Our Research
Our research is focused on understanding how the development and function of the mammalian nervous system is regulated by interactions between different cell types. The Birren Lab uses genetic approaches to alter the expression patterns of specific genes in vitro and in vivo to address questions in three areas of: How developing sympathetic neurons acquire their unique neurotransmitter properties; How initial contact with the muscle targets of neuronal innervation direct the final maturation of the neurons; and How these interactions control the release of neurotransmitters at different synaptic sites within the cardiac circuit. Myocyte interactions are involved in several important developmental transitions that include the global inhibition of neurite outgrowth following target contact, the local arborization of sympathetic fibers on the myocyte surface, and the development of synaptic structures and functional neurotransmission. Our work investigates the regulation of sympathetic neuron growth dynamics and the associated functional maturation of cardiac myocytes. We hypothesize that the ongoing myocyte maturation during the period of sympathetic innervation results in the dynamic expression of signaling proteins that ultimately promote maturation of neural function.
Our focus is on identifying the signals, receptors and signaling pathways that control these developmental and functional transitions at neuron-muscle junctions. By examining the developmental interactions between muscle and nerve cells we have defined novel growth pathways and target signals that are critical for the establishment of normal innervation patterns. We have also determined the role of many target and local factors in the regulation of neuronal excitability, synaptic function and sympathetic drive to cardiac targets.
Our research is focused on understanding how the development and function of the mammalian nervous system is regulated by interactions between different cell types. The Birren Lab uses genetic approaches to alter the expression patterns of specific genes in vitro and in vivo to address questions in three areas of: How developing sympathetic neurons acquire their unique neurotransmitter properties; How initial contact with the muscle targets of neuronal innervation direct the final maturation of the neurons; and How these interactions control the release of neurotransmitters at different synaptic sites within the cardiac circuit. Myocyte interactions are involved in several important developmental transitions that include the global inhibition of neurite outgrowth following target contact, the local arborization of sympathetic fibers on the myocyte surface, and the development of synaptic structures and functional neurotransmission. Our work investigates the regulation of sympathetic neuron growth dynamics and the associated functional maturation of cardiac myocytes. We hypothesize that the ongoing myocyte maturation during the period of sympathetic innervation results in the dynamic expression of signaling proteins that ultimately promote maturation of neural function.
Our focus is on identifying the signals, receptors and signaling pathways that control these developmental and functional transitions at neuron-muscle junctions. By examining the developmental interactions between muscle and nerve cells we have defined novel growth pathways and target signals that are critical for the establishment of normal innervation patterns. We have also determined the role of many target and local factors in the regulation of neuronal excitability, synaptic function and sympathetic drive to cardiac targets.
Lab Members
Susan Birren-Principal Investigator
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Publications
Neuroscience. Plasticity in the
