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1.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198910

RESUMO

Changes in structural and functional neuroplasticity have been implicated in various neurological disorders. Sterol regulatory element-binding protein (SREBP)-1c is a critical regulatory molecule of lipid homeostasis in the brain. Recently, our findings have shown the potential involvement of SREBP-1c deficiency in the alteration of novel modulatory molecules in the hippocampus and occurrence of schizophrenia-like behaviors in mice. However, the possible underlying mechanisms, related to neuronal plasticity in the hippocampus, are yet to be elucidated. In this study, we investigated the hippocampus-dependent memory function and neuronal architecture of hippocampal neurons in SREBP-1c knockout (KO) mice. During the passive avoidance test, SREBP-1c KO mice showed memory impairment. Based on Golgi staining, the dendritic complexity, length, and branch points were significantly decreased in the apical cornu ammonis (CA) 1, CA3, and dentate gyrus (DG) subregions of the hippocampi of SREBP-1c KO mice, compared with those of wild-type (WT) mice. Additionally, significant decreases in the dendritic diameters were detected in the CA3 and DG subregions, and spine density was also significantly decreased in the apical CA3 subregion of the hippocampi of KO mice, compared with that of WT mice. Alterations in the proportions of stubby and thin-shaped dendritic spines were observed in the apical subcompartments of CA1 and CA3 in the hippocampi of KO mice. Furthermore, the corresponding differential decreases in the levels of SREBP-1 expression in the hippocampal subregions (particularly, a significant decrease in the level in the CA3) were detected by immunofluorescence. This study suggests that the contributions of SREBP-1c to the structural plasticity of the mouse hippocampus may have underlain the behavioral alterations. These findings offer insights into the critical role of SREBP-1c in hippocampal functioning in mice.


Assuntos
Espinhas Dendríticas/genética , Memória/fisiologia , Neurônios/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Animais , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/fisiologia , Espinhas Dendríticas/patologia , Regulação da Expressão Gênica/genética , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Camundongos , Camundongos Knockout , Plasticidade Neuronal/genética , Neurônios/patologia , Proteína de Ligação a Elemento Regulador de Esterol 1/deficiência
2.
FASEB J ; 35(8): e21726, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34196433

RESUMO

Increasing evidence shows that astrocytes, by releasing and uptaking neuroactive molecules, regulate synaptic plasticity, considered the neurophysiological basis of memory. This study investigated the impact of l-α-aminoadipate (l-AA) on astrocytes which sense and respond to stimuli at the synaptic level and modulate hippocampal long-term potentiation (LTP) and memory. l-AA selectivity toward astrocytes was proposed in the early 70's and further tested in different systems. Although it has been used for impairing the astrocytic function, its effects appear to be variable in different brain regions. To test the effects of l-AA in the hippocampus of male C57Bl/6 mice we performed two different treatments (ex vivo and in vivo) and took advantage of other compounds that were reported to affect astrocytes. l-AA superfusion did not affect the basal synaptic transmission but decreased LTP magnitude. Likewise, trifluoroacetate and dihydrokainate decreased LTP magnitude and occluded the effect of l-AA on synaptic plasticity, confirming l-AA selectivity. l-AA superfusion altered astrocyte morphology, increasing the length and complexity of their processes. In vivo, l-AA intracerebroventricular injection not only reduced the astrocytic markers but also LTP magnitude and impaired hippocampal-dependent memory in mice. Interestingly, d-serine administration recovered hippocampal LTP reduction triggered by l-AA (2 h exposure in hippocampal slices), whereas in mice injected with l-AA, the superfusion of d-serine did not fully rescue LTP magnitude. Overall, these data show that both l-AA treatments affect astrocytes differently, astrocytic activation or loss, with similar negative outcomes on hippocampal LTP, implying that opposite astrocytic adaptive alterations are equally detrimental for synaptic plasticity.


