The mechanisms, dynamics, and consolidation of episodic memory in rodents

• Applicant: Professor Dr. Ekrem Dere
• Subject Area: General, Cognitive and Mathematical Psychology
• Term: from 2004 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5439022

• Final Report Year: 2008

Final Report Abstract

In humans deficits in episodic memory are observed in the course of normal aging, and after lesions to the medial temporal lobe, which includes the hippocampus and after lesions to diencephalic structures, such as the mediodorsal thalamus and the mammillary bodies, as well as the frontal cortex. Deficits in episodic memory are also found in a variety of neurodegenerative and psychiatric diseases such as Alzheimer's disease. Against this background it is desirable to have a valid animal model of episodic memory in order to evaluate possible therapeutic strategies. In order to test whether rodents are able to remember unique experiences in terms of what happened, as well as where and when it happened to serve as an animal model for episodic memory, we combined different versions of the novelty-preference paradigm into a single task. Since rodents are able to discriminate familiar and novel objects, can detect whether a familiar object is presented in a novel or familiar location and are able to discriminate in which temporal order the objects have been presented, we asked whether they are able to perform these discriminations simultaneously. We found that rats and mice are able to integrate or bind what, where and when information into an unified episodic-like memory. We also found that acute stress impaired the animal's performance in the episodic-like memory task, which, however, could be partially reversed by the N-Methyl-D-aspartate-receptors agonist D-cycloserine and the neurokinin 1 receptor antagonist SR140333. In pharmacological studies we found that pharmacological stimulation of NMDA receptors by D-Cycloserine and neurokinin 3 receptos by senktide can both promote episodic-like memory in mice under sub optimal learning conditions. In sum one can state that the different versions of the novelty-preference task can be combined to measure the remembrance of the content, place and temporal context of single experiences and that our episodic-like memory task is suitable to perform genetic, lesions and pharmacological studies. In terms of theory we proposed an alternative strictly operational definition of episodic memory applicable to both human and animal studies on the neurobiology and pathology of episodic memory.

Publications

• Dere E (2007) NMDA receptors and episodic-like memory in the rodent. European Brain and Behaviour Society. 39th EBBS meeting. September 15-18, 2007, Trieste, Italy.
  
  
• Dere E (2007) NMDA-receptors and episodic-like memory in the rodent. 2. BMFZ Klausurtagung. August 9-10, 2007, Wermelskirchen, Germany.
  
  
• De Souza Silva MA, Huston JP, Dere E (2005) Integrated memory for objects, places and temporal order: Evidence for episodic-like memory in mice. The European Brain and Behaviour Society (EBBS), 37th Meeting, September 24-28, Dublin, Ireland.
  
  
• Dere E (2007) Measuring episodic-like memory in mice and rats. European Brain and Behaviour Society. 39th EBBS meeting. September 15-18, 2007, Trieste, Italy.
  
  
• Dere E, De Souza Silva MA, Huston JP (2004) Higher order memories for objects encountered in different spatio-temporal contexts in mice: Evidence for episodic memory. Reviews in the Neurosciences 15, 231-240.
  
  
• Dere E, Easton A, Nadel L, Huston JP (Eds.) (2008) Handbook of Episodic Memory. Amsterdam. Elsevier Science. In press.
  
  
• Dere E, Huston JP, De Souza Silva MA (2005) Integrated Memory for objects, places and temporal order: evidence for episodic-like memory in mice. Neurobiology of Learning and Memory 84, 214-221.
  
  
• Dere E, Huston JP, De Souza Silva MA (2005) Protocol: Episodic-like memory in mice: Simultaneous assessment of object, place and temporal order memory. Brain Research Protocols 16, 10-19.
  
  
• Dere E, Huston JP, De Souza Silva MA (2007) The pharmacology, neuroanatomy, and neurogenetics of one-trial object recognition in rodents. Neuroscience and Biobehavioral Reviews 31, 673-704.
  
  
• Dere E, Kart-Teke E, Huston JP, De Souza Silva MA (2006) The case for episodic memory in animals. Neuroscience and Biobehavioral Reviews 30, 1206-1224.
  
  
• Dere E, Teke E, Huston JP, De Souza Silva MA (2005) Integrated memory for objects, places, and temporal order: Testing episodic-like memory in rodents. The Society for Neuroscience (SFN), Annual Meeting, November 12-16, Washington, DC.
  
  
• Kart-Teke E, De Souza Silva MA, Huston JP, Dere E (2006) Wistar rats show episodic-like memory for unique experiences. Neurobiology of Learning and Memory 85, 173-182.
  
  
• Kart-Teke E, Dere E, Brandao M, Huston JP, De Souza Silva MA (2007) Reinstatement of episodic-like memory in rats by NK-1 receptor antagonism. Neurobiology of Learning and Memory 87, 324-331.
  
  
• Zlomuzica A, De Souza Silva MA, Huston JP, Dere E (2007) NMDA-receptor modulation by D-Cycloserine promotes Episodic-like memory in mice. European Brain and Behaviour Society. 39th EBBS meeting. September 15- 18, 2007, Trieste, Italy.
  
  
• Zlomuzica A, De Souza Silva MA, Huston JP, Dere E (2007) NMDA-receptor modulation by D-cycloserine promotes episodic-like memory in mice. Psychopharmacology 193, 503-509.