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1.
Toxicol Lett ; 322: 98-103, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31954869

RESUMO

Patients intoxicated with organophosphorous compounds may need general anaesthesia to enable mechanical ventilation or for control of epileptiform seizures. It is well known that cholinergic overstimulation attenuates the efficacy of general anaesthetics to reduce spontaneous network activity in the cortex. However, it is not clear how propofol, the most frequently used intravenous anaesthetic today, is affected. Here, we investigated the effects of cholinergic overstimulation induced by soman and acetylcholine on the ability of propofol to depress spontaneous action potential activity in organotypic cortical slices measured by extracellular voltage recordings. Cholinergic overstimulation by co-application of soman and acetylcholine (10 µM each) did not reduce the relative inhibition of propofol (1.0 µM; mean normalized action potential firing rate 0.49 ± 0.06 of control condition, p < 0.001, Wilcoxon signed rank test) but clearly reduced its efficacy. Co-application of atropine (10 nM) did not improve the efficacy. Propofol preserved its relative inhibitory potential but did not produce a degree of neuronal depression which can be expected to assure hypnosis in humans. Since a combination with atropine did not improve its efficacy, an increase in dosage will probably be necessary when propofol is used in victims suffering from organophosphorous intoxication.


Assuntos
Acetilcolina/toxicidade , Potenciais de Ação/efeitos dos fármacos , Anestésicos Intravenosos/farmacologia , Rede Nervosa/efeitos dos fármacos , Propofol/farmacologia , Soman/toxicidade , Acetilcolina/administração & dosagem , Anestesia Geral , Anestésicos Intravenosos/administração & dosagem , Animais , Camundongos Endogâmicos C57BL , Neocórtex/efeitos dos fármacos , Neocórtex/fisiologia , Rede Nervosa/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Técnicas de Cultura de Órgãos , Intoxicação por Organofosfatos , Propofol/administração & dosagem , Soman/administração & dosagem
2.
Nat Commun ; 10(1): 4242, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31534123

RESUMO

Transiently storing information and mentally manipulating it is known as working memory. These operations are implemented by a distributed, fronto-parietal cognitive control network in the brain. The neural mechanisms controlling interactions within this network are yet to be determined. Here, we show that during a working memory task the brain uses an oscillatory mechanism for regulating access to prefrontal cognitive resources, dynamically controlling interactions between prefrontal cortex and remote neocortical areas. Combining EEG with non-invasive brain stimulation we show that fast rhythmical brain activity at posterior sites are nested into prefrontal slow brain waves. Depending on cognitive demand this high frequency activity is nested into different phases of the slow wave enabling dynamic coupling or de-coupling of the fronto-parietal control network adjusted to cognitive effort. This mechanism constitutes a basic principle of coordinating higher cognitive functions in the human brain.


Assuntos
Ondas Encefálicas/fisiologia , Cognição/fisiologia , Memória de Curto Prazo/fisiologia , Neocórtex/fisiologia , Córtex Pré-Frontal/fisiologia , Estimulação Encefálica Profunda/métodos , Eletroencefalografia , Feminino , Hipocampo/fisiologia , Humanos , Masculino
3.
World Neurosurg ; 132: 251-252, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520765

RESUMO

During functional-based resection under awake conditions of a left frontal isocitrate dehydrogenase-wildtype glioblastoma, the initial intralesional debulking performed to alleviate mass effect unmasked the right hemibody negative motor networks that were identified on the neocortex by direct electric stimulation. As compared with preoperative evaluation, the 3-month postoperative functional magnetic resonance imaging (MRI) confirmed unmasked cortical clusters for the right hemibody that were absent preoperatively using the same functional MRI parameters; language clusters were also better seen. The glioma-induced mass effect can mask eloquent brain areas, and surgical decompression can unmask intraoperatively eloquent brain areas.


