Memory Circuits

The objective of my team is to gain detailed insight in the neural circuitry that mediates the formation and retrieval of stable, long-lasting episodic memories

Research focus:
During learning, cellular and molecular changes take place that need to be stabilized in order for memory to be formed, stored and accurately retrieved. Although the neurobiological mechanisms that support the initial encoding and retrieval of learned associations received much attention, the processes that underlie the stabilization of new memories (<1 week old) into persistent remote memories (>3-4 weeks old) are poorly understood. Research by my team and others points to an important role of the prefrontal cortex in expression of remote memories. However, little is known about the time-dependent contribution of the different neuronal subtypes that are present within this brain region. Our ambition is to functionally dissect the spatial and temporal organization of long-lasting episodic memory in the prefrontal cortex.

To study memory formation and expression, we make use of mouse models of drug addiction (e.g. self-administration, conditioned place preference) and conditioned-fear. These models have in common that they produce stable memories that can persist for the life-time of the animal.

To functionally dissect neuronal circuitries involved in persistent memory formation and retrieval, we make use of transgenic mouse lines and viral vector approaches. In particular, optogenetics and DREADD technology is used to selectively interfere with the activity of genetically-defined neuronal subpopulations in specific brain regions of awake behaving animals. Importantly, we also use these tools to connect molecular and cellular plasticity to behaviour.

Memories related to drug self-administration/relapse are studied in collaboration with Taco de Vries. Adaptations at the level of the proteome and synapse physiology are examined in collaboration with respectively Ka Wan Li and Huib Mansvelder.

Mariana Matos, Michel van den Oever, Esther Visser

The extracellular matrix protein brevican limits time-dependent enhancement of cocaine conditioned place preference
Lubbers BR, Matos MR, Horn A, Visser E, Van der Loo RC, Gouwenberg Y, Meerhoff GF, Frischknecht R, Seidenbecher CI, Smit AB, Spijker S, van den Oever MC.
Neuropsychopharmacology (2016) doi: 10.1038/npp.2015.361

Optogenetic dissection of medial prefrontal cortex circuitry
Riga D, Matos MR, Glas A, Smit AB, Spijker S, Van den Oever MC.
Frontiers in systems neuroscience (2014) 8:230

Manipulating a “cocaine engram” in mice
Hsiang HL, Epp JR, van den Oever MC, Yan C, Rashid AJ, Insel N, Ye L, Niibori Y, Deisseroth K, Frankland PW, Josselyn SA.
Journal of Neuroscience (2014) 34:14115-14127

Ventromedial prefrontal cortex pyramidal cells have a temporal dynamic role in recall and extinction of cocaine-associated memory
Van den Oever MC, Rotaru DC, Heinsbroek JA, Gouwenberg Y, Deisseroth K, Stuber GD, Mansvelder HD, Smit AB.
Journal of Neuroscience (2013) 33:18225-18233

Extracellular matrix plasticity and GABAergic inhibition of prefrontal cortex pyramidal cells facilitates relapse to heroin seeking
Van den Oever MC, Lubbers BR, Goriounova NA, Li KW, Van der Schors RC, Loos M, Riga D, Wiskerke J, Binnekade R, Stegeman M, Schoffelmeer AN, Mansvelder HD, Smit AB, De Vries TJ, Spijker S.
Neuropsychopharmacology (2010) Sep;35(10):2120-33.

Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking
Van den Oever MC, Goriounova NA, Li KW, Van der Schors RC, Binnekade R, Schoffelmeer AN, Mansvelder HD, Smit AB, De Vries TJ, Spijker S.
Nature Neuroscience (2008) Sep;11(9):1053-8.

Team Leader
Michel van den Oever