Columbia University, September 2000 – October 2007
Ph.D. in Neurobiology and Behavior, October 2007; M.A. in Neurobiology and Behavior, May 2003.
Dissertation: Deficiency of the schizophrenia susceptibility gene Type III Neuregulin-1 reduces subsets of adult mouse forebrain interneurons.
Ph.D. in Neurobiology and Behavior, October 2007; M.A. in Neurobiology and Behavior, May 2003.
Dissertation: Deficiency of the schizophrenia susceptibility gene Type III Neuregulin-1 reduces subsets of adult mouse forebrain interneurons.
Selected Scientific Publications
Notch1 is required for maintenance of the reservoir of adult hippocampal stem cellsAbles JL, Decarolis NA, Johnson MA, Rivera PD, Gao Z, Cooper DC, Radtke F, Hsieh J, Eisch AJ.
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Abstract - Notch1 regulates neural stem cell (NSC) number during development, but its role in adult neurogenesis is unclear. We generated nestin-CreER(T2)/R26R-YFP/Notch1(loxP/loxP) [Notch1inducible knock-out (iKO)] mice to allow tamoxifen (TAM)-inducible elimination of Notch1 and concomitant expression of yellow fluorescent protein (YFP) in nestin-expressing Type-1 NSCs and their progeny in the adult hippocampal subgranular zone (SGZ). Consistent with previous research, YFP+ cells in all stages of neurogenesis were evident in the subgranular zone (SGZ) of wild-type (WT) mice (nestin-CreER(T2)/R26R-YFP/Notch1(w/w)) after tamoxifen (post-TAM), producing adult-generated YFP+ dentate gyrus neurons. Compared with WT littermates, Notch1 iKO mice had similar numbers of total SGZ YFP+ cells 13 and 30 d post-TAM but had significantly fewer SGZ YFP+ cells 60 and 90 d post-TAM. Significantly fewer YFP+ Type-1 NSCs and transiently amplifying progenitors (TAPs) resulted in generation of fewer YFP+ granule neurons in Notch1 iKO mice. Strikingly, 30 d of running rescued this deficit, as the total YFP+ cell number in Notch iKO mice was equivalent to WT levels. This was even more notable given the persistent deficits in the Type-1 NSC and TAP reservoirs. Our data show that Notch1signaling is required to maintain a reservoir of undifferentiated cells and ensure continuity of adult hippocampal neurogenesis, but that alternative Notch- and Type-1 NSC-independent pathways compensate in response to physical activity. These data shed light on the complex relationship between Type-1 NSCs, adult neurogenesis, the neurogenic niche, and environmental stimuli.
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Cell-intrinsic signals that regulate adult neurogenesis in vivo: insights from inducible approaches
Johnson MA, Ables JL, Eisch AJ.
Abstract - The process by which adult neural stem cells generate new and functionally integrated neurons in the adult mammalian brain has been intensely studied, but much more remains to be discovered. It is known that neural progenitors progress through distinct stages to become mature neurons, and this progression is tightly controlled by cell-cell interactions and signals in the neurogenic niche. However, less is known about the cell-intrinsic signaling required for proper progression through stages of adult neurogenesis. Techniques have recently been developed to manipulate genes specifically in adult neural stem cells and progenitors in vivo, such as the use of inducible transgenic mice and viral-mediated gene transduction. A critical mass of publications utilizing these techniques has been reached, making it timely to review which molecules are now known to play a cell-intrinsic role in regulating adult neurogenesis in vivo. By drawing attention to these isolated molecules (e.g. Notch), we hope to stimulate a broad effort to understand the complex and compelling cascades of intrinsic signaling molecules important to adult neurogenesis. Understanding this process opens the possibility of understanding brain functions subserved by neurogenesis, such as memory, and also of harnessing neural stem cells for repair of the diseased and injured brain.
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Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit componentsChen YJ, Johnson MA, Lieberman MD, Goodchild RE, Schobel S, Lewandowski N, Rosoklija G, Liu RC, Gingrich JA, Small S, Moore H, Dwork AJ, Talmage DA, Role LW.
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Abstract - Neuregulin-1 (Nrg1)/erbB signaling regulates neuronal development, migration, myelination, and synaptic maintenance. The Nrg1 gene is a schizophrenia susceptibility gene. To understand the contribution of Nrg1 signaling to adult brain structure and behaviors, we studied the regulation of type III Nrg1 expression and evaluated the effect of decreased expression of the type III Nrg1 isoforms. Type III Nrg1 is transcribed by a promoter distinct from those for other Nrg1 isoforms and, in the adult brain, is expressed in the medial prefrontal cortex, ventral hippocampus, and ventral subiculum, regions involved in the regulation of sensorimotor gating and short-term memory. Adult heterozygous mutant mice with a targeted disruption for type III Nrg1 (Nrg1(tm1.1Lwr+/-)) have enlarged lateral ventricles and decreased dendritic spine density on subicular pyramidal neurons. Magnetic resonance imaging of type III Nrg1 heterozygous mice revealed hypofunction in the medial prefrontal cortex and the hippocampal CA1 and subiculum regions. Type III Nrg1 heterozygous mice also have impaired performance on delayed alternation memory tasks, and deficits in prepulse inhibition (PPI). Chronic nicotine treatment eliminated differences in PPI between type III Nrg1 heterozygous mice and their wild-type littermates. Our findings demonstrate a role of type III Nrg1 signaling in the maintenance of corticostriatal components and in the neural circuits involved in sensorimotor gating and short-term memory.
