Functional Changes Research Articles

Comparison of local activation, functional connectivity, and structural connectivity in the N-back task.

The N-back task is widely used to investigate working memory. Previous functional magnetic resonance imaging (fMRI) studies have shown that local brain activation depends on the difficulty of the N-back task. Recently, changes in functional connectivity and local activation during a task, such as a single-hand movement task, have been reported to give the distinct information. However, previous studies have not investigated functional connectivity changes in the entire brain during N-back tasks. In this study, we compared alterations in functional connectivity and local activation related to the difficulty of the N-back task. Because structural connectivity has been reported to be associated with local activation, we also investigated the relationship between structural connectivity and accuracy in a N-back task using diffusion tensor imaging (DTI). Changes in functional connectivity depend on the difficulty of the N-back task in a manner different from local activation, and the 2-back task is the best method for investigating working memory. This indicates that local activation and functional connectivity reflect different neuronal events during the N-back task. The top 10 structural connectivities associated with accuracy in the 2-back task were locally activated during the 2-back task. Therefore, structural connectivity as well as fMRI will be useful for predicting the accuracy of the 2-back task.

Pulmonary MRI with hyperpolarized xenon-129 demonstrates novel alterations in gas transfer across the air-blood barrier in asthma.

Individuals with asthma can vary widely in clinical presentation, severity, and pathobiology. Hyperpolarized xenon-129 (Xe129) MRI is a novel imaging method to provide 3-D mapping of both ventilation and gas exchange in the human lung. To evaluate the functional changes in adults with asthma as compared to healthy controls using Xe129 MRI. All subjects (20 controls and 20 asthmatics) underwent lung function measurements and Xe129 MRI on the same day. Outcome measures included the pulmonary ventilation defect and transfer of inspired Xe129 into two soluble compartments: tissue and blood. Ten asthmatics underwent Xe129 MRI before and after bronchodilator to test whether gas transfer measures change with bronchodilator effects. Initial analysis of the results revealed striking differences in gas transfer measures based on age, hence we compared outcomes in younger (n=24, ≤ 35 years) versus older (n=16,>45 years) asthmatics and controls. The younger asthmatics exhibited significantly lower Xe129 gas uptake by lung tissue (Asthmatic: 0.98%±0.24%, Control: 1.17%±0.12%, P=0.035), and higher Xe129 gas transfer from tissue to the blood (Asthmatic: 0.40±0.10, Control: 0.31%±0.03%, P=0.035) than the younger controls. No significant difference in Xe129 gas transfer was observed in the older group between asthmatics and controls (P>0.05). No significant change in Xe129 transfer was observed before and after bronchodilator treatment. By using Xe129 MRI, we discovered heterogeneous alterations of gas transfer that have associations with age. This finding suggests a heretofore unrecognized physiological derangement in the gas/tissue/blood interface in young adults with asthma that deserves further study.

Thermodynamic and functional changes of alpha-chymotrypsin after interaction with gallic acid

In the present study, the interaction mechanism between gallic acid (GA) and α-Chymotrypsin (α-CT) was investigated by employing a series ofspectroscopic methods, computational docking and molecular dynamic (MD) simulation. Fluorescence spectra analysis indicated the formation of a stable complex between GA and α-CT, where the quenching of the fluorescence emission was predominantly characterized by a static mechanism. TheCA obtained binding constants for the α-CT-GA complex were in the order of 103 M−1, indicating the moderate binding affinity of GA for α-CT. The corresponding CD findings showed that the interaction between GA and α-CT resulted in an alteration of the protein's secondary structure. The findings of the enzyme activity investigation clearly showed that the presence of GA led to a notable decline in the enzymatic activity of α-CT, highlighting GA's function as an effective inhibitor for α-CT. The molecular docking simulations revealed the optimal binding site for the GA molecule within the α-CT structure and MD simulations confirmed the stability of the α-CT-GA complex. This research expands our comprehension regarding the behavior of enzymes in the presence of small-molecule ligands and opens avenues for food safety.

