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1.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807989

RESUMO

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility-partial deletion of the MAP6 gene, early-life stress-maternal separation, and pharmacological treatment-chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABAA receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.


Assuntos
Região CA1 Hipocampal/fisiopatologia , Potenciação de Longa Duração , Esquizofrenia/fisiopatologia , Transmissão Sináptica , Ritmo Teta , Animais , Região CA1 Hipocampal/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Mutantes , Esquizofrenia/genética , Esquizofrenia/patologia
2.
Neuron ; 109(6): 1029-1039.e8, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33567253

RESUMO

The theta rhythm organizes neural activity across hippocampus and entorhinal cortex. A role for theta oscillations in spatial navigation is supported by half a century of research reporting that theta frequency encodes running speed linearly so that displacement can be estimated through theta frequency integration. We show that this relationship is an artifact caused by the fact that the speed of freely moving animals could not be systematically disentangled from acceleration. Using an experimental procedure that clamps running speed at pre-set values, we find that the theta frequency of local field potentials and spike activity is linearly related to positive acceleration, but not negative acceleration or speed. The modulation by positive-only acceleration makes rhythmic activity at theta frequency unfit as a code to compute displacement or any other kinematic variable. Temporally precise variations in theta frequency may instead serve as a mechanism for speeding up entorhinal-hippocampal computations during accelerated movement.


Assuntos
Aceleração , Córtex Entorrinal/fisiologia , Hipocampo/fisiologia , Navegação Espacial/fisiologia , Ritmo Teta/fisiologia , Animais , Artefatos , Células de Grade/fisiologia , Masculino , Ratos , Ratos Long-Evans , Corrida/fisiologia
3.
Nat Commun ; 12(1): 253, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431847

RESUMO

Grid cells are part of a widespread network which supports navigation and spatial memory. Stable grid patterns appear late in development, in concert with extracellular matrix aggregates termed perineuronal nets (PNNs) that condense around inhibitory neurons. It has been suggested that PNNs stabilize synaptic connections and long-term memories, but their role in the grid cell network remains elusive. We show that removal of PNNs leads to lower inhibitory spiking activity, and reduces grid cells' ability to create stable representations of a novel environment. Furthermore, in animals with disrupted PNNs, exposure to a novel arena corrupted the spatiotemporal relationships within grid cell modules, and the stored representations of a familiar arena. Finally, we show that PNN removal in entorhinal cortex distorted spatial representations in downstream hippocampal neurons. Together this work suggests that PNNs provide a key stabilizing element for the grid cell network.


Assuntos
Células de Grade/citologia , Neurônios/citologia , Potenciais de Ação/fisiologia , Animais , Simulação por Computador , Córtex Entorrinal/citologia , Hipocampo/fisiologia , Masculino , Modelos Neurológicos , Ratos Long-Evans , Ritmo Teta/fisiologia , Fatores de Tempo
4.
Nat Commun ; 12(1): 413, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462202

RESUMO

Long-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA is activated, results in LTP that is associated with a transient increase in γ (LTPγ), caused by the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII is necessary and sufficient for LTPN whilst PKA is additionally required for LTPγ. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.


Assuntos
Região CA1 Hipocampal/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciação de Longa Duração/fisiologia , Receptores de AMPA/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Masculino , Memória de Longo Prazo/fisiologia , Técnicas de Patch-Clamp , Ratos , Ritmo Teta/fisiologia
5.
J Neurosci ; 41(7): 1505-1515, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33310755

