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17ß-estradiol (E2) is synthesized in the hippocampus of both sexes and acutely potentiates excitatory synapses in each sex. Previously, we found that the mechanisms for initiation of E2-induced synaptic potentiation differ between males and females, including in the molecular signaling involved. Here, we used electrical stimulation and two-photon glutamate uncaging in hippocampal slices from adult male and female rats to investigate whether the downstream consequences of distinct molecular signaling remain different between the sexes or converge to the same mechanism(s) of expression of potentiation. This showed that synaptic activity is necessary for expression of E2-induced potentiation in females but not males, which paralleled a sex-specific requirement in females for calcium-permeable AMPARs (cpAMPARs) to stabilize potentiation. Nonstationary fluctuation analysis of two-photon evoked unitary synaptic currents showed that the postsynaptic component of E2-induced potentiation occurs either through an increase in AMPAR conductance or in nonconductive properties of AMPARs (number of channels × open probability) and never both at the same synapse. In females, most synapses (76%) were potentiated via increased AMPAR conductance, whereas in males, more synapses (60%) were potentiated via an increase in nonconductive AMPAR properties. Inhibition of cpAMPARs eliminated E2-induced synaptic potentiation in females, whereas some synapses in males were unaffected by cpAMPAR inhibition; these synapses in males potentiated exclusively via increased AMPAR nonconductive properties. This sex bias in expression mechanisms of E2-induced synaptic potentiation underscores the concept of latent sex differences in mechanisms of synaptic plasticity in which the same outcome in each sex is achieved through distinct underlying mechanisms.SIGNIFICANCE STATEMENT Estrogens are synthesized in the brains of both sexes and potentiate excitatory synapses to the same degree in each sex. Despite this apparent similarity, the molecular signaling that initiates estrogen-induced synaptic potentiation differs between the sexes. Here we show that these differences extend to the mechanisms of expression of synaptic potentiation and result in distinct patterns of postsynaptic neurotransmitter receptor modulation in each sex. Such latent sex differences, in which the same outcome is achieved through distinct underlying mechanisms in males versus females, indicate that molecular mechanisms targeted for drug development may differ between the sexes even in the absence of an overt sex difference in behavior or disease.
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Estradiol , Hipocampo , Ratos , Feminino , Animais , Masculino , Estradiol/farmacologia , Hipocampo/fisiologia , Plasticidade Neuronal/fisiologia , Estrogênios/metabolismo , Sinapses/fisiologia , Potenciação de Longa Duração/fisiologiaRESUMO
The activity-dependent plasticity of synapses is believed to be the cellular basis of learning. These synaptic changes are mediated through the coordination of local biochemical reactions in synapses and changes in gene transcription in the nucleus to modulate neuronal circuits and behavior. The protein kinase C (PKC) family of isozymes has long been established as critical for synaptic plasticity. However, because of a lack of suitable isozyme-specific tools, the role of the novel subfamily of PKC isozymes is largely unknown. Here, through the development of fluorescence lifetime imaging-fluorescence resonance energy transfer activity sensors, we investigate novel PKC isozymes in synaptic plasticity in CA1 pyramidal neurons of mice of either sex. We find that PKCδ is activated downstream of TrkB and DAG production, and that the spatiotemporal nature of its activation depends on the plasticity stimulation. In response to single-spine plasticity, PKCδ is activated primarily in the stimulated spine and is required for local expression of plasticity. However, in response to multispine stimulation, a long-lasting and spreading activation of PKCδ scales with the number of spines stimulated and, by regulating cAMP response-element binding protein activity, couples spine plasticity to transcription in the nucleus. Thus, PKCδ plays a dual functional role in facilitating synaptic plasticity.SIGNIFICANCE STATEMENT Synaptic plasticity, or the ability to change the strength of the connections between neurons, underlies learning and memory and is critical for brain health. The protein kinase C (PKC) family is central to this process. However, understanding how these kinases work to mediate plasticity has been limited by a lack of tools to visualize and perturb their activity. Here, we introduce and use new tools to reveal a dual role for PKCδ in facilitating local synaptic plasticity and stabilizing this plasticity through spine-to-nucleus signaling to regulate transcription. This work provides new tools to overcome limitations in studying isozyme-specific PKC function and provides insight into molecular mechanisms of synaptic plasticity.
