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1.
J Neurosci ; 42(37): 7094-7109, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-35927034

RESUMO

The retrosplenial cortex (RSC) plays a significant role in spatial learning and memory and is functionally disrupted in the early stages of Alzheimer's disease (AD). In order to investigate neurophysiological correlates of spatial learning and memory in this region we employed in vivo electrophysiology in awake and freely moving male mice, comparing neural activity between wild-type and J20 mice, a transgenic model of AD-associated amyloidopathy. To determine the response of the RSC to environmental novelty local field potentials (LFPs) were recorded while mice explored novel and familiar recording arenas. In familiar environments we detected short, phasic bursts of ß (20-30 Hz) oscillations (ß bursts), which arose at a low but steady rate. Exposure to a novel environment rapidly initiated a dramatic increase in the rate, size and duration of ß bursts. Additionally, θ-α/ß cross-frequency coupling was significantly higher during novelty, and spiking of neurons in the RSC was significantly enhanced during ß bursts. Finally, excessive ß bursting was seen in J20 mice, including increased ß bursting during novelty and familiarity, yet a loss of coupling between ß bursts and spiking activity. These findings support the concept that ß bursting may be responsible for the activation and reactivation of neuronal ensembles underpinning the formation and maintenance of cortical representations, and that disruptions to this activity in J20 mice may underlie cognitive impairments seen in these animals.SIGNIFICANCE STATEMENT The retrosplenial cortex (RSC) is thought to be involved in the formation, recall and consolidation of contextual memory. The discovery of bursts of ß oscillations in this region, which are associated with increased neuronal spiking and strongly upregulated while mice explore novel environments, provides a potential mechanism for the activation of neuronal ensembles, which may underlie the formation of cortical representations of context. Excessive ß bursting in the RSC of J20 mice, a mouse model of Alzheimer's disease (AD), alongside the disassociation of ß bursting from neuronal spiking, may underlie spatial memory impairments previously shown in these mice. These findings introduce a novel neurophysiological correlate of spatial learning and memory, and a potentially new form of AD-related cortical dysfunction.


Assuntos
Doença de Alzheimer , Giro do Cíngulo , Doença de Alzheimer/genética , Animais , Modelos Animais de Doenças , Giro do Cíngulo/fisiologia , Hipocampo/fisiologia , Masculino , Camundongos , Neurônios/fisiologia , Memória Espacial/fisiologia
2.
FASEB J ; 36(9): e22456, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35969153

RESUMO

The dorsal hippocampus plays a pivotal role in spatial memory. However, the role of subregion-specific molecular pathways in spatial cognition remains unclear. We observed that the transcriptional coregulator C-terminal binding protein 2 (CtBP2) presented CA3-specific enrichment in expression. RNAi interference of CtBP2 in the dorsal CA3 (dCA3) neurons, but not the ventral CA3 (vCA3), specifically impaired spatial reference memory and reduced the expression of GluR2, the calcium permeability determinant subunit of AMPA receptors. Application of an antagonist for GluR2-absent calcium permeable AMPA receptors rescued spatial memory deficits in dCA3 CtBP2 knockdown animals. Transcriptomic analysis suggest that CtBP2 may regulate GluR2 protein level through post-translational mechanisms, especially by the endocytosis pathway which regulates AMPA receptor sorting. Consistently, CtBP2 deficiency altered the mRNA expression of multiple endocytosis-regulatory genes, and CtBP2 knockdown in primary hippocampal neurons enhanced GluR2-containing AMPA receptor endocytosis. Together, our results provide evidence that the dCA3 regulates spatial reference memory by the CtBP2/GluR2 pathway through the modulation of calcium permeable AMPA receptors.


