Disruption of elaborated motor coordination after destruction of the parietal and premotor association areas of the dog

In experiments on seven dogs with a previously elaborated complex food-procuring reflex consisting of two instrumental movements, isolated damage of the parietal and premotor cortical areas deteriorated the achievement of exact movement--lifting and holding of the foreleg at the set level for a certain period of time. A second movement of lifting and holding the leg, similar to the first one, but with simultaneous lowering of the head during eating (altered inborn coordination) remained unaffected through the holding of the leg was also less stable. Successive damage of the parietal and premotor areas, worsening, but not significantly, the exact movement carried out in the natural posture, led to decomposition of the elaborated motor coordination revealed earlier (M. E. Ioffe, 1975) in case of the sensorimotor area damage. The role of the associative cortical areas in organization of elaborated coordination program is discussed.     

Changes in the Parameters of Quantal Acetylcholine Release after Activation of PAR1-Type Thrombin Receptors at the Mouse Neuromuscular Junctions

In mature and newly formed neuromuscular synapses of mouse skeletal muscles, miniature endplate potentials (MEPPs) and multiquantal endplate potentials (EPPs) evoked by a single stimulation of the nerve were recorded using intracellular microelectrode technique. The mechanisms underlying the changes in spontaneous and evoked acetylcholine (ACh) release caused by the activation of PAR1-type muscle receptors induced by their peptide agonist TRAP6-NH₂ were studied. It has been shown for the first time that, in either mature or newly formed motor synapses, the activation of PAR1 that lack presynaptic localization causes a sustained increase in the MEPP amplitude due to the increase in the ACh quantal size at the presynaptic level. It was found that phospholipase C (PLC) participates in the signaling mechanism triggered by the PAR1 activation. Exogenously applied brain-derived neurotrophic factor (BDNF) mimics the effect of activation of PAR1 by TRAP6-NH₂. Moreover, an increase in the MEPP amplitude caused by the peptide PAR1 agonist was fully prevented by blocking the BDNF receptors–tropomyosin receptor kinases B (TrkB). Thus, it has been shown for the first time that the increase in ACh quantal size due to the activation of PAR1 in motor synapses is mediated by a complex signaling cascade that starts at the postsynaptic level of the motor synapse and ends at the presynaptic level. It is expected that the activation of PAR1 at the muscle fiber membrane followed by the PLC upregulation results in the release of neurotrophin BDNF as a retrograde signal. Its effect on the presynaptic TrkB receptors triggers the cascade leading to an increase in the quantal size of ACh.