RESUMO

Integrating information across different senses is a central feature of human perception. Previous research suggests that multisensory integration is shaped by a context-dependent and largely adaptive interplay between stimulus-driven bottom-up and top-down endogenous influences. One critical question concerns the extent to which this interplay is sensitive to the amount of available cognitive resources. In the present study, we investigated the influence of limited cognitive resources on audiovisual integration by measuring high-density electroencephalography (EEG) in healthy participants performing the sound-induced flash illusion (SIFI) and a verbal n-back task (0-back, low load and 2-back, high load) in a dual-task design. In the SIFI, the integration of a flash with two rapid beeps can induce the illusory perception of two flashes. We found that high compared with low load increased illusion susceptibility and modulated neural oscillations underlying illusion-related crossmodal interactions. Illusion perception under high load was associated with reduced early ß power (18-26 Hz, ∼70 ms) in auditory and motor areas, presumably reflecting an early mismatch signal and subsequent top-down influences including increased frontal θ power (7-9 Hz, ∼120 ms) in mid-anterior cingulate cortex (ACC) and a later ß power suppression (13-22 Hz, ∼350 ms) in prefrontal and auditory cortex. Our study demonstrates that integrative crossmodal interactions underlying the SIFI are sensitive to the amount of available cognitive resources and that multisensory integration engages top-down θ and ß oscillations when cognitive resources are scarce.SIGNIFICANCE STATEMENT The integration of information across multiple senses, a remarkable ability of our perceptual system, is influenced by multiple context-related factors, the role of which is highly debated. It is, for instance, poorly understood how available cognitive resources influence crossmodal interactions during multisensory integration. We addressed this question using the sound-induced flash illusion (SIFI), a phenomenon in which the integration of two rapid beeps together with a flash induces the illusion of a second flash. Replicating our previous work, we demonstrate that depletion of cognitive resources through a working memory (WM) task increases the perception of the illusion. With respect to the underlying neural processes, we show that when available resources are limited, multisensory integration engages top-down θ and ß oscillations.


Assuntos
Memória/fisiologia , Neurônios/fisiologia , Percepção/fisiologia , Sensação/fisiologia , Estimulação Acústica , Adulto , Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Ritmo beta/fisiologia , Eletroencefalografia , Feminino , Humanos , Ilusões , Masculino , Memória de Curto Prazo/fisiologia , Estimulação Luminosa , Córtex Pré-Frontal/fisiologia , Tempo de Reação/fisiologia , Ritmo Teta/fisiologia , Percepção Visual/fisiologia , Adulto Jovem
6.
J Neurosci ; 41(7): 1516-1528, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33310756

RESUMO

In recent years, several hierarchical extensions of well-known learning algorithms have been proposed. For example, when stimulus-action mappings vary across time or context, the brain may learn two or more stimulus-action mappings in separate modules, and additionally (at a hierarchically higher level) learn to appropriately switch between those modules. However, how the brain mechanistically coordinates neural communication to implement such hierarchical learning remains unknown. Therefore, the current study tests a recent computational model that proposed how midfrontal theta oscillations implement such hierarchical learning via the principle of binding by synchrony (Sync model). More specifically, the Sync model uses bursts at theta frequency to flexibly bind appropriate task modules by synchrony. The 64-channel EEG signal was recorded while 27 human subjects (female: 21, male: 6) performed a probabilistic reversal learning task. In line with the Sync model, postfeedback theta power showed a linear relationship with negative prediction errors, but not with positive prediction errors. This relationship was especially pronounced for subjects with better behavioral fit (measured via Akaike information criterion) of the Sync model. Also consistent with Sync model simulations, theta phase-coupling between midfrontal electrodes and temporoparietal electrodes was stronger after negative feedback. Our data suggest that the brain uses theta power and synchronization for flexibly switching between task rule modules, as is useful, for example, when multiple stimulus-action mappings must be retained and used.SIGNIFICANCE STATEMENT Everyday life requires flexibility in switching between several rules. A key question in understanding this ability is how the brain mechanistically coordinates such switches. The current study tests a recent computational framework (Sync model) that proposed how midfrontal theta oscillations coordinate activity in hierarchically lower task-related areas. In line with predictions of this Sync model, midfrontal theta power was stronger when rule switches were most likely (strong negative prediction error), especially in subjects who obtained a better model fit. Additionally, also theta phase connectivity between midfrontal and task-related areas was increased after negative feedback. Thus, the data provided support for the hypothesis that the brain uses theta power and synchronization for flexibly switching between rules.


Assuntos
Aprendizagem/fisiologia , Ritmo Teta/fisiologia , Adulto , Algoritmos , Cognição/fisiologia , Simulação por Computador , Eletroencefalografia , Retroalimentação Psicológica/fisiologia , Feminino , Lobo Frontal/fisiologia , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Reversão de Aprendizagem/fisiologia , Adulto Jovem
7.
Science ; 370(6513): 247-250, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033222

RESUMO

Neural networks display the ability to transform forward-ordered activity patterns into reverse-ordered, retrospective sequences. The mechanisms underlying this transformation remain unknown. We discovered that, during active navigation, rat hippocampal CA1 place cell ensembles are inherently organized to produce independent forward- and reverse-ordered sequences within individual theta oscillations. This finding may provide a circuit-level basis for retrospective evaluation and storage during ongoing behavior. Theta phase procession arose in a minority of place cells, many of which displayed two preferred firing phases in theta oscillations and preferentially participated in reverse replay during subsequent rest. These findings reveal an unexpected aspect of theta-based hippocampal encoding and provide a biological mechanism to support the expression of reverse-ordered sequences.


