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1.
Adv Exp Med Biol ; 1131: 965-984, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646541

RESUMO

Synaptic plasticity is a fundamental property of neurons referring to the activity-dependent changes in the strength and efficacy of synaptic transmission at preexisting synapses. Such changes can last from milliseconds to hours, days, or even longer and are involved in learning and memory as well as in development and response of the brain to injuries. Several types of synaptic plasticity have been described across neuronal types, brain regions, and species, but all of them share in one way or another capital importance of Ca2+-mediated processes. In this chapter, we will focus on the Ca2+-dependent events necessary for the induction and expression of multiple forms of synaptic plasticity.


Assuntos
Cálcio , Plasticidade Neuronal , Sinapses , Cálcio/metabolismo , Humanos , Potenciação de Longa Duração , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Transmissão Sináptica
2.
Nat Commun ; 10(1): 2937, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270315

RESUMO

During the generation of rhythmic movements, most spinal neurons receive an oscillatory synaptic drive. The neuronal architecture underlying this drive is unknown, and the corresponding network size and sparseness have not yet been addressed. If the input originates from a small central pattern generator (CPG) with dense divergent connectivity, it will induce correlated input to all receiving neurons, while sparse convergent wiring will induce a weak correlation, if any. Here, we use pairwise recordings of spinal neurons to measure synaptic correlations and thus infer the wiring architecture qualitatively. A strong correlation on a slow timescale implies functional relatedness and a common source, which will also cause correlation on fast timescale due to shared synaptic connections. However, we consistently find marginal coupling between slow and fast correlations regardless of neuronal identity. This suggests either sparse convergent connectivity or a CPG network with recurrent inhibition that actively decorrelates common input.


Assuntos
Medula Espinal/fisiologia , Animais , Feminino , Cinética , Masculino , Modelos Neurológicos , Neurônios/química , Neurônios/fisiologia , Medula Espinal/química , Sinapses/fisiologia , Transmissão Sináptica , Fatores de Tempo , Tartarugas
3.
Nat Neurosci ; 22(8): 1318-1326, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31346296

RESUMO

Direction-selective neurons respond to visual motion in a preferred direction. They are direction-opponent if they are also inhibited by motion in the opposite direction. In flies and vertebrates, direction opponency has been observed in second-order direction-selective neurons, which achieve this opponency by subtracting signals from first-order direction-selective cells with opposite directional tunings. Here, we report direction opponency in Drosophila that emerges in first-order direction-selective neurons, the elementary motion detectors T4 and T5. This opponency persists when synaptic output from these cells is blocked, suggesting that it arises from feedforward, not feedback, computations. These observations exclude a broad class of linear-nonlinear models that have been proposed to describe direction-selective computations. However, they are consistent with models that include dynamic nonlinearities. Simulations of opponent models suggest that direction opponency in first-order motion detectors improves motion discriminability by suppressing noise generated by the local structure of natural scenes.


Assuntos
Drosophila melanogaster/fisiologia , Percepção de Movimento/fisiologia , Animais , Retroalimentação Sensorial , Neurônios/fisiologia , Dinâmica não Linear , Estimulação Luminosa , Detecção de Sinal Psicológico , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Vias Visuais/fisiologia
4.
Yakugaku Zasshi ; 139(6): 923-929, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31155537