Co-delivery mechanism of curcumin/catechin complex by modified soy protein isolate: Emphasizing structure, functionality, and intermolecular interaction

Modifying proteins to enhance their affinity for polyphenols is essential for developing a practical and efficient delivery system that promotes the synergistic effects of bioactive substances. The study investigated the nanoparticle complexation in both pure soy protein isolate (SPI) or SPI modified by ultrasonic combined heat treatment (UHSPI) with varying concentrations of curcumin/catechin (CU/CA) complex, and its effects on the functionality, structure and conformational changes of protein-polyphenol nanocomplexes. Additionally, the intermolecular interaction and co-delivery mechanisms of nanocomplexes were analyzed. Results showed that the physical modification process (28/40 kHz, 90 °C, 15 min) and a rational concentration of CU/CA (0.6 mg/mL) improve the encapsulation efficiency of polyphenols by SPI (up to 77% for curcumin, and 93% for catechin), resulting in a higher DPPH and ABTS scavenging capacity, along with the highest emulsification activity index, as well as enhanced storage stability and thermal stability. The interaction between UHSPI and CU/CA disrupted the protein's secondary structure and exposed more hydrophobic residues to a hydrophilic environment, and exhibited stronger fluorescence quenching. Molecular docking analysis revealed that protein-polyphenol interactions primarily relied on hydrogen bonds and hydrophobic interactions, and 11S subunits exhibited higher affinity with CU/CA. FTIR, fluorescence spectra, and XRD further confirmed the enhanced interaction ability between UHSPI and CU/CA, resulting in the formation of a more stable nanocomplex. Overall, the modified SPI effectively facilitates the co-delivery of an appropriate concentration of curcumin/catechin complex.

Mechanism of Induction of P-gp Activity During MET Induced by DEX in Lung Cancer Cell Line

Lung cancer metastasis often leads to a poor prognosis for patients. Mesenchymal-epithelial transition (MET) is one key process associated with metastasis. MET has also been linked to multidrug drug resistance (MDR). MDR arises from the overactivity of drug efflux transporters such as P-glycoprotein (P-gp) which operate at the cell plasma membrane, under the regulatory control of the scaffold proteins ezrin (Ezr), radixin (Rdx), and moesin (Msn), collectively known as ERM proteins. The current study was intended to clarify the functional changing of P-gp and the underlying mechanisms in the context of dexamethasone (DEX)-induced MET in lung cancer cells. We found that the mRNA and membrane protein expression of Ezr and P-gp was increased in response to DEX treatment. Moreover, the DEX-treated group exhibited an increase in Rho123 efflux, and it was reversed by treatment with the P-gp inhibitor verapamil or Ezr siRNA. The decrease in cell viability with paclitaxel (PTX) treatment was mitigated by pretreatment with DEX. The increased expression and activation of P-gp during the progression of lung cancer MET was regulated by Ezr. The regulatory mechanism of P-gp expression and activity may differ depending on the cell status.

Prebiotics counteract the morphological and functional changes secondary to chronic cisplatin exposition in the proximal colon of mice.

Cisplatin is an antimitotic drug able to cause acute and chronic gastrointestinal side effects. Acute side effects are attributable to mucositis while chronic ones are due to neuropathy. Cisplatin has also antibiotic properties inducing dysbiosis which enhances the inflammatory response, worsening local damage. Thus, a treatment aimed at protecting the microbiota could prevent or reduce the toxicity of chemotherapy. Furthermore, since a healthy microbiota enhances the effects of some chemotherapeutic drugs, prebiotics could also improve this drug effectiveness. We investigated whether chronic cisplatin administration determined morphological and functional alterations in mouse proximal colon and whether a diet enriched in prebiotics had protective effects. The results showed that cisplatin caused lack of weight gain, increase in kaolin intake, decrease in stool production and mucus secretion. Prebiotics prevented increases in kaolin intake, changes in stool production and mucus secretion, but had no effect on the lack of weight gain. Moreover, cisplatin determined a reduction in amplitude of spontaneous muscular contractions and of Connexin (Cx)43 expression in the interstitial cells of Cajal, changes that were partially prevented by prebiotics. In conclusion, the present study shows that daily administration of prebiotics, likely protecting the microbiota, prevents most of the colonic cisplatin-induced alterations.

Advanced magnetic resonance neuroimaging techniques: feasibility and applications in long or post-COVID-19 syndrome - a review.

