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1.
J Neurosci ; 40(7): 1427-1439, 2020 02 12.
Article in English | MEDLINE | ID: mdl-31932417

ABSTRACT

Long-term memory (LTM) is stored as functional modifications of relevant neural circuits in the brain. A large body of evidence indicates that the initial establishment of such modifications through the process known as memory consolidation requires learning-dependent transcriptional activation and de novo protein synthesis. However, it remains poorly understood how the consolidated memory is maintained for a long period in the brain, despite constant turnover of molecular substrates. Using the Drosophila courtship conditioning assay of adult males as a memory paradigm, here, we show that in Drosophila, environmental light plays a critical role in LTM maintenance. LTM is impaired when flies are kept in constant darkness (DD) during the memory maintenance phase. Because light activates the brain neurons expressing the neuropeptide pigment-dispersing factor (Pdf), we examined the possible involvement of Pdf neurons in LTM maintenance. Temporal activation of Pdf neurons compensated for the DD-dependent LTM impairment, whereas temporal knockdown of Pdf during the memory maintenance phase impaired LTM in light/dark cycles. Furthermore, we demonstrated that the transcription factor cAMP response element-binding protein (CREB) is required in the memory center, namely, the mushroom bodies (MBs), for LTM maintenance, and Pdf signaling regulates light-dependent transcription via CREB. Our results demonstrate for the first time that universally available environmental light plays a critical role in LTM maintenance by activating the evolutionarily conserved memory modulator CREB in MBs via the Pdf signaling pathway.SIGNIFICANCE STATEMENT Temporary memory can be consolidated into long-term memory (LTM) through de novo protein synthesis and functional modifications of neuronal circuits in the brain. Once established, LTM requires continual maintenance so that it is kept for an extended period against molecular turnover and cellular reorganization that may disrupt memory traces. How is LTM maintained mechanistically? Despite the critical importance of LTM maintenance, its molecular and cellular underpinnings remain elusive. This study using Drosophila is significant because it revealed for the first time in any organism that universally available environmental light plays an essential role in LTM maintenance. Interestingly, light does so by activating the evolutionarily conserved transcription factor cAMP response element-binding protein via peptidergic signaling.


Subject(s)
Drosophila melanogaster/radiation effects , Light , Memory Consolidation/radiation effects , Memory, Long-Term/radiation effects , Animals , Circadian Rhythm , Conditioning, Classical , Courtship , Cyclic AMP Response Element-Binding Protein/physiology , Darkness , Drosophila Proteins/biosynthesis , Drosophila Proteins/genetics , Drosophila Proteins/physiology , Drosophila melanogaster/physiology , Gene Expression Regulation/radiation effects , Genes, Reporter , Male , Memory Consolidation/physiology , Mushroom Bodies/cytology , Mushroom Bodies/physiology , Mushroom Bodies/radiation effects , Neurons/physiology , Neurons/radiation effects , Neuropeptides/biosynthesis , Neuropeptides/genetics , Neuropeptides/physiology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Receptors, G-Protein-Coupled/physiology , Sleep Deprivation , Transcription, Genetic/physiology
2.
Probl Radiac Med Radiobiol ; 24: 395-410, 2019 Dec.
Article in English, Ukrainian | MEDLINE | ID: mdl-31841482

ABSTRACT

OBJECTIVE: to study the state of cognitive functions in children who were born and permanently live at radioactive contaminated territories (RCT) with pathology of the upper digestive tract, using pathopsychological testing; to increase the effectiveness of treatment and prophylactic measures aimed at preserving and restoring the health of RCT residents. DESIGN, PATIENTS AND METHODS: A randomized blind controlled clinical trial was conducted. There were examined, a total of 90 persons aged 6 to 17 years (35 boys and 55 girls) who were divided into two groups: the control group (I) included 30 persons of the conventional «clean¼ territories, and the main group (II) - 60 patients with patho- logy of the digestive organs who were born and live at the RCT. The study program included: the collection of anam- nesis, complaints; clinical and instrumental examinations. The following tests were applied by us: «What things are hidden in the drawings¼, Toulouse-Pieron, Raven, and Luria testing. For detecting the anxiety level, and the subjec- tive signs of autonomic dysfunctions were used the Spilberg-Hanin self-diagnosis and the Wein questionnaire, respectively. RESULTS: It was shown that in children aged 6-11 years, according to the results of the Toulouse-Pieron test, speed of cognitive information-processing was significantly decreased by 7.17 conventional units, while on the back- ground of the etiopathogenetic treatment of the digestive tract - by 10.24 conventional units relative to the va- lues of the control group. The long-term memory was statistically significantly decreased in the examined children of senior school age (from 12 to 17 years). A significant increase in reactive anxiety and a reverse correlation between the personal anxiety (PA) and speed of cognitive information-processing (r = -0.331) were recorded in patients aged 6-11 years. In older patients, PA was increased.Сonclusions. The obtained results indicate that the state of cognitive functions was characterized by a decrease in speed of cognitive information-processing, long-term memory and a high level of anxiety in children aged from 6 to 17 years residents of RСT with pathology of digestive organs, according to the used testing.


