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Areas of investigation/research focus

Significance

The complexity of the brain is reflected in the number of synapses between individual cells. It is estimated that the number of synapses in the human brain is approximately 10¹⁴. During synaptic plasticity, which is fundamental for learning and memory formation, neurons have the capability to shape the length, structure and distribution of synapses in order to refine local activity. Unfortunately, during pathological conditions, including neurodegenerative disorders such as Alzheimer’s disease, uncontrolled large-scale loss of synapses triggers local neuronal degeneration. Thus, loss of connectivity compromises neuronal activity and destabilizes neuronal information processing, which is a key determinant in the onset of cognitive decline. Understanding the pathways involved in the non-physiological dendritic spine remodeling will help to prevent excessive synaptic pruning and therefore will aid in the development of a cure against cognitive impairments associated with aging and neurodegenerative conditions.

Publications

Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice.

D Ehninger, Y Sano, P J de Vries, K Dies, D Franz, D H Geschwind, M Kaur, Y-S Lee, W Li, J K Lowe, J A Nakagawa, M Sahin, K Smith, V Whittemore, A J Silva; Mol Psychiatry. 2012 Jan;17(1):62-70. doi: 10.1038/mp.2010.115. Epub 2010 Nov 16.

Enriched environment and physical activity reduce microglia and influence the fate of NG2 cells in the amygdala of adult mice.

D Ehninger, LP Wang, F Klempin, B Römer, H Kettenmann, G Kempermann; Cell Tissue Res. 2011 Jul;345(1):69-86. Epub 2011 Jun 21.

Increased levels of anxiety-related behaviors in a Tsc2 dominant negative transgenic mouse model of tuberous sclerosis.

D Ehninger, AJ Silva; Behav Genet. 2011 May;41(3):357-63. doi: 10.1007/s10519-010-9398-1. Epub 2010 Sep 30.

Rapamycin for treatment of tuberous sclerosis and autism spectrum disorders.

Ehninger D, Silva AJ, Trends Mol Med. 2011 Feb;17(2):78-87. Epub 2010 Nov 4.

Increased levels of anxiety-related behaviors in a Tsc2 dominant negative transgenic mouse model of tuberous sclerosis.

Ehninger D, Silva AJ, Behavior Genetics, under review.

Neurofibromin Regulates Corticostriatal Inhibitory Networks During Working Memory Performance.

Shilyansky C, Karlsgodt KH, Cummings DM, Sidiropoulou K, Hardt M, James AS, Ehninger D, Bearden CE, Piorazi P, Jentsch JD, Cannon TD, Levine MS, Silva AJ, Proceedings of the National Academy of Sciences USA: 107(29) (2010) 13141-6.

Neuronal glucose transporter isoform 3 deficiency results in features of autism spectrum disorders.

Zhao ,  Fung C, Shin D, Shin BC, Thamotharan S, Sankar R, Ehninger D, Silva AJ, Devaskar SU, Molecular Psychiatry: 15(3) (2010) 286-99.

Additive effects of physical activity and environmental enrichment on adult hippocampal neurogenesis.

Fabel K, Wolf SA, Ehninger D, Babu H, Kempermann G, Frontiers in Neuroscience: 3:50 (2009).

Adult reversal of cognitive phenotypes in neurodevelopmental disorders.

Silva AJ, Ehninger D, Journal of Neurodevelopmental Disorders: 1(2) (2009) 150-7.

From mTOR to cognition: molecular and cellular mechanisms of cognitive impairments in tuberous sclerosis.

Ehninger D, de Vries PJ, Silva AJ, Journal of Intellectual Disability Research: 53(10) (2009) 838-51.

Genetics and neuropsychiatric disorders: treatment during adulthood.

Ehninger D, Silva AJ, Nature Medicine: 15(8) (2009) 849-50.

Reversing neurodevelopmental disorders in adults.

Ehninger D, Li W, Fox K, Stryker MP, Silva AJ, Neuron: 60(6) (2008) 950-60.

Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis.

Ehninger D, Han S, Shilyansky C, Zhou Y, Li W, Kwiatkowski DJ, Ramesh V, Silva AJ, Nature Medicine: 14(8) (2008) 843-8.

Neurogenesis in the adult hippocampus.

Ehninger D, Kempermann G, Cell & Tissue Research: 331(1) (2008) 243-50.

Interaction between the NR2B receptor and αCaMKII modulate synaptic plasticity and spatial learning.

Zhou Y, Takahashi E, Li W, Halt A, Wiltgen B, Ehninger D, Li GD, Hell JW, Kennedy MB, Silva AJ, Journal of Neuroscience: 27(50) (2007) 13843-53.

Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice.

Li W, Zhou Y, Jentsch JD, Brown RA, Tian X, Ehninger D, Hennah W, Peltonen L, Lönnqvist J, Huttunen MO, Kaprio J, Trachtenberg JT, Silva AJ, Cannon TD, Proceedings of the National Academy of Sciences USA: 104(46) (2007) 18280-5.

Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation.

Plümpe T, Ehninger D, Steiner B, Klempin F, Jessberger S, Brandt M, Römer B, Rodriguez GR, Kronenberg G, Kempermann G, BMC Neuroscience: 15 (2006) 7:77.

Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity.

Ehninger D, Kempermann, G, Genes, Brain & Behavior: 5(1) (2006) 29-39.

Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus.

Kronenberg G, Bick-Sander A, Bunk E, Wolf C, Ehninger D, Kempermann G, Neurobiology of Aging: 27(10) (2006) 1505-13.

Trafficking in emotions.

Ehninger D, Matynia A, Silva AJ, Nature Neuroscience: 8(5) (2005) 548-50.

Regional effects of wheel running and environmental enrichment on cell genesis and microglia proliferation in the adult murine neocortex.

Ehninger D, Kempermann G, Cerebral Cortex: 13 (2003) 845-51.