Long-term or post-COVID-19 syndrome (PCS) is a condition that affects people infected with SARS‑CoV‑2, the virus that causes COVID-19. PCS is characterized by a wide range of persistent or new symptoms that last months after the initial infection, such as fatigue, shortness of breath, cognitive dysfunction, and pain. Advanced magnetic resonance (MR) neuroimaging techniques can provide valuable information on the structural and functional changes in the brain associated with PCS as well as potential biomarkers for diagnosis and prognosis. In this review, we discuss the feasibility and applications of various advanced MR neuroimaging techniques in PCS, including perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), functional MR imaging (fMRI), diffusion tensor imaging (DTI), and tractography. We summarize the current evidence on neuroimaging findings in PCS, the challenges and limitations of these techniques, and the future directions for research and clinical practice. Although still uncertain, advanced MRI techniques show promise for gaining insight into the pathophysiology and guiding the management of COVID-19 syndrome, pending larger validation studies.

Resting state functional connectome in breast cancer patients with fear of cancer recurrence.

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.

Human leucocytes processed by fast-rate inertial microfluidics retain conventional functional characteristics.

The manufacturing of clinical cellular therapies is a complex process frequently requiring manipulation of cells, exchange of buffers and volume reduction. Current manufacturing processes rely on either low throughput open centrifugation-based devices, or expensive closed-process alternatives. Inertial focusing (IF) microfluidic devices offer the potential for high-throughput, inexpensive equipment which can be integrated into a closed system, but to date no IF devices have been approved for use in cell therapy manufacturing, and there is limited evidence for the effects that IF processing has on human cells. The IF device described in this study was designed to simultaneously separate leucocytes, perform buffer exchange and provide a volume reduction to the cell suspension, using high flow rates with high Reynolds numbers. The performance and effects of the IF device were characterized using peripheral blood mononuclear cells and isolated monocytes. Post-processing cell effects were investigated using multi-parameter flow cytometry to track cell viability, functional changes and fate. The IF device was highly efficient at separating CD14+ monocytes (approx. 97% to one outlet, approx. 60% buffer exchange, 15 ml min-1) and leucocyte processing was well tolerated with no significant differences in downstream viability, immunophenotype or metabolic activity when compared with leucocytes processed with conventional processing techniques. This detailed approach provides robust evidence that IF devices could offer significant benefits to clinical cell therapy manufacture.

Effect of fibers on starch structural changes during hydrothermal treatment: multiscale analyses, and evaluation of dilution effects on starch digestibility.

Dietary fibers (DFs) may influence the structural, nutritional and techno-functional properties of starch within food systems. Moreover, DFs have favorable effects on the digestive system and potentially a lower glycemic index. These potential benefits may change depending on DF type. Starch processed in the presence of soluble and insoluble fibers can undergo different structural and functional changes, and the present study investigated the effects of short-chain and long-chain inulin and cellulose on the structural and digestive properties of wheat starch. The combined use of differential scanning calorimetry, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) provided insights into the structural changes in starch and inulin at different levels. Short-chain and long-chain inulin had higher water retention capacity and a potential to limit starch gelatinization. The FTIR results revealed an interaction between starch and inulin. Scanning electron microscopy analysis showed morphological changes in starch and inulin after the hydrothermal treatment. Cellulose fiber was not affected by the hydrothermal treatment and had no influence on starch behavior. The structural differences observed through XRD, FTIR and scanning electron microscopy analyses between starch with and without inulin fibers did not significantly impact starch digestibility, except for the dilution effect caused by adding DFs. The present study highlights the importance of utilizing different analytical tools to assess changes in food samples at different scales. Although short-chain and long-chain inulin could potentially limit starch gelatinization, the duration of the heat treatment (90 °C for 10 min) was sufficient to ensure complete starch gelatinization. The dilution effect caused by adding fibers was the primary reason for the effect on starch digestibility. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

DPP-4 inhibitor sitagliptin treatment results in altered myocardial metabolic proteome and oxidative phosphorylation in a swine model of chronic myocardial ischemia.