RESUMO

Brain function is controlled by the balance between the excitatory and inhibitory systems. If this balance is disrupted and the excitatory system dominates, convulsions or epileptic seizures are induced. Neuronal hyperexcitability in the brain leads to marked changes in the function of the neurons, which adversely affect the stability of the neural network. Many of the currently used antiepileptic drugs are symptomatic treatments that suppress the electrical hyperexcitability of the cerebrum. Although patients with epilepsy should continuously take antiepileptic drugs to control their seizures, approximately 20% of patients are drug resistant. The brain has the ability to control neuronal functions within acceptable limits while it maintains the amount of synaptic inputs that form the basis of information accumulation. Neuronal self-regulation is known as homeostatic scaling by which the intensity of all excitatory synapses is suppressed when neuronal excitability is increased. However, the molecular mechanisms of homeostatic scaling and their pathophysiological significance in vivo remain unclear. Repeated treatment with a subconvulsive dosage of pentylenetetrazol (PTZ), a γ-aminobutyric acid (GABA)A receptor antagonist, is known to induce kindling in mice, which is a common animal model used to study epilepsy. We found that PTZ-induced kindling was potentiated in mice deficient in the transcription factor neuronal PAS domain protein 4 (Npas4), the expression of which is immediately induced in response to neuronal activity. At this symposium, we will discuss the possibility of Npas4 as a novel target molecule for epilepsy treatment.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Encéfalo/fisiologia , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Homeostase , Terapia de Alvo Molecular , Neurônios/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Modelos Animais de Doenças , Epilepsia/genética , Humanos , Excitação Neurológica , Camundongos , Sinapses/fisiologia
5.
Neuron ; 103(2): 217-234.e4, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31171447

RESUMO

Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes. SynGO annotations are exclusively based on published, expert-curated evidence. Using 2,922 annotations for 1,112 genes, we show that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes. Many SynGO terms are significantly overrepresented among gene variations associated with intelligence, educational attainment, ADHD, autism, and bipolar disorder and among de novo variants associated with neurodevelopmental disorders, including schizophrenia. SynGO is a public, universal reference for synapse research and an online analysis platform for interpretation of large-scale -omics data (https://syngoportal.org and http://geneontology.org).


Assuntos
Encéfalo/citologia , Ontologia Genética , Proteômica , Software , Sinapses/fisiologia , Animais , Encéfalo/fisiologia , Bases de Dados Genéticas , Humanos , Bases de Conhecimento , Potenciais Sinápticos/fisiologia , Sinaptossomos
6.
Sheng Li Xue Bao ; 71(3): 471-477, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31218338

RESUMO

The C1q family is one of the subcomponents of the C1 complex that recognizes immune complexes and initiates the classical pathway of the complement system. In addition, as a pattern recognition receptor (PRR), the C1q family binds to a wide variety of ligands. As a member of the C1q family, the secretory C1q includes several subtypes. The main subtypes are cerebellin (Cbln) and C1q-like protein (C1ql). In the nervous system, secretory C1q is involved in the formation and regulation of various types of synapses, thus secretory C1q is closely related to diseases of the central nervous system. In this article, we review the role of secretory C1q in synapse formation and regulation, and its relationship with some diseases of the central nervous system.


Assuntos
Complemento C1q/fisiologia , Sinapses/fisiologia , Complexo Antígeno-Anticorpo , Sistema Nervoso Central , Humanos
7.
Cell Mol Life Sci ; 76(16): 3141-3156, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31168660

RESUMO

Neurotrauma, a term referencing both traumatic brain and spinal cord injuries, is unique to neurodegeneration in that onset is clearly defined. From the perspective of matrix metalloproteinases (MMPs), there is opportunity to define their temporal participation in injury and recovery beginning at the level of the synapse. Here we examine the diverse roles of MMPs in the context of targeted insults (optic nerve lesion and hippocampal and olfactory bulb deafferentation), and clinically relevant focal models of traumatic brain and spinal cord injuries. Time-specific MMP postinjury signaling is critical to synaptic recovery after focal axonal injuries; members of the MMP family exhibit a signature temporal profile corresponding to axonal degeneration and regrowth, where they direct postinjury reorganization and synaptic stabilization. In both traumatic brain and spinal cord injuries, MMPs mediate early secondary pathogenesis including disruption of the blood-brain barrier, creating an environment that may be hostile to recovery. They are also critical players in wound healing including angiogenesis and the formation of an inhibitory glial scar. Experimental strategies to reduce their activity in the acute phase result in long-term neurological recovery after neurotrauma and have led to the first clinical trial in spinal cord injured pet dogs.