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Isoenzimas , Transdução de Sinais , Animais , Camundongos , Transdução de Sinais/fisiologia , Sinapses/fisiologia , Plasticidade Neuronal/fisiologia , Proteína Quinase C/metabolismoRESUMO
To evaluate bifunctional ligand reactivity involving NH acidic sites in the secondary coordination sphere of metal complexes, complexes where the proton has been substituted with a methyl group (NMe) are often investigated. An alternative strategy would involve substitution of the NH group for an O. This contribution considers and compares the merits of these approaches; the synthesis and characterization of cationic square planar Rh carbonyl complexes bearing diprotic bispyrazole pyridine ligand L1, and the bis-methylated pyrazole pyridine ligand L1Me are described. The syntheses and characterization of the novel monoprotic pyrazole isoxazole pyridine ligand L2 and aprotic bisisoxazole pyridine ligand L3, and their corresponding Rh carbonyl complexes are also described. The different CO stretching frequencies of all four Rh-complexes suggest that substitutions of NH with NMe, as well as O, lead to significant electronic differences, and these differences are further demonstrated to lead to different ligand addition/substitution reactivities of the four isoelectronic Rh-complexes. Overall, the results suggest that the electronic differences arising due to NH substitutions can be significant and must be accounted for prior to invoking the participation of the proton.
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OBJECTIVE: This proof-of-concept study assessed how confidently an artificial intelligence (AI) model can determine the sex of a fetus from an ultrasound image. STUDY DESIGN: Analysis was performed using 19,212 ultrasound image slices from a high-volume fetal sex determination practice. This dataset was split into a training set (11,769) and test set (7,443). A computer vision model was trained using a transfer learning approach with EfficientNetB4 architecture as base. The performance of the computer vision model was evaluated on the hold out test set. Accuracy, Cohen's Kappa and Multiclass Receiver Operating Characteristic area under the curve (AUC) were used to evaluate the performance of the model. RESULTS: The AI model achieved an Accuracy of 88.27% on the holdout test set and a Cohen's Kappa score 0.843. The ROC AUC score for Male was calculated to be 0.896, for Female a score of 0.897, for Unable to Assess a score of 0.916, and for Text Added a score of 0.981 was achieved. CONCLUSION: This novel AI model proved to have a high rate of fetal sex capture that could be of significant use in areas where ultrasound expertise is not readily available. KEY POINTS: · This is the first proof-of-concept AI model to determine fetal sex.. · This study adds to the growing research in ultrasound AI.. · Our findings demonstrate AI integration into obstetric care..
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BACKGROUND: The purpose of this study is to assess the viability of a knee arthroplasty prediction model using 3-view X-rays that helps determine if patients with knee pain are candidates for total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), or are not arthroplasty candidates. METHODS: Analysis was performed using radiographic and surgical data from a high-volume joint replacement practice. The dataset included 3 different X-ray views (anterior-posterior, lateral, and sunrise) for 2,767 patients along with information of whether that patient underwent an arthroplasty surgery (UKA or TKA) or not. This resulted in a dataset including 8,301 images from 2,707 patients. This dataset was then split into a training set (70%) and holdout test set (30%). A computer vision model was trained using a transfer learning approach. The performance of the computer vision model was evaluated on the holdout test set. Accuracy and multiclass receiver operating characteristic area under curve was used to evaluate the performance of the model. RESULTS: The artificial intelligence model achieved an accuracy of 87.8% on the holdout test set and a quadratic Cohen's kappa score of 0.811. The multiclass receiver operating characteristic area under curve score for TKA was calculated to be 0.97; for UKA a score of 0.96 and for No Surgery a score of 0.98 was achieved. An accuracy of 93.8% was achieved for predicting Surgery versus No Surgery and 88% for TKA versus not TKA was achieved. CONCLUSION: The artificial intelligence/machine learning model demonstrated viability for predicting which patients are candidates for a UKA, TKA, or no surgical intervention.