Assuntos
Região CA3 Hipocampal , Proteínas do Olho , Receptores de AMPA , Memória Espacial , Animais , Região CA3 Hipocampal/metabolismo , Cálcio/metabolismo , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de AMPA/genética , Receptores de AMPA/metabolismo
3.
Addict Biol ; 27(5): e13215, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36001432

RESUMO

Prenatal opioid exposures lead to extensive cognitive and emotion-regulation problems in children, persisting at least through school-age. Methadone, an opioid typically used for the treatment of opioid use disorder, has been approved for use in pregnant women for several decades. Importantly, however, the impacts of prenatal methadone exposure (PME), particularly on offspring as they progress into adulthood, has not been extensively examined. In recent years, children and young animal models have shown cognitive deficits related to PME, including evidence of hippocampal dysfunction. The present work aims to examine the persistent nature of these deficits, as well as determine how they may differ by sex. Pregnant Sprague-Dawley rats either received subcutaneous methadone or water injections twice daily from gestational days 3-20 or were left undisturbed. Following postnatal day 70, male and female offspring were behaviourally tested for impairments in recognition memory using the Novel Object Recognition task and working spatial memory through Spontaneous Alternation. Additionally, using whole-cell patch-clamp electrophysiology, hippocampal dentate granule cell function was examined in adult offspring. Results indicate that methadone-exposed females showed decreased excitability and increased inhibition of dentate granule cells compared to naïve controls, while males did not. These findings were accompanied by impairments in female working spatial memory and altered behaviour in the Object Recognition task. Overall, this work supports the continued investigation of the long-term effects of PME on adult male and female learning and memory, as well as promotes further exploration of adult hippocampal function as a neural mechanism impacted by this exposure.


Assuntos
Giro Denteado , Efeitos Tardios da Exposição Pré-Natal , Analgésicos Opioides/farmacologia , Animais , Feminino , Humanos , Masculino , Memória de Longo Prazo , Metadona/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Memória Espacial
4.
Neuropsychologia ; 174: 108341, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-35961387

RESUMO

Distinct brain systems are thought to support statistical learning over different timescales. Regularities encountered during online perceptual experience can be acquired rapidly by the hippocampus. Further processing during offline consolidation can establish these regularities gradually in cortical regions, including the medial prefrontal cortex (mPFC). These mechanisms of statistical learning may be critical during spatial navigation, for which knowledge of the structure of an environment can facilitate future behavior. Rapid acquisition and prolonged retention of regularities have been investigated in isolation, but how they interact in the context of spatial navigation is unknown. We had the rare opportunity to study the brain systems underlying both rapid and gradual timescales of statistical learning using intracranial electroencephalography (iEEG) longitudinally in the same patient over a period of three weeks. As hypothesized, spatial patterns were represented in the hippocampus but not mPFC for up to one week after statistical learning and then represented in the mPFC but not hippocampus two and three weeks after statistical learning. Taken together, these findings suggest that the hippocampus may contribute to the initial extraction of regularities prior to cortical consolidation.


Assuntos
Consolidação da Memória , Navegação Espacial , Humanos , Aprendizagem , Rememoração Mental , Córtex Pré-Frontal , Memória Espacial
5.
Neurosci Lett ; 788: 136840, 2022 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-35985509

RESUMO

Soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) signalling is important for healthy memory function and a healthy vascular system. Targeting sGC-cGMP signalling can therefore be a potential strategy to enhance memory processes. sGC can be targeted by using agonists, such as sGC stimulator riociguat. Therefore, this study aimed to target sGC using riociguat to investigate its acute effects on memory function and neuronal plasticity in mice. The effects of riociguat on long-term memory and a biperiden-induced memory deficit model for assessing short-term memory were tested in the object location task, and working memory was tested in the Y-maze continuous alternation task. Pharmacokinetic measurements were performed within brain tissue of mice, and hippocampal plasticity measures were assessed using western blotting. Acute oral administration with a low dose of 0.03 mg/kg riociguat was able to enhance working-, short-, and long-term spatial memory. Under cerebral vasoconstriction higher doses of riociguat were still effective on memory. Pharmacokinetic measurements revealed poor brain penetration of riociguat and its metabolite M-1. Increased activation of VASP was found, while no effects were found on other memory-related hippocampal plasticity measures. Memory enhancing effects of riociguat are most likely regulated by vascular peripheral effects on cGMP signalling. Yet, further research is needed to investigate the possible contribution of hemodynamic or metabolic effects of sGC stimulators on memory performance.


