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1.
Front Neural Circuits ; 16: 939235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389180

RESUMO

The prefrontal cortex plays a central role in the control of complex cognitive processes including action control and decision making. It also shows a specific pattern of delayed maturation related to unique behavioral changes during adolescence and allows the development of adult cognitive processes. The adolescent brain is extremely plastic and critically vulnerable to external insults. Related to this vulnerability, adolescence is also associated with the emergence of numerous neuropsychiatric disorders involving alterations of prefrontal functions. Within prefrontal microcircuits, the dopamine and the endocannabinoid systems have widespread effects on adolescent-specific ontogenetic processes. In this review, we highlight recent advances in our understanding of the maturation of the dopamine system and the endocannabinoid system in the prefrontal cortex during adolescence. We discuss how they interact with GABA and glutamate neurons to modulate prefrontal circuits and how they can be altered by different environmental events leading to long-term neurobiological and behavioral changes at adulthood. Finally, we aim to identify several future research directions to help highlight gaps in our current knowledge on the maturation of these microcircuits.


Assuntos
Dopamina , Endocanabinoides , Adolescente , Humanos , Adulto , Dopamina/fisiologia , Córtex Pré-Frontal/fisiologia , Período Crítico Psicológico , Encéfalo
2.
Front Neural Circuits ; 16: 875873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601531

RESUMO

From birth to adolescence, the brain adapts to its environmental stimuli through structural and functional remodeling of neural circuits during critical periods of heightened plasticity. They occur across modalities for proper sensory, motor, linguistic, and cognitive development. If they are disrupted by early-life adverse experiences or genetic deficiencies, lasting consequences include behavioral changes, physiological and cognitive deficits, or psychiatric illness. Critical period timing is orchestrated not only by appropriate neural activity but also by a multitude of signals that participate in the maturation of fast-spiking parvalbumin interneurons and the consolidation of neural circuits. In this review, we describe the various signaling factors that initiate critical period onset, such as BDNF, SPARCL1, or OTX2, which originate either from local neurons or glial cells or from extracortical sources such as the choroid plexus. Critical period closure is established by signals that modulate extracellular matrix and myelination, while timing and plasticity can also be influenced by circadian rhythms and by hormones and corticosteroids that affect brain oxidative stress levels or immune response. Molecular outcomes include lasting epigenetic changes which themselves can be considered signals that shape downstream cross-modal critical periods. Comprehensive knowledge of how these signals and signaling factors interplay to influence neural mechanisms will help provide an inclusive perspective on the effects of early adversity and developmental defects that permanently change perception and behavior.


Assuntos
Interneurônios , Parvalbuminas , Encéfalo/metabolismo , Período Crítico Psicológico , Matriz Extracelular/metabolismo , Interneurônios/fisiologia , Plasticidade Neuronal/fisiologia , Parvalbuminas/metabolismo
3.
Ber Wiss ; 45(1-2): 112-134, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35266169

RESUMO

This article offers a canine history of the "critical period" concept, situating its emergence within a growing, interdisciplinary network of canine behavior studies that connected eugenically minded American veterinarians, behavioral geneticists, and dog lovers with large institutional benefactors. These studies established both logistical and conceptual foundations for large-scale science with dogs while establishing a lingering interdependence between American dog science and eugenics. The article emphasizes the importance of dogs as subjects of ethological study, particularly in the United States, where some of the earliest organized efforts to analyze canine behavior began. Further, the article argues that the "critical period" is important not only for its lasting prominence in multiple fields of scientific inquiry, but also as a historiographical tool, one that invites reflection on the tendency of historians to emphasize a particular narrative structure of scientific advancement.


