Cholinergic Hippocampal Interneurons are critical for Early Spatial Memory Consolidation in Highly Capable Rats and Cholinergic Neocortical Interneurons and Projections are critical in Rats with Less Memory Consolidation Abilities

Mediator-specific components of functional neuronal networks underlie the study of brain functions in normal and pathological conditions. In the memory consolidation problem, cholinergic projection systems of the neocortex and hippocampus are intensively studied unlike the barely studied interneurons. 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 the abilities to 2s1 performance. 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 under cerebral hypoperfusion.