Why Transcortical Reflexes?

Experiments in humans and in monkeys have indicated that load perturbations, occurring during voluntary movements and postural activity, may be automatically compensated for. Overall muscle stiffness opposing load changes is determined by the viscoelastic properties of the muscle, by segmental reflex actions and finally by long-loop reflexes. Under certain circumstances, for instance when the subject or the experimental monkey is "prepared” to counteract perturbations which are unpredictable in time, the long-loop "reflexes” appear to be responsible for most of the corrective muscle tension. Experiments in anaesthetized monkeys revealed that signals from stretch afferents reach neurons of the motor cortex, possibly via a relay in the cortical area 3a. The latencies of these responses to well controlled muscle stretches were in the same range as motor cortical cell discharges recorded in alert monkeys subjected to load perturbations. Furthermore, these responses of cells in the motor cortex also had the appropriate timing to indicate a causal relationship with the long-latency electromyographic responses to load changes referred to above. These experimental results therefore strongly support the hypothesis, first proposed by Phillips (1969), of a transcortical servoloop adjusting motor cortical output according to the load conditions in which movements are performed. The major advantage of transcortical regulations as opposed to segmental regulations, seems to be a powerful gain control acting at the cortical level; it was repeatedly shown that the long-loop reflexes are strongly modifiable and under voluntary control. It is suggested that an adaptive gain control at the cortical level is a prerequisite to preserve the complex capabilities of the motor cortex as the chief "executive" for skilled, preprogrammed movements. A loss of this adaptive gain control may be, at least partly, the cause of motor disorders such as rigidity in Parkinsonian patients, as reported by Tatton and Lee (1975). It is suggested that further investigations of the control of transcortical reflexes may aid in the understanding of the pathophysiology of motor disabilitie

A mathematical model for the steady activation of a skeletal muscle

A skeletal muscle is composed of motor units, each consisting of a motoneuron and the muscle fibers it innervates. The input to the motor units is formed of electrical signals coming from higher motor centers and propagated to the motoneurons along a network of nerve fibers. Because of its complexity, this network still escapes actual direct observations. The present model describes the steady state activation of a muscle, i.e., of its motor units. It incorporates the network as an unknown quantity and, given the latter, predicts the input-force relation (activation curve) of the muscle. Conversely, given a suitable activation curve, our model enables the recovery of the network. This step is performed by using experimental data about the activation curve, and the whole activation process of a muscle can then be theoretically investigated. In this way, this approach provides a link between the macroscopic (activation curve) and microscopic (network) levels. From a mathematical viewpoint, solving the preceding inverse problem is equivalent to solving an integral equation of a new type

Identification of a lectin causing the degeneration of neuronal processes using engineered embryonic stem cells

Unlike the mechanisms involved in the death of neuronal cell bodies, those causing the elimination of processes are not well understood owing to the lack of suitable experimental systems. As the neurotrophin receptor p75(NTR) is known to restrict the growth of neuronal processes, we engineered mouse embryonic stem (ES) cells to express an Ngfr (p75(NTR)) cDNA under the control of the Mapt locus (the gene encoding tau), which begins to be active when ES cell-derived progenitors start elongating processes. This caused a progressive, synchronous degeneration of all processes, and a prospective proteomic analysis showed increased levels of the sugar-binding protein galectin-1 in the p75(NTR)-engineered cells. Function-blocking galectin-1 antibodies prevented the degeneration of processes, and recombinant galectin-1 caused the processes of wild-type neurons to degenerate first, followed by the cell bodies. In vivo, the application of a glutamate receptor agonist, a maneuver known to upregulate p75(NTR), led to an increase in the amount of galectin-1 and to the degeneration of neurons and their processes in a galectin-1-dependent fashion. Section of the sciatic nerve also rapidly upregulated levels of p75(NTR) and galectin-1 in terminal Schwann cells, and the elimination of nerve endings was delayed at the neuromuscular junction of mice lacking Lgals1 (the gene encoding galectin-1). These results indicate that galectin-1 actively participates in the elimination of neuronal processes after lesion, and that engineered ES cells are a useful tool for studying relevant aspects of neuronal degeneration that have been hitherto difficult to analyze