Assuntos
Neoplasias Encefálicas/cirurgia , Procedimentos Cirúrgicos de Citorredução , Descompressão Cirúrgica , Glioblastoma/cirurgia , Linguagem , Movimento , Neocórtex/fisiologia , Adulto , Mapeamento Encefálico , Estimulação Elétrica , Feminino , Neuroimagem Funcional , Humanos , Monitorização Neurofisiológica Intraoperatória , Imagem por Ressonância Magnética , Neocórtex/diagnóstico por imagem , Procedimentos Neurocirúrgicos
4.
PLoS Biol ; 17(9): e3000419, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31483783

RESUMO

Parvalbumin (PV)-positive interneurons modulate cortical activity through highly specialized connectivity patterns onto excitatory pyramidal neurons (PNs) and other inhibitory cells. PV cells are autoconnected through powerful autapses, but the contribution of this form of fast disinhibition to cortical function is unknown. We found that autaptic transmission represents the most powerful inhibitory input of PV cells in neocortical layer V. Autaptic strength was greater than synaptic strength onto PNs as a result of a larger quantal size, whereas autaptic and heterosynaptic PV-PV synapses differed in the number of release sites. Overall, single-axon autaptic transmission contributed to approximately 40% of the global inhibition (mostly perisomatic) that PV interneurons received. The strength of autaptic transmission modulated the coupling of PV-cell firing with optogenetically induced γ-oscillations, preventing high-frequency bursts of spikes. Autaptic self-inhibition represents an exceptionally large and fast disinhibitory mechanism, favoring synchronization of PV-cell firing during cognitive-relevant cortical network activity.


Assuntos
Interneurônios/fisiologia , Neocórtex/fisiologia , Sinapses , Transmissão Sináptica , Animais , Feminino , Masculino , Camundongos Endogâmicos C57BL
5.
Nat Commun ; 10(1): 3989, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488845

RESUMO

When an action is familiar, we are able to anticipate how it will change the state of the world. These expectations can result from retrieval of action-outcome associations in the hippocampus and the reinstatement of anticipated outcomes in visual cortex. How does this role for the hippocampus in action-based prediction change over time? We use high-resolution fMRI and a dual-training behavioral paradigm to examine how the hippocampus interacts with visual cortex during predictive and nonpredictive actions learned either three days earlier or immediately before the scan. Just-learned associations led to comparable background connectivity between the hippocampus and V1/V2, regardless of whether actions predicted outcomes. However, three-day-old associations led to stronger background connectivity and greater differentiation between neural patterns for predictive vs. nonpredictive actions. Hippocampal prediction may initially reflect indiscriminate binding of co-occurring events, with action information pruning weaker associations and leading to more selective and accurate predictions over time.


Assuntos
Aprendizagem por Associação/fisiologia , Hipocampo/fisiologia , Aprendizagem/fisiologia , Neocórtex/fisiologia , Adolescente , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Memória , Lobo Temporal/fisiologia , Fatores de Tempo , Córtex Visual , Adulto Jovem
6.
Nat Commun ; 10(1): 3581, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395862

RESUMO

The bimodal requisite for a genetic program and external stimuli is a key feature of sensory circuit formation. However, the contribution of cell-intrinsic codes to directing sensory-specific circuits remains unknown. Here, we identify the earliest molecular program that preselects projection neuron types in the sensory neocortex. Mechanistically, Foxg1 binds to an H3K4me1-enriched enhancer site to repress COUP-TFI, where ectopic acquisition of Foxg1 in layer 4 cells transforms local projection neurons to callosal projection neurons with pyramidal morphologies. Removal of Foxg1 in long-range projection neurons, in turn, derepresses COUP-TFI and activates a layer 4 neuron-specific program. The earliest segregation of projection subtypes is achieved through repression of Foxg1 in layer 4 precursors by early growth response genes, the major targets of the transforming growth factor-ß signaling pathway. These findings describe the earliest cortex-intrinsic program that restricts neuronal connectivity in sensory circuits, a fundamental step towards the acquisition of mammalian perceptual behavior.


