Electron microscopic analysis of the mesencephalic ventromedial tegmentum in the cat

We have studied the normal ultrastructure of the ventral mesencephalic tegmentum (VMT) in the cat, particularly the morphology and distribution of presynaptic terminals and the types of synaptic junctions. The following subnuclei of the region were examined: n. linearis rostralis (LR), n. paranigralis (PN), and n. interfascicularis (IF). The qualitative and quantitative data revealed significant ultrastructural differences between these subnuclei. Each subnucleus had a characteristic dendritic structure. In LR the dendrites were nonspinous and cylindrical and had presynaptic terminals randomly distributed over their surface. In PN we observed varicose dendrites with spines; the presynaptic terminals formed clusters on the narrow segments of the dendrites and around the spines. Dendrodendritic synapses were also observed in this nucleus. In IF, there was an internal division regarding dendritic structure: in the rostral part of the nucleus there were cylindrical dendrites while in the caudal part irregularly shaped dendrites bearing long spines were found. In IF and LR some of the cylindrical dendrites were seen to be in direct contact with the basal lamina of blood vessels. Four types of presynaptic terminals were distinguished by the morphology of their vesicles, and the proportion of each type in the total terminal population was determined. On this basis the compositions of the presynaptic terminal population in the three subnuclei were found to be very similar. Most terminals contained clear, round vesicles (62.6%), or both clear and dense-cored vesicles (35.1%). Few terminals were seen with dense-cored vesicles only (1.4%) or with pleomorphic vesicles (0.9%). The majority of synapses in the VMT were found to have symmetrical densities. LR had twice as many asymmetrical synapses as the other two subnuclei. Eighty percent of the terminals formed synapses with dendrites, although axosomatic and axoaxonic synapses were also seen. The density of the terminals was significantly different for each subnucleus: 191/1,000 micrometers 2 in IF, 120/1,000 micrometers 2 in PN, and 81/1,000 micrometers 2 in LR. These data indicate that while the subnuclei of the VMT receive morphologically similar afferents, each has a unique way of processing the information provided by them, through a different internal circuitry.     

Serotonin-like immunoreactive cells and fibres in the rat ventromedial mesencephalic tegmentum

The distribution and morphology of serotonin-like immunoreactive (5HT-IR) nerve cells, fibres and terminals in the rat ventromedial mesencephalic tegmentum (VMT) was studied using qualitative and quantitative immunohistochemical methods at light and electron microscopic levels. All five component nuclei were examined and the size, number and density of immunoreactive neurons and terminals determined. Thirty percent of all neurons in the caudal linear nucleus and 1% in the interfascicular nucleus were immunoreactive for serotonin. Different regions of the VMT had morphologically distinct 5HT-IR fibres and quantitative differences between the VMT nuclei were seen in the density of 5HT-IR terminals. In the lateral VMT, many thick, nonvaricose 5HT-IR fibres were found in the parabrachial pigmented nucleus while many fine, varicose 5HT-IR fibres were found in the paranigral nucleus. Fine, varicose 5HT-IR fibres were also seen in the rostral and caudal linear nuclei. Many 5HT-IR axon profiles formed synapses with small calibre dendrites. 5HT-IR fibres in the interfascicular nucleus were thick with variable sized varicosities at irregular intervals. Few 5HT-IR axon profiles formed synapses in this nucleus. A comparison between the number of 5HT-IR terminals and the total number of axon terminals in the VMT (25) reveals that the majority of all terminals in the paranigral and rostral linear nuclei can be labelled with serotonin. The effect of serotonin on VMT cells is therefore likely to be mediated by different types of 5HT-IR fibres which preferentially innervate particular VMT nuclei.     