Assuntos
Adaptação Psicológica/fisiologia , Região CA1 Hipocampal/fisiologia , Ritmo Teta , Animais , Masculino , Ratos , Ratos Endogâmicos LEC
8.
PLoS One ; 15(9): e0233942, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32937652

RESUMO

Age-related changes in the human brain functioning crucially affect the motor system, causing increased reaction time, low ability to control and execute movements, difficulties in learning new motor skills. The lifestyle and lowered daily activity of elderly adults, along with the deficit of motor and cognitive brain functions, might lead to the developed ambidexterity, i.e., the loss of dominant limb advances. Despite the broad knowledge about the changes in cortical activity directly related to the motor execution, less is known about age-related differences in the motor initiation phase. We hypothesize that the latter strongly influences the behavioral characteristics, such as reaction time, the accuracy of motor performance, etc. Here, we compare the neuronal processes underlying the motor initiation phase preceding fine motor task execution between elderly and young subjects. Based on the results of the whole-scalp sensor-level electroencephalography (EEG) analysis, we demonstrate that the age-related slowing down in the motor initiation before the dominant hand movements is accompanied by the increased theta activation within sensorimotor area and reconfiguration of the theta-band functional connectivity in elderly adults.


Assuntos
Envelhecimento/fisiologia , Cognição/fisiologia , Atividade Motora , Desempenho Psicomotor , Tempo de Reação , Adulto , Idoso , Mapeamento Encefálico , Eletroencefalografia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Sensório-Motor/fisiologia , Ritmo Teta , Adulto Jovem
9.
PLoS Biol ; 18(8): e3000851, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32822389

RESUMO

High levels of the amyloid-beta (Aß) peptide have been shown to disrupt neuronal function and induce hyperexcitability, but it is unclear what effects Aß-associated hyperexcitability may have on tauopathy pathogenesis or propagation in vivo. Using a novel transgenic mouse line to model the impact of human APP (hAPP)/Aß accumulation on tauopathy in the entorhinal cortex-hippocampal (EC-HIPP) network, we demonstrate that hAPP overexpression aggravates EC-Tau aggregation and accelerates pathological tau spread into the hippocampus. In vivo recordings revealed a strong role for hAPP/Aß, but not tau, in the emergence of EC neuronal hyperactivity and impaired theta rhythmicity. Chronic chemogenetic attenuation of EC neuronal hyperactivity led to reduced hAPP/Aß accumulation and reduced pathological tau spread into downstream hippocampus. These data strongly support the hypothesis that in Alzheimer's disease (AD), Aß-associated hyperactivity accelerates the progression of pathological tau along vulnerable neuronal circuits, and demonstrates the utility of chronic, neuromodulatory approaches in ameliorating AD pathology in vivo.


Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Córtex Entorrinal/metabolismo , Tauopatias/genética , Proteínas tau/genética , Potenciais de Ação/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/terapia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Dependovirus/genética , Dependovirus/metabolismo , Modelos Animais de Doenças , Eletrodos Implantados , Córtex Entorrinal/patologia , Feminino , Regulação da Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo , Neurônios/patologia , Agregados Proteicos , Técnicas Estereotáxicas , Tauopatias/metabolismo , Tauopatias/patologia , Tauopatias/terapia , Ritmo Teta/fisiologia , Transdução Genética , Transgenes , Proteínas tau/metabolismo
10.
Nat Commun ; 11(1): 3117, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561726

RESUMO

On-line comprehension of natural speech requires segmenting the acoustic stream into discrete linguistic elements. This process is argued to rely on theta-gamma oscillation coupling, which can parse syllables and encode them in decipherable neural activity. Speech comprehension also strongly depends on contextual cues that help predicting speech structure and content. To explore the effects of theta-gamma coupling on bottom-up/top-down dynamics during on-line syllable identification, we designed a computational model (Precoss-predictive coding and oscillations for speech) that can recognise syllable sequences in continuous speech. The model uses predictions from internal spectro-temporal representations of syllables and theta oscillations to signal syllable onsets and duration. Syllable recognition is best when theta-gamma coupling is used to temporally align spectro-temporal predictions with the acoustic input. This neurocomputational modelling work demonstrates that the notions of predictive coding and neural oscillations can be brought together to account for on-line dynamic sensory processing.