Awards and Honors
June 2008 – Ruth L. Kirschstein National Research Service Award recipient.
May 2006 – Selected to present at the National Institute of Mental Health Pre-Doctoral Research Festival.
March 2001 – Honorable Mention; Graduate Research Fellowship Program, National Science Foundation.
Technical Expertise
Immunohistochemistry; Standard and confocal microscopy; Analyses using Stereoinvestigator and Neurolucida; Intracardial perfusion; Microtome and cryostat sectioning; Immunoblot; PCR; familiarity with many other techniques including those used in electrophysiology and animal behavior.
June 2008 – Ruth L. Kirschstein National Research Service Award recipient.
May 2006 – Selected to present at the National Institute of Mental Health Pre-Doctoral Research Festival.
March 2001 – Honorable Mention; Graduate Research Fellowship Program, National Science Foundation.
Technical Expertise
Immunohistochemistry; Standard and confocal microscopy; Analyses using Stereoinvestigator and Neurolucida; Intracardial perfusion; Microtome and cryostat sectioning; Immunoblot; PCR; familiarity with many other techniques including those used in electrophysiology and animal behavior.
Peer-Reviewed Publications
J. L. Ables, M. A. Johnson, P. D. Rivera, Z. Gao, D. C. Cooper, F. Radtke, J. Hseih, A. J. Eisch. Notch1 is required for maintenance of the reservoir of adult hippocampal stem cells. (2010) J Neurosci. Aug 4;30(31):10484-92
Johnson MA, Ables JL, Eisch AJ. (2009) Cell-intrinsic signals that regulate adult neurogenesis in vivo: insights from inducible approaches. BMB Rep. May 31;42(5):245-59
Chen Y-J, Johnson MA, Lieberman MD, Goodchild RE, Schobel S, Lewandowski N, Rosoklija G, R-C Liu, Gingrich JA, Small S, Moore H, Dwork AJ, Talmage DA, Role LW. (2008) Type III Neuregulin-1 is required for normal sensorimotor gating, memory related behaviors and cortico-striatal circuit components. J Neurosci. 2008 Jul 2;28(27):6872-83.
Witkovsky P, Veisenberger E, LeSauter J, Yan L, Johnson M, Zhang DQ, McMahon D, Silver R. (2003) Cellular location and circadian rhythm of expression of the biological clock gene Period 1 in the mouse retina. J Neurosci. Aug 20;23(20):7670-6.
Johnson MA & Vardi N. (1998) Regional differences in GABA and GAD immunoreactivity in rabbit horizontal cells. Vis Neurosci. Jul-Aug;15(4):743-53.
Meeting Abstracts
J. L. Ables, M. A. Johnson, P. D. Rivera, Z. Gao, D. C. Cooper, F. Radtke, J. Hseih, A. J. Eisch. Notch1 is required for maintenance of adult hippocampal neural stem-like cells and progenitors but not activity-dependent neurogenesis. Program No. 29.10. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online.
A. Gallegos, M. A. Johnson, A. J. Eisch, C. Tamminga. Measuring the age effect and treatment effect of antipsychotics on proliferation in the subgranular zone. Program No. 29.6. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online.
M.A. Johnson, L.W. Role. Neuregulin/ErbB signaling and adult neurogenesis. Program No. 947.1. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2005. Online.
M.A. Johnson, J.A. Ramirez-Latorre, R.E. Goodchild, L.W. Role. Expression of Neuregulin-1 (Nrg1) protein vs. mRNA in mouse. Program No. 354.6. 2003 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2003. Online.
M.A. Johnson, P. Devay, L.W. Role. The cysteine-rich domain of the Neuregulin1 gene (CRD-NRG-1) is required for survival of a subset of neurons in the suprachiasmatic nucleus (SCN). Program No. 427.1. Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2002. Online.
J. Le Sauter, E. Veisenberger, M. Johnson, D. McMahon, R.- Silver, P. Witkovsky. Cellular location and diurnal rhythm of expression of Period1 in the mouse retina. Program No. 177.1. Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2002. Online.