Assuntos
Metaloproteinases da Matriz/metabolismo , Traumatismos da Medula Espinal/patologia , Animais , Axônios/metabolismo , Barreira Hematoencefálica/metabolismo , Hipocampo/metabolismo , Humanos , Bulbo Olfatório/metabolismo , Nervo Óptico/metabolismo , Traumatismos da Medula Espinal/metabolismo , Sinapses/fisiologia
8.
Life Sci ; 231: 116566, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31201846

RESUMO

AIMS: Diabetes mellitus can cause cognitive impairments, a state between normal aging and dementia. Effective clinical interventions are urgently needed to prevent or treat this complication. Liraglutide as a glucagon-like peptide 1 analog has been shown to exert memory-enhancing and neuroprotective effects on neurodegenerative diseases. This study aims to investigate the neuroprotective effects of liraglutide in streptozotocin (STZ)-induced diabetic mice with cognitive deficits. METHODS: Male C57BL/6J mice were intraperitoneal injected with STZ (65 mg/kg body weight daily for 5 days) to induce type 1 diabetes model. Then the mice were treated with liraglutide (250 mg/kg/day, for 6 weeks) or saline. Weekly changes of body weight and fasting blood glucose were measured. Cognitive performance was evaluated by Morris water maze test. The ultrastructure of hippocampus was observed by transmission electron microscope. The superoxide dismutase activities and malondialdehyde levels in the hippocampus were detected by biochemistry assay. Apoptosis-related proteins and phosphoinositide 3-kinase (PI3K)/protein kinase-B (Akt) signaling were detected by Western blotting. KEY FINDINGS: We found that STZ-induced diabetic mice exhibited impaired learning and memory, ultrastructure damage of hippocampal neurons and synapses, exacerbated oxidative stress and neuronal apoptosis, as compared to the control mice. These effects were attenuated by the treatment with liraglutide. Furthermore, liraglutide reversed diabetes-induced alterations in PI3K/Akt signaling pathway that plays an essential role in modulating neuronal survival, apoptosis and plasticity. SIGNIFICANCE: These data suggest that the neuroprotective effects of liraglutide on diabetes-induced cognitive impairments are associated with the improvements of hippocampal synapses and inhibition of neuronal apoptosis.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Complicações do Diabetes/tratamento farmacológico , Liraglutida/farmacologia , Animais , Apoptose/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Cognição/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipoglicemiantes/farmacologia , Liraglutida/metabolismo , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/efeitos adversos , Sinapses/efeitos dos fármacos , Sinapses/fisiologia
9.
Chaos ; 29(5): 053121, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31154794

RESUMO

Spatiotemporal chaos collapses to either a rest state or a propagating pulse in a ring network of diffusively coupled, excitable Morris-Lecar neurons. Adding global varying synaptic coupling to the ring network reveals complex transient behavior. Spatiotemporal chaos collapses into a transient pulse that reinitiates spatiotemporal chaos to allow sequential pattern switching until a collapse to the rest state. A domain of irregular neuron activity coexists with a domain of inactive neurons forming a transient chimeralike state. Transient spatial localization of the chimeralike state is observed for stronger synapses.


Assuntos
Neurônios/fisiologia , Dinâmica não Linear , Análise Espaço-Temporal , Modelos Neurológicos , Rede Nervosa/fisiologia , Sinapses/fisiologia
10.
PLoS Comput Biol ; 15(5): e1007074, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31150376

