The Retinohypothalamic tract: Comparison of axonal projection patterns from four major targets

The retinohypothalamic tract is one component of the optic nerve that transmits information about environmental luminance levels through medial and lateral branches to four major terminal fields in the hypothalamus. The spatial distribution and organization of axonal projections from each of these four terminal fields were analyzed and compared systematically with the anterograde pathway tracer PHAL in rats where the terminal fields had been labeled with intravitreal injections of a different anterograde pathway tracer, CTb. First, the well-known projections of two medial retinohypothalamic tract targets (the ventrolateral suprachiasmatic nucleus and perisuprachiasmatic region) were confirmed and extended. They share qualitatively similar projections to a well-known set of brain regions thought to control circadian rhythms. Second, the projections of a third medial tract target, the ventromedial part of the anterior hypothalamic nucleus, were analyzed for the first time and shown to resemble qualitatively those from the suprachiasmatic nucleus and perisuprachiasmatic region. And third, projections from the major lateral retinohypothalamic tract target were analyzed for the first time and shown to be quite different from those associated with medial tract targets. This target is a distinct core part of the ventral zone of the anterior group of the lateral hypothalamic area that lies just dorsal to the caudal two-thirds of the supraoptic nucleus. Its axonal projections are to neural networks that control a range of specific goal-oriented behaviors (especially drinking, reproductive, and defensive) along with adaptively appropriate and complementary visceral responses and adjustments to behavioral state.     

STN-stimulation in Parkinson's disease restores striatal inhibition of thalamocortical projection

To test the hypothesis that deep brain stimulation of the subthalamic nucleus (STN) restores the inhibitory output to the striatothalamocortical loop in Parkinson's disease, we obtained functional brain images of blood flow in 10 STN-stimulated patients with Parkinson's disease. Patients were immobile and off antiparkinsonian medication for 12 h. They were scanned with and without bilateral STN-stimulation with a 4-h interval between the two conditions. The order of DBS stimulation (ON or OFF) was randomized. Stimulation significantly raised regional cerebral blood flow (rCBF) bilaterally in the STN and in the left nucleus lentiformis. Conversely, flow declined in the left supplementary motor area (BA 6), ventrolateral nucleus of the left thalamus, and right cerebellum. Activation of the basal ganglia and deactivation of supplementary motor area and thalamus were both correlated with the improvement of motor function. The result is consistent with the explanation that stimulation in resting patients raises output from the STN with activation of the inhibitory basal ganglia output nuclei and subsequent deactivation of the thalamic anteroventral and ventrolateral nuclei and the supplementary motor area.     

Subchronic toxicity,toxicity to reproduction and prenatal developmental toxicity of vinyl laurate

Vinyl laurate (VL), is used in the manufacture of polyvinyl acetate vinyl laurate copolymer a component of gum base for chewing gum production. The potential toxicity of VL to reproduction was examined in a combined repeated dose and reproduction/developmental toxicity screening study (OECD test guideline 422) and a prenatal developmental toxicity screening study (OECD test guideline 414). VL was administered to Wistar rats by gavage at 0 (controls), 50, 250 and 1000 mg/kg bw/d. There were no signs of systemic toxicity in the parental animals of either study. Adverse effects on reproductive performance and fetal development that could be attributed to the VL treatment were not observed. Thus, the highest dose level tested was a NOAEL in these two studies.     

Active versus local vibration warm-up effects on knee extensors stiffness and neuromuscular performance of healthy young males

Objectives

To compare the effects of local-vibration and active warm-up on knee extensors muscle stiffness and neuromuscular performance.

Differential Usage of an Autoantibody-associated VH Gene, VH4-21, by Human B-cell Tumors

Selection of immunoglobulin variable region genes for recombination in B cells takes place from among those V_H and V_L gene segments available in the unrearranged germ line repertoire. In the case of neoplastic B cells, there is apparent deviation in the use of V-genes from that expected on a random basis, both for V_H and for V_L. Also, the preferred V-genes, and their patterns of mutation, differ among the various categories of B-cell tumor possibly reflecting the distinct origins and clonal histories on the individual tumor cells. This review focuses on a single V_H gene, V_H4-21, which is a member of the V_H4 family, and which appears selectively to encode immunoglobulins with autoantibody activity, particularly anti-red cell antibodies. The pattern of usage of this V_H gene by B-cell tumors demonstrates clear asymmetry among different tumor types. Also, the mutations detected in this relatively non-polymorphic gene indicate that antigen, possibly autoantigen, may influence the behavior of the tumor cell.     