Sterling P, Johnson, MA, Haarsma L, Kao YH, Demb JB. (1999) Ganglion cell types of the guinea pig retina. Invest Ophthal 40:S814
Kao YH, Demb JB, Haarsma L, Johnson, MA, Sterling, P. (1999) An axon-bearing amacrine cell tracer coupled to the OFF Y ganglion cell. Invest Ophthal 40:S813
J. L. Ables, M. A. Johnson, P. D. Rivera, Z. Gao, D. C. Cooper, F. Radtke, J. Hseih, A. J. Eisch. Notch1 is required for maintenance of the reservoir of adult hippocampal stem cells. (2010) J Neurosci. Aug 4;30(31):10484-92
Johnson MA, Ables JL, Eisch AJ. (2009) Cell-intrinsic signals that regulate adult neurogenesis in vivo: insights from inducible approaches. BMB Rep. May 31;42(5):245-59
Chen Y-J, Johnson MA, Lieberman MD, Goodchild RE, Schobel S, Lewandowski N, Rosoklija G, R-C Liu, Gingrich JA, Small S, Moore H, Dwork AJ, Talmage DA, Role LW. (2008) Type III Neuregulin-1 is required for normal sensorimotor gating, memory related behaviors and cortico-striatal circuit components. J Neurosci. 2008 Jul 2;28(27):6872-83.
Witkovsky P, Veisenberger E, LeSauter J, Yan L, Johnson M, Zhang DQ, McMahon D, Silver R. (2003) Cellular location and circadian rhythm of expression of the biological clock gene Period 1 in the mouse retina. J Neurosci. Aug 20;23(20):7670-6.
Johnson MA & Vardi N. (1998) Regional differences in GABA and GAD immunoreactivity in rabbit horizontal cells. Vis Neurosci. Jul-Aug;15(4):743-53.
Meeting Abstracts
J. L. Ables, M. A. Johnson, P. D. Rivera, Z. Gao, D. C. Cooper, F. Radtke, J. Hseih, A. J. Eisch. Notch1 is required for maintenance of adult hippocampal neural stem-like cells and progenitors but not activity-dependent neurogenesis. Program No. 29.10. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online.
A. Gallegos, M. A. Johnson, A. J. Eisch, C. Tamminga. Measuring the age effect and treatment effect of antipsychotics on proliferation in the subgranular zone. Program No. 29.6. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online.
M.A. Johnson, L.W. Role. Neuregulin/ErbB signaling and adult neurogenesis. Program No. 947.1. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2005. Online.
M.A. Johnson, J.A. Ramirez-Latorre, R.E. Goodchild, L.W. Role. Expression of Neuregulin-1 (Nrg1) protein vs. mRNA in mouse. Program No. 354.6. 2003 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2003. Online.
M.A. Johnson, P. Devay, L.W. Role. The cysteine-rich domain of the Neuregulin1 gene (CRD-NRG-1) is required for survival of a subset of neurons in the suprachiasmatic nucleus (SCN). Program No. 427.1. Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2002. Online.
J. Le Sauter, E. Veisenberger, M. Johnson, D. McMahon, R.- Silver, P. Witkovsky. Cellular location and diurnal rhythm of expression of Period1 in the mouse retina. Program No. 177.1. Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2002. Online.
Sterling P, Johnson, MA, Haarsma L, Kao YH, Demb JB. (1999) Ganglion cell types of the guinea pig retina. Invest Ophthal 40:S814
Kao YH, Demb JB, Haarsma L, Johnson, MA, Sterling, P. (1999) An axon-bearing amacrine cell tracer coupled to the OFF Y ganglion cell. Invest Ophthal 40:S813
Experience
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UT Southwestern Medical Center, Dallas, Texas
June 2008 – March 2010 Postdoctoral Fellow, Ruth L. Kirschstein National Research Service Award Department of Molecular Psychiatry Laboratory of Dr. Amelia Eisch SUNY Stony Brook, Stony Brook, NY October 2007 – June 2008 Postdoctoral Associate Department of Neurobiology and Behavior Laboratories of Dr. Lorna Role and Dr. David Talmage Columbia University, New York, NY September 2000 – October 2007 Graduate Research Assistant Graduate Program in Neurobiology and Behavior Laboratories of Dr. Lorna Role and Dr. David Talmage New York University, New York, NY September 1999 – September 2000 Research Assistant Department of Ophthalmology Laboratory of Dr. Paul Witkovsky |
University of Pennsylvania, Philadelphia, PA
June 1998 – July 1999 Research Assistant Department of Neuroscience Laboratory of Dr. Peter Sterling University of Pennsylvania, Philadelphia, PA February 1996 – June 1998 Research Technician Department of Neuroscience Laboratory of Dr. Noga Vardi University of Pennsylvania, Philadelphia, PA October 1993 – May 1995 Undergraduate work-study Department of Neurology Children’s Hospital of Philadelphia Laboratory of Dr. David Pleasure |