Assuntos
Regulação da Expressão Gênica/fisiologia , Neocórtex/fisiologia , Rede Nervosa/fisiologia , Neurônios/metabolismo , Percepção/fisiologia , Animais , Fator I de Transcrição COUP/metabolismo , Fatores de Transcrição de Resposta de Crescimento Precoce/metabolismo , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Masculino , Camundongos , Camundongos Knockout , Neocórtex/citologia , Rede Nervosa/citologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/metabolismo
7.
Genes Cells ; 24(10): 650-666, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442350

RESUMO

Neural progenitor cells (NPCs, also known as radial glial progenitors) produce neurons and then glial cells such as astrocytes during development of the mouse neocortex. Given that this sequential generation of neural cells is critical for proper brain formation, the neurogenic potential of NPCs must be precisely controlled. Here, we show that the transcription factor Plag1 plays an important role in the regulation of neurogenic potential in mouse neocortical NPCs. We found that Hmga2, a key neurogenic factor in neocortical NPCs, induces expression of the Plag1 gene. Analysis of the effects of over-expression or knockdown of Plag1 indicated that Plag1 promotes the production of neurons at the expense of astrocyte production in embryonic neocortical cultures. Furthermore, over-expression of Plag1 promoted and knockdown of Plag1 suppressed neuronal differentiation of neocortical NPCs in vivo. Transcriptomic analysis showed that Plag1 increases the expression of a set of neuronal genes in NPCs. Our results thus identify Plag1 as a regulator of neuronal gene expression and neuronal differentiation in NPCs of the developing mouse neocortex.


Assuntos
Proteínas de Ligação a DNA/genética , Neocórtex/fisiologia , Células-Tronco Neurais/fisiologia , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/metabolismo , Expressão Gênica , Regulação da Expressão Gênica , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Camundongos , Neocórtex/citologia , Neocórtex/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurogênese , Neurônios/citologia , Neurônios/metabolismo , Neurônios/fisiologia
8.
Nat Commun ; 10(1): 3903, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467291

RESUMO

In connectomics, the study of the network structure of connected neurons, great advances are being made on two different scales: that of macro- and meso-scale connectomics, studying the connectivity between populations of neurons, and that of micro-scale connectomics, studying connectivity between individual neurons. We combine these two complementary views of connectomics to build a first draft statistical model of the micro-connectome of a whole mouse neocortex based on available data on region-to-region connectivity and individual whole-brain axon reconstructions. This process reveals a targeting principle that allows us to predict the innervation logic of individual axons from meso-scale data. The resulting connectome recreates biological trends of targeting on all scales and predicts that an established principle of scale invariant topological organization of connectivity can be extended down to the level of individual neurons. It can serve as a powerful null model and as a substrate for whole-brain simulations.


Assuntos
Conectoma/métodos , Neocórtex/fisiologia , Animais , Encéfalo/fisiologia , Camundongos , Modelos Animais , Modelos Estatísticos , Rede Nervosa/fisiologia , Neurônios/fisiologia
9.
PLoS One ; 14(7): e0218655, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31329603

RESUMO

Primate brains differ in size and architecture. Hypotheses to explain this variation are numerous and many tests have been carried out. However, after body size has been accounted for there is little left to explain. The proposed explanatory variables for the residual variation are many and covary, both with each other and with body size. Further, the data sets used in analyses have been small, especially in light of the many proposed predictors. Here we report the complete list of models that results from exhaustively combining six commonly used predictors of brain and neocortex size. This provides an overview of how the output from standard statistical analyses changes when the inclusion of different predictors is altered. By using both the most commonly tested brain data set and the inclusion of new data we show that the choice of included variables fundamentally changes the conclusions as to what drives primate brain evolution. Our analyses thus reveal why studies have had troubles replicating earlier results and instead have come to such different conclusions. Although our results are somewhat disheartening, they highlight the importance of scientific rigor when trying to answer difficult questions. It is our position that there is currently no empirical justification to highlight any particular hypotheses, of those adaptive hypotheses we have examined here, as the main determinant of primate brain evolution.