Substance P-like immunoreactive fibres in the ventromedial mesencephalic tegmentum of rat

The distribution and morphology of the substance P-like immunoreactive (SP-IR) fibres and terminals in the rat ventromedial mesencephalic tegmentum (VMT) were studied using qualitative and quantitative immunohistochemical methods at light and electron microscopic levels. All five component nuclei of the VMT were examined and the size, number and density of immunoreactive terminals determined. The SP-IR fibres were distributed heterogeneously within the VMT. Under the electron microscope, SP-IR axon terminals contained both clear and dense-cored vesicles and made both symmetrical and asymmetrical synapses. The ultrastructure of the SP-IR terminals appeared to differ between nuclei. Small, clear vesicle terminals made symmetrical synaptic junctions with small calibre dendrites in the paranigral nucleus while large, clear and dense-cored vesicle terminals made asymmetrical junctions with somata and large calibre dendrites in the interfascicular nucleus. Quantitative differences between the VMT nuclei were also seen in the density of SP-IR terminals, the paranigral nucleus contained the highest density and the rostral linear nucleus the lowest. A comparison between the number of SP-IR terminals and the total number of axon terminals in the VMT reveals that the majority of all terminals in the paranigral nucleus were SP-IR, as well as the majority of axosomatic synapses in the interfascicular nucleus. These regional differences in the SP-IR innervation suggest that substance P and related peptides may perform several specific functions within the VMT and therefore have a more variable influence on this region than was previously thought.     

Bilateral paresis of the superior oblique muscle caused by hematoma of the mesencephalic tegmentum

Primary hematomas of the brain stem are rare. We report the case of a small spontaneous mesencephalic hematoma which occurred in a 50 year-old normotensive male patient. The hematoma produced paresis of the superior oblique muscle and a lesion of the left spinothalamic tract. The outcome was favourable.     

Seizures induced by thinking

A patient with generalized convulsions noted that seizures were reliably precipitated by mental arithmetic. The interictal electroencephalogram revealed only a mild, diffuse, nonspecific disturbance, but bursts of generalized epileptiform activity with no obvious clinical expression accompanied efforts at mental arithmetic with a significantly high incidence. Tasks involving multiplication, division, and manipulation of spatial information were significantly associated with discharges, but few, if any, discharges appeared when addition and subtraction tasks of equivalent difficulty were performed. Tasks involving the retention of numerical information in short-term memory (e.g., immediate repetition of a series of 8 digits) were never associated with paroxysmal EEG activity. It is argued that generalized epilepsy of this kind may be related to focal dysfunction in a manner analogous to the involvement of the occipital lobe in cases of pattern-sensitive epilepsy.     

Seizures induced by exercise

Three patients had a clinical history of epileptic seizures during exercise. In all three patients, generalized epileptiform EEG abnormalities were activated by exercise, whereas none had paroxysms during resting wakefulness or during hyperventilation, and only one had a paroxysmal discharge during sleep. Advice to epileptic patients about physical activity should be based on a careful history of individual tolerance. In doubtful cases, an EEG recorded during exercise can provide evidence for an epileptic mechanism.     

Behavioural deficits induced by an electrolytic lesion of the rat ventral mesencephalic tegmentum are corrected by a superimposed lesion of the dorsal noradrenergic system

The bilateral electrolytic lesion of the ventral mesencephalic tegmentum (VMT) induces, in the rat, behavioural deficits such as locomotor hyperactivity and disappearance of spontaneous alternation ('VMT syndrome'). When a specific 6-hydroxy dopamine (6-OHDA) destruction of the dorsal noradrenergic (NA) ascending pathway was superimposed to an electrolytic lesion of the VMT, animals recovered a normal locomotor activity and the possibility to alternate. Since many studies indicate that the development of the 'VMT syndrome' is linked to the disruption of the dopaminergic (DA) meso-cortico-limbic transmission, it is proposed that the recovery observed is due to an interaction between NA and DA ascending systems in cortical and/or subcortical structures; noradrenergic innervation would have a permissive role on the expression of the 'VMT syndrome', possibly via a mechanism of heteroregulation of DA receptors by NA fibers.     