Assuntos
Pirazóis , Memória Espacial , Animais , GMP Cíclico/metabolismo , Guanilato Ciclase/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Pirazóis/farmacologia , Pirimidinas/farmacologia , Guanilil Ciclase Solúvel/metabolismo , Vasodilatadores
6.
Nat Commun ; 13(1): 4826, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35974109

RESUMO

The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain.


Assuntos
Córtex Entorrinal , Potenciais Pós-Sinápticos Excitadores , Hipocampo , Neurônios , Memória Espacial , Animais , Córtex Entorrinal/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/fisiologia , Mamíferos , Camundongos , Neurônios/fisiologia , Células Piramidais/fisiologia , Memória Espacial/fisiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-36011585

RESUMO

Neuropsychological screening tools for mild cognitive impairment (MCI) have been widely used. However, to date, their sensitivity and specificity still remain unsatisfied. This study aims to investigate whether spatial memory can discriminate MCI better than neuropsychological screening tools. A total of 56 healthy older adults and 36 older adults with MCI participated in this study; they performed a spatial cognitive task based on virtual reality (SCT-VR), the Korean version of the Montreal Cognitive Assessment (MoCA-K), and the Wechsler Adult Intelligence Scale-Revised Block Design Test (WAIS-BDT). The discriminant power was compared between the SCT-VR and the MoCA-K, and the reliability and validity of the SCT-VR were analyzed. The spatial memory, assessed by the SCT-VR, showed better sensitivity and specificity (sensitivity: 0.944; specificity: 0.964) than the MoCA-K (sensitivity: 0.857; specificity: 0.746). The test-retest reliability of the SCT-VR was relatively high (ICCs: 0.982, p < 0.001) and the concurrent validity of the SCT-VR with the MoCA-K (r = -0.587, p < 0.001) and the WAIS-BDT (r = -0.594, p < 0.001) was statistically significant. These findings shed light on the importance of spatial memory as a behavioral marker of MCI. The ecologically validated spatial memory tasks based on VR need to be investigated by neuroscientific studies in the future.


Assuntos
Disfunção Cognitiva , Realidade Virtual , Idoso , Disfunção Cognitiva/diagnóstico , Humanos , Testes Neuropsicológicos , Reprodutibilidade dos Testes , Memória Espacial
8.
Physiol Biochem Zool ; 95(5): 390-399, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35930827

RESUMO

AbstractMammalian hibernation in ground squirrels is characterized by periods of torpor wherein body temperature approaches ambient temperature and metabolism is reduced to as low as 1/100th of active rates. It is unclear how hibernation affects long-term spatial memory, as tremendous remodeling of neurons is associated with torpor use. Given the suspected links between remodeling and memory formation and retention, we examined long-term spatial memory retention throughout a hibernation season. Animals were trained on a Barnes maze before entering torpor. Animals were tested for memory retention once a month throughout a hibernation season. Results indicate marked variation between individuals. Some squirrels retained memory across multiple torpor bouts, while other squirrels did not. No relationship was found between the number of torpor bouts, duration of bouts, or time spent torpid on long-term memory retention. However, that some squirrels successfully retain memory suggests that the profound remodeling of dendritic spines during torpor does not always lead to memory loss.


