Biomedical subjects

Zhuo Meng

Publications and source records attributed to Zhuo Meng.

5 recordsLinked to original sources

PubMed2004

Effect of forelimb use on postnatal development of the forelimb motor representation in primary motor cortex of the cat.

In the cat, the motor representation in motor cortex develops between wk 8 and wk 13. Motor map development is accompanied by a decrease in the current thresholds for evoking movements with a concomitant increase in the number of effective sites, an increase in the distal representation, and the representation of multijoint synergies. In this study we used intracortical microstimulation in anesthetized cats to examine how forelimb motor experiences influence development of map characteristics. To promote skilled movements during wks 8-13, animals were engaged in daily performance of a prehension task. Forelimb movements were prevented by intramuscular botulinum toxin injection or restraint. To determine whether experience-dependent changes were permanent, we examined the map in different animals between 1 wk and 1 yr after cessation of testing. Promoting forelimb use resulted in an increase in the number of sites from which multiple joint effects were produced by stimulation and the number of joints represented at those sites. The effect was maximal at 1 wk after cessation of testing, and became progressively less at 1 mo and at 4 mo. Preventing limb use resulted in a decreased number of effective sites, an increase in current thresholds for evoking responses, and a decreased representation of joints at multijoint sites. Our findings show that the motor map can respond to novel motor demands as it is forming during development but that it reverts back to one with the properties of a map in a control animal if those demands are not maintained in the animal's behavioral repertoire.

Age Factors↗

PubMed2004

Corticospinal system development depends on motor experience.

Early motor experiences have been shown to be important for the development of motor skills in humans and animals. However, little is known about the role of motor experience in motor system development. In this study, we address the question of whether early motor experience is important in shaping the development of the corticospinal (CS) tract. We prevented limb use by the intramuscular injection of botulinum toxin A into selected forelimb muscles to produce muscle paralysis during the period of development of CS connection specificity, which is between postnatal weeks 3 and 7. CS terminations were examined using an anterograde tracer. Preventing normal forelimb use during CS axon development produced defective development of CS terminations at week 8 and in maturity. There were reductions in the topographic distribution of axon terminals, in terminal and preterminal branching, and in varicosity density. This suggests that limb use is needed to refine CS terminals into topographically specific clusters of dense terminal branches and varicosities. To determine correlated effects on motor behavior, cats were tested in a prehension task, to reach and grasp a piece of food from a narrow food well, when the neuromuscular blockade dissipated (by week 10) and in maturity (week 16). Preventing normal limb use also produced a prehension deficit later in development and in maturity, in which there was a loss of the supination component of grasping. This component of prehension in the cat depends on CS projections from the paw representation of rostral motor cortex to the cervical enlargement. Our findings show that motor experiences are necessary for normal development of CS terminations and function.

Animals↗

PubMed2004

Engineering novel spinal circuits to promote recovery after spinal injury.

We have developed an innovative way to establish a functional bridge around a spinal lesion. We disconnected the T13 nerve from its muscle targets, leaving the proximal end intact. The cut end was inserted either into an intact spinal cord, to assess regeneration of T13 axons into the cord and synapse formation with spinal neurons, or caudal to a hemisection at L2/3, to assess restoration of function below the injury. Four to 28 weeks later, anterograde tracers indicated that axons from the inserted T13 nerve regenerated into the ventral horn, the intermediate zone, and dorsal horn base, both in intact and hemisected animals. Antibodies to cholinergic markers showed that many regenerating axons were from T13 motoneurons. Electrical stimulation of the T13 nerve proximal to the insertion site 4 weeks or more after insertion into the intact cord evoked local field potentials in the intermediate zone and ventral horn, which is where T13 axons terminated. Stimulation of T13 in 71% of the animals (8 hemisected, 7 intact) evoked contraction of the back or leg muscles, depending on the level of insertion. Animals in which T13 was inserted caudal to hemisection had significantly less spasticity and muscle wasting and greater mobility at the hip, knee, ankle, and digits in the ipsilateral hindlimb than did animals with a hemisection only. Thus, T13 motor axons form novel synapses with lumbosacral motor circuits. Because the T13 motor neurons retain their connections to the brain, these novel circuits might restore voluntary control to muscles paralyzed below a spinal lesion.

Animals↗

PubMed2004

The transition from development to motor control function in the corticospinal system.

During early postnatal development, corticospinal (CS) system stimulation, electrical or transcranial magnetic, is minimally effective in producing muscle contraction, despite having axon terminals that excite spinal neurons. Later, after stimulation becomes more effective, the cortical motor representation develops, and movements the system controls in maturity are expressed. We determined whether development of temporal facilitation (response enhancement produced by the second of a pair of pyramidal tract stimuli, or a higher stimulus multiple of a train of stimuli) correlated with these changes. Facilitation of the monosynaptic CS response was larger in older kittens and adults than younger kittens. When facilitation was strong, strong motor responses were evoked by pyramidal stimulation with small currents and few pulses. With strong facilitation in older kittens, corticospinal axon varicosities colocalize synaptophysin like adults, suggesting a presynaptic mechanism. With effective facilitation, control signals from the cortex can be sufficiently effective to provoke muscle contraction for guiding movements.

Action Potentials↗

PubMed2003

Postnatal development of corticospinal postsynaptic action.

The corticospinal system has a delayed and prolonged postnatal development. In the cat, lesion, inactivation, or stimulation of the system influence motor output minimally when corticospinal (CS) terminals have an immature topographic pattern but produce robust effects immediately after developing the mature pattern by weeks 6-7. In this study, we directly tested if the delay in expression of cortical motor functions is due to the inability of the corticospinal synapse to activate spinal neurons. We stimulated corticospinal axons in the pyramid and recorded evoked field potentials from the surface of the cervical spinal cord and locally from within the gray matter in anesthetized cats during development and in adults. Pyramidal stimulation in animals between week 4 and maturity evoked an initial corticospinal surface volley followed by a postsynaptic field response. Depth recordings from the superficial dorsal horn to the ventral white matter showed that local pre- and postsynaptic field potentials could be recorded over the full extent of the gray matter in 4- to 5-wk animals but were restricted to the intermediate zone in older animals and adults. Dorsoventral refinement of CS field potentials parallels anatomical refinement of individual CS axon terminals shown in our earlier studies. Our present findings indicate that the developing corticospinal system could influence the excitability of virtually the entire contralateral gray matter before cortical motor functions are expressed. Given the importance of activity-dependent axon terminal refinement, this capacity for activating spinal neurons during early postnatal life could play an important role in development of CS circuit connectivity.

Animals↗