Assuntos
Historiografia , Médicos Veterinários , Animais , Período Crítico Psicológico , Cães , Eugenia (Ciência) , Humanos , Estados Unidos
4.
J Neurosci ; 42(9): 1702-1718, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35031575

RESUMO

Cortical layer 1 (L1) contains a diverse population of interneurons that can modulate processing in superficial cortical layers, but the intracortical sources of synaptic input to these neurons and how these inputs change over development and with sensory experience is unknown. We here investigated the changing intracortical connectivity to L1 in the primary auditory cortex (A1) of mice of both sexes in in vitro slices across development using laser-scanning photostimulation. Before postnatal day (P)10, L1 cells receive excitatory input from within L1, L2/3, L4, and L5/6 as well as from subplate. Excitatory inputs from all layers increase, especially from L4, and peak during P10-P16, around the peak of the critical period for tonotopy. Inhibitory inputs followed a similar pattern. Functional circuit diversity in L1 emerges after P16. In adults, L1 neurons receive ascending inputs from L2/3 and L5/6, but only few inputs from L4. The transient hyperconnectivity from deep layers but not L2/3 is absent in deaf mice. Our results demonstrate that deep excitatory and superficial inhibitory circuits are tightly linked in early development and might provide a functional scaffold for the layers in between. These results suggest that early thalamically driven spontaneous and sensory activity in subplate can be relayed to L1 from the earliest ages on and shape L1 connectivity from deep layers. Our results also reveal a period of high transient columnar hyperconnectivity after ear opening coinciding with the critical period, suggesting that circuits originating in deep layers might play a key role in this process.SIGNIFICANCE STATEMENT L1 contains a diverse population of interneurons that can modulate processing in superficial cortical layers but the sources of synaptic input to these neurons and how these inputs change over development is unknown. We found that during the critical period a large fraction of excitatory inputs to L1 originated in L5/6 and the cortical subplate. This hyperconnectivity is absent in deaf mice. Our results directly demonstrate that deep excitatory and superficial inhibitory circuits are tightly linked in early development and might provide a functional scaffold for the layers in between.


Assuntos
Período Crítico Psicológico , Neurônios , Animais , Feminino , Interneurônios/fisiologia , Masculino , Camundongos , Neurônios/fisiologia
5.
Cereb Cortex ; 32(5): 970-986, 2022 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-34398233

RESUMO

During postnatal development, sensory experience shapes the organization and function of cortical circuits. Previous studies focusing on experience-dependent plasticity of neurons have revealed a variety of mechanisms underlying cortical circuit rewiring. Emerging evidence shows that astrocytes play important roles in shaping cortical circuits through extensive interactions with different types of neurons and other glia cells. However, it remains unclear how astrocytes respond to sensory experience during postnatal development. In the present study, we profiled the maturation of astrocytes in the primary visual cortex (V1) at different postnatal stages. We then investigated the anatomical and physiological changes of astrocytes in V1 induced by multiple types of visual experience within 4 postnatal weeks. Compared with monocular deprivation during the critical period, binocular deprivation showed stronger impact on reactive astrocytes in V1. Moreover, long-term binocular deprivation significantly reduced the density of reactive astrocytes in layer 2/3 of V1 while strengthening gap junction couplings between astrocytes at the same time. Therefore, our data demonstrated that cortical astrocytes could undergo homeostatic plasticity in response to long-term changes of sensory inputs. The plasticity of astrocytes may interact with the plasticity of neurons to cooperatively shape cortical circuit refinement during postnatal development.


Assuntos
Córtex Visual , Astrócitos , Período Crítico Psicológico , Plasticidade Neuronal/fisiologia , Privação Sensorial/fisiologia , Córtex Visual/fisiologia
6.
Cereb Cortex ; 32(8): 1769-1786, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-34470051

RESUMO

The molecular regulation of the temporal dynamics of circuit maturation is a key contributor to the emergence of normal structure-function relations. Developmental control of cortical MET receptor tyrosine kinase, expressed early postnatally in subpopulations of excitatory neurons, has a pronounced impact on the timing of glutamatergic synapse maturation and critical period plasticity. Here, we show that using a controllable overexpression (cto-Met) transgenic mouse, extending the duration of MET signaling after endogenous Met is switched off leads to altered molecular constitution of synaptic proteins, persistent activation of small GTPases Cdc42 and Rac1, and sustained inhibitory phosphorylation of cofilin. These molecular changes are accompanied by an increase in the density of immature dendritic spines, impaired cortical circuit maturation of prefrontal cortex layer 5 projection neurons, and altered laminar excitatory connectivity. Two photon in vivo imaging of dendritic spines reveals that cto-Met enhances de novo spine formation while inhibiting spine elimination. Extending MET signaling for two weeks in developing cortical circuits leads to pronounced repetitive activity and impaired social interactions in adult mice. Collectively, our data revealed that temporally controlled MET signaling as a critical mechanism for controlling cortical circuit development and emergence of normal behavior.