Small animal models have shown improved cardiac function with DPP-4 inhibition, but many human studies have shown worse outcomes or no benefit. We seek to bridge the gap by studying the DPP-4 inhibitor sitagliptin in a swine model of chronic myocardial ischemia using proteomic analysis. Thirteen Yorkshire swine underwent the placement of an ameroid constrictor on the left coronary circumflex artery to model chronic myocardial ischemia. Two weeks post-op, swine received either sitagliptin 100 mg daily (SIT, n = 5) or no drug (CON, n = 8). After 5 weeks of treatment, swine underwent functional measurements and tissue harvest. In the SIT group compared to CON, there was a trend towards decreased cardiac index (p = 0.06). The non-ischemic and ischemic myocardium had 396 and 166 significantly decreased proteins, respectively, in the SIT group compared to CON (all p < 0.01). This included proteins involved in fatty acid oxidation (FAO), myocardial contraction, and oxidative phosphorylation (OXPHOS). Sitagliptin treatment resulted in a trend towards decreased cardiac index and decreased expression of proteins involved in OXPHOS, FAO, and myocardial contraction in both ischemic and non-ischemic swine myocardium. These metabolic and functional changes may provide some mechanistic evidence for outcomes seen in clinical studies.

Physiological characterization of a macaque model of presbycusis

Age-related hearing loss (presbycusis) is the leading cause of hearing loss worldwide, but current human studies do not separate this pathology from lifetime noise exposure. Laboratory macaques live in environments with minimal noise-induced hearing trauma and have long lifespans, making them optimal presbycusis models. We describe age-related auditory changes using two clinical, non-invasive physiological measures in aging macaques: distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs). ABRs and DPOAEs were measured in anesthetized young (6–9 years old, n = 36 ears) and aging (26–35 years old, n = 20 ears) Macaca mulatta. ABR and DPOAE thresholds were elevated in aging subjects compared to young macaques at all tested frequencies. ABR thresholds were significantly correlated with age for frequencies &amp;gt;8 kHz, but DPOAE thresholds were not, a pattern likely attributable to a high-frequency ceiling effect for DPOAE measures. For frequencies &amp;lt;8 kHz, DPOAE thresholds showed significant correlation with age. However, this was not observed with ABR thresholds, suggesting differential sensitivity to age-related changes for auditory nerve and brainstem function compared to cochlear outer hair cell function. Ongoing analysis on temporal processing/adaptation metrics will further elucidate age-related changes. Future work will correlate these findings with histological analysis. [Work Supported by NIH R01-DC-015988.]

The Mouse Model of Internal Capsule Demyelination: A Novel Tool for Investigating Motor Functional Changes Caused by Demyelination and for Evaluating Drugs That Promote Remyelination.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, characterized by remyelination failure and axonal dysfunction. Remyelination by oligodendrocytes is critical for improvement of neurological deficits associated with demyelination. Rodent models of demyelination are frequently used to develop and evaluate therapies for MS. However, a suitable mouse model for assessing remyelination-associated recovery of motor functions is currently unavailable. In this review, we describe the development of the mouse model of internal capsule (IC) demyelination by focal injection of lysolecithin into brain and its application in the evaluation of drugs for demyelinating diseases. This mouse model exhibits motor deficits and subsequent functional recovery accompanying IC remyelination. Notably, this model shows enhancement of functional recovery as well as tissue regeneration when treated with clemastine, a drug that promotes remyelination. The IC demyelination mouse model should contribute to the development of novel drugs that promote remyelination and ameliorate neurological deficits in demyelinating diseases.

On the limits of 16S rRNA gene-based metagenome prediction and functional profiling.

Molecular profiling techniques such as metagenomics, metatranscriptomics or metabolomics offer important insights into the functional diversity of the microbiome. In contrast, 16S rRNA gene sequencing, a widespread and cost-effective technique to measure microbial diversity, only allows for indirect estimation of microbial function. To mitigate this, tools such as PICRUSt2, Tax4Fun2, PanFP and MetGEM infer functional profiles from 16S rRNA gene sequencing data using different algorithms. Prior studies have cast doubts on the quality of these predictions, motivating us to systematically evaluate these tools using matched 16S rRNA gene sequencing, metagenomic datasets, and simulated data. Our contribution is threefold: (i) using simulated data, we investigate if technical biases could explain the discordance between inferred and expected results; (ii) considering human cohorts for type two diabetes, colorectal cancer and obesity, we test if health-related differential abundance measures of functional categories are concordant between 16S rRNA gene-inferred and metagenome-derived profiles and; (iii) since 16S rRNA gene copy number is an important confounder in functional profiles inference, we investigate if a customised copy number normalisation with the rrnDB database could improve the results. Our results show that 16S rRNA gene-based functional inference tools generally do not have the necessary sensitivity to delineate health-related functional changes in the microbiome and should thus be used with care. Furthermore, we outline important differences in the individual tools tested and offer recommendations for tool selection.

