Cognitive impairments are common in depression and involve dysfunctional serotonin neurotransmission. The 5-HT 1B receptor (5-HT 1B R) regulates serotonin transmission, via presynaptic receptors, but can also affect transmitter release at heterosynaptic sites. This study aimed at investigating the roles of the 5-HT 1B R, and its adapter protein p11, in emotional memory and object recognition memory processes by the use of p11 knockout (p11KO) mice, a genetic model for aspects of depression-related states. 5-HT 1B R agonist treatment induced an impairing effect on emotional memory in wild type (WT) mice. In comparison, p11KO mice displayed reduced long-term emotional memory performance. Unexpectedly, 5-HT 1B R agonist stimulation enhanced memory in p11KO mice, and this atypical switch was reversed after hippocampal adeno-associated virus mediated gene transfer of p11. Notably, 5-HT 1B R stimulation increased glutamatergic neurotransmission in the hippocampus in p11KO mice, but not in WT mice, as measured by both pre-and postsynaptic criteria. Magnetic resonance spectroscopy demonstrated global hippocampal reductions of inhibitory GABA, which may contribute to the memory enhancement and potentiation of pre-and post-synaptic measures of glutamate transmission by a 5-HT 1B R agonist in p11KO mice. It is concluded that the level of hippocampal p11 determines the directionality of 5-HT 1B R action on emotional memory processing and modulates hippocampal functionality. These results emphasize the importance of using relevant disease models when evaluating the role of serotonin neurotransmission in cognitive deficits related to psychiatric disorders.
|Number of pages||10|
|State||Published - Oct 2013|
Bibliographical noteFunding Information:
We are grateful to Dr Nicoletta Schintu, Saurav Shrestha and Junfeng Yang for their excellent experimental and technical support, and Dr Stefan Brené and Dr Jeremy Young at the Experimental Magnetic Resonance Center at Karolinska Institutet. This work was supported by the Swedish Research Council, Söderberg’s stiftelse and Karolinska Institutet Faculty Funds (KID) (TME and AA), Quanteon, LLC and USPHS grant DA017186 (KNH and GAG), The Fischer Center for Alzheimer’s Research Foundation (PS and PG), W81XWH-09-1-0402 (PG), NIH MH090963 (PG), W81XWH-09-0381(MGK) and the European Union Seventh Framework Program under grant agreement no. PEOPLE-ITN-2008-238055 (BrainTrain).
- novel object recognition
- passive avoidance
ASJC Scopus subject areas
- Molecular Biology
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience