5-HT1A and NMDA receptors interact in the rat medial septum and modulate hippocampal-dependent spatial learning

✍ Scribed by Elin Elvander-Tottie; Therese M. Eriksson; Johan Sandin; Sven Ove Ögren

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 403 KB
• Volume: 19
• Category: Article
• ISSN: 1050-9631
• DOI: 10.1002/hipo.20596

✦ Synopsis

Cholinergic and GABAergic neurons in the medial septum/ vertical limb of the diagonal band of Broca (MS/vDB) projecting to the hippocampus, constitute the septohippocampal projection, which is important for hippocampal-dependent learning and memory. There is also evidence for an extrinsic as well as an intrinsic glutamatergic network within the MS/vDB. GABAergic and cholinergic septohippocampal neurons express the serotonergic 5-HT 1A receptor and most likely also glutamatergic NMDA receptors. The aim of the present study was to examine whether septal 5-HT 1A receptors are important for hippocampal-dependent long-term memory and whether these receptors interact with glutamatergic NMDA receptor transmission in a manner important for hippocampal-dependent spatial memory. Intraseptal infusion of the 5-HT 1A receptor agonist (R)-8-OH-DPAT (1 or 4 lg/rat) did not affect spatial learning in the water maze task but impaired emotional memory in the passive avoidance task at the higher dose tested (4 lg/rat). While intraseptal administration of (R)-8-OH-DPAT (4 lg) combined with a subthreshold dose of the NMDA receptor antagonist D-AP5 (1 lg) only marginally affected spatial acquisition, it produced a profound impairment in spatial memory. In conclusion, septal 5-HT 1A receptors appears to play a more prominent role in emotional than in spatial memory. Importantly, septal 5-HT 1A and NMDA receptors appear to interact in a manner, which is particularly critical for the expression or retrieval of hippocampal-dependent long-term spatial memory. It is proposed that NMDA receptor hypofunction in the septal area may unmask a negative effect of 5-HT 1A receptor activation on memory, which may be clinically relevant. V V