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Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Inteligência Artificial , Resultado do Tratamento , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Aprendizado de MáquinaRESUMO
Anant Jain (2021) Characteristics of early pleural effusions after orthotopic heart transplantation: comparison with coronary artery bypass graft surgery, (https://doi.org/10.4081/monaldi.2021.1740). The above article from the Monaldi Archives for Chest Disease published online on 24 November 2021, has been withdrawn by agreement between the journal's Editors-in-Chief, the Authors and PAGEPress Scientific Publications. This action has been agreed upon due to an administrative error by the publisher which caused the article to be published as an Accepted Article. The author is not responsible for this error. The publisher regrets any confusion this error may have caused.
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Excitatory synapses can be potentiated by chemical neuromodulators, including 17ß-estradiol (E2), or patterns of synaptic activation, as in long-term potentiation (LTP). Here, we investigated kinases and calcium sources required for acute E2-induced synaptic potentiation in the hippocampus of each sex and tested whether sex differences in kinase signaling extend to LTP. We recorded EPSCs from CA1 pyramidal cells in hippocampal slices from adult rats and used specific inhibitors of kinases and calcium sources. This revealed that, although E2 potentiates synapses to the same degree in each sex, cAMP-activated protein kinase (PKA) is required to initiate potentiation only in females. In contrast, mitogen-activated protein kinase, Src tyrosine kinase, and rho-associated kinase are required for initiation in both sexes; similarly, Ca2+/calmodulin-activated kinase II is required for expression/maintenance of E2-induced potentiation in both sexes. Calcium source experiments showed that L-type calcium channels and calcium release from internal stores are both required for E2-induced potentiation in females, whereas in males, either L-type calcium channel activation or calcium release from stores is sufficient to permit potentiation. To investigate the generalizability of a sex difference in the requirement for PKA in synaptic potentiation, we tested how PKA inhibition affects LTP. This showed that, although the magnitude of both high-frequency stimulation-induced and pairing-induced LTP is the same between sexes, PKA is required for LTP in females but not males. These results demonstrate latent sex differences in mechanisms of synaptic potentiation in which distinct molecular signaling converges to common functional endpoints in males and females.SIGNIFICANCE STATEMENT Chemical- and activity-dependent neuromodulation alters synaptic strength in both male and female brains, yet few studies have compared mechanisms of neuromodulation between the sexes. Here, we studied molecular signaling that underlies estrogen-induced and activity-dependent potentiation of excitatory synapses in the hippocampus. We found that, despite similar magnitude increases in synaptic strength in males and females, the roles of cAMP-regulated protein kinase, internal calcium stores, and L-type calcium channels differ between the sexes. Therefore, latent sex differences in which the same outcome is achieved through distinct underlying mechanisms in males and females include kinase and calcium signaling involved in synaptic potentiation, demonstrating that sex is an important factor in identification of molecular targets for therapeutic development based on mechanisms of neuromodulation.
