Spatial memory alterations by activation of septal 5HT1A receptors: no implication of cholinergic septohippocampal neurons

Abstract

In rats, activation of medial septum (MS) 5-HT(1A) receptors with the 5-HT(1A)/5-HT(7) receptor agonist 8-OH-DPAT disrupts encoding and consolidation, but not retrieval of a spatial memory in the water maze task. These findings might be explained by an action of 8-OH-DPAT on 5-HT(1A) receptors located on cholinergic neurons which the drug could transiently hyperpolarise. If so, selective damage of these neurons should mimic the effects of 8-OH-DPAT, or, at least, synergistically interfere with them. To test this hypothesis, rats were subjected to intraseptal infusions of 8-OH-DPAT (or phosphate-buffered saline) during acquisition of a water maze task before and/or after 192 IgG-saporin-induced MS cholinergic lesion (vs. sham-operated). We confirmed that only pre-acquisition intraseptal 8-OH-DPAT infusions prevented learning and subsequent drug-free retrieval of the platform location in intact rats and found that (1) the cholinergic lesion did not prevent recall of the platform location, and (2) the impairing effects of 8-OH-DPAT were similar in sham-operated and lesioned rats, whether naïve or not, to the task before lesion surgery. An action of 8-OH-DPAT on only MS cholinergic neurons is not sufficient to account for the drug-induced memory impairments. A concomitant 8-OH-DPAT-induced hyperpolarisation of cholinergic and/or GABAergic and/or glutamatergic neurons (intact rats), or of only GABAergic and/or glutamatergic ones after cholinergic lesion, might be necessary to obliterate task acquisition, confirming that, in the MS, (1) the three neuronal populations could cooperate to process hippocampal-dependent information, and (2) non-cholinergic septohippocampal neurons might be more important than cholinergic ones in serotonin-induced modulation of hippocampus-dependent memory processing.