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

2021 ◽  
Vol 15 ◽  
Author(s):  
Zinaida I. Storozheva ◽  
Elena I. Zakharova ◽  
Andrey T. Proshin

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.

2018 ◽  
Vol 29 (11) ◽  
pp. 4519-4529 ◽  
Author(s):  
Disha Shah ◽  
Marleen Verhoye ◽  
Annemie Van der Linden ◽  
Rudi D’Hooge

Abstract Learning has been proposed to coincide with changes in connections between brain regions. In the present study, we used resting-state fMRI (rsfMRI) to map brain-wide functional connectivity (FC) in mice that were trained in the hidden-platform version of the Morris water maze. C57BL6 mice were investigated in a small animal MRI scanner following 2, 10, or 15 days of acquisition learning, or 5 days of reversal learning. Spatial learning coincided with progressive and changing FC between telencephalic regions that have been implemented in spatial learning (such as hippocampus, cingulate, visual, and motor cortex). Search strategy assessment demonstrated that the use of cognitively advanced spatial strategies correlated positively with extensive telencephalic connectivity, whereas non-spatial strategies correlated negatively with connectivity. FC patterns were different and more extensive after reversal learning compared with after extended acquisition learning, which could explain why reversal learning has been shown to be more sensitive to subtle functional defects.


Author(s):  
Е.И. Захарова ◽  
З.И. Сторожева ◽  
А.Т. Прошин ◽  
М.Ю. Монаков ◽  
А.М. Дудченко

Цель - исследование холинергической синаптической организации функций обучения и памяти у крыс с разными когнитивными способностями. Методы. Крыс обучали на пространственной обстановочной модели в водном лабиринте Морриса. Через 2-3 сут. после окончания тренировок животных декапитировали, из неокортекса и гиппокампа с помощью центрифугирования выделяли субфракции синаптических мембран и синаптоплазмы легких и тяжелых синаптосом. В синаптических субфракциях определяли активность ключевого фермента холинергических нейронов холинацетилтрансферазы (ХАТ). Сравнивали результаты тестирования (время достижения скрытой платформы) и активность фермента у способных и неспособных к обучению крыс. Результаты. Были выявлены: 1) различия в холинергической организации исследованных функций в процессе обучения у способных и неспособных к обучению крыс, в том числе: положительные корреляции активности ХАТ в синапсах проекционных нейронов неокортекса у способных крыс со временем достижения платформы на промежуточных этапах обучения и в синапсах проекционных нейронов гиппокампа у неспособных крыс на позднем этапе обучения; разнонаправленные корреляции активности ХАТ в синапсах, предположительно, интернейронов гиппокампа (фракция тяжелых синаптосом) у способных и неспособных крыс на начальном и позднем этапах обучения; 2) индивидуальность холинергической организации функций на всех этапах обучения. Выводы. Полученные данные свидетельствуют в пользу представлений о специфике холинергической организации функций пространственного обстановочного обучения у крыс с выраженными и слабыми способностями к обучению, а также избирательной роли холинергических интернейронов гиппокампа на исходном этапе обучения и в консолидации памяти. In order to expand the knowledge about neuronal organization of the cognitive functions required for understanding plastic processes in the brain, we investigated the cholinergic synaptic organization of learning and memory functions in rats with different cognitive abilities. Methods. Rats were trained on a contextual situation model in the Morris water maze. At 2-3 days after the end of training, animals were decapitated, and subfractions of synaptic membranes and synaptoplasm of light and heavy synaptosomes were isolated from the cortex and the hippocampus by centrifugation. In synaptic subfractions, activity of the key enzyme of cholinergic neurons, choline acetyltransferase, was measured. We compared the test results (latent period to reach the hidden platform) and the enzyme activity in capable (lower quartile) and incapable of learning rats (upper quartile). Results. The following was found: 1) differences in the cholinergic organization of studied functions in capable and uncapable of learning rats during training, including: positive correlations of choline acetyltransferase activity in synapses of projection neurons in the cortex of capable rats with latency to reach the platform at intermediate stages of training and in the hippocampus ofincapable rats at late stages of training; multidirectional correlations of choline acetyltransferase activity in synapses of hippocampal, presumably, interneurons (heavy synaptosomes) in capable and incapable rats at early and late stages of training; 2) distinctness of the cholinergic organization of functions at all stages of training. Conclusions. The study demonstrated for the first time a specificity of the cholinergic organization of functions in spatial situational learning of rats with strong and poor learning abilities and a selective role of hippocampal cholinergic interneurons at the initial stage of learning and in memory consolidation.


Author(s):  
Mahmoud Hashemzaei ◽  
Najmeh Baratzadeh ◽  
Iraj Sharamian ◽  
Sahar Fanoudi ◽  
Mehdi Sanati ◽  
...  

