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1.
Nature ; 585(7824): 245-250, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32884146

RESUMO

Adaptive behaviour crucially depends on flexible decision-making, which in mammals relies on the frontal cortex, specifically the orbitofrontal cortex (OFC)1-9. How OFC encodes decision variables and instructs sensory areas to guide adaptive behaviour are key open questions. Here we developed a reversal learning task for head-fixed mice, monitored the activity of neurons of the lateral OFC using two-photon calcium imaging and investigated how OFC dynamically interacts with primary somatosensory cortex (S1). Mice learned to discriminate 'go' from 'no-go' tactile stimuli10,11 and adapt their behaviour upon reversal of stimulus-reward contingency ('rule switch'). Imaging individual neurons longitudinally across all behavioural phases revealed a distinct engagement of S1 and lateral OFC, with S1 neural activity reflecting initial task learning, whereas lateral OFC neurons responded saliently and transiently to the rule switch. We identified direct long-range projections from lateral OFC to S1 that can feed this activity back to S1 as value prediction error. This top-down signal updated sensory representations in S1 by functionally remapping responses in a subpopulation of neurons that was sensitive to reward history. Functional remapping crucially depended on top-down feedback as chemogenetic silencing of lateral OFC neurons disrupted reversal learning, as well as plasticity in S1. The dynamic interaction of lateral OFC with sensory cortex thus implements computations critical for value prediction that are history dependent and error based, providing plasticity essential for flexible decision-making.


Assuntos
Plasticidade Neuronal/fisiologia , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Reversão de Aprendizagem/fisiologia , Córtex Somatossensorial/citologia , Córtex Somatossensorial/fisiologia , Percepção do Tato/fisiologia , Adaptação Psicológica , Animais , Mapeamento Encefálico , Sinalização do Cálcio , Tomada de Decisões/fisiologia , Discriminação Psicológica/fisiologia , Masculino , Camundongos , Estimulação Física , Células Receptoras Sensoriais/metabolismo
2.
Nat Commun ; 11(1): 4819, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968048

RESUMO

In many parts of the nervous system, experience-dependent refinement of neuronal circuits predominantly involves synapse elimination. The role of sleep in this process remains unknown. We investigated the role of sleep in experience-dependent dendritic spine elimination of layer 5 pyramidal neurons in the visual (V1) and frontal association cortex (FrA) of 1-month-old mice. We found that monocular deprivation (MD) or auditory-cued fear conditioning (FC) caused rapid spine elimination in V1 or FrA, respectively. MD- or FC-induced spine elimination was significantly reduced after total sleep or REM sleep deprivation. Total sleep or REM sleep deprivation also prevented MD- and FC-induced reduction of neuronal activity in response to visual or conditioned auditory stimuli. Furthermore, dendritic calcium spikes increased substantially during REM sleep, and the blockade of these calcium spikes prevented MD- and FC-induced spine elimination. These findings reveal an important role of REM sleep in experience-dependent synapse elimination and neuronal activity reduction.


Assuntos
Córtex Cerebral/fisiologia , Espinhas Dendríticas/fisiologia , Sono REM/fisiologia , Animais , Condicionamento Clássico , Medo/fisiologia , Camundongos , Camundongos Transgênicos , Modelos Animais , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Células Piramidais/fisiologia , Privação Sensorial/fisiologia , Privação do Sono , Sinapses , Córtex Visual/fisiologia
3.
PLoS One ; 15(9): e0238454, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966302

RESUMO

In this work, we present a local intrinsic rule that we developed, dubbed IP, inspired by the Infomax rule. Like Infomax, this rule works by controlling the gain and bias of a neuron to regulate its rate of fire. We discuss the biological plausibility of the IP rule and compare it to batch normalisation. We demonstrate that the IP rule improves learning in deep networks, and provides networks with considerable robustness to increases in synaptic learning rates. We also sample the error gradients during learning and show that the IP rule substantially increases the size of the gradients over the course of learning. This suggests that the IP rule solves the vanishing gradient problem. Supplementary analysis is provided to derive the equilibrium solutions that the neuronal gain and bias converge to using our IP rule. An analysis demonstrates that the IP rule results in neuronal information potential similar to that of Infomax, when tested on a fixed input distribution. We also show that batch normalisation also improves information potential, suggesting that this may be a cause for the efficacy of batch normalisation-an open problem at the time of this writing.


