Cortical and nigral deafferentation and striatal cholinergic markers in the rat dorsal striatum: different effects on the expression of mRNAs encoding choline acetyltransferase and muscarinic m1 and m4 receptors

1999 ◽  
Vol 11 (10) ◽  
pp. 3659-3668 ◽  
Author(s):  
N. Kayadjanian ◽  
W. N. Schofield ◽  
J. Andren ◽  
D. J. S. Sirinathsinghji ◽  
M. -J. Besson
Keyword(s):  
Choline Acetyltransferase ◽  
Dorsal Striatum ◽  
Cholinergic Markers

scholarly journals Acetylcholine Levels and Choline Acetyltransferase Activity in Rat Cerebrovascular Bed after Uni- or Bilateral Sphenopalatine Ganglionectomy

1991 ◽  
Vol 11 (2) ◽  
pp. 253-260 ◽  
Author(s):  
François Dauphin ◽  
Jean W. Richard ◽  
Jacques Seylaz ◽  
Rémi Quirion ◽  
Edith Hamel
Keyword(s):  
Choline Acetyltransferase ◽  
Cerebral Arteries ◽  
Peripheral Arteries ◽  
Sphenopalatine Ganglion ◽  
Surgical Ablation ◽  
Chat Activity ◽  
Pial Vessels ◽  
Putative Origin ◽  
Cholinergic Markers ◽  
Choline Acetyltransferase Activity

Endogenous acetylcholine (ACh) levels and choline acetyltransferase (ChAT) activity were measured in several vascular segments (major cerebral arteries, cortical pial vessels, and peripheral arteries) and nervous tissues [including the sphenopalatine ganglion (SPG)] in the rat. The effects of uni- or bilateral surgical ablation of the SPG, a putative origin of the cholinergic cerebrovascular innervation, were investigated on these two specific cholinergic markers at various postoperative times. ChAT activity and ACh levels were enriched in the cerebral as compared to the peripheral arteries. Among the cerebrovascular tissues tested, ACh levels were particularly high in the circle of Willis and the vertebrobasilar segments and, to a lesser extent, in the middle cerebral artery. Lower levels were found in the small pial vessels and choroid plexus. Overall, ChAT activity measured in different arterial beds paralleled the distribution of ACh. Following uni- or bilateral removal of the SPG, slight reductions (18–36%, statistically not significant) were observed in ChAT activity in rostral cerebral arteries and pial vessels overlying the frontal cortex. Similarly, bilateral ganglionectomy resulted in minor decreases (11–22%, not significant) in the cerebrovascular contents of ACh in these same vascular segments. These results clearly show that the SPG does not or only partly contributes to the cholinergic fibers that supply the cerebrovascular bed.

Ultrastructural Localization of Acetylcholinesterase in the Arcuate Nucleus and Median Eminence of the Rat

1977 ◽  
Vol 35 ◽  
pp. 440-441
Author(s):  
K.A. Carson ◽  
C.B. Nemeroff ◽  
M.S. Rone ◽  
J.S. Kizer ◽  
J.S. Hanker
Keyword(s):  
Choline Acetyltransferase ◽  
Median Eminence ◽  
Arcuate Nucleus ◽  
Cholinergic Neurons ◽  
Ultrastructural Localization ◽  
Male Rats ◽  
Neonatal Rats ◽  
Good Marker ◽  
Chemical Studies ◽  
High Doses

Biochemical, physiological, pharmacological, and more recently enzyme histo- chemical data have indicated that cholinergic circuits exist in the hypothalamus. Ultrastructural correlates of these pathways such as acetylcholinesterase (AchE) positive neurons in the arcuate nucleus (ARC) and stained terminals in the median eminence (ME) have yet to be described. Initial studies in our laboratories utilizing chemical lesioning and microdissection techniques coupled with microchemical and light microscopic enzyme histo- chemical studies suggested the existence of cholinergic neurons in the ARC which project to the ME (1). Furthermore, in adult male rats with Halasz deafferentations (hypothalamic islands composed primarily of the isolated ARC and the ME) choline acetyltransferase (ChAc) activity, a good marker for cholinergic neurons, was not significantly reduced in the ME and was only somewhat reduced in the ARC (2). Treatment of neonatal rats with high doses of monosodium 1-glutamate (MSG) results in a lesion largely restricted to the neurons of the ARC.

CONTEXTUAL LEARNING IN THE MORRIS WATER MAZE

2018 ◽  
pp. 13-20
Author(s):  
Е.И. Захарова ◽  
З.И. Сторожева ◽  
А.Т. Прошин ◽  
М.Ю. Монаков ◽  
А.М. Дудченко
Keyword(s):  
Morris Water Maze ◽  
Choline Acetyltransferase ◽  
Water Maze ◽  
Synaptic Membranes ◽  
Projection Neurons ◽  
Synaptic Organization ◽  
Acetyltransferase Activity ◽  
Cholinergic Interneurons ◽  
Late Stages ◽  
Choline Acetyltransferase Activity

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.

The Effect of PAOPA, a Novel Allosteric Modulator of Dopamine D2 Receptors, on Select Signaling Proteins Following Sub-Chronic Administration in the Rat

2020 ◽  
Vol 13 ◽  
Author(s):  
Ritesh Daya ◽  
Joella Ho ◽  
Sharon Thomson ◽  
Jayant Bhandari ◽  
Ram K. Mishra
Keyword(s):  
Frontal Cortex ◽  
Mechanism Of Action ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dorsal Striatum ◽  
D2 Receptors ◽  
Dopamine D2 ◽  
Therapeutic Mechanism ◽  
Clinical Models ◽  
G Protein Coupled

Background: Allosteric modulators of G-protein coupled receptors regulate receptor activity by binding to sites other than the active site and have emerged as a new and highly desirable class of drugs. PAOPA (3(R)-[(2(S)- pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide), a peptidomimetic analog of Prolyl-Leucyl-Glycinamide, is a potent dopamine D2 receptor allosteric modulator. PAOPA has shown therapeutic effects in pre-clinical models of schizophrenia and extrapyramidal dysfunction. Objective: in this study, we sought to examine the biomolecular underpinnings of PAOPA‘s therapeutic outcomes in preclinical models of schizophrenia. Method: Following sub-chronic (daily for 7 days) administration of PAOPA, we assessed levels of dopamine D2 receptors, receptor kinases (GRK2 (G protein-coupled receptor kinase 2) and Arrestin-3), and phosphorylated mitogenactivated protein kinase (MAPKs), namely, extracellular signal-regulated kinases (ERK1/2) in the hippocampus, medial pre-frontal cortex, nucleus accumbens, pre-frontal cortex, and dorsal striatum via protein quantification. Results: Following 7 days of daily PAOPA treatment, we observed decreased GRK2 and increased dopamine D2 receptor expression in the dorsal striatum. These findings potentially underscore PAOPA’s therapeutic mechanism of action for the positive-like symptoms of schizophrenia in pre-clinical animal models. Additionally, we observed a decline in GRK2 in the hippocampus and an increase in phosphorylated ERK1 in the pre-frontal cortex, suggestive of a role for PAOPA in treating cognitive and/or affective dysfunction in pre-clinical models. Conclusion: While further studies are required to elucidate PAOPA’s mechanism of action, this study builds on prior investigations and develops an early framework to describe the therapeutic mechanism of action of PAOPA.

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