RESUMO

Several recent studies have shown that neural activity in vivo tends to be constrained to a low-dimensional manifold. Such activity does not arise in simulated neural networks with homogeneous connectivity and it has been suggested that it is indicative of some other connectivity pattern in neuronal networks. In particular, this connectivity pattern appears to be constraining learning so that only neural activity patterns falling within the intrinsic manifold can be learned and elicited. Here, we use three different models of spiking neural networks (echo-state networks, the Neural Engineering Framework and Efficient Coding) to demonstrate how the intrinsic manifold can be made a direct consequence of the circuit connectivity. Using this relationship between the circuit connectivity and the intrinsic manifold, we show that learning of patterns outside the intrinsic manifold corresponds to much larger changes in synaptic weights than learning of patterns within the intrinsic manifold. Assuming larger changes to synaptic weights requires extensive learning, this observation provides an explanation of why learning is easier when it does not require the neural activity to leave its intrinsic manifold.


Assuntos
Modelos Neurológicos , Rede Nervosa/fisiologia , Potenciais de Ação/fisiologia , Algoritmos , Animais , Biologia Computacional , Simulação por Computador , Haplorrinos/fisiologia , Haplorrinos/psicologia , Aprendizagem/fisiologia , Aprendizado de Máquina , Redes Neurais (Computação) , Neurônios/fisiologia , Sinapses/fisiologia
11.
Cell Mol Life Sci ; 76(14): 2719-2738, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31037336

RESUMO

Precise neuronal wiring is critical for the function of the nervous system and is ultimately determined at the level of individual synapses. Neurons integrate various intrinsic and extrinsic cues to form synapses onto their correct targets in a stereotyped manner. In the past decades, the nervous system of nematode (Caenorhabditis elegans) has provided the genetic platform to reveal the genetic and molecular mechanisms of synapse formation and specificity. In this review, we will summarize the recent discoveries in synapse formation and specificity in C. elegans.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Neurônios/metabolismo , Sinapses/fisiologia , Animais , Transdução de Sinais
12.
Neuron ; 103(1): 66-79.e12, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31104951

RESUMO

The precision and reliability of synaptic information transfer depend on the molecular organization of voltage-gated calcium channels (VGCCs) within the presynaptic membrane. Alternative splicing of exon 47 affects the C-terminal structure of VGCCs and their affinity to intracellular partners and synaptic vesicles (SVs). We show that hippocampal synapses expressing VGCCs either with exon 47 (CaV2.1+47) or without (CaV2.1Δ47) differ in release probability and short-term plasticity. Tracking single channels revealed transient visits (∼100 ms) of presynaptic VGCCs in nanodomains (∼80 nm) that were controlled by neuronal network activity. Surprisingly, despite harboring prominent binding sites to scaffold proteins, CaV2.1+47 persistently displayed higher mobility within nanodomains. Synaptic accumulation of CaV2.1 was accomplished by optogenetic clustering, but only CaV2.1+47 increased transmitter release and enhanced synaptic short-term depression. We propose that exon 47-related alternative splicing of CaV2.1 channels controls synapse-specific release properties at the level of channel mobility-dependent coupling between VGCCs and SVs.


Assuntos
Canais de Cálcio/genética , Plasticidade Neuronal/genética , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Sequência de Aminoácidos , Animais , Sítios de Ligação , Canais de Cálcio/efeitos da radiação , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Células HEK293 , Humanos , Luz , Neurotransmissores/metabolismo , Optogenética , Gravidez , Isoformas de Proteínas/genética , Ratos , Vesículas Sinápticas/fisiologia
13.
Mol Med Rep ; 19(6): 4897-4905, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059028

RESUMO

Amyloid ß (Aß) has been reported to have an important role in the cognitive deficits of Alzheimer's disease (AD), as oligomeric Aß promotes synaptic dysfunction and triggers neuronal death. Recent evidence has associated an endocytosis protein, endophilin 1, with AD, as endophilin 1 levels have been reported to be markedly increased in the AD brain. The increase in endophilin 1 levels in neurons is associated with an increase in the activation of the stress kinase JNK, with subsequent neuronal death. In the present study, whole­cell patch­clamp recording demonstrated that oligomeric Aß caused synaptic dysfunction and western blotting revealed that endophilin 1 was highly expressed prior to neuronal death of cultured hippocampal neurons. Furthermore, RNA interference and electrophysiological recording techniques in cultured hippocampal neurons demonstrated that knockdown of endophilin 1 prevented synaptic dysfunction induced by Aß. Thus, a potential role for endophilin 1 in Aß­induced postsynaptic dysfunction has been identified, indicating a possible direction for the prevention of postsynaptic dysfunction in cognitive impairment and suggesting that endophilin may be a potential target for the clinical treatment of AD.