Assuntos
Aprendizagem/fisiologia , Redes Neurais de Computação , Plasticidade Neuronal/fisiologia , Potenciais de Ação/fisiologia , Algoritmos , Simulação por Computador , Aprendizado Profundo/tendências , Modelos Neurológicos , Modelos Estatísticos , Modelos Teóricos , Neurônios/fisiologia , Sinapses/fisiologia , Transmissão Sináptica/fisiologia
4.
Stroke ; 51(10): 3169-3173, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32951539

RESUMO

The repair and recovery of the brain after stroke is a field that is emerging in its preclinical science and clinical trials. However, recent large, multicenter clinical trials have been negative, and conflicting results emerge on biological targets in preclinical studies. The coalescence of negative clinical translation and confusion in preclinical studies raises the suggestion that perhaps the field of stroke recovery faces a fate similar to stroke neuroprotection, with interesting science ultimately proving difficult to translate to the clinic. This review highlights improvements in 4 areas of the stroke neural repair field that should reorient the field toward successful clinical translation: improvements in rodent genetic models of stroke recovery, consideration of the biological target in stroke recovery, stratification in clinical trials, and the use of appropriate clinical trial end points.


Assuntos
Encéfalo/fisiopatologia , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica/fisiologia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/fisiopatologia , Animais , Modelos Animais de Doenças , Humanos
5.
Science ; 369(6505): 858-862, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32792401

RESUMO

The conversion of neural stem cells into neurons is associated with the remodeling of organelles, but whether and how this is causally linked to fate change is poorly understood. We examined and manipulated mitochondrial dynamics during mouse and human cortical neurogenesis. We reveal that shortly after cortical stem cells have divided, daughter cells destined to self-renew undergo mitochondrial fusion, whereas those that retain high levels of mitochondria fission become neurons. Increased mitochondria fission promotes neuronal fate, whereas induction of mitochondria fusion after mitosis redirects daughter cells toward self-renewal. This occurs during a restricted time window that is doubled in human cells, in line with their increased self-renewal capacity. Our data reveal a postmitotic period of fate plasticity in which mitochondrial dynamics are linked with cell fate.


Assuntos
Córtex Cerebral/crescimento & desenvolvimento , Mitocôndrias/fisiologia , Dinâmica Mitocondrial , Mitose , Células-Tronco Neurais/citologia , Neurogênese/fisiologia , Neurônios/citologia , Animais , Córtex Cerebral/citologia , Feminino , Células HEK293 , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Masculino , Camundongos , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Sirtuínas/metabolismo
6.
Nat Commun ; 11(1): 3845, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737295

RESUMO

Many experimental studies suggest that animals can rapidly learn to identify odors and predict the rewards associated with them. However, the underlying plasticity mechanism remains elusive. In particular, it is not clear how olfactory circuits achieve rapid, data efficient learning with local synaptic plasticity. Here, we formulate olfactory learning as a Bayesian optimization process, then map the learning rules into a computational model of the mammalian olfactory circuit. The model is capable of odor identification from a small number of observations, while reproducing cellular plasticity commonly observed during development. We extend the framework to reward-based learning, and show that the circuit is able to rapidly learn odor-reward association with a plausible neural architecture. These results deepen our theoretical understanding of unsupervised learning in the mammalian brain.


Assuntos
Condicionamento Clássico/fisiologia , Rede Nervosa , Plasticidade Neuronal/fisiologia , Condutos Olfatórios/fisiologia , Percepção Olfatória/fisiologia , Olfato/fisiologia , Animais , Teorema de Bayes , Simulação por Computador , Mamíferos , Neurônios/citologia , Neurônios/fisiologia , Odorantes/análise , Bulbo Olfatório/fisiologia , Recompensa
7.
PLoS Comput Biol ; 16(8): e1008118, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32764742