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Região CA1 Hipocampal/fisiologia , Potenciais Pós-Sinápticos Excitadores , Animais , Região CA1 Hipocampal/metabolismo , Canais de Cálcio Tipo L/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Potenciação de Longa Duração , Masculino , Ratos , Ratos Sprague-Dawley , Fatores SexuaisRESUMO
Risk of alcoholic cirrhosis is determined by genetic and environmental factors. We aimed to investigate if climate has a causal effect on alcohol consumption and its weight on alcoholic cirrhosis. We collected extensive data from 193 sovereign countries as well as 50 states and 3,144 counties in the United States. Data sources included World Health Organization, World Meteorological Organization, and the Institute on Health Metrics and Evaluation. Climate parameters comprised Koppen-Geiger classification, average annual sunshine hours, and average annual temperature. Alcohol consumption data, pattern of drinking, health indicators, and alcohol-attributable fraction (AAF) of cirrhosis were obtained. The global cohort revealed an inverse correlation between mean average temperature and average annual sunshine hours with liters of annual alcohol consumption per capita (Spearman's rho -0.5 and -0.57, respectively). Moreover, the percentage of heavy episodic drinking and total drinkers among population inversely correlated with temperature -0.45 and -0.49 (P < 0.001) and sunshine hours -0.39 and -0.57 (P < 0.001). Importantly, AAF was inversely correlated with temperature -0.45 (P < 0.001) and sunshine hours -0.6 (P < 0.001). At a global level, all included parameters in the univariable and multivariable analysis showed an association with liters of alcohol consumption and drinkers among population once adjusted by potential confounders. In the multivariate analysis, liters of alcohol consumption associated with AAF. In the United States, colder climates showed a positive correlation with the age-standardized prevalence of heavy and binge drinkers. Conclusion: These results suggest that colder climates may play a causal role on AAF mediated by alcohol consumption.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Clima Frio/efeitos adversos , Cirrose Hepática Alcoólica/epidemiologia , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos Transversais , Humanos , Internacionalidade , Cirrose Hepática Alcoólica/etiologia , Luz Solar , Estados Unidos/epidemiologiaAssuntos
Hipertensão Pulmonar , Neoplasias Pancreáticas , Embolia Pulmonar , Trombose Venosa , Humanos , Trombose Venosa/complicações , Trombose Venosa/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico por imagemRESUMO
Aluminium dross, which is otherwise a hazardous waste, can be used for the synthesis of Tamarugite. Since aluminium dross is a good source of aluminium, utilizing the aluminium dross for the generation of valuable products is a reliable method of recycling this industrial waste. The motivation of the present research is to jointly recycle aluminium dross and synthesize Tamarugite. In this research article, the synthesis of Tamarugite was carried out using the addition of NaOH and H2SO4 solutions to aluminium dross. The dross reacts with NaOH to form NaAl(OH)4 and the addition of H2SO4 results in the generation of NaAl(SO4)2.6H2O. Since Tamarugite is a relatively rare mineral, its applications have not yet been reported much. However, the authors have explored the possibility of using Tamarugite as a coagulant and found that the mineral has excellent coagulation tendency. The authors believe that present research shall expand the new horizon for utilization of Tamarugite and recycling of aluminium dross.
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The possibility that mechanisms of synaptic modulation differ between males and females has far-reaching implications for understanding brain disorders that vary between the sexes. We found recently that 17ß-estradiol (E2) acutely suppresses GABAergic inhibition in the hippocampus of female rats through a sex-specific estrogen receptor α (ERα), mGluR, and endocannabinoid-dependent mechanism. Here, we define the intracellular signaling that links ERα, mGluRs, and endocannabinoids in females and identify where in this pathway males and females differ. Using a combination of whole-cell patch-clamp recording and biochemical analyses in hippocampal slices from young adult rats, we show that E2 acutely suppresses inhibition in females through mGluR1 stimulation of phospholipase C, leading to inositol triphosphate (IP3) generation, activation of the IP3 receptor (IP3R), and postsynaptic endocannabinoid release, likely of anandamide. Analysis of sex differences in this pathway showed that E2 stimulates a much greater increase in IP3 levels in females than males, whereas the group I mGluR agonist DHPG increases IP3 levels equivalently in each sex. Coimmunoprecipitation showed that ERα-mGluR1 and mGluR1-IP3R complexes exist in both sexes but are regulated by E2 only in females. Independently of E2, a fatty acid amide hydrolase inhibitor, which blocks breakdown of anandamide, suppressed >50% of inhibitory synapses in females with no effect in males, indicating tonic endocannabinoid release in females that is absent in males. Together, these studies demonstrate sex differences in both E2-dependent and E2-independent regulation of the endocannabinoid system and suggest that manipulation of endocannabinoids in vivo could affect physiological and behavioral responses differently in each sex. SIGNIFICANCE STATEMENT: Many brain disorders vary between the sexes, yet the degree to which this variation arises from differential experience versus intrinsic biological sex differences is unclear. In this study, we demonstrate intrinsic sex differences in molecular regulation of a key neuromodulatory system, the endocannabinoid system, in the hippocampus. Endocannabinoids are involved in diverse aspects of physiology and behavior that involve the hippocampus, including cognitive and motivational state, responses to stress, and neurological disorders such as epilepsy. Our finding that molecular regulation of the endocannabinoid system differs between the sexes suggests mechanisms through which experiences or therapeutics that engage endocannabinoids could affect males and females differently.