Valorisation Process Using Lactic Acid Bacteria Fermentation Induces Significant Changes in the Physical and Functional Properties of Brewers Spent Yeast

Brewer’s spent yeast (BSY) is a plentiful by-product of the brewing process. Currently regarded as a waste product, this low-value material is used in animal feed formulations or disposed of. However, BSY is known to be nutritionally dense, particularly regarding high-quality proteins, fibre, vitamins, and minerals. Previous work has examined the effect of a process including fermentation with Lactobacillus amylovorus FST 2.11 on BSY and indicates a reduction in bitterness intensity and an increase in sour and fruity flavours. The current study expands on this previous work, examining the changes in composition and functionality resulting from this upcycling process. The major changes include protein degradation and a decrease in pH, leading to increased protein solubility by 41%, increased foam stability by up to 69% at pH 7, and improved emulsion stabilising characteristics as well as differences in rheological behaviour during heating. Compositional changes are also detailed, with evidence of glucan and trehalose degradation. These changes in the physical and functional properties of BSY provide useful information, particularly with regard to the incorporation of BSY into food products for human consumption.

Cocaine diminishes functional network robustness and destabilizes the energy landscape of neuronal activity in the medial prefrontal cortex.

We present analysis of neuronal activity recordings from a subset of neurons in the medial prefrontal cortex of rats before and after the administration of cocaine. Using an underlying modern Hopfield model as a description for the neuronal network, combined with a machine learning approach, we compute the underlying functional connectivity of the neuronal network. We find that the functional connectivity changes after the administration of cocaine with both functional-excitatory and functional-inhibitory neurons being affected. Using conventional network analysis, we find that the diameter of the graph, or the shortest length between the two most distant nodes, increases with cocaine, suggesting that the neuronal network is less robust. We also find that the betweenness centrality scores for several of the functional-excitatory and functional-inhibitory neurons decrease significantly, while other scores remain essentially unchanged, to also suggest that the neuronal network is less robust. Finally, we study the distribution of neuronal activity and relate it to energy to find that cocaine drives the neuronal network towards destabilization in the energy landscape of neuronal activation. While this destabilization is presumably temporary given one administration of cocaine, perhaps this initial destabilization indicates a transition towards a new stable state with repeated cocaine administration. However, such analyses are useful more generally to understand how neuronal networks respond to perturbations.

Cyy-287, a novel pyrimidine-2,4-diamine derivative, efficiently mitigates inflammatory responses, fibrosis, and lipid synthesis in obesity-induced cardiac and hepatic dysfunction.

Inflammation and metabolic disorders are important factors in the occurrence and development of obesity complications. In this study, we investigated the protective effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, Cyy-287, on mice fed a high-fat diet (HFD). The mice were randomly separated into four groups (n ≥ 7): control (regular diet), HFD, HFD with Cyy-287 (5 mg/kg), and HFD with Cyy-287 (20 mg/kg) following HFD feeding for 10 weeks. After a 10-week administration, ALT and AST enzymes, echocardiography, immunohistochemical (IHC), Western blot (WB), Masson and Sirius Red staining were used to evaluate functional and morphological changes to the heart and liver. Microsomes from the mouse liver were extracted to quantify the total amount of CYP450 enzymes after drug treatment. Cyy-287 decreased the levels of serum glucose, LDL, TC, ALT, and AST activities in HFD-treated mice. However, Cyy-287 administration increased ejection fraction (EF) and fractional shortening (FS) index of the heart. Cyy-287 inhibited histopathological changes in the heart and liver; decreased inflammatory activity; significantly diminished p38 mitogen-activated protein kinase (MAPK), the nuclear factor-kappa B (NF-κB) axis, and sterol regulatory element-binding protein-1c (SREBP-1c); and upregulated the AMP-activated protein kinase (AMPK) pathway in HFD-treated mice. Cyy-287 restored the content of hepatic CYP450 enzymes. These findings demonstrated that Cyy-287 protected heart and liver cells from obesity-induced damage by inhibiting inflammation, fibrosis, and lipid synthesis.