Assuntos
Neurônios , Sinapses , Animais , Período Crítico Psicológico , Espinhas Dendríticas/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-34611741

RESUMO

Cooperative behavior often arises when a common exploitable resource is generated. Cooperation can provide equitable distribution and protection from raiding of a common resource such as processed food. Under crowded conditions in liquid food, Drosophila larvae adopt synchronized feeding behavior which provides a fitness benefit. A key for this synchronized feeding behavior is the visually guided alignment of a 1-2 s locomotion stride between adjacent larvae in a feeding cluster. The locomotion stride is thought to be set by embryonic incubation temperature. This raises a question as to whether sib larvae will only cluster efficiently if they hatch at the same temperature. To test this, larvae were first collected and incubated in outdoor conditions. Morning hatched lower temperature larvae move slower than their afternoon higher temperature sibs. Both temperature types synchronize but tend to exclude the other type of larvae from their clusters. In addition, fitness, as measured by adult wing size, is highest when larvae cluster with their own temperature type. Thus, the temperature at which an egg is laid sets a type of behavioral stamp or password which locks in membership for later cooperative feeding.


Assuntos
Período Crítico Psicológico , Aglomeração , Processos Grupais , Parto/fisiologia , Temperatura , Percepção Visual/fisiologia , Animais , Comportamento Cooperativo , Drosophila melanogaster , Comportamento Alimentar/fisiologia , Feminino , Larva/fisiologia , Asas de Animais/crescimento & desenvolvimento
8.
Science ; 373(6550): 77-81, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34210880

RESUMO

Brain postnatal development is characterized by critical periods of experience-dependent remodeling of neuronal circuits. Failure to end these periods results in neurodevelopmental disorders. The cellular processes defining critical-period timing remain unclear. Here, we show that in the mouse visual cortex, astrocytes control critical-period closure. We uncover the underlying pathway, which involves astrocytic regulation of the extracellular matrix, allowing interneuron maturation. Unconventional astrocyte connexin signaling hinders expression of extracellular matrix-degrading enzyme matrix metalloproteinase 9 (MMP9) through RhoA-guanosine triphosphatase activation. Thus, astrocytes not only influence the activity of single synapses but also are key elements in the experience-dependent wiring of brain circuits.


Assuntos
Astrócitos/fisiologia , Período Crítico Psicológico , Plasticidade Neuronal , Córtex Visual/crescimento & desenvolvimento , Animais , Astrócitos/metabolismo , Conexina 30/metabolismo , Ativação Enzimática , GTP Fosfo-Hidrolases/metabolismo , Interneurônios/metabolismo , Interneurônios/fisiologia , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Sinapses/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
9.
Cognition ; 214: 104706, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34052616

RESUMO

The ability to attain native-like proficiency of a second language is heavily dependent on the age at which learning begins. However, the exact properties of this phenomenon remain unclear, and the literature is divided. Recently, Hartshorne, Tenenbaum, & Pinker presented a novel computational analysis of over 600,000 subjects, estimating that the ability to learn syntax drops at 17.4 years of age [Hartshorne, J. K., Tenenbaum, J. B., & Pinker, S. (2018). A critical period for second language acquisition: Evidence from 2/3 million English speakers. Cognition, 177, 263-277]. However, the novelty of the dataset and analyses raises questions and suggests caution [Frank, M. C. (2018). With great data comes great (theoretical) opportunity. Trends in cognitive sciences, 22(8), 669-671]. In the present paper, we address several such concerns by employing improved psychometric measurement, calculating confidence intervals, and considering alternative models. We also present data from an additional 466,607 subjects. The results support the prior report of a sharp decline in the ability to learn syntax, commencing at the tail end of adolescence.


