Electrical activity as a developmental regulator in the formation of spinal cord circuits.
ABSTRACT Spinal cord development is a complex process involving generation of the appropriate number of cells, acquisition of distinctive phenotypes and establishment of functional connections that enable execution of critical functions such as sensation and locomotion. Here we review the basic cellular events occurring during spinal cord development, highlighting studies that demonstrate the roles of electrical activity in this process. We conclude that the participation of different forms of electrical activity is evident from the beginning of spinal cord development and intermingles with other developmental cues and programs to implement dynamic and integrated control of spinal cord function.
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ABSTRACT: Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS) as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury (SCI). This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability.Frontiers in Neuroscience 01/2014; 8:21.
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ABSTRACT: Rhythmic waves of spontaneous electrical activity are widespread in the developing nervous systems of birds and mammals, and although many aspects of neural development are activity-dependent, it has been unclear if rhythmic waves are required for in vivo motor circuit development, including the proper targeting of motoneurons to muscles. We show here that electroporated channelrhodopsin-2 can be activated in ovo with light flashes to drive waves at precise intervals of approximately twice the control frequency in intact chicken embryos. Optical monitoring of associated axial movements ensured that the altered frequency was maintained. In embryos thus stimulated, motor axons correctly executed the binary dorsal-ventral pathfinding decision but failed to make the subsequent pool-specific decision to target to appropriate muscles. This observation, together with the previous demonstration that slowing the frequency by half perturbed dorsal-ventral but not pool-specific pathfinding, shows that modest changes in frequency differentially disrupt these two major pathfinding decisions. Thus, many drugs known to alter early rhythmic activity have the potential to impair normal motor circuit development, and given the conservation between mouse and avian spinal cords, our observations are likely relevant to mammals, where such studies would be difficult to carry out.Proceedings of the National Academy of Sciences 10/2013; · 9.81 Impact Factor
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ABSTRACT: During nervous system development the neurotransmitter identity changes and coexpression of several neurotransmitters is a rather generalized feature of developing neurons. In the mature nervous system, different physiological and pathological circumstances recreate this phenomenon. The rules of neurotransmitter respecification are multiple. Among them, the goal of assuring balanced excitability appears as an important driving force for the modifications in neurotransmitter phenotype expression. The functional consequences of these dynamic revisions in neurotransmitter identity span a varied range, from fine-tuning the developing neural circuit to modifications in addictive and locomotor behaviors. Current challenges include determining the mechanisms underlying neurotransmitter phenotype respecification and how they intersect with genetic programs of neuronal specialization.Neuropharmacology 12/2012; · 4.11 Impact Factor