Assuntos
Córtex Auditivo/fisiologia , Ritmo Gama/fisiologia , Modelos Neurológicos , Percepção da Fala/fisiologia , Ritmo Teta/fisiologia , Estimulação Acústica , Compreensão/fisiologia , Simulação por Computador , Sinais (Psicologia) , Humanos , Fonética
11.
Nat Neurosci ; 23(8): 992-1003, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32572235

RESUMO

Basal forebrain cholinergic neurons (BFCNs) modulate synaptic plasticity, cortical processing, brain states and oscillations. However, whether distinct types of BFCNs support different functions remains unclear. Therefore, we recorded BFCNs in vivo, to examine their behavioral functions, and in vitro, to study their intrinsic properties. We identified two distinct types of BFCNs that differ in their firing modes, synchronization properties and behavioral correlates. Bursting cholinergic neurons (Burst-BFCNs) fired synchronously, phase-locked to cortical theta activity and fired precisely timed bursts after reward and punishment. Regular-firing cholinergic neurons (Reg-BFCNs) were found predominantly in the posterior basal forebrain, displayed strong theta rhythmicity and responded with precise single spikes after behavioral outcomes. In an auditory detection task, synchronization of Burst-BFCNs to the auditory cortex predicted the timing of behavioral responses, whereas tone-evoked cortical coupling of Reg-BFCNs predicted correct detections. We propose that differential recruitment of two basal forebrain cholinergic neuron types generates behavior-specific cortical activation.


Assuntos
Prosencéfalo Basal/fisiologia , Neurônios Colinérgicos/fisiologia , Sincronização Cortical/fisiologia , Potenciais de Ação/fisiologia , Animais , Córtex Auditivo/fisiologia , Camundongos , Plasticidade Neuronal/fisiologia , Ritmo Teta/fisiologia
12.
Neuron ; 107(4): 731-744.e3, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32526196

RESUMO

Hippocampal theta oscillations coordinate neuronal firing to support memory and spatial navigation. The medial septum (MS) is critical in theta generation by two possible mechanisms: either a unitary "pacemaker" timing signal is imposed on the hippocampal system, or it may assist in organizing target subcircuits within the phase space of theta oscillations. We used temperature manipulation of the MS to test these models. Cooling of the MS reduced both theta frequency and power and was associated with an enhanced incidence of errors in a spatial navigation task, but it did not affect spatial correlates of neurons. MS cooling decreased theta frequency oscillations of place cells and reduced distance-time compression but preserved distance-phase compression of place field sequences within the theta cycle. Thus, the septum is critical for sustaining precise theta phase coordination of cell assemblies in the hippocampal system, a mechanism needed for spatial memory.


Assuntos
Hipocampo/fisiologia , Neurônios/fisiologia , Núcleos Septais/fisiologia , Memória Espacial/fisiologia , Ritmo Teta/fisiologia , Potenciais de Ação/fisiologia , Animais , Temperatura Baixa , Masculino , Modelos Neurológicos , Células de Lugar/fisiologia , Ratos , Ratos Long-Evans
13.
Neuron ; 107(3): 552-565.e10, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502462

RESUMO

The occurrence of dreaming during rapid eye movement (REM) sleep prompts interest in the role of REM sleep in hippocampal-dependent episodic memory. Within the mammalian hippocampus, the dentate gyrus (DG) has the unique characteristic of exhibiting neurogenesis persisting into adulthood. Despite their small numbers and sparse activity, adult-born neurons (ABNs) in the DG play critical roles in memory; however, their memory function during sleep is unknown. Here, we investigate whether young ABN activity contributes to memory consolidation during sleep using Ca2+ imaging in freely moving mice. We found that contextual fear learning recruits a population of young ABNs that are reactivated during subsequent REM sleep against a backdrop of overall reduced ABN activity. Optogenetic silencing of this sparse ABN activity during REM sleep alters the structural remodeling of spines on ABN dendrites and impairs memory consolidation. These findings provide a causal link between ABN activity during REM sleep and memory consolidation.