neurotransmitter repertoire. Birren SJ, Marder E. Science (2013) Neurotrophins regulate cholinergic synaptic transmission in cultured rat sympathetic neurons through a p75-dependent mechanism. Luther JA, Enes J, Birren SJ. J Neurophysiol. (2013) Genetically induced cholinergic hyper-innervation enhances taste learning. Neseliler S, Narayanan D, Fortis-Santiago Y, Katz DB, Birren SJ. Front Syst Neurosci. (2011) Segregation of the classical transmitters norepinephrine and acetylcholine and the neuropeptide Y in sympathetic neurons: modulation by ciliary neurotrophic factor or prolonged growth in culture. Vega A, Luther JA, Birren SJ, Morales MA. Dev Neurobiol. (2010) Neurotrophins and target interactions in the development and regulation of sympathetic neuron electrical and synaptic properties. Luther JA, Birren SJ. Auton Neurosci. (2009) p75 and TrkA signaling regulates sympathetic neuronal firing patterns via differential modulation of voltage-gated currents. Luther JA, Birren SJ. J Neurosci. (2009) Multiple signaling pathways converge to regulate bone morphogenetic protein-dependent glial gene expression. Dore JJ, DeWitt JC, Setty N, Donald MD, Joo E, Chesarone MA, Birren SJ. Dev Neurosci. (2009) Regulation of cardiac innervation and function via the p75 neurotrophin receptor. Habecker BA, Bilimoria P, Linick C, Gritman K, Lorentz CU, Woodward W, Birren SJ. Auton Neurosci. (2008) Target-dependent inhibition of sympathetic neuron growth via modulation of a BMP signaling pathway. Moon JI, Birren SJ. J Neurosci. (2008) Non-cell-autonomous regulation of GABAergic neuron development by neurotrophins and the p75 receptor. Lin PY, Hinterneder JM, Rollor SR, Birren SJ. Auton Neurosci. (2007) Nerve growth factor decreases potassium currents and alters repetitive firing in rat sympathetic neurons. Luther JA, Birren SJ. J Neurophysiol. (2006) Role for calcium/calmodulin-dependent protein kinase II in the p75-mediated regulation of sympathetic cholinergic transmission. Slonimsky JD, Mattaliano MD, Moon JI, Griffith LC, Birren SJ. Proc Natl Acad Sci (2006) Inhibition of glial maturation by bone morphogenetic protein 2 in a neural crest-derived cell line. Dore JJ, Crotty KL, Birren SJ. Dev Neurosci. (2005) BDNF and CNTF regulate cholinergic properties of sympathetic neurons through independent mechanisms. Slonimsky JD, Yang B, Hinterneder JM, Nokes EB, Birren SJ. Mol Cell Neurosci. (2003) A rapid switch in sympathetic neurotransmitter release properties mediated by the p75 receptor. Yang B, Slonimsky JD, Birren SJ. Nat Neurosci. (2002) Target cells promote the development and functional maturation of neurons derived from a sympathetic precursor cell line. Bharmal S, Slonimsky JD, Mead JN, Sampson CP, Tolkovsky AM, Yang B, Bargman R, Birren SJ. Dev Neurosci. (2001) Postmigratory enteric and sympathetic neural precursors share common, developmentally regulated, responses to BMP2. Pisano JM, Colón-Hastings F, Birren SJ. Dev Biol. (2000) Developmental regulation of GDNF response and receptor expression in the enteric nervous system. Worley DS, Pisano JM, Choi ED, Walus L, Hession CA, Cate RL, Sanicola M, Birren SJ. Development. (2000) Nerve growth factor collaborates with myocyte-derived factors to promote development of presynaptic sites in cultured sympathetic neurons. Lockhart ST, Mead JN, Pisano JM, Slonimsky JD, Birren SJ. J Neurobiol. (2000) Restriction of developmental potential during divergence of the enteric and sympathetic neuronal lineages. Pisano JM, Birren SJ. Development (1999) Nerve growth factor modulates synaptic transmission between sympathetic neurons and cardiac myocytes. Lockhart ST, Turrigiano GG, Birren SJ. J Neurosci. (1997) CNTF, FGF, and NGF collaborate to drive the terminal differentiation of MAH cells into postmitotic neurons. Ip NY, Boulton TG, Li Y, Verdi JM, Birren SJ, Anderson DJ, Yancopoulos GD. Neuron (1994) p75LNGFR regulates Trk signal transduction and NGF-induced neuronal differentiation in MAH cells. Verdi JM, Birren SJ, Ibáñez CF, Persson H, Kaplan DR, Benedetti M, Chao MV, Anderson DJ. Neuron (1994) Sympathetic neuroblasts undergo a developmental switch in trophic dependence. Birren SJ, Lo L, Anderson DJ. Development (1993) Membrane depolarization induces p140trk and NGF responsiveness, but not p75LNGFR, in MAH cells. Birren SJ, Verdi JM, Anderson DJ. Science (1992) CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130. Ip NY, Nye SH, Boulton TG, Davis S, Taga T, Li Y, Birren SJ, Yasukawa K, Kishimoto T, Anderson DJ, et al. Cell (1992) DNA binding and transcriptional regulatory activity of mammalian achaete-scute homologous (MASH) proteins revealed by interaction with a muscle-specific enhancer. Johnson JE, Birren SJ, Saito T, Anderson DJ. Proc Natl Acad Sci U S A. (1992) |