Assuntos
Aciltransferases/metabolismo , Peptídeos beta-Amiloides/farmacologia , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Sinapses/efeitos dos fármacos , Aciltransferases/antagonistas & inibidores , Aciltransferases/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células HEK293 , Humanos , Masculino , Camundongos , Neurônios/citologia , Neurônios/metabolismo , Polímeros/química , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Sinapses/fisiologia
14.
Science ; 364(6439)2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31048465

RESUMO

Central nervous system (CNS) circuit development requires subcellular control of synapse formation and patterning of synapse abundance. We identified the Drosophila membrane-anchored phosphatase of regenerating liver (Prl-1) as an axon-intrinsic factor that promotes synapse formation in a spatially restricted fashion. The loss of Prl-1 in mechanosensory neurons reduced the number of CNS presynapses localized on a single axon collateral and organized as a terminal arbor. Flies lacking all Prl-1 protein had locomotor defects. The overexpression of Prl-1 induced ectopic synapses. In mechanosensory neurons, Prl-1 modulates the insulin receptor (InR) signaling pathway within a single contralateral axon compartment, thereby affecting the number of synapses. The axon branch-specific localization and function of Prl-1 depend on untranslated regions of the prl-1 messenger RNA (mRNA). Therefore, compartmentalized restriction of Prl-1 serves as a specificity factor for the subcellular control of axonal synaptogenesis.


Assuntos
Axônios/fisiologia , Sistema Nervoso Central/crescimento & desenvolvimento , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/crescimento & desenvolvimento , Proteínas Tirosina Fosfatases/fisiologia , Sinapses/fisiologia , Animais , Axônios/enzimologia , Sistema Nervoso Central/enzimologia , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Locomoção/genética , Locomoção/fisiologia , Mecanorreceptores/enzimologia , Fosfatidilinositóis/metabolismo , Domínios Proteicos , Proteínas Tirosina Fosfatases/química , Proteínas Tirosina Fosfatases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Sinapses/enzimologia
15.
Genes Cells ; 24(7): 496-510, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31124270

RESUMO

In the Drosophila brain, neurons form genetically specified synaptic connections with defined neuronal targets. It is proposed that each central nervous system neuron expresses specific cell surface proteins, which act as identification tags. Through an RNAi screen of cell surface molecules in the Drosophila visual system, we found that the cell adhesion molecule Klingon (Klg) plays an important role in repressing the ectopic formation of extended axons, preventing the formation of excessive synapses. Cell-specific manipulation of klg showed that Klg is required in both photoreceptors and the glia, suggesting that the balanced homophilic interaction between photoreceptor axons and the glia is required for normal synapse formation. Previous studies suggested that Klg binds to cDIP and our genetic analyses indicate that cDIP is required in glia for ectopic synaptic repression. These data suggest that Klg play a critical role together with cDIP in refining synaptic specificity and preventing unnecessary connections in the brain.