Assuntos
Hibernação , Sciuridae , Animais , Temperatura Corporal/fisiologia , Hibernação/fisiologia , Sciuridae/fisiologia , Estações do Ano , Memória Espacial
9.
J Nat Med ; 76(4): 821-831, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35982366

RESUMO

Post-traumatic stress disorder (PTSD) is a serious mental disorder that can develop after exposure to extreme stress. Korean red ginseng, whose major active component is ginsenoside Rg3 (Rg3), is a widely used traditional antioxidant that has anti-inflammatory, anti-apoptotic and anxiolytics effects. This study investigated whether the administration of Rg3 ameliorated the memory deficit induced by a single prolonged stress (SPS) in rats. Male rats were dosed with Rg3 (25 or 50 mg/kg) once daily for 14 days after exposure to SPS. Rg3 administration improved fear memory and spatial memory might be involved in modulating the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and monoamine imbalance in the medial prefrontal cortex and hippocampus. It also increased the reduction in the brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) mRNAs expression, and the ratio of p-Akt/Akt in the hippocampus. Thus, Rg3 exerted memory-improving actions might be involved in regulating HPA axis and activating BDNF-TrkB pathway. Our findings suggest that Rg3 could be useful for preventing traumatic stress, such as PTSD.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Transtornos de Estresse Pós-Traumáticos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Medo , Ginsenosídeos , Hipocampo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Memória Espacial , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/metabolismo
10.
STAR Protoc ; 3(3): 101501, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-35776641

RESUMO

Social observation facilitates spatial learning by activation of hippocampal place cell patterns. Here, we describe an observational spatial working memory task to investigate the neural circuits underlying observational learning. This approach trains observer rats to learn to run a T-maze by observing a demonstrator's spatial trajectory while recording their hippocampal CA1 place cell activities in a course of several hours. The protocol provides a tool to study neural activities at population level in a social setting. For complete details on the use and execution of this protocol, please refer to Mou et al. (2021).


Assuntos
Células de Lugar , Animais , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/fisiologia , Ratos , Memória Espacial
11.
J Chem Neuroanat ; 124: 102137, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35842017

RESUMO

OBJECTIVE: Methamphetamine (METH) is one of the most widely used addictive drugs, and addiction to it is on the rise all over the world. METH abuse has long-term damaging effects that reduce memory and impair cognitive functions. According to studies, the observed effects are strongly related to the nerve cell damage caused by METH, which leads to neurotoxicity. Some of these intra-neuronal events include dopamine oxidation, excitotoxicity, and oxidative stress. Erythropoietin (EPO) is a hormone produced primarily by the kidneys and, in small quantities, by the liver. Studies have shown that EPO exhibits considerable neuroprotective effects. This study aimed to investigate the protective effects of EPO on METH neurotoxicity. METHODS: Initially, 48 male Wistar rats, weighing 250-300 g, were randomly assigned to four groups: control (n = 12), METH (n = 12), and METH+EPO (2500, 5000 IU/kg/IP- n = 12). METH was injected intraperitoneally at a dose of 40 mg per kg of body weight (four injections of 10 mg every two hours) to induce neurotoxicity. EPO was injected at doses of 2500 and 5000 IU/kg seven days after the last METH administration (ip). Morris water maze test was performed following EPO injection (1 day after the last dose) to assess spatial memory. The brains were removed after the behavioral test, biochemical evaluations and immunohistochemistry (caspase-3 and GFAP) was performed. RESULTS: The results showed that EPO treatment significantly improved spatial memory impairment (P < 0.01), compared to the METH group, EPO was a significant reduction in malondialdehyde and TNF-α (P < 0.01), as well as an increase in superoxide dismutase (P < 0.05) and glutathione-PX (P < 0.01). Furthermore, EPO treatment significantly reduced the number of GFAP positive cells (P < 0.01) and caspase 3 (P < 0.001) in the hippocampus (CA1 region). CONCLUSIONS: The study findings suggested that EPO may have great neuroprotective effects on METH neurotoxicity due to its anti-inflammatory, antioxidant, and antiapoptotic properties.


