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Forschungsarbeit

Epigenetic Modification of Prefrontal Cortex Activity allows Extinction of Fear Memory

Von Dr. Roger Marek (29.10.2014)

Responding to fearful events is a vital behavioral response in many species, including humans. Traumatizing personal events (e.g. war-zone exposure and natural catastrophes) can cause persistent changes to the neural network that encodes the fear response, possibly leading to a development of anxiety disorders such as posttraumatic stress disorder (PTSD) and phobias. The understanding of the underlying mechanism for the extinction of such fear, which is thought to be a form of new memory rather than an erasure of the learned fear, is crucial to find more effective treatment.

In mammals, the core structure that gates fear responses is called the amygdala. The amygdala receives fear-related messages from multiple sensory systems and converts this fear-encoded information into a behavioral response that can be long lasting. Even though the fear response is a rather primitive behavior, it requires prefrontal cortical structures for proper integration and is thus a promising pharmacological target for possible treatments.

In the presented investigations, we used modulators for epigenetic targets to see if the extinction of fear memory can be altered. Epigenetics refers to changes in genes activity without alterations in the DNA sequence. By using an animal model and specific modulators of an epigenetic process called acetylation, we were able to show that these modulators significantly alter prefrontal brain activity during the extinction of fear. Moreover, the same epigenetic modulators caused equivalent prefrontal changes in long-term potentiation, which is widely accepted to be an underlying mechanism in memory formation. Even though this research is at an early stage, these findings could possibly contribute to the identification of pharmacological targets to cure anxiety disorders.

 

References:

Marek R, Coelho CM, Sullivan RK, Baker-Andresen D, Li X, et al. 2011. Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300. J Neurosci. 31:7486–91

W. Wei, C.M. Coelho, X. Li, R. Marek, S. Yan, S. Anderson, D. Meyers, C. Mukherjee, G. Sbardella, S. Castellano, C. Milite, D. Rotili, A. Mai, P.A. Cole, P. Sah, M.S. Kobor, T.W. Bredy. 2012. P300/CBP-associated factor selectively regulates the extinction of conditioned fear. J Neurosci, 32:11930–11941

 

Bild: Süleyman Kösem


Scientific career
  • 2000-2004
  • BSc in Chemistry at the Zurich University of Applied Sciences, Winterthur, Switzerland
  • 2006-2007
  • DipGrad in Neuroscience at the University of Otago, Dunedin, New Zealand
  • 2007-2009
  • MSc in the Elite Graduate Program Experimental and Clinical Neuroscience at the University of Regensburg, Regensburg, Germany
  • 2009-2013
  • PhD in Neuroscience at the Queensland Brain Institute, University of Queensland, Brisbane, Australia
  • since 2013
  • Postdoctoral Research Fellow, Queensland Brain Institute, University of Queensland, Brisbane, Australia

Scholarships and Awards
  • * Stipend from the Dr. Gadient Engi-Stiftung der Novartis AG, Switzerland
  • * International Research Tuition Award from the University of Queensland, Australia

Selected Publications
  • * Suárez et al. (2014) Balanced interhemispheric cortical activity is required for correct targeting of the corpus callosum. Neuron, accepted
  • * Marek et al. (2013) The amygdala and medial prefrontal cortex: partners in the fear circuit. Journal of Physiology, 591 10: 2381-2391.
  • * Michel et al. (2013) Mechanism of bilateral communication in the suprachiasmatic nucleus. European Journal of Neuroscience, 37 6: 964-971.