Subject(s)
Anxiety/etiology , Chernobyl Nuclear Accident , Dyspepsia/etiology , Fatigue/etiology , Gastritis/etiology , Neurasthenia/etiology , Pain/etiology , Adolescent , Anxiety/physiopathology , Child , Cognition/radiation effects , Digestive System/pathology , Digestive System/physiopathology , Digestive System/radiation effects , Dyspepsia/physiopathology , Fatigue/physiopathology , Female , Gastritis/physiopathology , Humans , Male , Memory, Long-Term/radiation effects , Nervous System/pathology , Nervous System/physiopathology , Nervous System/radiation effects , Neurasthenia/physiopathology , Pain/physiopathology , Radiation Exposure/adverse effects , Radioactive Fallout/adverse effects , Surveys and Questionnaires , Ukraine
3.
Neurobiol Learn Mem ; 155: 92-103, 2018 11.
Article in English | MEDLINE | ID: mdl-29964163

ABSTRACT

Although the functional role for newborn neurons in neural circuits is still matter of investigation, there is no doubt that neurogenesis modulates learning and memory in rodents. In general, boosting neurogenesis before learning, using genetic-target tools or drugs, improves hippocampus-dependent memories. However, inhibiting neurogenesis may yield contradictory results depending on the type of memory evaluated. Here we tested the hypothesis that inhibiting constitutive neurogenesis would compromise social recognition memory (SRM). Male Swiss mice were submitted to three distinct procedures to inhibit neurogenesis: (1) intra-cerebral infusion of Cystosine-ß-D-Arabinofuranoside (AraC); (2) intra-peritoneal injection of temozolomide (TMZ) and (3) cranial gamma irradiation. All three methods decreased cell proliferation and neurogenesis in the dentate gyrus of the dorsal (dDG) and ventral hippocampus (vDG), and the olfactory bulb (OB). However, the percentage inhibition diverged between methods and brain regions. Ara-C, TMZ and gamma irradiation impaired SRM, though only gamma irradiation did not cause side effects on weight gain, locomotor activity and anxiety. Finally, we examined the contribution of cell proliferation in vDG, dDG and OB to SRM. The percent of inhibition in the dDG correlates with SRM, independently of the method utilized. This correlation was observed for granular cell layer of OB and vDG, only when the inhibition was induced by gamma irradiation. Animal's performance was restrained by the inhibition of dDG cell proliferation, suggesting that cell proliferation in the dDG has a greater contribution to SRM. Altogether, our results demonstrate that SRM, similarly to other hippocampus-dependent memories, has its formation impaired by reducing constitutive neurogenesis.


Subject(s)
Cell Proliferation/physiology , Hippocampus/physiology , Memory, Long-Term/physiology , Neurogenesis/physiology , Olfactory Bulb/physiology , Recognition, Psychology/physiology , Social Perception , Animals , Antineoplastic Agents, Alkylating/pharmacology , Behavior, Animal/drug effects , Behavior, Animal/physiology , Behavior, Animal/radiation effects , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Glycoside Hydrolases/pharmacology , Hippocampus/drug effects , Hippocampus/radiation effects , Male , Memory, Long-Term/drug effects , Memory, Long-Term/radiation effects , Mice , Neurogenesis/drug effects , Neurogenesis/radiation effects , Olfactory Bulb/drug effects , Olfactory Bulb/radiation effects , Radiation Injuries, Experimental , Recognition, Psychology/drug effects , Recognition, Psychology/radiation effects , Temozolomide/pharmacology
4.
Int J Radiat Oncol Biol Phys ; 98(1): 63-74, 2017 05 01.
Article in English | MEDLINE | ID: mdl-28587054

ABSTRACT

PURPOSE: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. METHODS AND MATERIALS: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. RESULTS: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significant changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. CONCLUSION: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.


Subject(s)
Behavior, Animal/radiation effects , Hippocampus/radiation effects , Neurogenesis/radiation effects , Prenatal Exposure Delayed Effects , Affect/physiology , Affect/radiation effects , Age Factors , Animals , Behavior, Animal/physiology , Body Weight/radiation effects , Cognition/physiology , Cognition/radiation effects , Exploratory Behavior/physiology , Exploratory Behavior/radiation effects , Female , Hippocampus/embryology , Hippocampus/pathology , Immobility Response, Tonic/physiology , Immobility Response, Tonic/radiation effects , Locomotion/physiology , Locomotion/radiation effects , Male , Maze Learning/radiation effects , Memory, Long-Term/physiology , Memory, Long-Term/radiation effects , Mice , Mice, Inbred C57BL , Motor Skills/physiology , Motor Skills/radiation effects , Neurogenesis/physiology , Pregnancy , Radiation Dosage , Sex Factors
5.
Agora USB ; 15(2): 393-400, jul.-dic. 2015.
Article in Spanish | LILACS | ID: lil-777770

ABSTRACT

En el presente texto se desarrollan algunas rutas de análisis en torno a la pregunta ¿cómo incorporar éticamente el problema en sus acciones cotidianas, y del mismo modo, cómo evitar las exitosas estrategias del olvido y la indiferencia?; Se hace énfasis en la ganada importancia que tienen los procesos populares sobre todo juveniles, en tanto que, gracias a sus narrativas, acrecientan y triunfan cotidianamente sobre las retóricas autoritarias quebuscan silenciar la memoria.