Assuntos
Evolução Biológica , Encéfalo/fisiologia , Neocórtex/fisiologia , Primatas/fisiologia , Animais , Tamanho Corporal , Feminino , Humanos , Masculino
10.
PLoS One ; 14(7): e0218089, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269041

RESUMO

In this manuscript, we compare two commonly used methods to perform cortical mapping based on myelination of the human neocortex. T1w/T2w and R1 maps with matched total acquisition times were obtained from a young cohort in randomized order and using a test-retest design. Both methodologies showed cortical myelin maps that enhanced similar anatomical features, namely primary sensory regions known to be myelin rich. T1w/T2w maps showed increased robustness to movement artifacts in comparison to R1 maps, while the test re-test reproducibility of both methods was comparable. Based on Brodmann parcellation, both methods showed comparable variability within each region. Having parcellated cortical myelin maps into VDG11b areas of 4a, 4p, 3a, 3b, 1, 2, V2, and MT, both methods behave identically with R1 showing an increased variability between subjects. In combination with the test re-test evaluation, we concluded that this increased variability between subjects reflects relevant tissue variability. A high level of correlation was found between the R1 and T1w/T2w regions with regions of higher deviations being co-localized with those where the transmit RF field deviated most from its nominal value. We conclude that R1 mapping strategies might be preferable when studying different population cohorts where cortical properties are expected to be altered while T1w/T2w mapping will have advantages when performing cortical based segmentation.


Assuntos
Mapeamento Encefálico , Imagem por Ressonância Magnética , Bainha de Mielina/metabolismo , Neocórtex/diagnóstico por imagem , Neocórtex/fisiologia , Adulto , Feminino , Humanos , Masculino
11.
Neuron ; 103(4): 673-685.e5, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31230762

RESUMO

Autism spectrum disorder (ASD) is strongly associated with de novo gene mutations. One of the most commonly affected genes is SCN2A. ASD-associated SCN2A mutations impair the encoded protein NaV1.2, a sodium channel important for action potential initiation and propagation in developing excitatory cortical neurons. The link between an axonal sodium channel and ASD, a disorder typically attributed to synaptic or transcriptional dysfunction, is unclear. Here we show that NaV1.2 is unexpectedly critical for dendritic excitability and synaptic function in mature pyramidal neurons in addition to regulating early developmental axonal excitability. NaV1.2 loss reduced action potential backpropagation into dendrites, impairing synaptic plasticity and synaptic strength, even when NaV1.2 expression was disrupted in a cell-autonomous fashion late in development. These results reveal a novel dendritic function for NaV1.2, providing insight into cellular mechanisms probably underlying circuit and behavioral dysfunction in ASD.


Assuntos
Transtorno do Espectro Autista/genética , Dendritos/fisiologia , Canal de Sódio Disparado por Voltagem NAV1.2/fisiologia , Córtex Pré-Frontal/fisiologia , Células Piramidais/fisiologia , Potenciais de Ação , Animais , Sinalização do Cálcio , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Heterozigoto , Hipocampo/citologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Potenciais Pós-Sinápticos em Miniatura/fisiologia , N-Metilaspartato/análise , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Neocórtex/citologia , Neocórtex/crescimento & desenvolvimento , Neocórtex/fisiologia , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/crescimento & desenvolvimento , Engenharia de Proteínas , Comportamento Social , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/análise
12.
Nat Commun ; 10(1): 2478, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171779

RESUMO

During non-rapid eye movement (NREM) sleep, neuronal populations in the mammalian forebrain alternate between periods of spiking and inactivity. Termed the slow oscillation in the neocortex and sharp wave-ripples in the hippocampus, these alternations are often considered separately but are both crucial for NREM functions. By directly comparing experimental observations of naturally-sleeping rats with a mean field model of an adapting, recurrent neuronal population, we find that the neocortical alternations reflect a dynamical regime in which a stable active state is interrupted by transient inactive states (slow waves) while the hippocampal alternations reflect a stable inactive state interrupted by transient active states (sharp waves). We propose that during NREM sleep in the rodent, hippocampal and neocortical populations are excitable: each in a stable state from which internal fluctuations or external perturbation can evoke the stereotyped population events that mediate NREM functions.