Assuntos
Condicionamento Psicológico , Giro Denteado/fisiologia , Consolidação da Memória/fisiologia , Neurônios/fisiologia , Sono REM/fisiologia , Animais , Cálcio/metabolismo , Giro Denteado/citologia , Eletroencefalografia , Eletromiografia , Medo , Hipocampo , Aprendizagem , Camundongos , Neurogênese , Optogenética , Ritmo Teta
14.
J Vis Exp ; (159)2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32449716

RESUMO

Although there has been recent interest in how mindfulness meditation can affect episodic memory as well as brain structure and function, no study has examined the behavioral and neural effects of mindfulness meditation on episodic memory. Here we present a protocol that combines mindfulness meditation training, an episodic memory task, and EEG to examine how mindfulness meditation changes behavioral performance and the neural correlates of episodic memory. Subjects in a mindfulness meditation experimental group were compared to a waitlist control group. Subjects in the mindfulness meditation experimental group spent four weeks training and practicing mindfulness meditation. Mindfulness was measured before and after training using the Five Facet Mindfulness Questionnaire (FFMQ). Episodic memory was measured before and after training using a source recognition task. During the retrieval phase of the source recognition task, EEG was recorded. The results showed that mindfulness, source recognition behavioral performance, and EEG theta power in right frontal and left parietal channels increased following mindfulness meditation training. In addition, increases in mindfulness correlated with increases in theta power in right frontal channels. Therefore, results obtained from combining mindfulness meditation training, an episodic memory task, and EEG reveal the behavioral and neural effects of mindfulness meditation on episodic memory.


Assuntos
Comportamento , Eletroencefalografia , Meditação , Memória Episódica , Atenção Plena , Adulto , Encéfalo/fisiologia , Feminino , Humanos , Masculino , Inquéritos e Questionários , Ritmo Teta/fisiologia , Adulto Jovem
15.
Nat Commun ; 11(1): 2469, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424312

RESUMO

Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4-10 Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta's function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior-posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3 Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes.


Assuntos
Hipocampo/fisiologia , Ritmo Teta/fisiologia , Adulto , Eletrodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Memória Espacial/fisiologia , Análise e Desempenho de Tarefas , Adulto Jovem
16.
Cell Physiol Biochem ; 54(3): 493-507, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32415763

RESUMO

BACKGROUND/AIMS: Status epilepticus (SE) might be followed by temporal lobe epilepsy (TLE), a common neurologic disorder characterized by spontaneous recurrent seizures (SRSs). However, the relationship between SE and TLE is still incompletely characterized. For this reason, in a model of TLE we evaluated the lesion extent and the onset of SRSs to determine if they were influenced by the SE dynamics. METHODS: Sixty-two adult male Sprague-Dawley rats were implanted for video-electrocorticographic (v-ECoG) monitoring and intraperitoneally treated with saline or kainic acid (KA, 15 mg/kg) at 8 weeks of age. v-ECoG recordings were obtained during SE, in the following 9 weeks, and assessed by amplitude or power band spectrum. Rats were euthanized 3 or 64 days after SE to evaluate the lesion. RESULTS: SE lasted about 10 h during which the mean duration of convulsive seizures (CSs) increased from 39 s, at 30 min, to 603 s at 4 h. The gamma power peaked 30 min after the SE onset and its peak was correlated (r²=0.13, p=0.042) with the overall SE duration. Subsequently, the gamma power was reduced under the baseline until the end of SE. The theta power increased at approximately 150% of basal levels 3 h after KA injection, but it went back to basal levels with the full development of CSs. Interestingly, the timing of the first SRS in chronic epilepsy was correlated with the latency to develop the first CS with loss of posture during SE (r²=0.60, p<0.001). Additionally, the overall duration of CSs observed during SE was related to the number of damaged brain regions (r²=0.60, p=0.005), but it did not influence the timing of the first SRS in chronic epilepsy. CONCLUSION: Overall, our results show that the onset of chronic epilepsy is modulated by SE dynamics, whereas brain damage is related to prolonged convulsions in SE.


Assuntos
Encéfalo/patologia , Epilepsia do Lobo Temporal/patologia , Convulsões/patologia , Estado Epiléptico/patologia , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Morte Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia do Lobo Temporal/induzido quimicamente , Ritmo Gama/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Ácido Caínico , Masculino , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Estado Epiléptico/induzido quimicamente , Ritmo Teta/efeitos dos fármacos
17.
Nat Commun ; 11(1): 2217, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32371879

RESUMO

Theta oscillations play a major role in temporarily defining the hippocampal rate code by translating behavioral sequences into neuronal representations. However, mechanisms constraining phase timing and cell-type-specific phase preference are unknown. Here, we employ computational models tuned with evolutionary algorithms to evaluate phase preference of individual CA1 pyramidal cells recorded in mice and rats not engaged in any particular memory task. We applied unbiased and hypothesis-free approaches to identify effects of intrinsic and synaptic factors, as well as cell morphology, in determining phase preference. We found that perisomatic inhibition delivered by complementary populations of basket cells interacts with input pathways to shape phase-locked specificity of deep and superficial pyramidal cells. Somatodendritic integration of fluctuating glutamatergic inputs defined cycle-by-cycle by unsupervised methods demonstrated that firing selection is tuneable across sublayers. Our data identify different mechanisms of phase-locking selectivity that are instrumental for flexible dynamical representations of theta sequences.