Some routes of analyses around the following question: How to incorporate ethically the problem in their daily actions, and similarly, how to avoid the successful strategies of oblivion and indifference? are addressed in this paper. Certain emphasis is made on thegained importance that the popular processes have specially those related to the youth, while, thanks to their narratives, they increase and succeed, on a daily basis, over the authoritarian rhetoric seeking to silence memory.


Subject(s)
Memory, Long-Term , Memory, Long-Term/classification , Memory, Long-Term , Memory, Long-Term/radiation effects , Memory, Long-Term/physiology
6.
Behav Brain Res ; 252: 275-86, 2013 Sep 01.
Article in English | MEDLINE | ID: mdl-23714078

ABSTRACT

In adult rodents, decreasing hippocampal neurogenesis experimentally using different approaches often impairs performance in hippocampus-dependent processes. Nonetheless, functional relevance of adult neurogenesis is far from being unraveled, and deficits so far described in animal models often lack reproducibility. One hypothesis is that such differences might be the consequence of the extent of the methodological specificity used to alter neurogenesis rather than the extent to which adult neurogenesis is altered. To address this, we focused on cranial irradiation, the most widely used technique to impair hippocampal neurogenesis and consequentially induce hippocampus-dependent behavioral deficits. To investigate the specificity of the technique, we thus exposed 4-5 months old female cyclin D2 knockout mice, a model lacking physiological levels of olfactory and hippocampal neurogenesis, to an X-ray dose of 10 Gy, reported to specifically affect transiently amplifying precursors. After a recovery period of 1.5 months, behavioral tests were performed and probed for locomotor activity, habituation, anxiety, and spatial learning and memory. Spatial learning in the Morris water maze was intact in all experimental groups. Although spatial memory retention assessed 24h following acquisition was also intact in all mice, irradiated wild type and cyclin D2 knockout mice displayed memory deficits one week after acquisition. In addition, we observed significant differences in tests addressing anxiety and locomotor activity dependent on the technique used to alter neurogenesis. Whereas irradiated mice were hyperactive regardless of their genotype, cyclin D2 knockout mice were hypoactive in most of the tests and displayed altered habituation. The present study emphasizes that different approaches aimed at decreasing adult hippocampal neurogenesis may result in distinct behavioral impairments related to locomotion and anxiety. In contrast, spatial long-term memory retention is consistently altered after both approaches suggesting a plausible implication of hippocampal neurogenesis in this cognitive process.


Subject(s)
Memory Disorders , Memory, Long-Term/physiology , Neurogenesis/physiology , Retention, Psychology/physiology , Adaptation, Physiological/genetics , Adaptation, Physiological/radiation effects , Analysis of Variance , Animals , Cyclin D2/deficiency , Cyclin D2/genetics , Exploratory Behavior/physiology , Exploratory Behavior/radiation effects , Female , Locomotion/genetics , Male , Maze Learning/physiology , Maze Learning/radiation effects , Memory Disorders/genetics , Memory Disorders/pathology , Memory Disorders/physiopathology , Memory, Long-Term/radiation effects , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neurogenesis/genetics , Neurogenesis/radiation effects , Organ Size/genetics , Organ Size/radiation effects , Retention, Psychology/radiation effects , X-Rays
7.
Learn Mem ; 19(12): 588-92, 2012 Nov 16.
Article in English | MEDLINE | ID: mdl-23161447

ABSTRACT

Nr4a1 and Nr4a2 are transcription factors and immediate early genes belonging to the nuclear receptor Nr4a family. In this study, we examine their role in long-term memory formation for object location and object recognition. Using siRNA to block expression of either Nr4a1 or Nr4a2, we found that Nr4a2 is necessary for both long-term memory for object location and object recognition. In contrast, Nr4a1 appears to be necessary only for object location. Indeed, their roles in these different types of long-term memory may be dependent on their expression in the brain, as NR4A2 was found to be expressed in hippocampal neurons (associated with object location memory) as well as in the insular and perirhinal cortex (associated with object recognition memory), whereas NR4A1 showed minimal neuronal expression in these cortical areas. These results begin to elucidate how NR4A1 and NR4A2 differentially contribute to object location versus object recognition memory.


Subject(s)
Memory, Long-Term/radiation effects , Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism , Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism , Recognition, Psychology/physiology , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Hippocampus/cytology , Hippocampus/drug effects , Hippocampus/metabolism , Learning , Male , Memory, Long-Term/drug effects , Mice , Mice, Inbred C57BL , Neurons/drug effects , Neurons/metabolism , Nuclear Receptor Subfamily 4, Group A, Member 1/genetics , Nuclear Receptor Subfamily 4, Group A, Member 2/genetics , Phosphopyruvate Hydratase/metabolism , RNA, Messenger/metabolism , RNA, Small Interfering/pharmacology , Recognition, Psychology/drug effects , Time Factors
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