Assuntos
Ondas Encefálicas/fisiologia , Hipocampo/fisiologia , Neocórtex/fisiologia , Neurônios/fisiologia , Sono de Ondas Lentas/fisiologia , Animais , Eletroencefalografia , Masculino , Modelos Neurológicos , Ratos , Sono/fisiologia , Fases do Sono/fisiologia
13.
PLoS Biol ; 17(6): e3000290, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31158216

RESUMO

Sensory experience elicits complex activity patterns throughout the neocortex. Projections from the neocortex converge onto the medial temporal lobe (MTL), in which distributed neocortical firing patterns are distilled into sparse representations. The precise nature of these neuronal representations is still unknown. Here, we show that population activity patterns in the MTL are governed by high levels of semantic abstraction. We recorded human single-unit activity in the MTL (4,917 units, 25 patients) while subjects viewed 100 images grouped into 10 semantic categories of 10 exemplars each. High levels of semantic abstraction were indicated by representational similarity analyses (RSAs) of patterns elicited by individual stimuli. Moreover, pattern classifiers trained to decode semantic categories generalised successfully to unseen exemplars, and classifiers trained to decode exemplar identity more often confused exemplars of the same versus different categories. Semantic abstraction and generalisation may thus be key to efficiently distill the essence of an experience into sparse representations in the human MTL. Although semantic abstraction is efficient and may facilitate generalisation of knowledge to novel situations, it comes at the cost of a loss of detail and may be central to the generation of false memories.


Assuntos
Memória/fisiologia , Neurônios/fisiologia , Lobo Temporal/diagnóstico por imagem , Adulto , Mapeamento Encefálico/métodos , Epilepsia/fisiopatologia , Feminino , Humanos , Conhecimento , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neocórtex/fisiologia , Estimulação Luminosa/métodos , Semântica , Análise de Célula Única/métodos , Lobo Temporal/fisiologia
14.
Front Neural Circuits ; 13: 22, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31068793

RESUMO

The neocortex is capable of anticipating the sensory results of movement but the neural mechanisms are poorly understood. In the entorhinal cortex, grid cells represent the location of an animal in its environment, and this location is updated through movement and path integration. In this paper, we propose that sensory neocortex incorporates movement using grid cell-like neurons that represent the location of sensors on an object. We describe a two-layer neural network model that uses cortical grid cells and path integration to robustly learn and recognize objects through movement and predict sensory stimuli after movement. A layer of cells consisting of several grid cell-like modules represents a location in the reference frame of a specific object. Another layer of cells which processes sensory input receives this location input as context and uses it to encode the sensory input in the object's reference frame. Sensory input causes the network to invoke previously learned locations that are consistent with the input, and motor input causes the network to update those locations. Simulations show that the model can learn hundreds of objects even when object features alone are insufficient for disambiguation. We discuss the relationship of the model to cortical circuitry and suggest that the reciprocal connections between layers 4 and 6 fit the requirements of the model. We propose that the subgranular layers of cortical columns employ grid cell-like mechanisms to represent object specific locations that are updated through movement.


