Facilitation of a stereotyped motor behavior (climbing behavior) by previous stimulation of dopaminergic receptors: hyposensitivity of autoreceptors?]

The sensitivity of dopamine receptors in Mouse striatum has been evaluated both behaviourally (responsiveness to apomorphine as regarviour) and biochemically (striatal level of homovanillic acid and its decrease induced by apomorphine) After a single administration of apomorphine (0.25 mg.kg-1 or 5 mg.kg-1) or piribedil, another dopamine agonist, a state of "behavioural facilitation" develops which differs from the state of hypersensitivity following blockade. This state of facilitation is characterized by a lower threshold dose of apomorphine eliciting the stereotyped behaviour, without modification of the response to higher doses. In contrast with the state of hypersensitivity, the level of homovanillic acid is not modified and the decrease of this level by a low dose of apomorphine is less important. The hypothesis is put forward that "behavioural facilitation" results from the hyposensitivity of a class of dopamine receptors, possibly autoreceptors, mediating an impaired activity of dopaminergic neurons and, consequently, inhibitory behavioural effects.     

Cortical control of a prosthetic arm for self-feeding

Arm movement is well represented in populations of neurons recorded from the motor cortex. Cortical activity patterns have been used in the new field of brain-machine interfaces to show how cursors on computer displays can be moved in two- and three-dimensional space. Although the ability to move a cursor can be useful in its own right, this technology could be applied to restore arm and hand function for amputees and paralysed persons. However, the use of cortical signals to control a multi-jointed prosthetic device for direct real-time interaction with the physical environment ('embodiment') has not been demonstrated. Here we describe a system that permits embodied prosthetic control; we show how monkeys (Macaca mulatta) use their motor cortical activity to control a mechanized arm replica in a self-feeding task. In addition to the three dimensions of movement, the subjects' cortical signals also proportionally controlled a gripper on the end of the arm. Owing to the physical interaction between the monkey, the robotic arm and objects in the workspace, this new task presented a higher level of difficulty than previous virtual (cursor-control) experiments. Apart from an example of simple one-dimensional control, previous experiments have lacked physical interaction even in cases where a robotic arm or hand was included in the control loop, because the subjects did not use it to interact with physical objects-an interaction that cannot be fully simulated. This demonstration of multi-degree-of-freedom embodied prosthetic control paves the way towards the development of dexterous prosthetic devices that could ultimately achieve arm and hand function at a near-natural level.     

Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production

Energy and glucose homeostasis are regulated by food intake and liver glucose production, respectively. The upper intestine has a critical role in nutrient digestion and absorption. However, studies indicate that upper intestinal lipids inhibit food intake as well in rodents and humans by the activation of an intestine-brain axis. In parallel, a brain-liver axis has recently been proposed to detect blood lipids to inhibit glucose production in rodents. Thus, we tested the hypothesis that upper intestinal lipids activate an intestine-brain-liver neural axis to regulate glucose homeostasis. Here we demonstrate that direct administration of lipids into the upper intestine increased upper intestinal long-chain fatty acyl-coenzyme A (LCFA-CoA) levels and suppressed glucose production. Co-infusion of the acyl-CoA synthase inhibitor triacsin C or the anaesthetic tetracaine with duodenal lipids abolished the inhibition of glucose production, indicating that upper intestinal LCFA-CoAs regulate glucose production in the preabsorptive state. Subdiaphragmatic vagotomy or gut vagal deafferentation interrupts the neural connection between the gut and the brain, and blocks the ability of upper intestinal lipids to inhibit glucose production. Direct administration of the N-methyl-d-aspartate ion channel blocker MK-801 into the fourth ventricle or the nucleus of the solitary tract where gut sensory fibres terminate abolished the upper-intestinal-lipid-induced inhibition of glucose production. Finally, hepatic vagotomy negated the inhibitory effects of upper intestinal lipids on glucose production. These findings indicate that upper intestinal lipids activate an intestine-brain-liver neural axis to inhibit glucose production, and thereby reveal a previously unappreciated pathway that regulates glucose homeostasis.     

Role of tropomyosin in the sensitivity of (Na+ + K+) ATPase to ouabain]

EDTA treatment of isolated plasma membranes from MF2S cells increased 1,000 fold the sensitivity of (Na+ + K+) ATPase activity to ouabain. The original sensitivity of the enzyme to the drug is recovered after addition of tropomyosin together with Ca++ ions to the treated membranes.     

Position of the methionine residue in bovine neurophysin II

Zusammenfassung Durch Spaltung mit CNBr wurde gezeigt, dass Neurophysin II aus Rinderhypophyse nur eine Methionin-Einheit enthält und dass die N-terminale Sequenz Ala-Met ist.

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This work was supported by NIH Grants No. AM-13567, No. AM-10080, by NSF Grant No. GB-17046 and by the City University of New York. The authors are indebted to Dr.L. Abrash for helpful discussion and MissM. Wahrenburg and Mr.V. S. Sapirstein for the assays.

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Predoctoral fellow of the Department of Physiology.     

Growth processes in teeth distinguish modern humans from Homo erectus and earlier hominins.

A modern human-like sequence of dental development, as a proxy for the pace of life history, is regarded as one of the diagnostic hallmarks of our own genus Homo. Brain size, age at first reproduction, lifespan and other life-history traits correlate tightly with dental development. Here we report differences in enamel growth that show the earliest fossils attributed to Homo do not resemble modern humans in their development. We used daily incremental markings in enamel to calculate rates of enamel formation in 13 fossil hominins and identified differences in this key determinant of tooth formation time. Neither australopiths nor fossils currently attributed to early Homo shared the slow trajectory of enamel growth typical of modern humans; rather, both resembled modern and fossil African apes. We then reconstructed tooth formation times in australopiths, in the approximately 1.5-Myr-old Homo erectus skeleton from Nariokotome, Kenya, and in another Homo erectus specimen, Sangiran S7-37 from Java. These times were shorter than those in modern humans. It therefore seems likely that truly modern dental development emerged relatively late in human evolution.     

Proposed effects of brain noradrenaline on neuronal activity and cerebral blood flow during REM sleep.

We propose that the observed increases of both neuronal activity and cerebral blood flow seen throughout the brain during REM sleep may be effects of decreased central noradrenaline release.     

Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics

A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. The D3 receptor is localized to limbic areas of the brain, which are associated with cognitive, emotional and endocrine functions. It seems to mediate some of the effects of antipsychotic drugs and drugs used against Parkinson's disease, that were previously thought to interact only with D2 receptors.