projecting axons into the lateral forebrain bundle had piriform or pyramidal perikarya. Long apical dendrites usually arborized in a narrow space, whereas widely arborizing secondary dendrites originated from short dendritic trunks. The other neurons that contributed to the lateral forebrain bundle were fusiform or multipolar cells. Striatal efferents terminated in the pretectal area and in the anterodorsal, anteroventral and posteroventral tegmental nuclei.     

The effect of medial forebrain bundle lesion on thyrotropin secretion in the rat

The medial forebrain bundle (MFB) was partially lesioned with 6-hydroxydopamine (6-OHDA) in order to investigate the effect of deficient central noradrenergic regulation on thyrotropin (TSH) secretion in the rat. 6-OHDA injection into the MFB significantly reduced the noradrenaline (NA), dopamine (DA) and serotonin (5-HT) content of the whole hypothalamus. NA and 5-HT concentrations were also significantly decreased in the paraventricular nucleus (PVN). The MFB lesion did not affect the clonidine (250 g/kg, i.p.) induced stimulation of TSH release or the isoproterenol (1 mg/kg i.p.) induced decrease in TSH levels. Thyrotropin releasing hormone (TRH, 5 g/kg i.v.) caused a similar significant stimulation of TSH secretion in lesioned and non-lesioned rats. The present results do not support the hypothesis that the blunted TSH response to TRH observed in depressed patients results from a deficiency in noradrenergic neurotransmission.     

The effect of unilateral medial forebrain bundle lesion on 5-hydroxytryptamine in the pigeon brain

Summary The amount of 5-HT was spectrofluorimetrically determined in the brains of normal pigeons and pigeons that had been operated in the left diencephalon. The highest concentration of 5-HT was encountered in a small medial and anterior part of mesencephalon, where both tryptaminergic nerve cell bodies and preterminals occurred. Considerably lower concentrations were found in the diencephalon after removal of the organon vasculosum, which is very rich in both 5-HT and catecholamines. The lowest concentration was recorded in corpora striata, where 5-HT occurs in the form of mostly sub-light-microscopical nerve terminals. After a transversal section of the medial forebrain bundle it could be concluded, on both histochemical and biochemical grounds, that 5-HT is formed and transported in special neurons with their cell bodies in the mesencephalon and nerve terminals in both diencephalon and corpora striata. The most apparent evidence for this was the clear reduction of 5-HT level in the corpora striata of the operated side and the apparent accumulation of fluorescent material proximal to the lesion. An interesting change was also the increase in 5-HT concentration in mesencephalon, diencephalon and corpora striata of the unoperated half of the brain. The opinion was put forward that such an increase could imply some kind of compensation for the reduced transmitter content in the contralateral hemi-brain.     

Polysensory properties of the horizontal region of the diagonal bundle from the cat forebrain

Sharply different wave forms and parameters of averaged evoked potentials (EP) in response to single visual and somatic stimuli were observed in the same points of the horizontal limb nucleus of the diagonal band (NDB) in cats under nembutal anesthesia. The existence of heterogenic EPs in NDB makes it possible to consider this part of the nucleus as a polysensory structure. Decreased EP latency, as compared to that in the neocortex, indicates that heterogenic impulses reach NDB by higher speed Ways than the cortex. The comparison of NDB EP refractory periods during paired stimulation of one or different sensory systems shows that polyvalent impulses affect independently functioning neuronal populations. It is suggested that a common principle of specific heterogenic signals arrival to distinct neuronal complexes exists for polysensory structures at different levels of the central nervous system.     

Light and electron microscopic studies on the medial forebrain bundle in the rat. ii. nerve terminals from the medial hypothalamus.

After the surgical interruption of connections between the medial and lateral hypothalamus of the rat axonal (transient) and nerve terminal degeneration was shown in the medial forebrain bundle (MFB) with light and electron microscopy. Following 1 mm long parasagittal cuts at various rostro-caudal levels the degeneration pattern within the MFB indicated a certain territoral arrangement of terminating fibres from the medial hypothalamus. After a parasagittal cut through the lateral retrochiasmatic area, degeneration was observed in the full length of the MFB. This suggests that a number of axons connect the medial and lateral hypothalamus through this area. With the aid of a parasagittal cut separating totally the medial and lateral hypothalamus, the degeneration of dendrites in the middle portion of the lateral hypothalamus was also revealed. These proved to derive from cells of the ventromedial nucleus.     

Effects of dopaminergic drugs and acute medial forebrain bundle lesions on striatal acetylcholine levels.

Placement of radio frequency lesions in the medial forebrain bundle resulted in a 50% depletion of striatal acetylcholine levels but did not change hippocampal levels. A similar result was obtained with the administration of chlorpromazine, haloperidol and pimozide. When these drugs were administered simultaneously with placement of lesions, there was the same 50% depletion of striatal acetylcholine. Apomorphine reversed the depletion due to lesions. These results suggest that the action of antipsychotic drugs on the cholinergic system in the striatum is primarily due to their action at dopamine receptors rather than a direct action on cholinergic receptors which would be due to their anticholinergic activity.     