Assuntos
Células de Grade/fisiologia , Modelos Neurológicos , Neocórtex/fisiologia , Percepção Visual/fisiologia , Animais , Humanos , Aprendizagem/fisiologia
15.
Elife ; 82019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-31032798

RESUMO

Most neurons do not simply convert inputs into firing rates. Instead, moment-to-moment firing rates reflect interactions between synaptic inputs and intrinsic currents. Few studies investigated how intrinsic currents function together to modulate output discharges and which of the currents attenuated by synthetic cholinergic ligands are actually modulated by endogenous acetylcholine (ACh). In this study we optogenetically stimulated cholinergic fibers in rat neocortex and find that ACh enhances excitability by reducing Ether-à-go-go Related Gene (ERG) K+ current. We find ERG mediates the late phase of spike-frequency adaptation in pyramidal cells and is recruited later than both SK and M currents. Attenuation of ERG during coincident depolarization and ACh release leads to reduced late phase spike-frequency adaptation and persistent firing. In neuronal ensembles, attenuating ERG enhanced signal-to-noise ratios and reduced signal correlation, suggesting that these two hallmarks of cholinergic function in vivo may result from modulation of intrinsic properties.


Assuntos
Acetilcolina/fisiologia , Adaptação Fisiológica , Canais de Potássio Éter-A-Go-Go/fisiologia , Neocórtex/fisiologia , Potenciais de Ação/fisiologia , Animais , Canais de Potássio Éter-A-Go-Go/efeitos dos fármacos , Feminino , Cinética , Masculino , Potenciais da Membrana , Neurônios , Bloqueadores dos Canais de Potássio/farmacologia , Células Piramidais/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/metabolismo
16.
Nat Commun ; 10(1): 1907, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015423

RESUMO

Transforming the barrage of sensory signals into a coherent multisensory percept relies on solving the binding problem - deciding whether signals come from a common cause and should be integrated or, instead, segregated. Human observers typically arbitrate between integration and segregation consistent with Bayesian Causal Inference, but the neural mechanisms remain poorly understood. Here, we presented people with audiovisual sequences that varied in the number of flashes and beeps, then combined Bayesian modelling and EEG representational similarity analyses. Our data suggest that the brain initially represents the number of flashes and beeps independently. Later, it computes their numbers by averaging the forced-fusion and segregation estimates weighted by the probabilities of common and independent cause models (i.e. model averaging). Crucially, prestimulus oscillatory alpha power and phase correlate with observers' prior beliefs about the world's causal structure that guide their arbitration between sensory integration and segregation.


Assuntos
Percepção Auditiva/fisiologia , Modelos Neurológicos , Neocórtex/fisiologia , Sensação/fisiologia , Percepção Visual/fisiologia , Estimulação Acústica , Adulto , Teorema de Bayes , Sinais (Psicologia) , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neocórtex/anatomia & histologia , Estimulação Luminosa
17.
Nat Commun ; 10(1): 1225, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30874549

RESUMO

Although cortical interneurons are apparently well-placed to suppress seizures, several recent reports have highlighted a paradoxical role of perisomatic-targeting parvalbumin-positive (PV+) interneurons in ictogenesis. Here, we use an acute in vivo model of focal cortical seizures in awake behaving mice, together with closed-loop optogenetic manipulation of PV+ interneurons, to investigate their function during seizures. We show that photo-depolarization of PV+ interneurons rapidly switches from an anti-ictal to a pro-ictal effect within a few seconds of seizure initiation. The pro-ictal effect of delayed photostimulation of PV+ interneurons was not shared with dendrite-targeting somatostatin-positive (SOM+) interneurons. We also show that this switch can be prevented by overexpression of the neuronal potassium-chloride co-transporter KCC2 in principal cortical neurons. These results suggest that strategies aimed at improving the ability of principal neurons to maintain a trans-membrane chloride gradient in the face of excessive network activity can prevent interneurons from contributing to seizure perpetuation.