Assuntos
Ácido 2-Aminoadípico/toxicidade , Astrócitos/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Ácido 2-Aminoadípico/administração & dosagem , Ácido 2-Aminoadípico/antagonistas & inibidores , Trifosfato de Adenosina/metabolismo , Animais , Astrócitos/patologia , Astrócitos/fisiologia , Células Cultivadas , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/toxicidade , Proteína Glial Fibrilar Ácida/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/patologia , Técnicas In Vitro , Injeções Intraventriculares , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Serina/administração & dosagem , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia
3.
Int J Mol Sci ; 22(9)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063730

RESUMO

Based on recent findings that show that depletion of factor XII (FXII) leads to better posttraumatic neurological recovery, we studied the effect of FXII-deficiency on post-traumatic cognitive and behavioral outcomes in female and male mice. In agreement with our previous findings, neurological deficits on day 7 after weight-drop traumatic brain injury (TBI) were significantly reduced in FXII-/- mice compared to wild type (WT) mice. Also, glycoprotein Ib (GPIb)-positive platelet aggregates were more frequent in brain microvasculature of WT than FXII-/- mice 3 months after TBI. Six weeks after TBI, memory for novel object was significantly reduced in both female and male WT but not in FXII-/- mice compared to sham-operated mice. In the setting of automated home-cage monitoring of socially housed mice in IntelliCages, female WT mice but not FXII-/- mice showed decreased exploration and reacted negatively to reward extinction one month after TBI. Since neuroendocrine stress after TBI might contribute to trauma-induced cognitive dysfunction and negative emotional contrast reactions, we measured peripheral corticosterone levels and the ration of heart, lung, and spleen weight to bodyweight. Three months after TBI, plasma corticosterone levels were significantly suppressed in both female and male WT but not in FXII-/- mice, while the relative heart weight increased in males but not in females of both phenotypes when compared to sham-operated mice. Our results indicate that FXII deficiency is associated with efficient post-traumatic behavioral and neuroendocrine recovery.


Assuntos
Lesões Encefálicas Traumáticas/genética , Disfunção Cognitiva/genética , Deficiência do Fator XII/genética , Fator XII/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/complicações , Disfunção Cognitiva/patologia , Corticosterona/sangue , Modelos Animais de Doenças , Deficiência do Fator XII/sangue , Deficiência do Fator XII/complicações , Deficiência do Fator XII/patologia , Humanos , Memória/fisiologia , Camundongos , Camundongos Knockout , Agregação Plaquetária/genética , Complexo Glicoproteico GPIb-IX de Plaquetas
4.
Nat Commun ; 12(1): 3915, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168140

RESUMO

Memory is supported by a specific collection of neurons distributed in broad brain areas, an engram. Despite recent advances in identifying an engram, how the engram is created during memory formation remains elusive. To explore the relation between a specific pattern of input activity and memory allocation, here we target a sparse subset of neurons in the auditory cortex and thalamus. The synaptic inputs from these neurons to the lateral amygdala (LA) are not potentiated by fear conditioning. Using an optogenetic priming stimulus, we manipulate these synapses to be potentiated by the learning. In this condition, fear memory is preferentially encoded in the manipulated cell ensembles. This change, however, is abolished with optical long-term depression (LTD) delivered shortly after training. Conversely, delivering optical long-term potentiation (LTP) alone shortly after fear conditioning is sufficient to induce the preferential memory encoding. These results suggest a synaptic plasticity-dependent competition rule underlying memory formation.


Assuntos
Memória/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/fisiologia , Encéfalo/citologia , Encéfalo/fisiologia , Condicionamento Clássico/fisiologia , Potenciais Evocados Auditivos , Medo/fisiologia , Halorrodopsinas/genética , Halorrodopsinas/metabolismo , Aprendizagem/fisiologia , Potenciação de Longa Duração/fisiologia , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Optogenética
5.
J Abnorm Psychol ; 130(4): 346-364, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34180700