Assuntos
Eritropoetina , Metanfetamina , Fármacos Neuroprotetores , Síndromes Neurotóxicas , Animais , Apoptose , Eritropoetina/farmacologia , Eritropoetina/uso terapêutico , Hipocampo , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Estresse Oxidativo , Ratos , Ratos Wistar , Memória Espacial
12.
Neuroscience ; 498: 235-248, 2022 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-35863680

RESUMO

Endocytosis of GluA2-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in CA1 of the hippocampus regulates forgetting; deficits in forgetting nociceptive memory can induce serious stress disorders. As a transporter of GluA2-containing AMPAR, the functions of glutamate receptor interacting protein 1 (GRIP1) in forgetting and possible stress responses remain unclear. Lentivirus-mediated interference of GRIP1 expression or function in the dorsal CA1 of the hippocampus in mice indicated that GRIP1 overexpression enhanced spatial memory, impaired forgetting in a Barnes maze, and induced anxiety-like behavior in the open field and elevated plus-maze test. In contrast, GRIP1 knockdown impaired learning capacity. Furthermore, inhibition of the PDZ2 and PDZ4/5 domains of GRIP1 and GluA2-dn enhanced learning capacity, whereas GluA2-dn impaired spatial memory; inhibition of the PDZ2 and PDZ4/5 domains of GRIP1 also decreased forgetting capacity to some extent. Importantly, inhibition of both the PDZ2 and PDZ4/5 domains of GRIP1 induced anxiety-like behavior but not GluA2-dn. Furthermore, optogenetic control of both GluA1 and GluA2 insertion into the postsynaptic membrane impaired memory and induced anxiety-like behavior. In vitro experiments showed that GRIP1-ov and -dn, inhibition of PDZ2 and PDZ4/5 domains of GRIP1, and GluA2-dn decreased glycine-induced GluA1 and GluA2 exocytosis; meanwhile, GRIP1-ov and -dn, and interference of PDZ2 and PDZ4/5 domains of GRIP1 blocked AMPA- and NMDA-induced GluA1 and GluA2 endocytosis. Overall, these results suggest that GRIP1 drives AMPA receptor endocytosis and exocytosis bidirectionally; furthermore, GRIP1-induced stabilization of anchoring postsynaptic GluA1 and GluA2 impairs forgetting and induces anxiety-like behavior. GRIP1 may provide a potential therapeutic target in posttraumatic syndromes and anxiety disorders.


Assuntos
Hipocampo , Sinapses , Proteínas Adaptadoras de Transdução de Sinal , Animais , Ansiedade , Proteínas de Transporte , Endocitose , Exocitose , Camundongos , Proteínas do Tecido Nervoso , Memória Espacial , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico
13.
Brain Behav ; 12(8): e32723, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35861689

RESUMO

BACKGROUND: Multiple sclerosis (MS) is the most common autoimmune disease. Progressive depletion of the brain and spinal cord tissue appears at the onset of the disease. Several studies have shown the increased size of the ventricles of the brain and decreases in the area of the corpus callosum and the width of the brain. Other important symptoms of this disease are cognitive, learning, and memory disorders. AIM: The aim of this study was to compare morphometric, histological, and functional changes in the demyelination model in both sexes. MATERIALS AND METHODS: In this experimental study, male and female Wistar rats were studied in four experimental groups. Demyelination was induced by the injection of ethidium bromide in the ventricular region. The chronic effect of demyelination on spatial memory, movement, and coordination was investigated using the Morris Water Maze (MWM), and clinical and balance beam tests, respectively. Myelin degradation, cell death and neurogenesis were estimated using Luxol Fast Blue staining and immunohistochemistry (Caspase-3 and Nestin markers). In addition, morphometric findings were recorded for the brain and hippocampus (weight, volume, length, width). RESULT: Demyelination increased the time and distance index and decreased the residence time in the target quarter in the water maze test (p < .001). It also increases the neuromuscular and modified neurological severity score (p < .01). Demyelination increases caspase-3 (p < .05) expression and decreases Nestin expression (p < .001), which are directly related to the extent of damage. CONCLUSION: This study showed an interaction between hippocampal structural and functional networks in explaining spatial learning and memory in the early stages of MS.


