Evaluation of the Activity of Choline Acetyltransferase From Different Synaptosomal Fractions at the Distinct Stages of Spatial Learning in the Morris Water Maze

Abstract

Accumulated data have evidenced that brain cholinergic circuits play a crucial role in learning and memory; however, our knowledge about the participation of neocortical and hippocampal cholinergic systems in spatial learning needs to be refined. The aim of this study was to evaluate the association of the activity of membrane-bound and soluble choline acetyltransferase (ChAT) in the synaptosomal sub-fractions of the neocortex and hippocampus with performance of the spatial navigation task in the Morris water maze at different temporal stages of memory trace formation. To identify distinct stages of memory formation, rats were trained using a 5-day protocol with four trials per day. The mean escape latency for each trial was collected, and the entire dataset was subjected to principal component analysis. Based on the Morris water maze protocol, there were three relatively distinct stages of memory formation: days 1–2, day 3, and days 4–5. The remotely stored memory trace tested in repeated and reversal learning beginning on day 19 (14 days after the end of initial learning) was associated at the individual level mainly with performance during the second trial on day 21 (the third day or repeated or reversal learning). The ChAT activity data suggest the participation of cortical cholinergic projections mainly in the first stage of spatial learning (automatic sensory processing) and the involvement of hippocampal interneurons in the second stage (error-corrected learning). Cholinergic cortical interneurons participated mainly in the stage of asymptotic performance (days 4–5). It is advisable to evaluate other signalling pathways at the identified stages of memory formation.

Cholinergic Internal and Projection Systems of Hippocampus and Neocortex Critical for Early Spatial Memory Consolidation in Normal and Chronic Cerebral Hypoperfusion Conditions in Rats with Different Abilities to Consolidation: The Role of Cholinergic Interneurons of the Hippocampus

“…This is an important and interesting problem. Rats that are incapable of the consolidation of spatial memory during the course of learning (4 days), after a two-week break show the high abilities for memory consolidation [ 17 ], the mechanisms of which are unknown.…”

“…Our biochemical data on the ratio of cholinergic activity in the ‘light’ and ‘heavy’ fractions of synaptosomes in both brain structures are in good agreement with these data [ 16 ]. In addition, in our studies we have revealed functional differences (differences in response to the experimental effects) in cholinergic presynapses from light and heavy synaptosomes [ 16 , 17 , 18 , 19 ]. This approach has allowed for a high probability that interneuron presynapses are concentrated in the heavy synaptosomes and, thus, a differentiated study of cholinergic indicators in these synaptosomes makes it possible to identify the individual contribution of different populations of cholinergic neurons to the studied functions.…”

“…Hence, the selection of individual cohorts of animals with different learning dynamics could be used as an experimental approach. The feasibility of this approach has been emphasised in some studies [ 17 , 20 ]. This endeavour could be especially fruitful to identify multiple and, possibly, non-linear mechanisms of involvement of various mediator components in memory formation, as well as to assess the adaptive and compensatory capabilities of mediator systems in CNS dysfunction.…”

“…To identify stable boundaries between quartiles of rats, we processed a statistically sufficient array of animals (see Section 2.6 ). The results represent the analysis of cholinergic correlates with memory consolidation in the normal brain and the two-vessel occlusion (2VO) model of chronic brain hypoperfusion at an early stage of the MWM, namely 2s1, which is the first trial on the second day of training, when skill automation is still absent [ 17 ].…”

Rosinidin Protects Streptozotocin-Induced Memory Impairment-Activated Neurotoxicity by Suppressing Oxidative Stress and Inflammatory Mediators in Rats

“…Ach was then added to the buffer. After which, sodium tetraphenylborate was added and the organic phase was separated and measured by beta counter [ 31 ].…”