RESUMO

Even though memory performance is a commonly researched aspect of obsessive-compulsive disorder (OCD), a coherent and unified explanation of the role of specific cognitive factors has remained elusive. To address this, the present meta-analysis examined the predictive validity of Harkin and Kessler's (2011b) executive function, binding complexity, and memory load (EBL) Classification System concerning affected versus unaffected memory performance in OCD. We employed a multilevel meta-analytic approach (Viechtbauer, 2010) to accommodate the interdependent nature of the EBL model and interdependency of effect sizes (305 effect sizes from 144 studies, including 4,424 OCD patients). Results revealed that the EBL model predicted memory performance; that is, as EBL demand increases, those with OCD performed progressively worse on memory tasks. Executive function was the driving mechanism behind the EBL's impact on OCD memory performance, as it negated binding complexity, memory load, and visual or verbal task differences. Comparisons of subtask effect sizes were also generally in accord with the cognitive parameters of the EBL taxonomy. We conclude that standardized coding of tasks along individual cognitive dimensions and multilevel meta-analyses provides a new approach to examine multidimensional models of memory and cognitive performance in OCD and other disorders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Memória/fisiologia , Transtorno Obsessivo-Compulsivo/psicologia , Humanos , Modelos Psicológicos , Análise Multinível
6.
BMC Neurol ; 21(1): 223, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126956

RESUMO

BACKGROUND: Since subjects with Rett syndrome (RTT) focus their attention mainly on the faces of people with whom they interact, in this study the role of a human-like smart interactive agent (an avatar) in enhancing cognitive processes is examined. More in depth, this study aimed to understand if, and to what extent, the use of an avatar can improve attention and memory abilities in subjects with RTT. METHOD: Thirty-six subjects with RTT participated in the study. All participants performed over-selectivity and memory tasks, for a total of six trials. These trials were randomly presented in two different conditions: with and without virtual avatar. RESULTS: The results indicated that the participants improved their attention and memory abilities when they performed the tasks with the avatar. There were no improvements when they performed the tasks without the avatar. DISCUSSION: The results were discussed considering the relationship between motivation, attention and memory in RTT.


Assuntos
Atenção/fisiologia , Memória/fisiologia , Síndrome de Rett , Realidade Virtual , Humanos , Síndrome de Rett/fisiopatologia , Síndrome de Rett/terapia
7.
Nat Commun ; 12(1): 3443, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103527

RESUMO

Polyunsaturated free fatty acids (FFAs) such as arachidonic acid, released by phospholipase activity on membrane phospholipids, have long been considered beneficial for learning and memory and are known modulators of neurotransmission and synaptic plasticity. However, the precise nature of other FFA and phospholipid changes in specific areas of the brain during learning is unknown. Here, using a targeted lipidomics approach to characterise FFAs and phospholipids across the rat brain, we demonstrated that the highest concentrations of these analytes were found in areas of the brain classically involved in fear learning and memory, such as the amygdala. Auditory fear conditioning led to an increase in saturated (particularly myristic and palmitic acids) and to a lesser extent unsaturated FFAs (predominantly arachidonic acid) in the amygdala and prefrontal cortex. Both fear conditioning and changes in FFA required activation of NMDA receptors. These results suggest a role for saturated FFAs in memory acquisition.


Assuntos
Ácidos Graxos não Esterificados/metabolismo , Memória/fisiologia , Estimulação Acústica , Animais , Comportamento Animal , Encéfalo/metabolismo , Análise por Conglomerados , Condicionamento Clássico , Medo , Masculino , Fosfolipídeos/metabolismo , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo
8.
Exp Psychol ; 68(1): 18-31, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34109806

RESUMO

According to the embodied approach of language, concepts are grounded in sensorimotor mental states, and when we process language, the brain simulates some of the perceptions and actions that are involved when interacting with real objects. Moreover, several studies have highlighted that cognitive performances are dependent on the overlap between the motor action simulated and the motor action required by the task. On the other hand, in the field of memory, the role of action is under debate. The aim of this work was to show that performing an action at the stage of retrieval influences memory performance in a recognition task (experiment 1) and a cued recall task (experiment 2), even if the participants were never instructed to consider the implied action. The results highlighted an action-based memory effect at the retrieval stage. These findings contribute to the debate about the implication of motor system in action verb processing and its role for memory.