Assuntos
Período Crítico Psicológico , Desenvolvimento da Linguagem , Adolescente , Cognição , Humanos , Idioma , Aprendizagem
10.
Neurosci Res ; 167: 3-10, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33872635

RESUMO

Experience-dependent plasticity within visual cortex is controlled by postnatal maturation of inhibitory circuits, which are both morphologically diverse and precisely connected. Gene-targeted disruption of the voltage-dependent potassium channel Kv3.1 broadens action potentials and reduces net inhibitory function of parvalbumin (PV)-positive GABA subtypes within the neocortex. In mice lacking Kv3.1, the rate of input loss from an eye deprived of vision was slowed two-fold, despite otherwise normal critical period timecourse and receptive field properties. Rapid ocular dominance plasticity was restored by local or systemic enhancement of GABAergic transmission with acute benzodiazepine infusion. Diazepam instead exacerbated a global suppression of slow-wave oscillations during sleep described previously in these mutant mice, which therefore did not account for the rescued plasticity. Rapid ocular dominance shifts closely reflected Kv3.1 gene dosage that prevented prolonged spike discharge of their target pyramidal cells in vivo or the spike amplitude decrement of fast-spiking cells during bouts of high-frequency firing in vitro. Late postnatal expression of this unique channel in fast-spiking interneurons thus subtly regulates the speed of critical period plasticity with implications for mental illnesses.


Assuntos
Neocórtex , Canais de Potássio Shaw , Animais , Período Crítico Psicológico , Interneurônios/metabolismo , Camundongos , Neocórtex/metabolismo , Plasticidade Neuronal , Parvalbuminas/metabolismo , Canais de Potássio Shaw/genética , Canais de Potássio Shaw/metabolismo
11.
Nature ; 592(7854): 360-361, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33828277
12.
Nature ; 592(7854): 414-420, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33828296

RESUMO

Critical periods-brief intervals during which neural circuits can be modified by activity-are necessary for proper neural circuit assembly. Extended critical periods are associated with neurodevelopmental disorders; however, the mechanisms that ensure timely critical period closure remain poorly understood1,2. Here we define a critical period in a developing Drosophila motor circuit and identify astrocytes as essential for proper critical period termination. During the critical period, changes in activity regulate dendrite length, complexity and connectivity of motor neurons. Astrocytes invaded the neuropil just before critical period closure3, and astrocyte ablation prolonged the critical period. Finally, we used a genetic screen to identify astrocyte-motor neuron signalling pathways that close the critical period, including Neuroligin-Neurexin signalling. Reduced signalling destabilized dendritic microtubules, increased dendrite dynamicity and impaired locomotor behaviour, underscoring the importance of critical period closure. Previous work defined astroglia as regulators of plasticity at individual synapses4; we show here that astrocytes also regulate motor circuit critical period closure to ensure proper locomotor behaviour.


Assuntos
Astrócitos/fisiologia , Período Crítico Psicológico , Drosophila melanogaster/citologia , Drosophila melanogaster/fisiologia , Vias Eferentes/fisiologia , Neurônios Motores/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Moléculas de Adesão Celular Neuronais/metabolismo , Dendritos/fisiologia , Feminino , Locomoção/fisiologia , Masculino , Microtúbulos/metabolismo , Neurópilo/fisiologia , Receptores de Superfície Celular/metabolismo , Transdução de Sinais , Sinapses/fisiologia , Fatores de Tempo
13.
Neurobiol Learn Mem ; 180: 107415, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33647449