Assuntos
Moléculas de Adesão Celular/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiologia , Proteínas do Olho/metabolismo , Neuroglia/fisiologia , Células Fotorreceptoras de Invertebrados/fisiologia , Sinapses/fisiologia , Vias Visuais , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/fisiologia , Axônios/fisiologia , Moléculas de Adesão Celular/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas do Olho/genética , Feminino
16.
PLoS Comput Biol ; 15(5): e1006892, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31050662

RESUMO

In order to record the stream of autobiographical information that defines our unique personal history, our brains must form durable memories from single brief exposures to the patterned stimuli that impinge on them continuously throughout life. However, little is known about the computational strategies or neural mechanisms that underlie the brain's ability to perform this type of "online" learning. Based on increasing evidence that dendrites act as both signaling and learning units in the brain, we developed an analytical model that relates online recognition memory capacity to roughly a dozen dendritic, network, pattern, and task-related parameters. We used the model to determine what dendrite size maximizes storage capacity under varying assumptions about pattern density and noise level. We show that over a several-fold range of both of these parameters, and over multiple orders-of-magnitude of memory size, capacity is maximized when dendrites contain a few hundred synapses-roughly the natural number found in memory-related areas of the brain. Thus, in comparison to entire neurons, dendrites increase storage capacity by providing a larger number of better-sized learning units. Our model provides the first normative theory that explains how dendrites increase the brain's capacity for online learning; predicts which combinations of parameter settings we should expect to find in the brain under normal operating conditions; leads to novel interpretations of an array of existing experimental results; and provides a tool for understanding which changes associated with neurological disorders, aging, or stress are most likely to produce memory deficits-knowledge that could eventually help in the design of improved clinical treatments for memory loss.


Assuntos
Dendritos/fisiologia , Memória/fisiologia , Recognição (Psicologia)/fisiologia , Animais , Encéfalo/fisiologia , Simulação por Computador , Dendritos/metabolismo , Humanos , Aprendizagem/fisiologia , Modelos Neurológicos , Redes Neurais (Computação) , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia
17.
PLoS Comput Biol ; 15(5): e1006998, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060045

RESUMO

Cortico-basal-ganglia-thalamic (CBGT) networks are critical for adaptive decision-making, yet how changes to circuit-level properties impact cognitive algorithms remains unclear. Here we explore how dopaminergic plasticity at corticostriatal synapses alters competition between striatal pathways, impacting the evidence accumulation process during decision-making. Spike-timing dependent plasticity simulations showed that dopaminergic feedback based on rewards modified the ratio of direct and indirect corticostriatal weights within opposing action channels. Using the learned weight ratios in a full spiking CBGT network model, we simulated neural dynamics and decision outcomes in a reward-driven decision task and fit them with a drift diffusion model. Fits revealed that the rate of evidence accumulation varied with inter-channel differences in direct pathway activity while boundary height varied with overall indirect pathway activity. This multi-level modeling approach demonstrates how complementary learning and decision computations can emerge from corticostriatal plasticity.


Assuntos
Tomada de Decisões/fisiologia , Neurônios Dopaminérgicos/fisiologia , Rede Nervosa/fisiologia , Animais , Gânglios da Base , Corpo Estriado , Retroalimentação , Humanos , Aprendizagem , Modelos Neurológicos , Vias Neurais/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Reforço (Psicologia) , Recompensa , Sinapses/fisiologia , Tálamo
18.
PLoS Comput Biol ; 15(5): e1006999, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31095556

RESUMO

GABAergic interneurons play an important role in shaping the activity of excitatory pyramidal cells (PCs). How the various inhibitory cell types contribute to neuronal information processing, however, is not resolved. Here, we propose a functional role for a widespread network motif consisting of parvalbumin- (PV), somatostatin- (SOM) and vasoactive intestinal peptide (VIP)-expressing interneurons. Following the idea that PV and SOM interneurons control the distribution of somatic and dendritic inhibition onto PCs, we suggest that mutual inhibition between VIP and SOM cells translates weak inputs to VIP interneurons into large changes of somato-dendritic inhibition of PCs. Using a computational model, we show that the neuronal and synaptic properties of the circuit support this hypothesis. Moreover, we demonstrate that the SOM-VIP motif allows transient inputs to persistently switch the circuit between two processing modes, in which top-down inputs onto apical dendrites of PCs are either integrated or cancelled.