Assuntos
Memória/fisiologia , Rememoração Mental/fisiologia , Adulto , Feminino , Humanos , Idioma , Masculino , Adulto Jovem
9.
Psychol Aging ; 36(4): 475-490, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34124921

RESUMO

People use memory for observed actions to guide current perceptions. When actions change from one situation to the next, one must register the change to update memory. Research suggests that older adults may sometimes update memory for naturalistic action changes less effectively than younger adults. We examined whether this deficit reflects age differences in attention allocation by cuing attention to changed action features and testing memory for those features. Older (N = 47) and younger (N = 73) adults watched movies of an actor performing everyday activities on two fictive "days" in her life. Some activities began identically on both days (e.g., reaching for dessert) and ended with features that changed across days (e.g., cookie vs. brownie). Half of the changed activities included audio-visual cues on both days that signaled changed features, whereas the other half did not include cues. Memory updating was assessed through cued recall and two-alternative forced choice recognition (2AFC recognition) of recent action features. Cuing attention improved cued recall but not 2AFC recognition of recent action features for both older and younger adults. These recall benefits were associated with improved recollection that changes had earlier occurred. The present findings suggest that although older adults sometimes experience deficits in aspects of attention, using cues to guide their attention to features of everyday activities can enhance their event memory updating when the later memory test emphasizes recollection-based retrieval. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Atenção/fisiologia , Memória/fisiologia , Envelhecimento , Feminino , Humanos , Masculino
10.
Nat Commun ; 12(1): 3112, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035303

RESUMO

Sleep is thought to support memory consolidation via reactivation of prior experiences, with particular electrophysiological sleep signatures (slow oscillations (SOs) and sleep spindles) gating the information flow between relevant brain areas. However, empirical evidence for a role of endogenous memory reactivation (i.e., without experimentally delivered memory cues) for consolidation in humans is lacking. Here, we devised a paradigm in which participants acquired associative memories before taking a nap. Multivariate decoding was then used to capture endogenous memory reactivation during non-rapid eye movement (NREM) sleep in surface EEG recordings. Our results reveal reactivation of learning material during SO-spindle complexes, with the precision of SO-spindle coupling predicting reactivation strength. Critically, reactivation strength (i.e. classifier evidence in favor of the previously studied stimulus category) in turn predicts the level of consolidation across participants. These results elucidate the memory function of sleep in humans and emphasize the importance of SOs and spindles in clocking endogenous consolidation processes.


Assuntos
Encéfalo/fisiologia , Aprendizagem/fisiologia , Consolidação da Memória/fisiologia , Memória/fisiologia , Sono/fisiologia , Sinais (Psicologia) , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Estimulação Luminosa , Polissonografia/métodos , Desempenho Psicomotor/fisiologia , Adulto Jovem
11.
Nat Commun ; 12(1): 2881, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001888

RESUMO

The mechanisms by which sleep benefits learning and memory remain unclear. Sleep may further strengthen the synapses potentiated by learning or promote broad synaptic weakening while protecting the newly potentiated synapses. We tested these ideas by combining a motor task whose consolidation is sleep-dependent, a marker of synaptic AMPA receptor plasticity, and repeated two-photon imaging to track hundreds of spines in vivo with single spine resolution. In mouse motor cortex, sleep leads to an overall net decrease in spine-surface GluA1-containing AMPA receptors, both before and after learning. Molecular changes in single spines during post-learning sleep are correlated with changes in performance after sleep. The spines in which learning leads to the largest increase in GluA1 expression have a relative advantage after post-learning sleep compared to sleep deprivation, because sleep weakens all remaining spines. These results are obtained in adult mice, showing that sleep-dependent synaptic down-selection also benefits the mature brain.