Assuntos
Doenças Desmielinizantes , Esclerose Múltipla , Animais , Caspase 3 , Doenças Desmielinizantes/induzido quimicamente , Modelos Animais de Doenças , Feminino , Hipocampo/patologia , Masculino , Esclerose Múltipla/patologia , Nestina , Ratos , Ratos Wistar , Memória Espacial
14.
Sci Rep ; 12(1): 12675, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879365

RESUMO

The Active Allothetic Place Avoidance task is an alternative setup to Morris Water Maze that allows studying spatial memory in a dynamic world in the presence of conflicting information. In this task, a rat, freely moving on a rotating circular arena, has to avoid a sector defined within the room frame where shocks are presented. While for Morris Water Maze several studies have identified animal strategies which specifically affect performance, there were no such studies for the Active Allothetic Place Avoidance task. Using standard machine learning methods, we were able to reveal for the first time, to the best of our knowledge, explainable strategies that the animals employ in this task and demonstrate that they can provide a high-level interpretation for performance differences between an animal group treated with silver nanoparticles (AgNPs) and the control group.


Assuntos
Aprendizagem da Esquiva , Nanopartículas Metálicas , Animais , Aprendizagem em Labirinto , Ratos , Ratos Long-Evans , Prata , Memória Espacial
15.
Neurobiol Aging ; 118: 77-87, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35901557

RESUMO

Recent work suggests that the relationship between age and memory-related brain activity are different for men and women. We sought to extend this work by examining sex differences in the association between age, memory performance, and brain signal variability during context memory tasks in neurotypical adults (aged 19-76 years; N = 128, 87 women). We measured blood oxygen level-dependent standard deviation (BOLD SD) during encoding and retrieval in easy and difficult spatial context memory tasks and investigated sex-specific, age- and performance-associated BOLD SD patterns. Behavioral analysis revealed age-related decreases in memory retrieval, but no sex differences nor an age-by-sex interaction. Imaging results indicated that both sexes showed a negative correlation between BOLD SD and retrieval accuracy in memory-related regions. We also identified significant sex differences: women exhibited age-associated increases in BOLD SD which were negatively associated with performance. Men exhibited both age-associated decreases and increases, which were not related to performance. Our results revealed sex differences in the relationship between age and BOLD SD during high-demand episodic memory tasks.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Idoso , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Caracteres Sexuais , Memória Espacial
16.
Neurosci Lett ; 786: 136769, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35792300

RESUMO

Our knowledge concerning visual-spatial memory related phase synchronization within the ipsilateral hippocampus or between contralateral hippocampi during memory encoding in humans is currently limited. The present study examines the relationship between phase synchronization within the hippocampus and memory performance during virtual navigation in an object-location memory navigation task using intracranial depth electrodes in human subjects. Specifically, we focus on the phase synchronization ratio between periods when the target object was in and out of visual focus. Our findings indicate that there is a significant relationship between this phase synchronization ratio and object-location memory performance in the theta band (p = 0.015, R = -0.71), but not in the delta or alpha bands. Importantly, this theta coherence has a significant linear relationship with memory performance between contralateral hippocampus electrode pairs (p = 0.006, R = -0.77), but not ipsilateral electrode pairs (p = 0.79, R = -0.09). In addition, this theta coherence has a significant linear relationship with memory performance during stationary periods (p = 0.002, R = -0.82), but not movement periods (p = 0.10, R = -0.51). These findings suggest that, during navigation, interhemispheric hippocampal theta coherence when stationary and focusing on the target object may be a critical determinant of successful object-location memory.