Abstract Objectives H-89 (a protein kinase AII [PKA II] inhibitor) impairs the spatial memory in the Morris water maze task in rats. In the present study, we aimed to study the protective effects of nicotine and O-acetyl-L-carnitine against H-89-induced spatial memory deficits. Methods Spatial memory impairment was induced by the bilateral intrahippocampal administration of 10 µM H-89 (dissolved in dimethyl sulfoxide, DMSO) to rats. The rats then received bilateral administrations of either nicotine (1 μg/μL, dissolved in saline) or O-acetyl-L-carnitine (100 μM/side, dissolved in deionized water) alone and in combination. Control groups received either saline, deionized water, or DMSO. Results The H-89-treated animals showed significant increases in the time and distance travelled to find hidden platforms, and there was also a significant decrease in the time spent in the target quadrant compared to DMSO-treated animals. Nicotine and O-acetyl-L-carnitine had no significant effects on H-89-induced spatial learning impairments alone, but the bilateral intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevented H-89-induced spatial learning deficits and increased the time spent in the target quadrant in comparison with H-89-treated animals. Conclusions Our results indicated the potential synergistic effects of nicotine and O-acetyl-L-carnitine in preventing protein kinase AII inhibitor (H-89)-induced spatial learning impairments.


2018 ◽  
Vol 56 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Kaveh Tabrizian ◽  
Mahmoud Hashemzaei ◽  
Ali Akbar Nasiri ◽  
Sheyda Najafi ◽  
Fatemeh Amelinia ◽  
...  

2001 ◽  
Vol 41 (2) ◽  
pp. 210-219 ◽  
Author(s):  
M.L Woolley ◽  
J.C Bentley ◽  
A.J Sleight ◽  
C.A Marsden ◽  
K.C.F Fone

2019 ◽  
Vol 9 (9) ◽  
pp. 236 ◽  
Author(s):  
Xue Li ◽  
Lu Wang ◽  
Shuling Zhang ◽  
Xiang Hu ◽  
Huijun Yang ◽  
...  

This study was designed to investigate beneficial effects of swimming exercise training on learning/memory, synaptic plasticity and CREB (cAMP response element binding protein) expression in hippocampus in a rat model of d-galactose-induced aging (DGA). Eighty adult male rats were randomly divided into four groups: Saline Control (group C), DGA (group A), Swimming exercise before DGA (group S1), and Swimming during DGA (group S2). These four groups of animals were further divided into Morris water maze training group (M subgroup) and sedentary control group (N subgroup). Spatial learning/memory was tested using Morris water maze training. The number and density of synaptophysin (Syp) and metabotropic glutamate receptor 1 (mGluR1) in hippocampal dentate gyrus area, CREB mRNA and protein expression and DNA methylation levels were determined respectively with immunohistochemistry, western blot, real-time PCR, and MassArray methylation detection platform. We found that compared with group C, DGA rats showed aging-like poor health and weight loss as well as hippocampal neurodegenerative characteristics. Exercise training led to a time-dependent decrease in average escape latency and improved spatial memory. Exercise training group (S2M) had significantly increased swim distance as compared with controls. These functional improvements in S2M group were associated with higher Syp and mGluR1 values in hippocampus (p < 0.01) as well as higher levels of hippocampal CREB protein/mRNA expression and gene methylation. In conclusion, swimming exercise training selectively during drug-induced aging process protected hippocampal neurons against DGA-elicited degenerative changes and in turn maintained neuronal synaptic plasticity and learning/memory function, possibly through upregulation of hippocampal CREB protein/mRNA and reduction of DGA-induced methylation of CREB.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Nawel Yagoubi ◽  
Yosra Jomni ◽  
Mohsen Sakly

The aim of this study was to characterize a novel animal model hyperthermia-induced febrile seizure and to investigate the impacts of repetitive febrile seizures on spatial learning and memory performances in immature rats.Methods. Rats were subjected to hyperthermia exposure one, two, or three times in 10-day intervals during 30 min in a water bath warmed at 45–50°C and their behaviour was monitored. Morris water maze spatial learning and memory were examined for control and treated groups. Results showed that rats subjected to 30-minute hyperthermia hot water developed rapidly myoclonic jerks and then generalized seizures. After a single hyperthermia exposure, the time for generalised tonic-clonic seizures appearance was 16.08 ± 0.60 min and it decreased gradually with repetitive exposure to reach 12.46 ± 0.39 min by the third exposure. Febrile seizures altered the spatial learning and memory abilities in Morris water maze and increased the time spent to attain the platform after one or two exposures, while after a third exposure rats exhibited the same latency compared to controls. Similar results were obtained in probe test where rats, subjected to hyperthermia for one or two episodes, spent less time in the target quadrant compared to corresponding controls. Further, when platform was moved from northwest to southwest quadrant, memory transfer test indicated that after one or two hyperthermia exposures cognitive performances were slightly altered, while after a third exposure the latency to escape increased significantly compared to untreated group. It was concluded that 30 min of hyperthermia hot water was sufficient to induce febrile seizures in immature rats and an increase of susceptibility was observed with repetitive hyperthermia exposure. Hyperthermia treatment impaired cognitive performances but the effects were mostly transient and moderate.


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