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Hipocampo/metabolismo , Inibição Neural/fisiologia , Caracteres Sexuais , Transdução de Sinais/fisiologia , Sinapses/metabolismo , Animais , Ácidos Araquidônicos/metabolismo , Endocanabinoides/metabolismo , Estradiol/farmacologia , Feminino , Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Alcamidas Poli-Insaturadas/metabolismo , Ratos , Receptores de Glutamato Metabotrópico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfolipases Tipo C/metabolismoRESUMO
Motor kinematics decoding (MKD) using brain signal is essential to develop Brain-computer interface (BCI) system for rehabilitation or prosthesis devices. Surface electroencephalogram (EEG) signal has been widely utilized for MKD. However, kinematic decoding from cortical sources is sparsely explored. In this work, the feasibility of hand kinematics decoding using EEG cortical source signals has been explored for grasp and lift task. In particular, pre-movement EEG segment is utilized. A residual convolutional neural network (CNN) - long short-term memory (LSTM) based kinematics decoding model is proposed that utilizes motor neural information present in pre-movement brain activity. Various EEG windows at 50 ms prior to movement onset, are utilized for hand kinematics decoding. Correlation value (CV) between actual and predicted hand kinematics is utilized as performance metric for source and sensor domain. The performance of the proposed deep learning model is compared in sensor and source domain. The results demonstrate the viability of hand kinematics decoding using pre-movement EEG cortical source data.
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Mãos , Redes Neurais de Computação , Fenômenos Biomecânicos , Extremidade Superior , Eletroencefalografia/métodosRESUMO
The ability to reconstruct the kinematic parameters of hand movement using noninvasive electroencephalography (EEG) is essential for strength and endurance augmentation using exoskeleton/exosuit. For system development, the conventional classification-based brain-computer interface (BCI) controls external devices by providing discrete control signals to the actuator. A continuous kinematic reconstruction from EEG signal is better suited for practical BCI applications. The state-of-the-art multivariable linear regression (mLR) method provides a continuous estimate of hand kinematics, achieving a maximum correlation of up to 0.67 between the measured and the estimated hand trajectory. In this work, three novel source aware deep learning models are proposed for motion trajectory prediction (MTP). In particular, multilayer perceptron (MLP), convolutional neural network-long short-term memory (CNN-LSTM), and wavelet packet decomposition (WPD) for CNN-LSTM are presented. In addition, novelty in the work includes the utilization of brain source localization (BSL) [using standardized low-resolution brain electromagnetic tomography (sLORETA)] for the reliable decoding of motor intention. The information is utilized for channel selection and accurate EEG time segment selection. The performance of the proposed models is compared with the traditionally utilized mLR technique on the reach, grasp, and lift (GAL) dataset. The effectiveness of the proposed framework is established using the Pearson correlation coefficient (PCC) and trajectory analysis. A significant improvement in the correlation coefficient is observed when compared with the state-of-the-art mLR model. Our work bridges the gap between the control and the actuator block, enabling real-time BCI implementation.
