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5‐HT 1A and NMDA receptors interact in the rat medial septum and modulate hippocampal‐dependent spatial learning
Author(s) -
ElvanderTottie Elin,
Eriksson Therese M.,
Sandin Johan,
Ögren Sven Ove
Publication year - 2009
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20596
Subject(s) - neuroscience , hippocampal formation , nmda receptor , hippocampus , glutamatergic , ifenprodil , long term depression , cholinergic , gabaergic , psychology , serotonergic , receptor , glutamate receptor , ampa receptor , medicine , serotonin , inhibitory postsynaptic potential
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 μg/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 μg/rat). While intraseptal administration of ( R )‐8‐OH‐DPAT (4 μg) combined with a subthreshold dose of the NMDA receptor antagonist D‐AP5 (1 μg) 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. © 2009 Wiley‐Liss, Inc.