A proposed conceptual reorganization of the basal ganglia and telencephalon.

A reordering of priorities applied to the criteria for grouping neuronal populations suggests a simpler conceptual organization of the basal ganglia and telencephalon than that currently in general use. The proposed scheme reduces the emphasis of the obvious geographical divisions imposed by the major white matter bundles and the cerebral ventricle, and emphasizes instead such criteria as a common internal histology, similar input-output patterns and characteristic neurotransmitters.By these reordered criteria, almost the entire telencephalon can be subdivided into three concentric tiers. The outermost tier (tier I) encompasses the structures derived embryologically from the pallium, the neocortex and the allocortex. The second tier (tier II) includes the caudate nucleus, the putamen, the nucleus accumbens septi and parts of the olfactory tubercle. The third tier (tier III) is composed of the external pallidal segment, the internal paltidal segment, the nondopaminergic part of the substantia nigra, and perhaps also parts of the substantial innominata.It is suggested that while many characteristics of the telencephalon and basal ganglia lend themselves to subdivision into ‘sensory’, ‘motor’, ‘associational’ and ‘limbic’ sectors, at least some features of organization appear to transgress such distinctions. The proposed reorganization does not deny the existence of such classical functional and anatomical subdivisions but focuses attention instead on two distinct telencephalic outflow systems each of which appears to serve overlapping and widespread parts of the telecephalon. One outflow system leaves the structures in tier I to influence monosynaptically the diencephalon, mesencephalon, pons, medulla or even the spinal cord, while the other outflow system follows a polysynaptic route with at least two intermediate synapses, the first between the tier I and tier II neurons and a second between the tier II and tier III neurons.Some implications of this perspective perhaps useful to the physiologist, pathologist and clinician are discussed.     

Distribution and properties of diencephalic neuronal responses to genital stimulation in the female cat

Responses of single units and unit clusters to vaginal stimulation were recorded from the thalamus, subthalamus, and hypothalamus of lightly sedated estrous and anestrous cats. Pronounced, short-latency neuronal responses were found to be distributed widely in the diencephalon generally, but with a relatively low density in the hypothalamus. Most of the unit responses to genital stimulation were accelerative changes in firing which outlasted the stimulus by many seconds or minutes. Units responding to vaginal stimulation were usually also responsive to a tail pinch or to tactile stimulation of the face, limbs, or trunk. The response properties of the diencephalic neurons were quite similar to those of genitally sensitive neurons in the midbrain and pons which have been described previously.     

Botulinum neurotoxins and botulism: a novel therapeutic approach

Specific treatment is not available for human botulism. Current remedial mainstay is the passive administration of polyclonal antibody to botulinum neurotoxin (BoNT) derived from heterologous species (immunized animal or mouse hybridoma) together with supportive and symptomatic management. The antibody works extracellularly, probably by blocking the binding of receptor binding (R) domain to the neuronal receptors; thus inhibiting cellular entry of the holo-BoNT. The antibody cannot neutralize the intracellular toxin. Moreover, a conventional antibody with relatively large molecular size (150 kDa) is not accessible to the enzymatic groove and, thus, cannot directly inhibit the BoNT zinc metalloprotease activity. Recently, a 15-20 kDa single domain antibody (V(H)H) that binds specifically to light chain of BoNT serotype A was produced from a humanized-camel VH/V(H)H phage display library. The V(H)H has high sequence homology (>80%) to the human VH and could block the enzymatic activity of the BoNT. Molecular docking revealed not only the interface binding between the V(H)H and the toxin but also an insertion of the V(H)H CDR3 into the toxin enzymatic pocket. It is envisaged that, by molecular linking the V(H)H to a cell penetrating peptide (CPP), the CPP-V(H)H fusion protein would be able to traverse the hydrophobic cell membrane into the cytoplasm and inhibit the intracellular BoNT. This presents a novel and safe immunotherapeutic strategy for botulism by using a cell penetrating, humanized-single domain antibody that inhibits the BoNT by means of a direct blockade of the groove of the menace enzyme.