Discharges of neurons in the midpontine dorsal tegmentum of mesencephalic cat during locomotion

Discharges of neurons in the midpontine dorsal tegmental field (DTF neurons) were recorded and analyzed during locomotion and were compared with those of reticulospinal neurons (RS neurons) located lateral to the DTF area. The conduction velocity of the descending axon of the DTF neurons was significantly smaller than that of the RS neurons. During locomotion, the DTF neurons showed a tonic increase in the discharge rate. In contrast, the discharge rate of the RS neurons showed cyclic modulation in step with locomotion.     

Rhythmic slow wave activity recorded in the ventral mesencephalic tegmentum in the rat.

1. Slow rhythmic theata-type waves were recorded in the sub-interpeduncular ventral mesencephalic tegmentum (VMT) in the rat. This region is one of the parts of the "limbic midbrain area". These waves are recorded during certain attentive waking states, during the execution of voluntary movements and during paradoxical sleep. 2. These rhythmic VMT waves seem to be of the same nature as the theta rhythm recorded in the limbic structures. A lesion of the septum suppresses the slow rhythmic waves at the mesencephalic level as well as at the telencephalic level. 3. Although we have now shown that the mesencephalic and telencephalic slow rhythmic waves have the same pacemaker, the pathways which transmit the theta rhythm to the VMT are not well known. However, it is reasonable to suppose that the fibres of the post-commissural fornix are involved in this transmission.     

Radiofrequency lesion of the ventral mesencephalic tegmentum: Neurological and behavioral considerations

Radiofrequency ablation of the ventral mesencephalic tegmentum provoked hyperactivity and hyper-reactivity in rats. The critical lesion zone for the appearance of hyperactivity surrounds the nucleus interpeduncularis, a region occupied by fibers corresponding to the fasciculus medialis prosencephali and by the A10 group of mesolimbic dopaminergic cells. The behavioral syndrome appeared 8 days after the lesions and persisted throughout the experiment (210 days), whereas only minor sleep disturbances were observed in animals with lesions. A role of the A10 mesolimbic dopaminergic system in the behavioral effects of these lesions in rats is discussed.     

Seizures induced by playing music

A 67-year-old organist and minister with diabetes mellitus had stereotyped focal seizures of the left lower face, jaw, and neck. Attacks occurred spontaneously or were induced when he played a specific hymn on the organ. The seizures were not induced by reading, singing, hearing, or playing the hymn silently. The patient had interictal weakness of the left lower face and left side of the tongue. Focal seizures were recorded on an electroencephalogram (EEG) at the right temporofrontal area. This patient illustrates partial seizures induced by playing music.     

Release of dopamine from coaggregate cultures of mesencephalic tegmentum and corpus striatum

Dissociated dopamine (DA) neurons from 14-day fetal mice were dissected from the rostral mesencephalic tegmentum (RMT) and were allowed to reaggregate in vitro with cells from the corpus striatum (CS). As previously demonstrated under these conditions, DA neurons develop punctate fluorescent varicosities and the capacity to synthesize, accumulate, and retain DA (Kotake, C., P. C. Hoffmann, and A. Heller (1982) J. Neurosci. 2: 1307-1315). After 17 to 22 days in culture, the RMT-CS coaggregates were assessed for their ability to release DA. Coaggregates were incubated in 5.6 x 10(-6) M [3H]DA, washed, and then superfused at 100 microliters/min for 2 hr. Fractions were collected every 2 min. Basal efflux of [3H]DA/2 min was 1% of tissue stores of 3H. K+, 70 mM infused for 8 min induced a peak release of 5.87% of tissue stores of 3H, and 50 mM K+ induced a peak release of 2.13%. The potassium-induced release of [3H]DA was calcium dependent. When d-amphetamine was infused for 12 min, 100 microM solutions induced a peak release of 8.91%, 10 microM induced a peak release of 4.36%, and 1 microM induced a peak release of 1.85% of tissue stores of 3H. Substance P at 100 microM induced a peak release of 2.19% of tissue stores of 3H. Tetrodotoxin (0.5 and 2.5 microM) decreased basal efflux by 40%, blocked substance P-induced release, but did not affect either potassium- or d-amphetamine-induced release of [3H]dopamine.