RESUMO

Organisms have the unique ability to adapt to their environment by making use of external inputs. In the process, the brain is shaped by experiences that go hand-in-hand with optimisation of neural circuits. As such, there exists a time window for the development of different brain regions, each unique for a particular sensory modality, wherein the propensity of forming strong, irreversible connections are high, referred to as a critical period of development. Over the years, this domain of neurodevelopmental research has garnered considerable attention from many scientists, primarily because of the intensive activity-dependent nature of development. This review discusses the cellular, molecular, and neurophysiological bases of critical periods of different sensory modalities, and the disorders associated in cases the regulators of development are dysfunctional. Eventually, the neurobiological bases of the behavioural abnormalities related to developmental pathologies are discussed. A more in-depth insight into the development of the brain during the critical period of plasticity will eventually aid in developing potential therapeutics for several neurodevelopmental disorders that are categorised under critical period disorders.


Assuntos
Encéfalo/crescimento & desenvolvimento , Período Crítico Psicológico , Transtornos do Neurodesenvolvimento/fisiopatologia , Animais , Ansiedade , Transtorno do Espectro Autista/fisiopatologia , Diferenciação Celular/fisiologia , Córtex Cerebral/crescimento & desenvolvimento , Humanos , Deficiência Intelectual/fisiopatologia , Neurogênese/fisiologia , Neuroglia , Plasticidade Neuronal/fisiologia , Comportamento Social
14.
Neural Plast ; 2021: 6611922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777134

RESUMO

Throughout life, sensory systems adapt to the sensory environment to provide optimal responses to relevant tasks. In the case of a developing system, sensory inputs induce changes that are permanent and detectable up to adulthood. Previously, we have shown that rearing rat pups in a complex acoustic environment (spectrally and temporally modulated sound) from postnatal day 14 (P14) to P28 permanently improves the response characteristics of neurons in the inferior colliculus and auditory cortex, influencing tonotopical arrangement, response thresholds and strength, and frequency selectivity, along with stochasticity and the reproducibility of neuronal spiking patterns. In this study, we used a set of behavioral tests based on a recording of the acoustic startle response (ASR) and its prepulse inhibition (PPI), with the aim to extend the evidence of the persistent beneficial effects of the developmental acoustical enrichment. The enriched animals were generally not more sensitive to startling sounds, and also, their PPI of ASR, induced by noise or pure tone pulses, was comparable to the controls. They did, however, exhibit a more pronounced PPI when the prepulse stimulus was represented either by a change in the frequency of a background tone or by a silent gap in background noise. The differences in the PPI of ASR between the enriched and control animals were significant at lower (55 dB SPL), but not at higher (65-75 dB SPL), intensities of background sound. Thus, rearing pups in the acoustically enriched environment led to an improvement of the frequency resolution and gap detection ability under more difficult testing conditions, i.e., with a worsened stimulus clarity. We confirmed, using behavioral tests, that an acoustically enriched environment during the critical period of development influences the frequency and temporal processing in the auditory system, and these changes persist until adulthood.


Assuntos
Estimulação Acústica/métodos , Percepção Auditiva/fisiologia , Período Crítico Psicológico , Meio Ambiente , Discriminação da Altura Tonal/fisiologia , Reflexo de Sobressalto/fisiologia , Fatores Etários , Animais , Animais Recém-Nascidos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Feminino , Ratos , Ratos Long-Evans
15.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670945

RESUMO

During restricted time windows of postnatal life, called critical periods, neural circuits are highly plastic and are shaped by environmental stimuli. In several mammalian brain areas, from the cerebral cortex to the hippocampus and amygdala, the closure of the critical period is dependent on the formation of perineuronal nets. Perineuronal nets are a condensed form of an extracellular matrix, which surrounds the soma and proximal dendrites of subsets of neurons, enwrapping synaptic terminals. Experimentally disrupting perineuronal nets in adult animals induces the reactivation of critical period plasticity, pointing to a role of the perineuronal net as a molecular brake on plasticity as the critical period closes. Interestingly, in the adult brain, the expression of perineuronal nets is remarkably dynamic, changing its plasticity-associated conditions, including memory processes. In this review, we aimed to address how perineuronal nets contribute to the maturation of brain circuits and the regulation of adult brain plasticity and memory processes in physiological and pathological conditions.