Axonal transport in nigro-striatal and nigro-thalamic neurons: effects of medial forebrain bundle lesions and 6-hydroxydopamine

—Axonal transport was studied in two efferent projections of the substantia nigra: (1) the nigro-striatal system; and (2) the nigro-thalamic system. [¹⁴C]leucine was injected stereotaxically into the left substantia nigra of rats. At various intervals thereafter significant amounts of [¹⁴C]protein were found in the midbrain (which surrounded the injection site), hypothalamus, thalamus and corpus striatum on the injected side of the brain. By determining the temporal characteristics of the distribution of [¹⁴C]protein, axonal transport from the substantia nigra to the thalamus and corpus striatum could be inferred. Fast (approximately 50 mm/day) and slow (approximately 1 mm/day) rates of flow were evident in both systems. Either electrolytic lesions of the medial forebrain bundle or intraventricular pretreatment with 6-hydroxydopamine (200 μg) produced a substantial decrease in the amount of labelled protein reaching the corpus striatum but not in that reaching the thalamus. The decrease following electrolytic lesions correlated significantly with the decrease in the activity of striatal tyrosine hydroxylase, but after 6-hydroxydopamine the decrease in axonal transport was consistently less than the loss of striatal tyrosine hydroxylase. This difference indicated that a portion (perhaps as much as 20 per cent) of the nigro-striatal neurons are non-catecholaminergic. Finally, we present data which suggest that in contrast to effects on peripheral neurons, 6-hydroxydopamine destroys the cell bodies as well as nerve terminals of adrenergic neurons in the central nervous system.     

Cell types within the medial forebrain bundle: a Golgi study of preoptic and hypothalamic neurons in the rat

The morphology of lateral preoptic (POL) and lateral hypothalamic (HLA) neurons was studied in 14- to 200-day-old rats with the chlorate-formaldehyde modification of the Golgi method. Drawings of 91 POL and HLA neurons revealed three distinct neuronal types within the MFB based on somatic size and shape and dendritic morphology. Class I neurons, which accounted for 75-80% of the neurons in the MFB, has fusiform or multipolar somata averaging 21 X 14 micron and 2-5 sparsely branched dendrites with a moderate number of sticklike spines. The extensive dendritic domains of Class I neurons ranged from 700 to 1,500 micron and were usually oriented perpendicular to the longitudinal fibers of the MFB. Both nonoriented and oriented Class I neurons were encountered. Nonoriented Class I neurons had expansive dendritic arbors which reached nearly all regions of the MFB in the coronal plane. Oriented Class I neurons had dendritic domains which were confined to specific regions (e.g., ventral-lateral) of the MFB. Class II neurons, which made up approximately 10% of the MFB neurons, had large multipolar somata averaging 30 X 17 micron and 2-5 stout dendrites which were densely covered with hairlike spines. Class II neurons also exhibited spines on their somata and proximal dendritic trunks and had dendritic domains of 700-1,000 micron. Class III neurons had small somata averaging 15 X 12 micron and restricted dendritic arbors of 500-700 micron in diameter. Class III neurons exhibited both spiny and spine-free dendrites and made up 10% of MFB neurons. Because of the parcellation of chemically coded fiber systems within the MFB, individual POL and HLA neurons may not be homogeneous in the type of afferents they receive from other brain areas.     

Kinetic analysis of 3H-serotonin accumulation in four regions of rat brain after lesions in the medial forebrain bundle

Kinetic analysis of ³H-serotonin accumulation by crude synaptosomal suspensions of neocortex, hippocampus and caudate or by whole homogenates of cerebellum revealed the presence of a high affinity uptake component having an apparent K_m for serotonin which ranged from 2.8 to 6.0 × 10^?8 M. A second, low affinity, uptake component with an apparent K_m of 7 × 10^?6 M was present in caudate. A comparable low affinity uptake component for serotonin was not observed in neocortex, hippocampus or cerebellum. Lesions in the medial forebrain bundle produced significant decreases in serotonin comtent of neocortes, hippocampus and caudate (66 to 75%) and a significant increase in serotonin content of cerebellum (25%). The lesions did not affect the apparent K_m of the high affinity uptake system but did produce change in V_max which paralleled the changes in content of serotonin. The lesions also produced decreases in dopamine and norepinephrine content of caudate and a comparable decrease in the V_max of the low affinity uptake system with no change in the apparent K_m. There was a correlation of 0.97 between the endogenous content of serotonin and the V_max of the high affinity uptake system. These results support the view that the high and low affinity components of serotonin uptake represent accumulation into serotonergic and catecholaminergic neurons, respectively.     

