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Dr. Maren Engelhardt

During development of the mammalian central nervous system, complex connections are established that serve to transmit all incoming sensory information via action potentials. The development of sensory systems (vision, hearing, touch, etc.) largely depends on incoming synaptic activity. For the generation of action potentials, a specialized axonal domain, the axon initial segment (AIS) is essential. Structure and function of the AIS is essentially regulated by the membrane scaffolding protein AnkyrinG (ANK3 gene), which clusters voltage-gated ion channels at the AIS.

Furthermore, the AIS plays a fundamental role for the establishment of neuronal polarity, a key requisite for normal neuronal function. Mutations in ANK3 and the resulting structural perturbations have been associated with various human cognitive diseases as well as certain forms of epilepsy. Therefore, we focus our work on uncovering the mechanisms that drive developmental AIS maturation as well as its plasticity both during development and in the adult.

Currently, our major topics are:

  • AIS plasticity in sensory systems
  • developmental neurobiolgy of axonal domains in the visual system
  • Ankyrin variants in models of human CNS diseases
(A) A pyramidal neuron in an organotypic culture, biolistically transfected with mCherry (red) with its AIS (βIV-spectrin, green) after immunofluorescence (Collaboration project with P. Wahle, Developmental Neurobiology, RUB Bochum), Image from Höfflin et al., in preparation. (B) Molecular composition of the AIS, section from the axonal membrane and cytoskeleton (© A. Schlüter). (C) Summary of our data regarding AIS plasticity from the visual and somatosensory cortex: Sensory deprivation results in massive elongation of the AIS (cells are more excitable); over-excitation rapidly (3 hr) results in AIS shortening (cells are less excitable). From Gutzmann et al., 2014 and Jamann et al., in preparation.

Selection of recent publications

  1. Schlüter A, del Turco D, Deller T, Gutzmann A, Schultz C, Engelhardt M: Dynamic regulation of synaptopodin in the axon initial segment during visual cortex development. Cer Cor, 2017, in press
  2. Jamann N, Jordan M, Engelhardt M: Activity-dependent axonal plasticity in sensory systems. Neurosci, 2017, in press
  3. Engelhardt M, Di Cristo G, Grabert J, Patz S, Maffei L, Berardi N, Wahle P: Leukemia inhibitory factor impairs structural and neurochemical development of rat visual cortex in vivo. Mol Cell Neurosci 2017; 79
  4. Kübler J, Kirschner S, Hartmann L, Welzel G, Engelhardt M, Herskind C, Veldwijk MR, Schultz C, Felix M, Glatting G, Maier P, Wenz F, Brockmann MA, Giordano FA: The HIV-derived protein Vpr52-96has anti-glioma activity in vitro and in vivo. Oncology 2016; 7(29)
  5. Gutzmann A, Ergül N, Grossmann R, Schultz C, Wahle P, Engelhardt M: A period of structural plasticity at the axon initial segment in developing visual cortex. Front Neuroanat 2014; 8:1
  6. Thome C, Kerry T, Yanez A, Schultz C, Engelhardt M, Cambridge SB, Both M, Draguhn A, Beck H, Egerov AV: Axon-carrying dendrites convey privileged synaptic input in hippocampal neurons. Neuron 2014, 83(6): 1418-30.
  7. Hirth M, Rukwied R, Gromann A, Turnquist B, Weinkauf B, Francke K, Albrecht P, Rice F, Hägglöf B, Ringkamp M, Engelhardt M, Schultz C, Schmelz M, Obreja O: Nerve growth factor induces sensitization of nociceptors without evidence for increased intraepidermal nerve fiber density. Pain 2013; Nov;154(11): 2500-11.
  8. Engelhardt M*, Vorwald S, Sobotzik MJ, Bennett V, Schultz, C: Ankyrin-B structurally defines terminal microdomains of peripheral somatosensory axons. Brain Res Func 2013; 218(4):1005-1016. *corresponding author
  9. Engelhardt M, Tosha C, Lopes VS, Chen B, Nguyen, L, Nusinowitz S, Williams DS: Functional and morphological analysis of the subretinal injection of retinal pigment epithelium cells. Vis Neurosci 2012; 29(2): 83-93.
  10. Engelhardt M, Di Cristo G, Wahle P, Berardi N, Maffei L: Differential effects of NT-4, NGF and BDNF on development of neurochemical architecture and cell size regulation in rat visual cortex during the critical period. Eur J Neurosci 2007; 25 (2): 529-540.

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