Assuntos
Encéfalo/fisiologia , Matriz Extracelular , Plasticidade Neuronal , Animais , Encéfalo/crescimento & desenvolvimento , Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/fisiologia , Período Crítico Psicológico , Humanos
16.
J Comp Neurol ; 529(11): 2883-2910, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33683706

RESUMO

In Long Evans rats, ocular dominance columns (ODCs) in V1 overlap with patches of callosal connections. Using anatomical tracers, we found that ODCs and callosal patches are present at postnatal day 10 (P10), several days before eye opening, and about 10 days before the activation of the critical period for ocular dominance plasticity (~P20). In rats monocularly enucleated at P10 and perfused ~P20, ODCs ipsilateral to the remaining eye desegregated, indicating that rat ODCs are highly susceptible to monocular enucleation during a precritical period. Monocular enucleation during the critical period exerted significant, although smaller, effects. Monocular eye lid suture during the critical period led to a significant expansion of the ipsilateral projection from the nondeprived eye, whereas the contralateral projection invaded into, and intermixed with, ipsilateral ODCs innervated by the deprived eye. We propose that this intermixing allows callosal connections to contribute to the effects of monocular deprivation assessed in the hemisphere ipsilateral to the nondeprived eye. The ipsilateral and contralateral projections from the deprived eye did not undergo significant shrinkage. In contrast, we found that callosal patches are less susceptible to imbalance of eye input. In rats monocularly enucleated during either the precritical or critical periods, callosal patches were maintained in the hemisphere ipsilateral to the remaining eye, but desegregated in the hemisphere ipsilateral to the enucleated orbit. Callosal patches were maintained in rats binocularly enucleated at P10 or later. Similarly, monocular deprivation during the critical period had no significant effect on callosal patches in either hemisphere.


Assuntos
Corpo Caloso/crescimento & desenvolvimento , Período Crítico Psicológico , Dominância Ocular/fisiologia , Visão Monocular/fisiologia , Córtex Visual/crescimento & desenvolvimento , Vias Visuais/crescimento & desenvolvimento , Fatores Etários , Animais , Animais Recém-Nascidos , Corpo Caloso/química , Estimulação Luminosa/métodos , Ratos , Ratos Long-Evans , Privação Sensorial/fisiologia , Córtex Visual/química , Vias Visuais/química
17.
Prog Brain Res ; 259: 287-317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33541680

RESUMO

The adult brain is the result of a multistages complex neurodevelopmental process involving genetic, molecular and microenvironmental factors as well as diverse patterns of electrical activity. In the postnatal life, immature neuronal circuits undergo an experience-dependent maturation during critical periods of plasticity, but the brain still retains plasticity during adult life. In all these stages, the neurotransmitter GABA plays a pivotal role. In this chapter, we will describe the interaction of 5-HT with GABA in regulating neurodevelopment and plasticity.


Assuntos
Córtex Visual , Período Crítico Psicológico , Plasticidade Neuronal , Serotonina , Ácido gama-Aminobutírico
18.
J Neurosci ; 41(6): 1218-1241, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33402421

