Development and hormonal regulation of neurons and neural circuits
People in the Levine laboratory share 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. We are using the molecular and genetic power of Drosophila and mammalian systems to explore the neural circuits that control movement 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 we are describing the biophysical properties, dendritic anatomy, and synaptic connections of individual motoneurons. Recent experiments explore the role of calcium and potassium currents in determining the functional properties of identified motoneurons that participate in locomotor and respiratory behavior.
Worrell, JC and Levine, RB (2008) Characterization of Voltage-Dependent Ca2+ Currents in Identified Drosophila Motoneurons in situ. J Neurophysiol. 100:868-878.
Pilarski JQ, Wakefield HE, Fuglevand AJ, Levine RB, Fregosi RF (2011) Developmental nicotine exposure alters neurotransmission and excitability in hypoglossal motoneurons. J Neurophysiol. 105:423-433
Pilarski JQ, Wakefield HE, Fuglevand AJ, Levine RB, Fregosi RF. (2012) Increased nicotinic receptor desensitization in hypoglossal motor neurons following chronic developmental nicotine exposure. J Neurophysiol 107(1):257-64
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
Below is a list of ongoing or completed (during the last three years) research projects (federal and non-federal support). Begin with the projects that are most relevant to the research proposed in this application. Briefly indicate the overall goals of the projects and your role (e.g. PI, Co-Investigator, Consultant) in the research project. Do not list award amounts or percent effort in 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 is 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 are 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 is 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.