Assuntos
Hipocampo , Ritmo Teta , Humanos , Movimento , Memória Espacial
17.
Physiol Behav ; 254: 113912, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35835179

RESUMO

Interaction of oscillatory rhythms at different frequencies is considered to provide a neuronal mechanism for information processing and transmission. These interactions have been suggested to have a vital role in cognitive functions such as working memory and decision-making. Here, we investigated the medial prefrontal cortex (mPFC), which is known to have a critical role in successful execution of spatial working memory tasks. We recorded local field potential oscillations from mPFC while rats performed a delayed-non-match-to-place (DNMTP) task. In the DNMTP task, the rat needed to decide actively about the pathway based on the information remembered in the first phase of each trial. Our analysis revealed a dynamic phase-amplitude coupling (PAC) between theta and high frequency oscillations (HFOs). This dynamic coupling emerged near the turning point and diminished afterward. Further, theta activity during the delay period, which is thought of as the maintenance phase, in the absence of the coupling, can predict task completion time. We previously reported diminished rat performance in the DNMTP task in response to electromagnetic radiation. Here, we report an increase in the theta rhythm during delay activity besides diminishing the coupling after electromagnetic radiation. These findings suggest that the different roles of the mPFC in working memory could be supported by separate mechanisms: Theta activity during the delay period for information maintenance and theta-HFOs phase-amplitude coupling relating to the decision-making procedure.


Assuntos
Memória de Curto Prazo , Memória Espacial , Animais , Memória de Curto Prazo/fisiologia , Neurônios , Córtex Pré-Frontal/fisiologia , Ratos , Memória Espacial/fisiologia , Ritmo Teta/fisiologia
18.
J Neurosci ; 42(31): 6090-6107, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35760529

RESUMO

Alzheimer's disease (AD) is characterized pathologically by the structural and functional impairments of synapses in the hippocampus, inducing the learning and memory deficiencies. Ras GTPase is closely related to the synaptic function and memory. This study was to investigate the effects of farnesyl transferase inhibitor lonafarnib on the synaptic structure and function in AD male mice and explore the potential mechanism. Our results showed 50 mg/kg lonafarnib (intraperitoneal) rescued the impaired spatial memory and improved the damaged synaptic transmission and plasticity of Aß1-42 mice. In addition, lonafarnib ameliorated the morphology of synaptic dendrites and spines in Aß1-42 mice. Furthermore, lonafarnib enhanced α7nAChR cell surface expression and phosphorylation of downstream Akt and CaMKII in Aß1-42 mice, which were inhibited by α7nAChR antagonist methyl lycaconitine (MLA), and increased the phosphorylation of CREB in a CaMKII- but not ERK-dependent way. Lonafarnib enhanced hippocampal brain-derived neurotrophic factor (BDNF) concentration in Aß1-42 mice, which was sensitive to MLA and KN93 (an inhibitor of CaMKII), but not related to ERK and Akt pathways. H-Ras, but not Rhes, was related to the lonafarnib induced improvement of α7nAChR cell surface expression and BDNF content. Interestingly, lonafarnib induced improvement of synaptic transmission, plasticity and spatial cognition in Aß1-42 mice was abolished by BDNF deprivation with TrkB/Fc chimera protein. Our results indicate that lonafarnib can rescue the structural and functional impairments of synapses in the Aß1-42 mice, which may be related to the improvement of BDNF content through the H-Ras-α7nAChR-dependent CaMKII-CREB pathway, leading to the improvement of spatial cognition.SIGNIFICANCE STATEMENT Alzheimer's disease (AD) is characterized pathologically by the structural and functional impairments of synapses in the hippocampus, inducing the learning and memory deficiencies. However, no effective drugs have not been developed for the treatment of AD synaptic. This study for the first time reported the beneficial effects of Ras inhibitor lonafarnib on the synaptic structure and function in AD mice, providing an alternative way for the treatment of "synaptic disease" in AD patients.