Assuntos
Células Dendríticas/fisiologia , Interneurônios/fisiologia , Células Piramidais/fisiologia , Animais , Simulação por Computador , Dendritos/fisiologia , Neurônios GABAérgicos/fisiologia , Humanos , Neurônios/metabolismo , Parvalbuminas/metabolismo , Córtex Somatossensorial/fisiologia , Somatostatina/metabolismo , Sinapses/fisiologia , Peptídeo Intestinal Vasoativo/metabolismo
19.
Nature ; 569(7755): 208-214, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31068721

RESUMO

Software implementations of brain-inspired computing underlie many important computational tasks, from image processing to speech recognition, artificial intelligence and deep learning applications. Yet, unlike real neural tissue, traditional computing architectures physically separate the core computing functions of memory and processing, making fast, efficient and low-energy computing difficult to achieve. To overcome such limitations, an attractive alternative is to design hardware that mimics neurons and synapses. Such hardware, when connected in networks or neuromorphic systems, processes information in a way more analogous to brains. Here we present an all-optical version of such a neurosynaptic system, capable of supervised and unsupervised learning. We exploit wavelength division multiplexing techniques to implement a scalable circuit architecture for photonic neural networks, successfully demonstrating pattern recognition directly in the optical domain. Such photonic neurosynaptic networks promise access to the high speed and high bandwidth inherent to optical systems, thus enabling the direct processing of optical telecommunication and visual data.


Assuntos
Biomimética/métodos , Modelos Neurológicos , Redes Neurais (Computação) , Reconhecimento Automatizado de Padrão/métodos , Fótons , Aprendizado de Máquina Supervisionado , Aprendizado de Máquina não Supervisionado , Potenciais de Ação , Sistemas de Computação , Computadores , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Sinapses/fisiologia
20.
PLoS Comput Biol ; 15(5): e1007012, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31083649

RESUMO

Neuronal synapses transmit electrochemical signals between cells through the coordinated action of presynaptic vesicles, ion channels, scaffolding and adapter proteins, and membrane receptors. In situ structural characterization of numerous synaptic proteins simultaneously through multiplexed imaging facilitates a bottom-up approach to synapse classification and phenotypic description. Objective automation of efficient and reliable synapse detection within these datasets is essential for the high-throughput investigation of synaptic features. Convolutional neural networks can solve this generalized problem of synapse detection, however, these architectures require large numbers of training examples to optimize their thousands of parameters. We propose DoGNet, a neural network architecture that closes the gap between classical computer vision blob detectors, such as Difference of Gaussians (DoG) filters, and modern convolutional networks. DoGNet is optimized to analyze highly multiplexed microscopy data. Its small number of training parameters allows DoGNet to be trained with few examples, which facilitates its application to new datasets without overfitting. We evaluate the method on multiplexed fluorescence imaging data from both primary mouse neuronal cultures and mouse cortex tissue slices. We show that DoGNet outperforms convolutional networks with a low-to-moderate number of training examples, and DoGNet is efficiently transferred between datasets collected from separate research groups. DoGNet synapse localizations can then be used to guide the segmentation of individual synaptic protein locations and spatial extents, revealing their spatial organization and relative abundances within individual synapses. The source code is publicly available: https://github.com/kulikovv/dognet.


Assuntos
Modelos Neurológicos , Redes Neurais (Computação) , Sinapses/fisiologia , Sinapses/ultraestrutura , Animais , Córtex Cerebral/fisiologia , Córtex Cerebral/ultraestrutura , Biologia Computacional , Simulação por Computador , Bases de Dados Factuais , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Camundongos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Microscopia de Fluorescência por Excitação Multifotônica/estatística & dados numéricos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/fisiologia , Neurônios/ultraestrutura , Software , Transmissão Sináptica/fisiologia
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