Assuntos
Interneurônios/fisiologia , Neocórtex/fisiologia , Inibição Neural/fisiologia , Convulsões/fisiopatologia , Simportadores/metabolismo , Animais , Cloretos/metabolismo , Modelos Animais de Doenças , Eletrocorticografia , Eletrodos , Feminino , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Lentivirus/genética , Masculino , Camundongos , Neocórtex/citologia , Vias Neurais/fisiologia , Optogenética/instrumentação , Optogenética/métodos , Parvalbuminas/metabolismo , Técnicas de Patch-Clamp , Estimulação Luminosa , Convulsões/diagnóstico , Somatostatina/metabolismo , Simportadores/genética
18.
Science ; 363(6430): 975-978, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30819961

RESUMO

Episodic memory retrieval relies on the recovery of neural representations of waking experience. This process is thought to involve a communication dynamic between the medial temporal lobe memory system and the neocortex. How this occurs is largely unknown, however, especially as it pertains to awake human memory retrieval. Using intracranial electroencephalographic recordings, we found that ripple oscillations were dynamically coupled between the human medial temporal lobe (MTL) and temporal association cortex. Coupled ripples were more pronounced during successful verbal memory retrieval and recover the cortical neural representations of remembered items. Together, these data provide direct evidence that coupled ripples between the MTL and association cortex may underlie successful memory retrieval in the human brain.


Assuntos
Memória Episódica , Rememoração Mental , Neocórtex/fisiologia , Lobo Temporal/fisiologia , Adulto , Mapeamento Encefálico , Epilepsia Resistente a Medicamentos , Eletrocorticografia , Eletrodos , Feminino , Humanos , Masculino , Testes de Memória e Aprendizagem
19.
PLoS Genet ; 15(2): e1007890, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30726206

RESUMO

During CNS development, the nuclear protein SATB2 is expressed in superficial cortical layers and determines projection neuron identity. In the adult CNS, SATB2 is expressed in pyramidal neurons of all cortical layers and is a regulator of synaptic plasticity and long-term memory. Common variation in SATB2 locus confers risk of schizophrenia, whereas rare, de novo structural and single nucleotide variants cause severe intellectual disability and absent or limited speech. To characterize differences in SATB2 molecular function in developing vs adult neocortex, we isolated SATB2 protein interactomes at the two ontogenetic stages and identified multiple novel SATB2 interactors. SATB2 interactomes are highly enriched for proteins that stabilize de novo chromatin loops. The comparison between the neonatal and adult SATB2 protein complexes indicates a developmental shift in SATB2 molecular function, from transcriptional repression towards organization of chromosomal superstructure. Accordingly, gene sets regulated by SATB2 in the neocortex of neonatal and adult mice show limited overlap. Genes encoding SATB2 protein interactors were grouped for gene set analysis of human GWAS data. Common variants associated with human cognitive ability are enriched within the genes encoding adult but not neonatal SATB2 interactors. Our data support a shift in the function of SATB2 in cortex over lifetime and indicate that regulation of spatial chromatin architecture by the SATB2 interactome contributes to cognitive function in the general population.


Assuntos
Cognição/fisiologia , Proteínas de Ligação à Região de Interação com a Matriz/genética , Neocórtex/fisiologia , Fatores de Transcrição/genética , Adulto , Animais , Humanos , Memória de Longo Prazo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Transcrição Genética/genética
20.
Neurosci Biobehav Rev ; 100: 77-84, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30790633

RESUMO

According to traditional systems consolidation theories neocortical long-term plasticity (i.e., cellular consolidation) lags behind, and is dependent upon, hippocampal long-term plasticity. In this review, we examine accumulating evidence that local neocortical and hippocampal cellular consolidation occurs with a similar time-course. The implication is that the rate-limiting step for systems consolidation is the time it takes for cellular consolidation in longer connections throughout a more distributed extra-hippocampal system that comes to coordinate distributed neocortical activity during recall. The hippocampus is, thus, crucial for the development of this extra-hippocampal coordinating system, and acts to coordinate activities crucial for recall until it develops. Recent work on schema formation, engram cells, and the role of sleep in consolidation add substantial evidence for this "unified theory" of systems and cellular consolidation. Here, we discuss this evidence, its implications, and consider remaining questions.


Assuntos
Hipocampo/fisiologia , Consolidação da Memória/fisiologia , Modelos Neurológicos , Neocórtex/fisiologia , Animais , Humanos , Vias Neurais/fisiologia , Sono
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