RESUMO

Hebbian plasticity, a mechanism believed to be the substrate of learning and memory, detects and further enhances correlated neural activity. Because this constitutes an unstable positive feedback loop, it requires additional homeostatic control. Computational work suggests that in recurrent networks, the homeostatic mechanisms observed in experiments are too slow to compensate instabilities arising from Hebbian plasticity and need to be complemented by rapid compensatory processes. We suggest presynaptic inhibition as a candidate that rapidly provides stability by compensating recurrent excitation induced by Hebbian changes. Presynaptic inhibition is mediated by presynaptic GABA receptors that effectively and reversibly attenuate transmitter release. Activation of these receptors can be triggered by excess network activity, hence providing a stabilising negative feedback loop that weakens recurrent interactions on sub-second timescales. We study the stabilising effect of presynaptic inhibition in recurrent networks, in which presynaptic inhibition is implemented as a multiplicative reduction of recurrent synaptic weights in response to increasing inhibitory activity. We show that networks with presynaptic inhibition display a gradual increase of firing rates with growing excitatory weights, in contrast to traditional excitatory-inhibitory networks. This alleviates the positive feedback loop between Hebbian plasticity and network activity and thereby allows homeostasis to act on timescales similar to those observed in experiments. Our results generalise to spiking networks with a biophysically more detailed implementation of the presynaptic inhibition mechanism. In conclusion, presynaptic inhibition provides a powerful compensatory mechanism that rapidly reduces effective recurrent interactions and thereby stabilises Hebbian learning.


Assuntos
Modelos Neurológicos , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Animais , Biologia Computacional , Homeostase , Aprendizagem , Memória , Neurônios/fisiologia
8.
PLoS Comput Biol ; 16(8): e1007659, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32764745

RESUMO

The brain consists of many interconnected networks with time-varying, partially autonomous activity. There are multiple sources of noise and variation yet activity has to eventually converge to a stable, reproducible state (or sequence of states) for its computations to make sense. We approached this problem from a control-theory perspective by applying contraction analysis to recurrent neural networks. This allowed us to find mechanisms for achieving stability in multiple connected networks with biologically realistic dynamics, including synaptic plasticity and time-varying inputs. These mechanisms included inhibitory Hebbian plasticity, excitatory anti-Hebbian plasticity, synaptic sparsity and excitatory-inhibitory balance. Our findings shed light on how stable computations might be achieved despite biological complexity. Crucially, our analysis is not limited to analyzing the stability of fixed geometric objects in state space (e.g points, lines, planes), but rather the stability of state trajectories which may be complex and time-varying.


Assuntos
Modelos Neurológicos , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Algoritmos , Animais , Encéfalo/fisiologia , Biologia Computacional , Simulação por Computador , Humanos
9.
Nat Commun ; 11(1): 4030, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788588

RESUMO

Sensory information processing in robot skins currently rely on a centralized approach where signal transduction (on the body) is separated from centralized computation and decision-making, requiring the transfer of large amounts of data from periphery to central processors, at the cost of wiring, latency, fault tolerance and robustness. We envision a decentralized approach where intelligence is embedded in the sensing nodes, using a unique neuromorphic methodology to extract relevant information in robotic skins. Here we specifically address pain perception and the association of nociception with tactile perception to trigger the escape reflex in a sensorized robotic arm. The proposed system comprises self-healable materials and memtransistors as enabling technologies for the implementation of neuromorphic nociceptors, spiking local associative learning and communication. Configuring memtransistors as gated-threshold and -memristive switches, the demonstrated system features in-memory edge computing with minimal hardware circuitry and wiring, and enhanced fault tolerance and robustness.


Assuntos
Robótica , Processamento de Sinais Assistido por Computador , Transistores Eletrônicos , Potenciais de Ação/fisiologia , Lógica , Plasticidade Neuronal/fisiologia , Nociceptividade , Terminações Pré-Sinápticas/fisiologia
10.
Neuron ; 107(3): 580-589.e6, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32778224

RESUMO

To induce brain plasticity in humans, we casted the dominant upper extremity for 2 weeks and tracked changes in functional connectivity using daily 30-min scans of resting-state functional MRI (rs-fMRI). Casting caused cortical and cerebellar regions controlling the disused extremity to functionally disconnect from the rest of the somatomotor system, while internal connectivity within the disused sub-circuit was maintained. Functional disconnection was evident within 48 h, progressed throughout the cast period, and reversed after cast removal. During the cast period, large, spontaneous pulses of activity propagated through the disused somatomotor sub-circuit. The adult brain seems to rely on regular use to maintain its functional architecture. Disuse-driven spontaneous activity pulses may help preserve functionally disconnected sub-circuits.


