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.

Highlights

  • Brain cholinergic circuits play a crucial role in learning and memory, so evaluating the involvement of acetylcholine (ACh) signalling pathways in different stages of memory trace formation is important for understanding cognitive processes and the aetiopathogenesis of age-related dementia, Alzheimer’s disease and post-stroke mental disorders, among other conditions

  • Spatial Memory and Choline Acetyltransferase researchers have evidenced the participation of ACh in the mechanisms of spatial navigation (Deiana et al, 2011)

  • Some data evidenced the possibility of the involvement of the forebrain cholinergic circuits in the mechanisms that supply the flexibility of memory trace including the transfer of acquired experience and learning rule across behavioural problems (Conner et al, 2003; Sarter et al, 2003)

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Summary

Introduction

Brain cholinergic circuits play a crucial role in learning and memory, so evaluating the involvement of acetylcholine (ACh) signalling pathways in different stages of memory trace formation is important for understanding cognitive processes and the aetiopathogenesis of age-related dementia, Alzheimer’s disease and post-stroke mental disorders, among other conditions. Some data evidenced the possibility of the involvement of the forebrain cholinergic circuits in the mechanisms that supply the flexibility of memory trace including the transfer of acquired experience and learning rule across behavioural problems (Conner et al, 2003; Sarter et al, 2003). All these statements and hypotheses need further verification and development

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