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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- "Although previous research on tweety gene expression has been limited primarily to cell lines and adult tissues, for the one example of embryonic expression for ttyh1 in mice, the results presented here remain consistent with that study. The growing recognition of the key role that ion fluxes play in normal development, regenerative processes, and pathogenesis, make these genes intriguing candidates for further investigation (Borodinsky et al., 2012; Levin, 2014; Rosenberg and Spitzer, 2011). The broad phylogenetic distribution of this gene family, their proposed role in calcium dynamics and the discrete expression patterns of the tweety genes in the developing nervous system presented here suggest an important role for tweety genes in neural proliferation and differentiation. "
ABSTRACT: The tweety family of genes encode large-conductance chloride channels and have been implicated in a wide array of cellular processes including cell division, cell adhesion, regulation of calcium activity, and tumorigenesis, particularly in neuronal cells. However, their expression patterns during early development remain largely unknown. Here, we describe the spatial and temporal patterning of ttyh1, ttyh2, and ttyh3 in Xenopus laevis during early embryonic development. Ttyh1 and ttyh3 are initially expressed at the late neurula stage are and primarily localized to the developing nervous system, however ttyh1 and ttyh3 both show transient expression in the somites. By swimming tadpole stages, all three genes are expressed in the brain, spinal cord, eye, and cranial ganglia. While ttyh1 is restricted to proliferative, ventricular zones, ttyh3 is primarily localized to postmitotic regions of the developing nervous system. Ttyh2, however, is strongly expressed in cranial ganglia V, VII, IX and X. The differing temporal and spatial expression patterns of ttyh1, ttyh2, and ttyh3 suggest that they may play distinct roles throughout embryonic development. Copyright © 2014. Published by Elsevier B.V.Gene Expression Patterns 12/2014; 17(1). DOI:10.1016/j.gep.2014.12.002 · 1.38 Impact Factor
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- "Neuronal activity is an important regulator of multiple components of the nervous system, including the critical barriers to neuronal survival, differentiation, axonal growth, and synaptogenesis (For reviews see Spitzer, 2006; Borodinsky et al., 2012; Morimoto et al., 2012). The influential role of activity begins during the early stages of development and continues in the mature nervous system. "
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 02/2014; 8(8):21. DOI:10.3389/fnins.2014.00021 · 3.66 Impact Factor
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- "L.N. Borodinsky et al. / Neuropharmacology xxx (2012) 1e6 4 Please cite this article in press as: Borodinsky, L.N., et al., Dynamic regulation of neurotransmitter specification: Relevance to nervous system homeostasis, Neuropharmacology (2012), http://dx.doi.org/10.1016/j.neuropharm.2012.12.005 lab is supported by the Klingenstein Foundation Award in Neuroscience 2008, Basil O'Connor Award #5-FY09-131, March of Dimes, NSF 1120796, NIH-NINDS R01NS073055 and SHC 86500-NCA grants to L.N.B. "
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; 78. DOI:10.1016/j.neuropharm.2012.12.005 · 5.11 Impact Factor