Assuntos
Espinhas Dendríticas/metabolismo , Aprendizagem/fisiologia , Córtex Motor/fisiologia , Receptores de AMPA/metabolismo , Sono/fisiologia , Animais , Feminino , Masculino , Memória/fisiologia , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Atividade Motora/fisiologia , Córtex Motor/citologia , Córtex Motor/metabolismo , Privação do Sono/fisiopatologia , Sinapses/metabolismo , Sinapses/fisiologia
12.
Acta Neurol Scand ; 144(1): 81-91, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33881170

RESUMO

OBJECTIVE: It is assumed that temporal lobe resection in older people is associated with worse seizure outcomes and potential postsurgical memory decline. We studied postsurgical memory development and surgical efficacy in patients over 45 years of age compared with younger patients. METHODS: We studied 88 patients (51 male and 37 female) after temporal lobe surgery, which involved hippocampal resection. The patients were evaluated before surgery and in the first (72 patients) and/or third (57 patients) postsurgical year. The Wechsler Memory Scale III test was performed to evaluate the MQ postsurgical development. Engel's classification was used to evaluate the postsurgical seizure outcome. RESULTS: The presurgical MQ (median 88) in ≥45 years age group was significantly lower than in both younger groups (median MQ = 100 for ≤30 years age group, p = 0.002; median MQ = 107 for 31-44 years age group, p = 0.002). Three years after the surgery, the MQ decreased significantly in ≤30 years age group (p = 0.012), while only non-significant MQ decline was observed in both older groups. We found no significant impact of age on the surgical outcome. CONCLUSION: Higher age at the time of surgery does not significantly increase the risk for postsurgical memory decline; however, older patients are more likely to have lowered presurgical MQ. We did not find significant differences in the impact of surgery on seizure outcome among the age groups. Epilepsy surgery appears to be a safe and effective method in the age over 45 years even though an earlier surgery should be preferred.


Assuntos
Epilepsia do Lobo Temporal/psicologia , Epilepsia do Lobo Temporal/cirurgia , Transtornos da Memória/psicologia , Memória/fisiologia , Procedimentos Neurocirúrgicos/psicologia , Cuidados Pré-Operatórios/psicologia , Adolescente , Adulto , Idoso , Epilepsia do Lobo Temporal/diagnóstico , Feminino , Seguimentos , Hipocampo/cirurgia , Humanos , Masculino , Transtornos da Memória/diagnóstico , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/tendências , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Lobo Temporal/cirurgia , Resultado do Tratamento , Escalas de Wechsler , Adulto Jovem
13.
Psychol Aging ; 36(2): 186-199, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33793261

RESUMO

Older adults often demonstrate a monitoring deficit by producing more high-confidence memory errors on recognition memory tests. To eliminate lower memory performance by older adults (OA) as a candidate explanation, we studied how distinctive encoding enhances the retrieval-monitoring accuracy in older adults and younger adults (YA) under different delays (2-day delay for OA, 7-day delay for YA). Individuals viewed items consisting of four randomly selected exemplars (e.g., SALMON, BASS, PERCH, and SHARK) from a taxonomic category (e.g., FISH), one being designated as the to-be-remembered target. Participants were randomly assigned to two encoding conditions: Shared (generate a shared feature of all exemplars, e.g., GILLS) or Distinctive (generate a distinctive feature of the designated target). We collected retrospective confidence judgments (RCJs) after a five-alternative forced-choice (5AFC) recognition test, with the lures being either previously presented (old) exemplars or new category exemplars. Recall and recognition memory were better with distinctive encoding, with shared feature generation producing more high-confidence false alarms (HCFAs). Distinctive encoding dramatically reduced HCFAs and improved RCJ resolution. Comparison of OA with 2-day delay YA revealed age differences in HCFA consistent with previous studies. As important, age differences in memory for OA and 7-day delay YA were minimized, eliminating age deficits in HCFAs. Matching OAs to a subset of 7-day delay YAs on recognition memory produced additional evidence favoring the null hypothesis of age-equivalence in HCFAs. The results therefore indicated that age differences in recognition-based retrieval monitoring in a forced-choice recognition test are an epiphenomenon of age differences in memory. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Envelhecimento/psicologia , Rememoração Mental/fisiologia , Reconhecimento Psicológico/fisiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
14.
Nat Neurosci ; 24(5): 677-684, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33795883