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Interfaces Cérebro-Computador , Aprendizado Profundo , Algoritmos , Fenômenos Biomecânicos , Eletroencefalografia/métodos , MãosRESUMO
Bronchoscopy has garnered increased popularity in the biopsy of peripheral lung lesions. The development of navigational guided bronchoscopy systems along with radial endobronchial ultrasound (REBUS) allows clinicians to access and sample peripheral lesions. The development of robotic bronchoscopy improved localization of targets and diagnostic accuracy. Despite such technological advancements, published diagnostic yield remains lower compared to computer tomography (CT)-guided biopsy. The discordance between the real-time location of peripheral lesions and anticipated location from preplanned navigation software is often cited as the main variable impacting accurate biopsies. The utilization of cone beam CT (CBCT) with navigation-based bronchoscopy has been shown to assist with localizing targets in real-time and improving biopsy success. The resources, costs, and radiation associated with CBCT remains a hindrance in its wider adoption. Recently, digital tomosynthesis (DT) platforms have been developed as an alternative for real-time imaging guidance in peripheral lung lesions. In North America, there are several commercial platforms with distinct features and adaptation of DT. Early studies show the potential improvement in peripheral lesion sampling with DT. Despite the results of early observational studies, the true impact of DT-based imaging devices for peripheral lesion sampling cannot be determined without further prospective randomized trials and meta-analyses.
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The insulin superfamily of peptides is essential for homeostasis as well as neuronal plasticity, learning, and memory. Here, we show that insulin-like growth factors 1 and 2 (IGF1 and IGF2) are differentially expressed in hippocampal neurons and released in an activity-dependent manner. Using a new fluorescence resonance energy transfer sensor for IGF1 receptor (IGF1R) with two-photon fluorescence lifetime imaging, we find that the release of IGF1 triggers rapid local autocrine IGF1R activation on the same spine and more than several micrometers along the stimulated dendrite, regulating the plasticity of the activated spine in CA1 pyramidal neurons. In CA3 neurons, IGF2, instead of IGF1, is responsible for IGF1R autocrine activation and synaptic plasticity. Thus, our study demonstrates the cell type-specific roles of IGF1 and IGF2 in hippocampal plasticity and a plasticity mechanism mediated by the synthesis and autocrine signaling of IGF peptides in pyramidal neurons.
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Comunicação Autócrina , Espinhas Dendríticas , Espinhas Dendríticas/fisiologia , Hipocampo/fisiologia , Plasticidade Neuronal/fisiologia , Células Piramidais/metabolismoRESUMO
The meta-reinforcement learning (meta-RL) framework, which involves RL over multiple timescales, has been successful in training deep RL models that generalize to new environments. It has been hypothesized that the prefrontal cortex may mediate meta-RL in the brain, but the evidence is scarce. Here we show that the orbitofrontal cortex (OFC) mediates meta-RL. We trained mice and deep RL models on a probabilistic reversal learning task across sessions during which they improved their trial-by-trial RL policy through meta-learning. Ca2+/calmodulin-dependent protein kinase II-dependent synaptic plasticity in OFC was necessary for this meta-learning but not for the within-session trial-by-trial RL in experts. After meta-learning, OFC activity robustly encoded value signals, and OFC inactivation impaired the RL behaviors. Longitudinal tracking of OFC activity revealed that meta-learning gradually shapes population value coding to guide the ongoing behavioral policy. Our results indicate that two distinct RL algorithms with distinct neural mechanisms and timescales coexist in OFC to support adaptive decision-making.
