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Neuropeptide Y Y2 receptors modulate trace fear conditioning and spatial memory in the dorsal hippocampus


Neuropeptide Y (NPY), a highly conserved 36 amino acid peptide is widely distributed in the central nervous system. Besides its functions in various metabolic processes NPY has attracted considerable attention in modulating emotional-affective behavior. NPY exerts a pronounced anxiolytic effect most likely mediated by Y1 receptors, whereas stimulation of predominantly pre-synaptic Y2 receptors results in increased anxiety. The role of NPY Y2 receptors in the processing of emotional learning, however, remains still elusive.


The current study aims to investigate the role of NPY Y2 receptors in Pavlovian fear conditioning, a simple form of associative learning and in a spatial memory task, the Barnes maze. Y2-KO mice were subjected to delay (amygdala-dependent) and trace (hippocampus-dependent) fear conditioning paradigms.


While in delay fear conditioning Y2-KO mice performed similar to wild-type controls, recall of a trace fear memory was significantly increased in Y2-KO mice. Furthermore, Y2-KO mice exhibited an improved long-term memory in the Barnes maze test, a paradigm investigating spatial learning. Trace fear conditioning and spatial memory are predominantly mediated by the dorsal hippocampus. For investigating the specific contribution of Y2 receptors in the adult dorsal hippocampus in trace fear conditioning and spatial memory formation we locally deleted hippocampal Y2 receptors in conditional Y2-KO mice by injection of a rAAV-CreGFP vector. Moreover we over-expressed NPY3–36, an Y2 receptor preferring agonist, at the same brain sites.


Our data indicate that while Y2 receptors are not involved in amygdala-dependent delay fear conditioning, they seem to play an inhibitory role on the acquisition of trace fear memories. Moreover, Y2 receptors in the dorsal hippocampus are crucial for spatial memory formation. These actions are probably mediated by inhibition of glutamate release in dorsal hippocampal circuitries.


This work was funded by the Austrian Science fund (S10204 and P22830-B18).

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Correspondence to Ramon O Tasan.

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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Tasan, R.O., Verma, D., Mietzsch, M. et al. Neuropeptide Y Y2 receptors modulate trace fear conditioning and spatial memory in the dorsal hippocampus. BMC Pharmacol 11 (Suppl 2), A2 (2011).

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