RESUMO

Reconsolidation may be a viable therapeutic target to inhibit pathological fear memories. In the clinic, incidental or imaginal reminders are used for safe retrieval of traumatic memories of experiences that occurred elsewhere. However, it is unknown whether indirectly retrieved traumatic memories are sensitive to disruption. Here we used a backward (BW) conditioning procedure to indirectly retrieve and manipulate a hippocampus (HPC)-dependent contextual fear engram in male rats. We show that conditioned freezing to a BW conditioned stimulus (CS) is mediated by fear to the conditioning context, activates HPC ensembles that can be covertly captured and chemogenetically activated to drive fear, and is impaired by post-retrieval protein synthesis inhibition. These results reveal that indirectly retrieved contextual fear memories reactivate HPC ensembles and undergo protein synthesis-dependent reconsolidation. Clinical interventions that rely on indirect retrieval of traumatic memories, such as imaginal exposure, may open a window for editing or erasure of neural representations that drive pathological fear.


Assuntos
Condicionamento Psicológico/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Animais , Masculino , Consolidação da Memória/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos
15.
Nat Neurosci ; 24(5): 715-726, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33821001

RESUMO

Cognition depends on integrating sensory percepts with the memory of recent stimuli. However, the distributed nature of neural coding can lead to interference between sensory and memory representations. Here, we show that the brain mitigates such interference by rotating sensory representations into orthogonal memory representations over time. To study how sensory inputs and memories are represented, we recorded neurons from the auditory cortex of mice as they implicitly learned sequences of sounds. We found that the neural population represented sensory inputs and the memory of recent stimuli in two orthogonal dimensions. The transformation of sensory information into a memory was facilitated by a combination of 'stable' neurons, which maintained their selectivity over time, and 'switching' neurons, which inverted their selectivity over time. Together, these neural responses rotated the population representation, transforming sensory inputs into memory. Theoretical modeling showed that this rotational dynamic is an efficient mechanism for generating orthogonal representations, thereby protecting memories from sensory interference.


Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Cognição/fisiologia , Memória/fisiologia , Neurônios/fisiologia , Estimulação Acústica , Animais , Memória de Curto Prazo/fisiologia , Camundongos , Modelos Neurológicos
16.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915732

RESUMO

The neuropeptide galanin (GAL), which is expressed in limbic brain structures, has a strong impact on the regulation of mood and behavior. GAL exerts its effects via three G protein-coupled receptors (GAL1-3-R). Little is known about the effects of aging and loss of GAL-Rs on hippocampal-mediated processes connected to neurogenesis, such as learning, memory recall and anxiety, and cell proliferation and survival in the dorsal dentate gyrus (dDG) in mice. Our results demonstrate that loss of GAL3-R, but not GAL2-R, slowed learning and induced anxiety in older (12-14-month-old) mice. Lack of GAL2-R increased cell survival (BrdU incorporation) in the dDG of young mice. However, normal neurogenesis was observed in vitro using neural stem and precursor cells obtained from GAL2-R and GAL3-R knockouts upon GAL treatment. Interestingly, we found sub-strain differences between C57BL/6J and C57BL/6N mice, the latter showing faster learning, less anxiety and lower cell survival in the dDG. We conclude that GAL-R signaling is involved in cognitive functions and can modulate the survival of cells in the neurogenic niche, which might lead to new therapeutic applications. Furthermore, we observed that the mouse sub-strain had a profound impact on the behavioral parameters analyzed and should therefore be carefully considered in future studies.


Assuntos
Ansiedade/etiologia , Suscetibilidade a Doenças , Aprendizagem/fisiologia , Memória/fisiologia , Receptor Tipo 2 de Galanina/genética , Receptor Tipo 3 de Galanina/genética , Fatores Etários , Envelhecimento/genética , Envelhecimento/metabolismo , Envelhecimento/psicologia , Animais , Ansiedade/metabolismo , Ansiedade/psicologia , Biomarcadores , Giro Denteado/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Imuno-Histoquímica , Aprendizagem em Labirinto , Camundongos , Camundongos Knockout , Neuropeptídeos/metabolismo , Receptor Tipo 2 de Galanina/metabolismo , Receptor Tipo 3 de Galanina/metabolismo , Aprendizagem Espacial , Especificidade da Espécie
17.
Nature ; 593(7859): 411-417, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33883745