Assuntos
Região CA1 Hipocampal/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia , Ritmo Teta/fisiologia , Potenciais de Ação/fisiologia , Algoritmos , Animais , Região CA1 Hipocampal/citologia , Simulação por Computador , Feminino , Cinética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Neurológicos , Técnicas de Patch-Clamp , Células Piramidais/fisiologia , Ratos Wistar
18.
Proc Natl Acad Sci U S A ; 117(23): 12729-12740, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32457143

RESUMO

Prior functional magnetic resonance imaging (fMRI) studies indicate that a core network of brain regions, including the hippocampus, is jointly recruited during episodic memory, episodic simulation, and divergent creative thinking. Because fMRI data are correlational, it is unknown whether activity increases in the hippocampus, and the core network more broadly, play a causal role in episodic simulation and divergent thinking. Here we employed fMRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of hippocampal brain networks impairs both episodic simulation and divergent thinking. For each of two TMS sessions, continuous θ-burst stimulation (cTBS) was applied to either a control site (vertex) or to a left angular gyrus target region. The target region was identified on the basis of a participant-specific resting-state functional connectivity analysis with a hippocampal seed region previously associated with memory, simulation, and divergent thinking. Following cTBS, participants underwent fMRI and performed a simulation, divergent thinking, and nonepisodic control task. cTBS to the target region reduced the number of episodic details produced for the simulation task and reduced idea production on divergent thinking. Performance in the control task did not statistically differ as a function of cTBS site. fMRI analyses revealed a selective and simultaneous reduction in hippocampal activity during episodic simulation and divergent thinking following cTBS to the angular gyrus versus vertex but not during the nonepisodic control task. Our findings provide evidence that hippocampal-targeted TMS can specifically modulate episodic simulation and divergent thinking, and suggest that the hippocampus is critical for these cognitive functions.


Assuntos
Conectoma , Hipocampo/fisiologia , Memória Episódica , Pensamento , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Ritmo Teta , Estimulação Magnética Transcraniana
20.
Brain Stimul ; 13(3): 554-561, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32289676

RESUMO

BACKGROUND: Chronic orofacial pain (COP) patients often perceive the painful face area as "swollen" without clinical signs; such self-reported illusions of the face are termed perceptual distortion (PD). The pathophysiological mechanisms underlying PD remain elusive. OBJECTIVE: To test the neuromodulatory effect of repetitive transcranial magnetic stimulation (rTMS) on PD in healthy individuals, to gain insight into the cortical mechanisms underlying PD. METHODS: PD was induced experimentally by injections of local anesthetic (LA) around the infraorbital nerve and measured as perceived size changes of the affected area. Participants were randomly allocated to inhibitory rTMS (n = 26) or sham rTMS (n = 26) group. The participants rated PD at baseline, 6 min after LA, immediately, 20 and 40 min after rTMS. The rTMS (inhibitory and sham) was applied to face (lip) representation area of primary somatosensory cortex (SI) as an intervention at 10 min after the LA, when the magnitude of PD is large. As inhibitory rTMS, continuous theta-burst stimulation paradigm (50 Hz) for 40s was employed to inhibit cortical activity. RESULTS: We demonstrated a significant decrease in the magnitude of PD immediately and 20 min after the application of inhibitory rTMS compared with sham rTMS (P < 0.006). In two control experiments, we also showed that peripheral muscle stimulation and stimulation of a cortical region other than the lip representation area had no effect on the magnitude of the PD. CONCLUSIONS: Inhibitory rTMS applied to a somatotopical-relevant cortical region modulates PD of the face in healthy individuals and could potentially have therapeutic implications for COP patients.


Assuntos
Dor Facial/terapia , Transtornos da Percepção/terapia , Distorção da Percepção , Estimulação Magnética Transcraniana/métodos , Adulto , Nervo Facial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ritmo Teta
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