RESUMO

Critical periods are developmental windows during which neural circuits effectively adapt to the new sensory environment. Animal models of fragile X syndrome (FXS), a common monogenic autism spectrum disorder (ASD), exhibit profound impairments of sensory experience-driven critical periods. However, it is not known whether the causative fragile X mental retardation protein (FMRP) acts uniformly across neurons, or instead manifests neuron-specific functions. Here, we use the genetically-tractable Drosophila brain antennal lobe (AL) olfactory circuit of both sexes to investigate neuron-specific FMRP roles in the odorant experience-dependent remodeling of the olfactory sensory neuron (OSN) innervation during an early-life critical period. We find targeted OSN class-specific FMRP RNAi impairs innervation remodeling within AL synaptic glomeruli, whereas global dfmr1 null mutants display relatively normal odorant-driven refinement. We find both OSN cell autonomous and cell non-autonomous FMRP functions mediate odorant experience-dependent remodeling, with AL circuit FMRP imbalance causing defects in overall glomerulus innervation refinement. We find OSN class-specific FMRP levels bidirectionally regulate critical period remodeling, with odorant experience selectively controlling OSN synaptic terminals in AL glomeruli. We find OSN class-specific FMRP loss impairs critical period remodeling by disrupting responses to lateral modulation from other odorant-responsive OSNs mediating overall AL gain control. We find that silencing glutamatergic AL interneurons reduces OSN remodeling, while conversely, interfering with the OSN class-specific GABAA signaling enhances remodeling. These findings reveal control of OSN synaptic remodeling by FMRP with neuron-specific circuit functions, and indicate how neural circuitry can compensate for global FMRP loss to reinstate normal critical period brain circuit remodeling.SIGNIFICANCE STATEMENT Fragile X syndrome (FXS), the leading monogenic cause of intellectual disability and autism spectrum disorder (ASD), manifests severe neurodevelopmental delays. Likewise, FXS disease models display disrupted neurodevelopmental critical periods. In the well-mapped Drosophila olfactory circuit model, perturbing the causative fragile X mental retardation protein (FMRP) within a single olfactory sensory neuron (OSN) class impairs odorant-dependent remodeling during an early-life critical period. Importantly, this impairment requires activation of other OSNs, and the olfactory circuit can compensate when FMRP is removed from all OSNs. Understanding the neuron-specific FMRP requirements within a developing neural circuit, as well as the FMRP loss compensation mechanisms, should help us engineer FXS treatments. This work suggests FXS treatments could use homeostatic mechanisms to alleviate circuit-level deficits.


Assuntos
Período Crítico Psicológico , Proteína do X Frágil de Retardo Mental/metabolismo , Síndrome do Cromossomo X Frágil/metabolismo , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Córtex Olfatório/crescimento & desenvolvimento , Córtex Olfatório/metabolismo , Animais , Animais Geneticamente Modificados , Drosophila , Feminino , Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/genética , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/química , Neurônios/efeitos dos fármacos , Odorantes , Bulbo Olfatório/química , Bulbo Olfatório/metabolismo , Córtex Olfatório/química , Neurônios Receptores Olfatórios/química , Neurônios Receptores Olfatórios/metabolismo , Optogenética/métodos
19.
Cognition ; 206: 104478, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33075566

RESUMO

Hartshorne et al. (2018) used a very large sample in order to disentangle the effects of age, years of experience, and age of exposure from each other in context of second-language acquisition. Participants were administered an online test of English grammar. Results revealed a critical period ending around 17 years of age for the most effective acquisition of a second language (L2). The findings of a late cutoff indicate the age range of late childhood to late adolescence as crucial for learning an L2. In this piece, we argue that these results can be conceptualized by emergentist models of language acquisition in which both behavior and brain interactively reorganize across development.


Assuntos
Multilinguismo , Adolescente , Criança , Período Crítico Psicológico , Humanos , Idioma , Desenvolvimento da Linguagem , Linguística
20.
Bioessays ; 43(1): e2000246, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33215730

RESUMO

Many sensory processing regions of the central brain undergo critical periods of experience-dependent plasticity. During this time ethologically relevant information shapes circuit structure and function. The mechanisms that control critical period timing and duration are poorly understood, and this is of special importance for those later periods of development, which often give rise to complex cognitive functions such as social behavior. Here, we review recent findings in Drosophila, an organism that has some unique experimental advantages, and introduce novel views for manipulating plasticity in the post-embryonic brain. Critical periods in larval and young adult flies resemble classic vertebrate models with distinct onset and termination, display clear connections with complex behaviors, and provide opportunities to control the time course of plasticity. These findings may extend our knowledge about mechanisms underlying extension and reopening of critical periods, a concept that has great relevance to many human neurodevelopmental disorders.


Assuntos
Drosophila , Transtornos do Neurodesenvolvimento , Animais , Encéfalo , Período Crítico Psicológico , Humanos , Plasticidade Neuronal
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