Donders Institute for Brain, Cognition and Behaviour
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Theme 3: Plasticity and Memory

Molecular Neurophysiology

Donders-PLASTICITY-MEMORY-screen thema 3The general interest of our research group is to understand the underlying molecular events, leading to changes in synaptic structure and function and how these changes relate to learning and memory.

As a molecular entry point for this research we focus on the functional characterization of genes associated with intellectual disability (ID), a disease characterized by synaptic deficits (synaptopathy). Great progress has been made over recent years towards the identification of ID genes, resulting in a list of more than 400 genes.

A largely remaining challenge, however, is to connect the genetic causes of ID to processes that establish and/or modify neuronal circuit function. Because learning deficit is a constant feature of ID patients, it is tempting to attribute some of ID traits to alterations in synaptic structure and function (synaptopathy). Our current efforts are geared towards understanding how synaptic properties are acquired and change during development.

To this end we are investigating the role Rho GTPase signaling and chromatin remodeling pathways (epigenetics). To gain insight into these pathways we take a multidisciplinary approach that includes: (i) electrophysiological assessment of synaptic transmission (ii) two-photon imaging of neuronal structures (iii) manipulation of proteins of interest in subsets of neurons and (iv) molecular biology techniques to characterize proteins that regulate synaptic development and are involved in cognitive disorders.

Contact
Name: Nael Nadif Kasri
Telephone: 024-3614242
Email: n.nadif@donders.ru.nl
Fax: 024-3541435
Visiting address: Department of Cognitive Neuroscience
Radboud University Nijmegen Medical Centre / 855
Geert Grooteplein Zuid 10
6525 EZ Nijmegen
The Netherlands
Postal address: Department of Cognitive Neuroscience
Radboud University Nijmegen Medical Centre / HP 855
P.O. Box 9101
6500 HB Nijmegen
The Netherlands
Key grants
  1. CAS-NWO: Mechanistic understanding of long-range connections in auditory perception: from molecule to circuitry
  2. Inscopix-NIH: Imaging memory formation and consolidation in mouse models for intelelectual disability
  3. open ALW NWO: Harnessing the potential of induced pluripotent stem cells for cognitive disorders
  4. FP7-Marie Curie International Reintegration Grant
  5. Hypatia fellowship
Key publications
  • Frega M, van Gestel S, Linda K, van der Raadt J, Keller J, van Rhijn JR, Schubert D, Albers CA, Nadif Kasri N Rapid neuronal differentiation of induced pluripotent stem cells for measuring network activity on micro-electrode arrays 2017 JOVE, doi: 10.3791/54900.
  • Martens M, Frega M, Classen J, Epping L, Bijvank E, Benevento M, van Bokhoven H, Tiesinga P, Schubert D, Nadif Kasri N. Euchromatin histone methyltransferase 1 regulates cortical neuronal network development. Sci Rep. 2016 6:35756.
  • Benevento M, Iacono G, Selten M, Ba W, Oudakker A, Frega M, Keller J, Mancini M, Lewerissa E, Kleefstra T, Stunnenberg HG, Zhou H, van Bokhoven H and Nadif Kasri N. Histone methylation by the Kleefstra syndrome protein EHMT1 mediates homeostatic synaptic scaling. Neuron 2016, 91:341-55
  • Ba W, Selten MM, van der Raadt J, van Veen H, Li LL, Benevento M, Oudakker AR, Lasabuda RSE, Letteboer SJ, Roepman R, van Wezel RJA, Courtney MJ, van Bokhoven H and Nadif Kasri N. ARHGAP12 functions as a developmental brake on excitatory synapse function. Cell Reports 2016, 4:1355-68
  • Nadif Kasri N#, Nakano-Kobayashi# A and van Aelst, L. Rapid synthesis of the X-linked mental retardation protein OPHN1 mediates mGluR-dependent LTD through interaction with the endocytic machinery. Neuron 2011, 72, 300–315

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Theme 3:
Plasticity and Memory

Donders
Research Group
Molecular Neurophysiology


Principal Investigator
N. Nadif Kasri

Group members

Postdocs
Wei Ba
Monica Frega

PhDs (in alphabetical order)
Yanfen Chen
Linda Katrin
Teun Klein Gunnewiek 
Britt Mossink
Moritz Negwer
Jori van der Raadt 
Jon-Ruben van Rhijn
Anouk  Verboven

Technicians
Jason Keller
Astrid Oudakker

Master students
Rhode Erbrink
Hawra Kadhim

EL update Apr 17
*Open group photo (png, 350 kB)