RESUMO

The ability to categorize sensory stimuli is crucial for an animal's survival in a complex environment. Memorizing categories instead of individual exemplars enables greater behavioural flexibility and is computationally advantageous. Neurons that show category selectivity have been found in several areas of the mammalian neocortex1-4, but the prefrontal cortex seems to have a prominent role4,5 in this context. Specifically, in primates that are extensively trained on a categorization task, neurons in the prefrontal cortex rapidly and flexibly represent learned categories6,7. However, how these representations first emerge in naive animals remains unexplored, leaving it unclear whether flexible representations are gradually built up as part of semantic memory or assigned more or less instantly during task execution8,9. Here we investigate the formation of a neuronal category representation throughout the entire learning process by repeatedly imaging individual cells in the mouse medial prefrontal cortex. We show that mice readily learn rule-based categorization and generalize to novel stimuli. Over the course of learning, neurons in the prefrontal cortex display distinct dynamics in acquiring category selectivity and are differentially engaged during a later switch in rules. A subset of neurons selectively and uniquely respond to categories and reflect generalization behaviour. Thus, a category representation in the mouse prefrontal cortex is gradually acquired during learning rather than recruited ad hoc. This gradual process suggests that neurons in the medial prefrontal cortex are part of a specific semantic memory for visual categories.


Assuntos
Aprendizagem/fisiologia , Modelos Neurológicos , Reconhecimento Visual de Modelos/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Feminino , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Estimulação Luminosa , Córtex Pré-Frontal/citologia , Fatores de Tempo
18.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33808976

RESUMO

The mammalian hippocampal dentate gyrus is a unique memory circuit in which a subset of neurons is continuously generated throughout the lifespan. Previous studies have shown that the dentate gyrus neuronal population can hold fear memory traces (i.e., engrams) and that adult-born neurons (ABNs) support this process. However, it is unclear whether ABNs themselves hold fear memory traces. Therefore, we analyzed ABN activity at a population level across a fear conditioning paradigm. We found that fear learning did not recruit a distinct ABN population. In sharp contrast, a completely different ABN population was recruited during fear memory retrieval. We further provide evidence that ABN population activity remaps over time during the consolidation period. These results suggest that ABNs support the establishment of a fear memory trace in a different manner to directly holding the memory. Moreover, this activity remapping process in ABNs may support the segregation of memories formed at different times. These results provide new insight into the role of adult neurogenesis in the mammalian memory system.


Assuntos
Consolidação da Memória/fisiologia , Memória/fisiologia , Neurogênese/genética , Neurônios/metabolismo , Animais , Condicionamento Psicológico , Giro Denteado/metabolismo , Giro Denteado/fisiologia , Medo/fisiologia , Hipocampo/metabolismo , Hipocampo/fisiologia , Humanos , Aprendizagem/fisiologia , Camundongos , Neurônios/fisiologia
19.
J Med Case Rep ; 15(1): 185, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33883015