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Reforço Psicológico , Recompensa , Camundongos , Animais , Córtex Pré-Frontal/fisiologia , Reversão de Aprendizagem/fisiologiaRESUMO
Neocortical spiking dynamics control aspects of behavior, yet how these dynamics emerge during motor learning remains elusive. Activity-dependent synaptic plasticity is likely a key mechanism, as it reconfigures network architectures that govern neural dynamics. Here, we examined how the mouse premotor cortex acquires its well-characterized neural dynamics that control movement timing, specifically lick timing. To probe the role of synaptic plasticity, we have genetically manipulated proteins essential for major forms of synaptic plasticity, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Cofilin, in a region and cell-type-specific manner. Transient inactivation of CaMKII in the premotor cortex blocked learning of new lick timing without affecting the execution of learned action or ongoing spiking activity. Furthermore, among the major glutamatergic neurons in the premotor cortex, CaMKII and Cofilin activity in pyramidal tract (PT) neurons, but not intratelencephalic (IT) neurons, is necessary for learning. High-density electrophysiology in the premotor cortex uncovered that neural dynamics anticipating licks are progressively shaped during learning, which explains the change in lick timing. Such reconfiguration in behaviorally relevant dynamics is impeded by CaMKII manipulation in PT neurons. Altogether, the activity of plasticity-related proteins in PT neurons plays a central role in sculpting neocortical dynamics to learn new behavior.
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Behavioral time scale plasticity (BTSP), is a form of non-Hebbian plasticity induced by integrating pre- and postsynaptic components separated by behavioral time scale (seconds). BTSP in the hippocampal CA1 neurons underlies place cell formation. However, the molecular mechanisms underlying this behavioral time scale (eligibility trace) and synapse specificity are unknown. CaMKII can be activated in a synapse-specific manner and remain active for a few seconds, making it a compelling candidate for the eligibility trace during BTSP. Here, we show that BTSP can be induced in a single dendritic spine using 2-photon glutamate uncaging paired with postsynaptic current injection temporally separated by behavioral time scale. Using an improved CaMKII sensor, we saw no detectable CaMKII activation during this BTSP induction. Instead, we observed a dendritic, delayed, and stochastic CaMKII activation (DDSC) associated with Ca 2+ influx and plateau 20-40 s after BTSP induction. DDSC requires both pre-and postsynaptic activity, suggesting that CaMKII can integrate these two signals. Also, optogenetically blocking CaMKII 30 s after the BTSP protocol inhibited synaptic potentiation, indicating that DDSC is an essential mechanism of BTSP. IP3-dependent intracellular Ca 2+ release facilitates both DDSC and BTSP. Thus, our study suggests that the non-synapse specific CaMKII activation provides an instructive signal with an extensive time window over tens of seconds during BTSP.
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Herein we report a hydrogen-bonded three-dimensional network originating from a single source precursor, sym-triisopropylaminotriazine, that is both a donor and an acceptor of hydrogen bonds. The C3h symmetric design allowed the formation of intermolecular hydrogen bonds leading to helices in all three directions. The eccentric Piedfort units present in the framework with a distance of 8.15 Å between the two triazine rings allowed the CHCl3 guest to be parked.
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Syntheses of Vaska-type complexes [IrP2X(CO)] (P = phosphine, X = halide) with all four common halides (fluoride, chloride, bromide, and iodide) was attempted using a protic and hemilabile imidazolyl di-tert-butyl phosphine ligand. In the solid-state, all four complexes were found to be ionic with the halides in the outer-sphere, and the fourth coordination site of the square plane occupied by the imidazole arm of the ligand. In solution, however, the chloride complex was found to be in equilibrium with an octahedral IrIII-H species at room temperature. For the bromide and iodide analogs, the corresponding IrIII-H species were also observed but only after heating the solutions. The neutral IrI Vaska's analogs for X = Cl, Br, and I were obtained upon addition of excess halide salt, albeit heating was required for X = Br and I. The IrIII-H species are proposed to originate from tautomerization of minor amounts of the electron rich neutral Vaska analog (halide inner-sphere and phosphines monodentate) that are in equilibrium with the ionic species. Heating is required for the larger anions of bromide and iodide to overcome a kinetic barrier associated with their movement to an inner-sphere position prior to tautormerization. For the fluoride analog, the IrIII-H was not observed, attributable to strong hydrogen bonding interactions of the imidazolyl proton with the fluoride anion.