The rostromedial tegmental nucleus modulates the development of stress-induced helpless behavior.

A growing body of clinical and preclinical research suggests that structural and functional changes in the habenula, a component of the epithalamus, are associated with major depressive disorder. A major excitatory, efferent projection from the habenula targets the rostromedial tegmentum (RMTg), a mesopontine region that provides significant input to the ventral tegmentum and raphe nuclei. While the RMTg contributes to monoaminergic responses to aversive events, its role in stress-based animal models of depression has yet to be determined. In the present study, we test the hypothesis that the RMTg is a component of the circuitry mediating the development of a maladaptive behavior in which rats repeatedly exposed to inescapable footshock, fail to avoid or escape the same stressor when subsequently given the opportunity to do so. Excitotoxic lesions of the RMTg significantly diminished the frequency of these escape failures 24 h after exposure to inescapable footshock. Conversely, electrical stimulation of the Hb during the initial uncontrollable aversive event, a manipulation that enhances excitatory input to the RMTg, increased the number of trials in which subjects failed to escape an aversive stimulus when presented the option 24 h later. These complementary results provide evidence supporting a role for the RMTg in the expression of stress-induced helpless phenotype and are an important step in understanding the contribution made by this region to the development of depression-related maladaptive behaviors.

Dystonia associated with pontomesencephalic lesions.

Secondary dystonia is well known subsequent to lesions of the basal ganglia or the thalamus. There is evidence that brainstem lesions may also be associated with dystonia, but little is known about pathoanatomical correlations. Here, we report on a series of four patients with acquired dystonia following brainstem lesions. There were no basal ganglia or thalamic lesions. Three patients suffered tegmental pontomesencephalic hemorrhage and one patient diffuse axonal injury secondary to severe craniocerebral trauma. Dystonia developed with a delay of 1 to 14 months, at a mean delay of 6 months. The patients' mean age at onset was 33 years (range 4-56 years). All patients presented with hemidystonia combined with cervical dystonia, and two patients had craniofacial dystonia in addition. Three patients had postural or kinetic tremors. Dystonia was persistent in three patients, and improved gradually in one. There was little response to medical treatment. One patient with hemidystonia combined with cervical dystonia improved after thalamotomy. Overall, the phenomenology of secondary dystonia due to pontomesencephalic lesions is similar to that caused by basal ganglia or thalamic lesions. Structures involved include the pontomesencephalic tegmentum and the superior cerebellar peduncles. Such lesions are often associated with fatal outcome. While delayed occurrence of severe brainstem dystonia appears to be rare, it is possible that mild manifestations of dystonia might be ignored or not be emphasized in the presence of other disabling deficits.

Lesions of the dorsal noradrenergic bundle augment the renin response to blood loss but do not alter hypothalamic Fos expression.

The goal of this study was to determine if the dorsal noradrenergic bundle (DNAB) plays an essential role in mediating increased plasma renin activity (PRA) and hypothalamic activation, as indicated by increased Fos expression, in response to a small volume blood loss in unanesthetized animals. Male Sprague-Dawley rats were prepared with bilateral 6-hydroxydopamine or sham lesions of the dorsal noradrenergic bundle. In both groups of animals, blood pressure decreased by only 10-15 mmHg following hemorrhage (10 ml/kg over 15 min). Plasma renin activity increased similarly in both groups after 5 ml/kg blood loss, but showed a significantly greater increase after 10 ml/kg blood loss in animals with 6-hydroxydopamine lesions than in those with sham lesions (increase of 13.8 +/- 2.0 ng/ml/h versus 8.4 +/- 1.2 ng/ml/h; P < 0.025). There were numerous Fos-immunoreactive cell nuclei in the supraoptic nucleus (SON) and parvicellular paraventricular hypothalamic nucleus (PVN) of hemorrhaged animals. The number of Fos-positive neurons did not differ between groups, indicating that the dorsal noradrenergic bundle does not convey the primary drive for supraoptic and paraventricular nucleus activation during blood loss. However, one or more of the forebrain regions innervated by the dorsal noradrenergic bundle may attenuate the sympathetic outflow that initiates renin release in response to hemorrhage.

Experimental parkinsonism in primates.

Early in the 1960s the primate model of Parkinson's disease was first introduced by placing an electrolytic lesion in the midbrain. In the 1980s, a dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was accidentally shown to induce parkinsonism in humans, and subsequently was confirmed to reproduce an almost perfect model of parkinsonism in primates. In the late 1980s chemical manipulations of the basal ganglia were shown to induce parkinson symptoms, especially dyskinesia, and more recently, chemical lesioning of the pedunculopontine tegmental nucleus has also been shown to induce parkinsonism. We still do not have a perfect animal model of parkinsonism, however, these models have offered excellent opportunities to study the basic mechanisms in parkinsonism and the function of the basal ganglia.