Development and hormonal regulation of neurons and neural circuits
Throughout his career, members of the Levine laboratory shared a common interest in the function and development of neuromuscular systems. Neuromuscular systems, including the motoneurons that control movement and the muscles that they innervate, are modified throughout life by many factors including hormones, learning, training, and aging. The laboratory used the molecular and genetic power of Drosophila and mammalian systems to explore the neural circuits that control movement and respiration, and the mechanisms through which steroid hormones regulate their function and postembryonic modification. Using techniques such as intracellular and whole-cell patch recording, dye injection, confocal microscopy and cell culture they described the biophysical properties, dendritic anatomy, and synaptic connections of individual motoneurons. Currently, Dr. Levine is collaborating with Dr. Ralph Fregosi, in the UA Department of Physiology, to investigate the consequences of nicotine exposure for the development of neural circuits responsible for breathing. He is also developing and teaching a course for the online Neuroscience degree program, NSCS 200 Fundamental of Neuroscience and Cognitive Science.
Wollman LB, Levine RB, Fregosi RF. Developmental plasticity of GABAergic neurotransmission to brainstem motoneurons. J Physiol. 2018 Dec;596(23):5993-6008. doi: 10.1113/JP274923. Epub 2018 Feb 25. PMID: 29352468; PMCID: PMC6265538.
Wealing JC, Cholanian M, Flanigan EG, Levine RB, Fregosi RF. Diverse physiological properties of hypoglossal motoneurons innervating intrinsic and extrinsic tongue muscles. J Neurophysiol. 2019 Nov 1;122(5):2054-2060. doi: 10.1152/jn.00478.2019. Epub 2019 Sep 18. PMID: 31533009; PMCID: PMC6879950.
Buls Wollman L, Clarke J, DeLucia CM, Levine RB, Fregosi RF. Developmental Nicotine Exposure Alters Synaptic Input to Hypoglossal Motoneurons and Is Associated with Altered Function of Upper Airway Muscles. eNeuro. 2019 Nov 15;6(6):ENEURO.0299-19.2019. doi: 10.1523/ENEURO.0299-19.2019. PMID: 31712219; PMCID: PMC6860987.
Wollman LB, Levine RB, Fregosi RF. Developmental nicotine exposure alters glycinergic neurotransmission to hypoglossal motoneurons in neonatal rats. J Neurophysiol. 2018 Sep 1;120(3):1135-1142. doi: 10.1152/jn.00600.2017. Epub 2018 May 30. PMID: 29847237; PMCID: PMC6171071.
Cholanian M, Wealing J, Levine RB, Fregosi RF. Developmental nicotine exposure alters potassium currents in hypoglossal motoneurons of neonatal rat. J Neurophysiol. 2017 Apr 1;117(4):1544-1552. doi: 10.1152/jn.00774.2016. Epub 2017 Feb 1. PMID: 28148643; PMCID: PMC5376599.
Cholanian M, Powell GL, Levine RB, Fregosi RF. Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons. Exp Neurol. 2017 Jan;287(Pt 2):254-260. doi: 10.1016/j.expneurol.2016.07.023. Epub 2016 Jul 29. PMID: 27477858; PMCID: PMC5120997.
Wollman LB, Haggerty J, Pilarski JQ, Levine RB, Fregosi RF. Developmental nicotine exposure alters cholinergic control of respiratory frequency in neonatal rats. Dev Neurobiol. 2016 Oct;76(10):1138-49. doi: 10.1002/dneu.22380. Epub 2016 Feb 17. PMID: 26818254; PMCID: PMC4965345.
Powell GL, Gaddy J, Xu F, Fregosi RF, Levine RB. Developmental nicotine exposure disrupts dendritic arborization patterns of hypoglossal motoneurons in the neonatal rat. Dev Neurobiol. 2016 Oct;76(10):1125-37. doi: 10.1002/dneu.22379. Epub 2016 Feb 8. PMID: 26818139; PMCID: PMC4965347.
Pilarski JQ, Wakefield HE, Fuglevand AJ, Levine RB, Fregosi RF. Developmental nicotine exposure alters neurotransmission and excitability in hypoglossal motoneurons. J Neurophysiol. 2011 Jan;105(1):423-33. doi: 10.1152/jn.00876.2010. Epub 2010 Nov 10. PMID: 21068261; PMCID: PMC3023378.
Powell GL, Levine RB, Frazier AM, Fregosi RF. Influence of developmental nicotine exposure on spike-timing precision and reliability in hypoglossal motoneurons. J Neurophysiol. 2015 Mar 15;113(6):1862-72. doi: 10.1152/jn.00838.2014. Epub 2014 Dec 30. PMID: 25552642; PMCID: PMC4359999.