Effect of destruction of the medial forebrain bundle on synaptic organization of the supraoptic nucleus of the rat hypothalamus

An electron-microscopic investigation was made of the synaptic organization of the supraoptic nucleus (SON) of the albino rat hypothalamus before and after electrolytic destruction of fibers of the medial forebrain bundle (MFB). Two types of axon terminals, tentatively of cholinergic (type I) and monoaminergic (type II) nature, are described in the nucleus. In intact animals type I terminals account for 30% and type II for 70%. Both types of terminals form axo-dendritic, axo-somatic, and axo-axonal contacts. Five days after bilateral electrolytic destruction of MFB 13.5% of terminals degenerated in SON, as shown by swelling of the synaptic vesicles, their redistribution in the terminal, and vacuolation of the terminal. Quantitative analysis of preserved endings and comparison with results obtained on intact animals show that mainly type II axon terminals, presumably monoaminergic in nature, degenerate. The decrease in the number of these terminals after destruction of MFB is evidence of the mainly monoaminergic nature of fibers running in this bundle to SON, and it enables the pattern of distribution of different types of axon terminals in the nucleus to be characterized quantitatively.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 227–232, May–June, 1982.     

Descending monoaminergic pathways in the primate spinal cord.

The distribution of monoamine axons and terminals within the spinal cord of a primate (Macaca mulatta) was studied with the Falck-Hillarp histofluorescence technique for the demonstration of biogenic amines. Catecholamine and indoleamine varicosities appeared qualitatively similar to those previously reported for the rat although the indoleamine terminals were difficult to visualize and were not studied in great detail. Catecholamine fibers innervate the substantia gelatinosa, marginal layer, intermediolateral cell column, ventral horn and the region surrounding the central canal. The location of monoamine axons, as revealed by spinal cord ligation, corresponds to that in the rat and cat with the exception of the dorsolateral region of white matter where fluorescent axons are not visible in the primate.     

ACTH-immunoreactive neurons and their projections in the cat forebrain

The organization of adrenocorticotropin (ACTH)-immunoreactive (IR) cell bodies and fibers in the cat forebrain is described. ACTH-IR cell bodies are found only in and around the arcuate nucleus of the hypothalamus (ARH). They are not detected elsewhere even after pretreatment with colchicine. ACTH-IR fibers are present in discrete areas of the hypothalamus, the septo-limbic areas and in the paraventricular thalamic nucleus. Complete electrolytic lesions of the ARH destroy ACTH-IR cell bodies as well as fibers in all parts of the brain. These results suggest that, in the cat forebrain, the ARH is the only source of ACTH-IR fibers.     

6-羟基多巴胺损毁大鼠内侧前脑束早期黑质-纹状体系统的铁水平与多巴胺能神经元退变的关系

应用快速周期伏安法(fast cyclic vohammetry,FCV)、原子吸收分光光度法及免疫组织化学方法,观察了6-羟基多巴胺(6-hydroxydopamine,6-OHDA)单侧损毁大鼠内侧前脑束(medial forebrain bundle,MFB)早期黑质(sub-stantia nigra,sN)铁水平与多巴胺(dopamine,DA)神经元损伤的变化,以及纹状体(striatum,Str)的DA释放。结果如下：6-OHDA单侧损毁大鼠MFB1d和3d后,SN的酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性细胞分别下降了45％和66％;与正常鼠和未损毁侧相比,损毁侧SN的铁染色增强,铁浓度增加,而Str的DA释放量不变;6-OHDA损毁后1d与3d组相比,损毁侧的铁染色、铁浓度及DA释放量差别无显著性。上述结果表明,6-OHDA单侧损毁大鼠MFB的早期阶段,SN的DA能神经元数目中等程度减少时,铁染色及铁浓度即有增加,由于DA能神经系统有强大的代偿功能,使得Str的DA释放量仍趋于正常。     

Theory for the impact of basal turnover on dopamine clearance kinetics in the rat striatum after medial forebrain bundle stimulation and pressure ejection

Although microdialysis measurements suggest that extracellular dopamine concentrations in the rat striatum are in the low nanomolar range, some recent voltammetry studies suggest that the concentration may be considerably higher, perhaps in the micromolar range. The presence of such high dopamine levels in the extracellular space has to be rationalized with the rapid, linear clearance of extracellular dopamine observed after electrical stimulation of the medial forebrain bundle. Kinetic analysis of dopamine clearance after evoked release suggests that the basal extracellular dopamine concentration is below the K(M) of dopamine uptake, which is near 0.2 microm. However, dopamine clearance after pressure ejection of dopamine into the rat striatum is slow and non-linear, which may alternatively be a sign that basal dopamine release is only slightly slower than the maximal velocity of dopamine uptake, Vmax. A high basal extracellular dopamine concentration would exist if basal dopamine release were only slightly slower than the Vmax of uptake. This report introduces a new kinetic analysis of dopamine uptake that sheds light on the possible source of the different clearance rates observed following evoked dopamine release and dopamine pressure ejection. Furthermore, the analysis rationalizes the rapid dopamine clearance after evoked release with the possibility that basal extracellular dopamine levels are above the K(M) of the transporter.