RESUMO

BACKGROUND: Dementia is among the most common chronic noncommunicable neurodegenerative diseases. In the long term, it causes disability and loss of autonomy and independence. It is estimated that there are 35.6 million people with Alzheimer's disease worldwide. Several clinical aspects of this disease have been widely studied, but the main focus of study has been memory loss, which is one of the first symptoms. The present study proposes an innovative intervention that combines cognitive training and multisite transcranial direct current stimulation, which interferes with other clinical aspects of the subject. CASE PRESENTATION: In this study, we present two subjects diagnosed with mild Alzheimer's disease. Subject 1 is an 82-year-old Brazilian Latin American woman with a high school education who was diagnosed with Alzheimer's disease 8 years ago and uses an Exelon patch. Subject 2 is an 88-year-old Brazilian Latin American woman with an incomplete primary education who was diagnosed with Alzheimer's disease 1 year ago and received medical orientation to temporarily discontinue medications for Alzheimer's disease. Both participants were subjected to intermittent cognitive training sessions and concomitant transcranial stimulation in three weekly 30-minute sessions in which a brain area was stimulated every 10 minutes for a total of 24 sessions, with a 2-month follow-up. Transcranial stimulation was applied to six different regions of the cortex: the dorsolateral prefrontal cortex bilaterally, the somatosensory association cortex bilaterally and Broca's and Wernicke's areas. Comparing the results of tests performed before and after the treatment period, a 1-point improvement was observed for both subjects on the Word Recall task of the Alzheimer Disease Assessment Scale, which evaluates symptoms related to the decline of episodic memory. Improvement in the executive functions domain was also observed through the results of the Stroop test, Victoria version. CONCLUSIONS: The results from the two presented cases show that multisite transcranial stimulation associated with cognitive training is an effective adjuvant method for the treatment of patients diagnosed with mild Alzheimer's disease. Its effects can benefit patients' daily routines by reducing cognitive deficits by keeping intact areas active and/or compensating for lost functions. Trial registration NCT02772185. Registered 13 May 2016, http://www.clinicaltrials.gov/ct2/show/NCT02772185 . Retrospectively registered.


Assuntos
Doença de Alzheimer/terapia , Cognição/fisiologia , Memória Episódica , Memória/fisiologia , Estimulação Transcraniana por Corrente Contínua , Idoso de 80 Anos ou mais , Brasil , Função Executiva , Feminino , Humanos , Resultado do Tratamento
20.
Anesthesiology ; 134(5): 734-747, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33684203

RESUMO

BACKGROUND: Anesthetics aim to prevent memory of unpleasant experiences. The amygdala and dorsal anterior cingulate cortex participate in forging emotional and valence-driven memory formation. It was hypothesized that this circuitry maintains its role under sedation. METHODS: Two nonhuman primates underwent aversive tone-odor conditioning under sedative states induced by ketamine or midazolam (1 to 8 and 0.1 to 0.8 mg/kg, respectively). The primary outcome was behavioral and neural evidence suggesting memory formation. This study simultaneously measured conditioned inspiratory changes and changes in firing rate of single neurons in the amygdala and the dorsal anterior cingulate cortex in response to an expected aversive olfactory stimulus appearing during acquisition and tested their retention after recovery. RESULTS: Aversive memory formation occurred in 26 of 59 sessions under anesthetics (16 of 29 and 10 of 30, 5 of 30 and 21 of 29 for midazolam and ketamine at low and high doses, respectively). Single-neuron responses in the amygdala and dorsal anterior cingulate cortex were positively correlated between acquisition and retention (amygdala, n = 101, r = 0.51, P < 0.001; dorsal anterior cingulate cortex, n = 121, r = 0.32, P < 0.001). Neural responses during acquisition under anesthetics were stronger in sessions exhibiting memory formation than those that did not (amygdala median response ratio, 0.52 versus 0.33, n = 101, P = 0.021; dorsal anterior cingulate cortex median response ratio, 0.48 versus 0.32, n = 121, P = 0.012). The change in firing rate of amygdala neurons during acquisition was correlated with the size of stimuli-conditioned inspiratory response during retention (n = 101, r = 0.22 P = 0.026). Thus, amygdala and dorsal anterior cingulate cortex responses during acquisition under anesthetics predicted retention. Respiratory unconditioned responses to the aversive odor anesthetics did not differ from saline controls. CONCLUSIONS: These results suggest that the amygdala-dorsal anterior cingulate cortex circuit maintains its role in acquisition and maintenance of aversive memories in nonhuman primates under sedation with ketamine and midazolam and that the stimulus valence is sufficient to drive memory formation.


Assuntos
Tonsila do Cerebelo/fisiologia , Giro do Cíngulo/fisiologia , Ketamina/administração & dosagem , Memória/fisiologia , Midazolam/administração & dosagem , Neurônios/fisiologia , Anestésicos Dissociativos/administração & dosagem , Animais , Aprendizagem da Esquiva/fisiologia , Relação Dose-Resposta a Droga , Hipnóticos e Sedativos/administração & dosagem , Macaca fascicularis , Masculino , Modelos Animais
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