Acetylcholine beyond bronchoconstriction:Roles in inflammation and remodeling

Acetylcholine is the primary parasympathetic neurotrans. mitter in the airways, where it not only induces bronchoconstriction and mucus secretion, but also regulates airway inflammation and remodeling. In this review, we propose that these effects are all primarily mediated via the muscarinic M-3 receptor. Acetylcholine promotes inflammation and remodeling via direct effects on airway cells, and via mechanical stress applied to the airways sequential to bronchoconstriction. The effects on inflammation and remodeling are regulated by both neuronal and non-neuronal acetylcholine. Taken together, we believe that the combined effects of anticholinergic therapy on M-3-mediated bronchoconstriction, mucus secretion, inflammation, and remodeling may account for the positive outcome of treatment with these drugs for patients with chronic pulmonary obstructive disease (COPD) or asthma.</p

Can proprioceptive training improve motor learning?

Recent work has investigated the link between motor learning and sensory function in arm movement control. A number of findings are consistent with the idea that motor learning is associated with systematic changes to proprioception (Haith A, Jackson C, Mial R, Vijayakumar S. Adv Neural Inf Process Syst 21: 593-600, 2008; Ostry DJ, Darainy M, Mattar AA, Wong J, Gribble PL. J Neurosci 30: 5384-5393, 2010; Vahdat S, Darainy M, Milner TE, Ostry DJ. J Neurosci 31: 16907- 16915, 2011). Here, we tested whether motor learning could be improved by providing subjects with proprioceptive training on a desired hand trajectory. Subjects were instructed to reproduce both the time-varying position and velocity of novel, complex hand trajectories. Subjects underwent 3 days of training with 90 movement trials per day. Active movement trials were interleaved with demonstration trials. For control subjects, these interleaved demonstration trials consisted of visual demonstration alone. A second group of subjects received visual and proprioceptive demonstration simultaneously; this group was presented with the same visual stimulus, but, in addition, their limb was moved through the target trajectory by a robot using servo control. Subjects who experienced the additional proprioceptive demonstration of the desired trajectory showed greater improvements during training movements than control subjects who only received visual information. This benefit of adding proprioceptive training was seen in both movement speed and position error. Interestingly, additional control subjects who received proprioceptive guidance while actively moving their arm during demonstration trials did not show the same improvement in positional accuracy. These findings support the idea that the addition of proprioceptive training can augment motor learning, and that this benefit is greatest when the subject passively experiences the goal movement. © 2012 the American Physiological Society

Is equilibrium point control feasible for fast goal-directed single-joint movements?

Several types of equilibrium point (EP) controllers have been proposed for the control of posture and movement. EP controllers are appealing from a computational perspective because they do not require solving the "inverse dynamic problem" (i.e., computation of the torques required to move a system along a desired trajectory). It has been argued that EP controllers are not capable of controlling fast single-joint movements. To refute this statement, several extensions have been proposed, although these have been tested using models in which only the tendon compliance, force-length-velocity relation, and mechanical interaction between tendon and contractile element were not adequately represented. In the present study, fast elbow-joint movements were measured and an attempt was made to reproduce these using a realistic musculoskeletal model of the human arm. Three types of EP controllers were evaluated: an open-loop α-controller, a closed-loop λ-controller, and a hybrid open- and closed-loop controller. For each controller we considered a continuous version and a version in which the control signals were sent out intermittently. Only the intermittent hybrid EP controller was capable of generating movements that were as fast as those of the subjects. As a result of the nonlinear muscle properties, the hybrid EP controller requires a more detailed representation of static muscle properties than generally assumed in the context of EP control. In sum, this study shows that fast single-joint movements can be realized without explicitly solving the inverse dynamics problem, but in a less straightforward manner than implied by proponents of conventional EP controllers. Copyright © 2006 The American Physiological Society