Assuntos
Córtex Motor/diagnóstico por imagem , Plasticidade Neuronal/fisiologia , Restrição Física , Atividades Cotidianas , Moldes Cirúrgicos , Feminino , Lateralidade Funcional , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Motor/fisiologia , Destreza Motora/fisiologia , Força Muscular/fisiologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Extremidade Superior
11.
PLoS One ; 15(8): e0237933, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822407

RESUMO

Defining the relationship between maternal care, sensory development and brain gene expression in neonates is important to understand the impact of environmental challenges during sensitive periods in early life. In this study, we used a selection approach to test the hypothesis that variation in maternal licking and grooming (LG) during the first week of life influences sensory development in Wistar rat pups. We tracked the onset of the auditory brainstem response (ABR), the timing of eye opening (EO), middle ear development with micro-CT X-ray tomography, and used qRT-PCR to monitor changes in gene expression of the hypoxia-sensitive pathway and neurotrophin signaling in pups reared by low-LG or high-LG dams. The results show the first evidence that the transcription of genes involved in the hypoxia-sensitive pathway and neurotrophin signaling is regulated during separate sensitive periods that occur before and after hearing onset, respectively. Although the timing of ABR onset, EO, and the relative mRNA levels of genes involved in the hypoxia-sensitive pathway did not differ between pups from different LG groups, we found statistically significant increases in the relative mRNA levels of four genes involved in neurotrophin signaling in auditory brain regions from pups of different LG backgrounds. These results suggest that sensitivity to hypoxic challenge might be widespread in the auditory system of neonate rats before hearing onset, and that maternal LG may affect the transcription of genes involved in experience-dependent neuroplasticity.


Assuntos
Comportamento Animal/fisiologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Asseio Animal/fisiologia , Comportamento Materno/fisiologia , Fatores de Crescimento Neural/metabolismo , Animais , Animais Recém-Nascidos , Olho/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Audição , Hipóxia/genética , Hipóxia/metabolismo , Fatores de Crescimento Neural/genética , Plasticidade Neuronal/fisiologia , Ratos , Ratos Wistar , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Microtomografia por Raio-X
12.
Proc Natl Acad Sci U S A ; 117(34): 20881-20889, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32788365

RESUMO

Language processing involves the ability to store and integrate pieces of information in working memory over short periods of time. According to the dominant view, information is maintained through sustained, elevated neural activity. Other work has argued that short-term synaptic facilitation can serve as a substrate of memory. Here we propose an account where memory is supported by intrinsic plasticity that downregulates neuronal firing rates. Single neuron responses are dependent on experience, and we show through simulations that these adaptive changes in excitability provide memory on timescales ranging from milliseconds to seconds. On this account, spiking activity writes information into coupled dynamic variables that control adaptation and move at slower timescales than the membrane potential. From these variables, information is continuously read back into the active membrane state for processing. This neuronal memory mechanism does not rely on persistent activity, excitatory feedback, or synaptic plasticity for storage. Instead, information is maintained in adaptive conductances that reduce firing rates and can be accessed directly without cued retrieval. Memory span is systematically related to both the time constant of adaptation and baseline levels of neuronal excitability. Interference effects within memory arise when adaptation is long lasting. We demonstrate that this mechanism is sensitive to context and serial order which makes it suitable for temporal integration in sequence processing within the language domain. We also show that it enables the binding of linguistic features over time within dynamic memory registers. This work provides a step toward a computational neurobiology of language.


Assuntos
Memória de Curto Prazo/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Animais , Humanos , Idioma , Modelos Neurológicos , Redes Neurais de Computação , Neurônios/metabolismo , Sinapses/fisiologia
13.
Nat Commun ; 11(1): 3935, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769979

RESUMO

GABAA/glycine-mediated neuronal inhibition critically depends on intracellular chloride (Cl-) concentration which is mainly regulated by the K+-Cl- co-transporter 2 (KCC2) in the adult central nervous system (CNS). KCC2 heterogeneity thus affects information processing across CNS areas. Here, we uncover a gradient in Cl- extrusion capacity across the superficial dorsal horn (SDH) of the spinal cord (laminae I-II: LI-LII), which remains concealed under low Cl- load. Under high Cl- load or heightened synaptic drive, lower Cl- extrusion is unveiled in LI, as expected from the gradient in KCC2 expression found across the SDH. Blocking TrkB receptors increases KCC2 in LI, pointing to differential constitutive TrkB activation across laminae. Higher Cl- lability in LI results in rapidly collapsing inhibition, and a form of activity-dependent synaptic plasticity expressed as a continuous facilitation of excitatory responses. The higher metaplasticity in LI as compared to LII differentially affects sensitization to thermal and mechanical input. Thus, inconspicuous heterogeneity of Cl- extrusion across laminae critically shapes plasticity for selective nociceptive modalities.