Pilarski JQ, Wakefield HE, Fuglevand AJ, Levine RB, Fregosi RF. Increased nicotinic receptor desensitization in hypoglossal motor neurons following chronic developmental nicotine exposure. J Neurophysiol. 2012 Jan;107(1):257-64. doi: 10.1152/jn.00623.2011. Epub 2011 Oct 19. PMID: 22013232; PMCID: PMC3349681.
Ryglewski S, Lance K, Levine RB, Duch C. Ca(v)2 channels mediate low and high voltage-activated calcium currents in Drosophila motoneurons. J Physiol 2012 Feb 15;590(Pt 4):809-25. Epub 2011 Dec 19. PubMed PMID: 22183725
Srinivasan S, Lance K, Levine RB. Contribution of EAG to excitability and potassium currents in Drosophila larval motoneurons. J Neurophysiol. 2012 May;107(10):2660-71. Epub 2012 Feb 8. PubMed PMID: 22323637; PubMed Central PMCID: PMC3362287
Schaefer JE, Worrell JW, Levine RB. 2008. Role of intrinsic properties in Drosophila motoneuron recruitment during fictive crawling. J Neurophysiol. [Epub ahead of print]
Hartwig C, Worrell J, Levine RB, Ramaswami M, and Sanyal S. 2008. Normal dendrite growth in Drosophila motor neurons requires the AP-1 transcription factor. Devel Neurobiology, 68 (10):1225-45
Worrell JC, and Levine RB. 2008. Characterization of Voltage-Dependent Ca2+ Currents in Identified Drosophila Motoneurons in situ.. J Neurophysiology, 100:868-878
Barbee SA, Estes PS, Cziko AM, Hillebrand J, Luedeman RA, Coller JM, Johnson N, Howlett IC, Geng C, Ueda R, Brand AH, Newbury SF, Wilhelm JE, Levine RB, Nakamura A, Parker R, Ramaswami M. 2006. Staufen- and FMRP-containing neuronal RNPs are structurally and functionally related to somatic P bodies. Neuron, 52:997-1009
Miller JE Levine RB. 2006. Steroid hormone activation of wandering in the isolated nervous system of Manduca sexta. J Comp Physiol A Neuroethol Sens Neural Behav Phys, 192:1049-62
Dulcis D, Levine RB, Ewer J. 2005. Role of the neuropeptide CCAP in Drosophila cardiac function. J Neurobiol, 64:259-74
Consoulas C, Levine RB, Restifo LL. 2005. The steroid hormone-regulated gene Broad Complex is required for dendritic growth of motoneurons during metamorphosis of Drosophila. J Comp Neurol, 485:321-37
Dulcis D, Levine RB. 2005. Glutamatergic innervation of the heart initiates retrograde contractions in adult Drosophila melanogaster. J Neurosci, 25:271-80
Recent Completed Projects:
NSF 094905, Probing Motoneuron Dendritic Integration during Locomotion with Targeted Ion Channel Manipulation in Drosophila
6/2010 – 5/2013
RB Levine, C Duch, Co-PIs
The goal of this project was to use genetic approaches and whole-cell voltage-clamp to understand the roles of voltage-gated calcium and potassium channels in determining the recruitment patterns of identified motoneurons during locomotion.
NIH, 1R01 HD071302 Chronic nicotine and synaptic transmission in brainstem respiratory neurons.
8/2012 – 7/2017
PI, Fregosi RF, Co-PI, Levine RB.
The goals of this project were to examine the influence of in utero nicotine exposure on inhibitory synaptic transmission, soma-dendritic morphology and inhibitory neurotransmitter receptor expression in neonatal hypoglossal motoneurons.
American Heart Association, 12GRNT12050345. Influence of Developmental Nicotine Exposure on the Function and Structure of Brainstem Respiratory neurons.
7/2012 – 6/2014
PI, Fregosi RF, Co-PI, Levine RB
The goal of this proposal was to examine the influence of in utero nicotine exposure on excitatory glutamatergic neurotransmission and the expression of AMPA receptors in neonatal hypoglossal motoneurons.
NIH R01 NS057637, Postembryonic development of drosophila motoneurons.
2/2007 – 5/2012
PI, RB Levine
The goal of this project was to use genetic approaches and whole-cell voltage-clamp to understand the roles of voltage-gated calcium and potassium channels and activity-dependent developmental processes that influence the differentiation and postembryonic development of motoneurons.