A role for dystonia-associated genes in spinal GABAergic interneuron circuitry Journal Article
| Authors: | Zhang, J.; Weinrich, J. A. P.; Russ, J. B.; Comer, J. D.; Bommareddy, P. K.; DiCasoli, R. J.; Wright, C. V. E.; Li, Y.; van Roessel, P. J.; Kaltschmidt, J. A. |
| Article Title: | A role for dystonia-associated genes in spinal GABAergic interneuron circuitry |
| Abstract: | Spinal interneurons are critical modulators of motor circuit function. In the dorsal spinal cord, a set of interneurons called GABApre presynaptically inhibits proprioceptive sensory afferent terminals, thus negatively regulating sensory-motor signaling. Although deficits in presynaptic inhibition have been inferred in human motor diseases, including dystonia, it remains unclear whether GABApre circuit components are altered in these conditions. Here, we use developmental timing to show that GABApre neurons are a late Ptf1a-expressing subclass and localize to the intermediate spinal cord. Using a microarray screen to identify genes expressed in this intermediate population, we find the kelch-like family member Klhl14, implicated in dystonia through its direct binding with torsion-dystonia-related protein Tor1a. Furthermore, in Tor1a mutant mice in which Klhl14 and Tor1a binding is disrupted, formation of GABApre sensory afferent synapses is impaired. Our findings suggest a potential contribution of GABApre neurons to the deficits in presynaptic inhibition observed in dystonia. GABApre spinal interneurons gate sensory inputs onto motor neurons. Zhang et al. localize GABApre neurons to the intermediate spinal cord and show that these interneurons express hereditary dystonia-related genes Klhl14 and Tor1a. In Tor1a mutant mice, GABApre synapse formation is disrupted, suggesting that spinal circuits may be affected in dystonia. © 2017 The Authors |
| Keywords: | spinal cord; synapses; dystonia; neuronal circuitry; inhibitory interneuron; gabapre neuron; klhl14; tor1a |
| Journal Title: | Cell Reports |
| Volume: | 21 |
| Issue: | 3 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2017-10-17 |
| Start Page: | 666 |
| End Page: | 678 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2017.09.079 |
| PROVIDER: | scopus |
| PMCID: | PMC5658202 |
| PUBMED: | 29045835 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2017 -- Source: Scopus |
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