Assuntos
Sensibilização do Sistema Nervoso Central/fisiologia , Cloretos/metabolismo , Plasticidade Neuronal/fisiologia , Nociceptividade/fisiologia , Células do Corno Posterior/fisiologia , Animais , Células Cultivadas , Masculino , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/metabolismo , Camundongos , Modelos Neurológicos , Optogenética , Cultura Primária de Células , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Ratos , Receptor trkB/antagonistas & inibidores , Receptor trkB/metabolismo , Simportadores/metabolismo
14.
Proc Natl Acad Sci U S A ; 117(33): 20254-20264, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32747543

RESUMO

Correlated activation of cortical neurons often occurs in the brain and repetitive correlated neuronal firing could cause long-term modifications of synaptic efficacy and intrinsic excitability. We found that repetitive optogenetic activation of neuronal populations in the mouse cortex caused enhancement of optogenetically evoked firing of local coactivated neurons as well as distant cortical neurons in both ipsilateral and contralateral hemispheres. This global enhancement of evoked responses required coactivation of a sufficiently large population of neurons either within one cortical area or distributed in several areas. Enhancement of neuronal firing was saturable after repeated episodes of coactivation, diminished by inhibition of N-methyl-d-aspartic acid receptors, and accompanied by elevated excitatory postsynaptic potentials, all consistent with activity-induced synaptic potentiation. Chemogenetic inhibition of neuronal activity of the thalamus decreased the enhancement effect, suggesting thalamic involvement. Thus, correlated excitation of large neuronal populations leads to global enhancement of neuronal excitability.


Assuntos
Potenciais de Ação/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Excitabilidade Cortical , Corantes Fluorescentes , Masculino , Camundongos , Rede Nervosa , Transmissão Sináptica/fisiologia
16.
Nat Commun ; 11(1): 4276, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32848151

RESUMO

The structural organization of excitatory inputs supporting spike-timing-dependent plasticity (STDP) remains unknown. We performed a spine STDP protocol using two-photon (2P) glutamate uncaging (pre) paired with postsynaptic spikes (post) in layer 5 pyramidal neurons from juvenile mice. Here we report that pre-post pairings that trigger timing-dependent LTP (t-LTP) produce shrinkage of the activated spine neck and increase in synaptic strength; and post-pre pairings that trigger timing-dependent LTD (t-LTD) decrease synaptic strength without affecting spine shape. Furthermore, the induction of t-LTP with 2P glutamate uncaging in clustered spines (<5 µm apart) enhances LTP through a NMDA receptor-mediated spine calcium accumulation and actin polymerization-dependent neck shrinkage, whereas t-LTD was dependent on NMDA receptors and disrupted by the activation of clustered spines but recovered when separated by >40 µm. These results indicate that synaptic cooperativity disrupts t-LTD and extends the temporal window for the induction of t-LTP, leading to STDP only encompassing LTP.


Assuntos
Espinhas Dendríticas/fisiologia , Plasticidade Neuronal/fisiologia , Potenciais de Ação/fisiologia , Animais , Sinalização do Cálcio/fisiologia , Técnicas In Vitro , Potenciação de Longa Duração/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência por Excitação Multifotônica , Modelos Neurológicos , Células Piramidais/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia
17.
PLoS Comput Biol ; 16(7): e1007955, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32649658

RESUMO

During the exploration of novel environments, place fields are rapidly formed in hippocampal CA1 neurons. Place cell firing rate increases in early stages of exploration of novel environments but returns to baseline levels in familiar environments. Although similar in amplitude and width, place fields in familiar environments are more stable than in novel environments. We propose a computational model of the hippocampal CA1 network, which describes the formation, dynamics and stabilization of place fields. We show that although somatic disinhibition is sufficient to form place fields, dendritic inhibition along with synaptic plasticity is necessary for place field stabilization. Our model suggests that place cell stability can be attributed to strong excitatory synaptic weights and strong dendritic inhibition. We show that the interplay between somatic and dendritic inhibition balances the increased excitatory weights, such that place cells return to their baseline firing rate after exploration. Our model suggests that different types of interneurons are essential to unravel the mechanisms underlying place field plasticity. Finally, we predict that artificially induced dendritic events can shift place fields even after place field stabilization.


