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The role of cholinergic projection systems of the neocortex and hippocampus in memory consolidation in healthy and neuropathological conditions has been subject to intensive research. On the contrary, the significance of cholinergic cortical and hippocampal interneurons in learning has hardly been studied. We aimed to evaluate the role of both cholinergic projection neurons and interneurons of the neocortex and hippocampus at an early stage of spatial memory consolidation (2s1) in normal and chronic brain hypoperfusion conditions. Control rats and rats subjected to permanent two-vessel occlusion were trained with the Morris water maze, and the activity of membrane-bound and water-soluble choline acetyltransferase was evaluated in the sub-fractions of ‘light’ and ‘heavy’ synaptosomes of the neocortex and hippocampus, in which the presynapses of cholinergic projections and interneurons, respectively, are concentrated. Animals were ranked into quartiles according to their performance on stage 2s1. We found: (1) quartile-dependent cholinergic composition of 2s1 function and dynamics of cholinergic synaptic plasticity under cerebral hypoperfusion; (2) cholinergic hippocampal interneurons are necessary for successful 2s1 consolidation; (3) cholinergic neocortical interneurons and projections can be critical for 2s1 consolidation in less learning rats. We conclude that targeted modulation of cholinergic synaptic activity in the hippocampus and neocortex can be effective in reversing the cognitive disturbance of cerebral hypoperfusion. We discuss the possible ways to restore the impaired spatial memory 2s1 in the presence of cerebral hypoperfusion. Full article

(1) Background. A one-time moderate hypobaric hypoxia (HBH) has a preconditioning effect whose neuronal mechanisms are not studied well. Previously, we found a stable correlation between the HBH efficiency and acoustic startle prepulse inhibition (PPI). This makes it possible to predict the individual efficiency of HBH in animals and to study its potential adaptive mechanisms. We revealed a bi-directional action of nicotinic α7 receptor agonist PNU-282987 and its solvent dimethyl sulfoxide on HBH efficiency with the level of PPI > or < 40%. (2) The aim of the present study was to estimate cholinergic mechanisms of HBH effects in different brain regions. (3) Methods: in rats pretested for PPI, we evaluated the activity of synaptic membrane-bound and water-soluble choline acetyltransferase (ChAT) in the sub-fractions of ‘light’ and ‘heavy’ synaptosomes of the neocortex, hippocampus and caudal brainstem in the intact brain and after HBH. We tested the dose-dependent influence of PNU-282987 on the HBH efficiency. (4) Results: PPI level and ChAT activity correlated negatively in all brain structures of the intact animals, so that the values of the latter were higher in rats with PPI < 40% compared to those with PPI > 40%. After HBH, this ChAT activity difference was leveled in the neocortex and caudal brainstem, while for membrane-bound ChAT in the ‘light’ synaptosomal fraction of hippocampus, it was reversed to the opposite. In addition, a pharmacological study revealed that PNU-282987 in all used doses and its solvent displayed corresponding opposite effects on HBH efficiency in rats with different levels of PPI. (5) Conclusion: We substantiate that in rats with low and high PPI two opposite hippocampal cholinergic mechanisms are involved in hypoxic preconditioning, and both are implemented by forebrain projections via nicotinic α7 receptors. Possible causes of association between general protective adaptation, HBH, PPI, forebrain cholinergic system and hippocampus are discussed. Full article