Assuntos
Doença de Alzheimer , Fator Neurotrófico Derivado do Encéfalo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Hipocampo/metabolismo , Masculino , Transtornos da Memória , Camundongos , Fragmentos de Peptídeos , Piperidinas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas , Memória Espacial , Sinapses/fisiologia , Regulação para Cima , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
19.
Horm Behav ; 144: 105206, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35653829

RESUMO

Many patients with Parkinson's disease (PD) experience cognitive or memory impairments with few therapeutic options available to mitigate them. This has fueled interest in determining how factors including sex and sex hormones modulate higher order function in this disease. The objective of this study was to use the Novel Object Recognition (NOR) and Object-in-Place (OiP) paradigms to compare the effects of a bilateral neostriatal 6-hydroxydopamine (6-OHDA) lesion model of PD in gonadally intact male and female rats, in orchidectomized male rats and in orchidectomized males supplemented with 17ß-estradiol or testosterone propionate on measures of recognition memory similar to those at risk in PD. These studies showed that 6-ODHA lesions impaired discrimination in both tasks in males but not females. Further, 6-OHDA lesions disrupted NOR performance similarly in all males regardless of whether they were gonadally intact, orchidectomized or hormone-supplemented. In contrast, OiP performance was disrupted in males that were orchidectomized or 6-OHDA-lesioned but was spared in orchidectomized and orchidectomized, 6-OHDA lesioned males supplemented with 17ß-estradiol. The distinct effects that sex and/or sex hormones have on 6-OHDA lesion-induced NOR vs. OiP deficits identified here also differ from corresponding impacts recently described for 6-OHDA lesion-induced deficits in spatial working memory and episodic memory. Together, the collective data provide strong evidence for effects of sex and sex hormones on cognition and memory in PD as being behavioral task and behavioral domain specific. This specificity could explain why a cohesive clinical picture of endocrine impacts on higher order function in PD has remained elusive.


Assuntos
Doença de Parkinson , Animais , Estradiol/farmacologia , Masculino , Memória de Curto Prazo , Oxidopamina/farmacologia , Doença de Parkinson/etiologia , Ratos , Memória Espacial
20.
J Psychiatr Res ; 152: 97-103, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35717867

RESUMO

BACKGROUND: Major depressive disorder (MDD) is associated with impairments in spatial learning and memory and with altered functioning of central mineralocorticoid receptors (MR) and glutamatergic N-methyl-D-aspartate receptors (NMDA-R). Both receptors are highly expressed in the hippocampus and prefrontal cortex - brain areas that are critical for spatial learning and memory. Here, we examined the effects of separate and combined MR and NMDA-R stimulation on spatial learning and memory in individuals with MDD and healthy controls. METHODS: We used a randomized, double-blind, placebo-controlled between-group study design to examine the effects of separate and combined stimulation of the MR (with 0.4 mg fludrocortisone) and NMDA-R (with 250 mg D-cycloserine) in 116 unmedicated individuals with MDD (mean age: 34.7 ± 13.3 years; 78.4% women) and 116 age-, sex-, and education-matched healthy controls. Participants were randomly assigned to one of four conditions: 1) placebo; 2) MR stimulation; 3) NMDA-R stimulation; and 4) combined MR/NMDA-R stimulation. Three hours after drug administration, spatial learning and memory were assessed using a virtual Morris Water Maze task. RESULTS: Individuals with MDD and healthy controls did not differ in spatial learning and memory performance. Neither separate nor combined MR or NMDA-R stimulation altered measures of spatial performance. CONCLUSION: In this study of relatively young, predominantly female, and unmedicated individuals, we found no effect of MDD and no effect of separate or combined MR and NMDA-R stimulation on spatial learning and memory.


Assuntos
Transtorno Depressivo Maior , Aprendizagem Espacial , Adulto , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Hipocampo/metabolismo , Humanos , Masculino , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Pessoa de Meia-Idade , Mineralocorticoides/farmacologia , N-Metilaspartato/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Aprendizagem Espacial/fisiologia , Memória Espacial/fisiologia , Adulto Jovem
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