Assuntos
Região CA1 Hipocampal , Dendritos/fisiologia , Inibição Neural/fisiologia , Células de Lugar/fisiologia , Potenciais de Ação/fisiologia , Animais , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/fisiologia , Biologia Computacional , Camundongos , Modelos Neurológicos , Plasticidade Neuronal/fisiologia
18.
Nat Commun ; 11(1): 3625, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681001

RESUMO

Recurrently connected networks of spiking neurons underlie the astounding information processing capabilities of the brain. Yet in spite of extensive research, how they can learn through synaptic plasticity to carry out complex network computations remains unclear. We argue that two pieces of this puzzle were provided by experimental data from neuroscience. A mathematical result tells us how these pieces need to be combined to enable biologically plausible online network learning through gradient descent, in particular deep reinforcement learning. This learning method-called e-prop-approaches the performance of backpropagation through time (BPTT), the best-known method for training recurrent neural networks in machine learning. In addition, it suggests a method for powerful on-chip learning in energy-efficient spike-based hardware for artificial intelligence.


Assuntos
Encéfalo/fisiologia , Modelos Neurológicos , Rede Nervosa/fisiologia , Neurônios/fisiologia , Recompensa , Potenciais de Ação/fisiologia , Animais , Encéfalo/citologia , Aprendizado Profundo , Humanos , Camundongos , Plasticidade Neuronal/fisiologia
19.
Nat Commun ; 11(1): 3791, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728089

RESUMO

Brain organoids are promising tools for disease modeling and drug development. For proper neuronal network formation excitatory and inhibitory neurons as well as glia need to co-develop. Here, we report the directed self-organization of human induced pluripotent stem cells in a collagen hydrogel towards a highly interconnected neuronal network at a macroscale tissue format. Bioengineered Neuronal Organoids (BENOs) comprise interconnected excitatory and inhibitory neurons with supportive astrocytes and oligodendrocytes. Giant depolarizing potential (GDP)-like events observed in early BENO cultures mimic early network activity of the fetal brain. The observed GABA polarity switch and reduced GDPs in >40 day BENO indicate progressive neuronal network maturation. BENOs demonstrate expedited complex network burst development after two months and evidence for long-term potentiation. The similarity of structural and functional properties to the fetal brain may allow for the application of BENOs in studies of neuronal plasticity and modeling of disease.


Assuntos
Encéfalo/citologia , Neurogênese , Plasticidade Neuronal/fisiologia , Organoides/fisiologia , Engenharia Tecidual/métodos , Potenciais de Ação/fisiologia , Encéfalo/crescimento & desenvolvimento , Técnicas de Cultura de Células , Diferenciação Celular , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Neurônios/fisiologia , Ácido gama-Aminobutírico/metabolismo
20.
Med Sci (Paris) ; 36(6-7): 581-591, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32614308

RESUMO

Following partial or total loss of peripheral vestibular inputs, a phenomenon called central vestibular compensation takes place in the hours and days following the injury. This neuroplasticity process involves a mosaic of profound rearrangements within the brain stem vestibular nuclei. Among them, the setting of a new neuronal network is maybe the most original and unexpected, as it involves an adult reactive neurogenesis in a brain area not reported as neurogenic so far. Both the survival and functionality of this newly generated neuronal network will depend on its integration to pre-existing networks in the deafferented structure. Far from being aberrant, this new structural organization allows the use of inputs from other sensory modalities (vision and proprioception) to promote the restoration of the posture and equilibrium. We choose here to detail this model, which does not belong to the traditional niches of adult neurogenesis, but it is the best example so far of the reparative role of the adult neurogenesis. Not only it represents an original neuroplasticity mechanism, interesting for basic neuroscience, but it also opens new medical perspectives for the development of therapeutic approaches to alleviate vestibular disorders.


Assuntos
Encéfalo/citologia , Neurogênese/fisiologia , Neurônios/fisiologia , Postura/fisiologia , Doenças Vestibulares/reabilitação , Núcleos Vestibulares/lesões , Adulto , Células-Tronco Adultas/citologia , Células-Tronco Adultas/fisiologia , Animais , Encéfalo/fisiologia , Humanos , Células-Tronco Neurais/fisiologia , Plasticidade Neuronal/fisiologia , Doenças Vestibulares/fisiopatologia , Núcleos Vestibulares/patologia , Núcleos Vestibulares/fisiologia , Vestíbulo do Labirinto/lesões , Vestíbulo do Labirinto/patologia , Vestíbulo do Labirinto/fisiologia
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