Convergent evolution of parrot plumage coloration.

Parrots have remarkable plumage coloration that result in part from a unique ability to produce pigments called psittacofulvins that yield yellow to red feather colors. Little is known about the evolution of psittacofulvin-based pigmentation. Widespread color mutations of captive-bred parrots provide perfect opportunities to study the genetic basis of this trait. An earlier study on blue budgerigars, which do not possess psittacofulvins, reveals the involvement of an uncharacterized polyketide synthase (MuPKS) in yellow psittacofulvin synthesis. The blue phenotype had repeatedly appeared in different parrot species, similar to independent experimental replications allowing the study of convergent evolution and molecular mechanism of psittacofulvin-based pigmentation. Here, we investigated the genetic basis of the blue phenotypes in two species of Agapornis parrots, Fischer's lovebird (A. fischeri) and Yellow-collared lovebird (A. personatus). Using whole-genome data, we identified a single genomic region with size <2 Mb to be strongly associated with the color difference between blue and wild-type (WT) birds in both species. Surprisingly, we discovered that the mutation associated with the blue Agapornis phenotype was identical to the previously described substitution causing the functional change of MuPKS in budgerigars. Together with the evidence of shared blue-associated haplotypes and signatures of a selective sweep in this genomic region in both species, we demonstrated both de novo mutation and interspecific introgression play a role in the evolution of this trait in different Agapornis species. The convergent substitution in the same gene in both lovebirds and budgerigars also indicates a strong evolutionary constraint on psittacofulvin-based coloration.

Cdc42 activation is necessary for heterosynaptic cooperation and competition

Synapses change their weights in response to neuronal activity and in turn, neuronal networks alter their response properties and ultimately allow the brain to store information as memories. As for memories, not all events are maintained over time. Maintenance of synaptic plasticity depends on the interplay between functional changes at synapses and the synthesis of plasticity-related proteins that are involved in stabilizing the initial functional changes. Different forms of synaptic plasticity coexist in time and across the neuronal dendritic area. Thus, homosynaptic plasticity refers to activity-dependent synaptic modifications that are input-specific, whereas heterosynaptic plasticity relates to changes in non-activated synapses. Heterosynaptic forms of plasticity, such as synaptic cooperation and competition allow neurons to integrate events that occur separated by relatively large time windows, up to one hour. Here, we show that activation of Cdc42, a Rho GTPase that regulates actin cytoskeleton dynamics, is necessary for the maintenance of long-term potentiation (LTP) in a time-dependent manner. Inhibiting Cdc42 activation does not alter the time-course of LTP induction and its initial expression but blocks its late maintenance. We show that Cdc42 activation is involved in the phosphorylation of cofilin, a protein involved in modulating actin filaments and that weak and strong synaptic activation leads to similar levels on cofilin phosphorylation, despite different levels of LTP expression. We show that Cdc42 activation is required for synapses to interact by cooperation or competition, supporting the hypothesis that modulation of the actin cytoskeleton provides an activity-dependent and time-restricted permissive state of synapses allowing synaptic plasticity to occur. We found that under competition, the sequence in which synapses are activated determines the degree of LTP destabilization, demonstrating that competition is an active destabilization process. Taken together, we show that modulation of actin cytoskeleton by Cdc42 activation is necessary for the expression of homosynaptic and heterosynaptic forms of plasticity. Determining the temporal and spatial rules that determine whether synapses cooperate or compete will allow us to understand how memories are associated.

Linking structural and functional changes during aging using multilayer brain network analysis

Brain structure and function are intimately linked, however this association remains poorly understood and the complexity of this relationship has remained understudied. Healthy aging is characterised by heterogenous levels of structural integrity changes that influence functional network dynamics. Here, we use the multilayer brain network analysis on structural (diffusion weighted imaging) and functional (magnetoencephalography) data from the Cam-CAN database. We found that the level of similarity of connectivity patterns between brain structure and function in the parietal and temporal regions (alpha frequency band) is associated with cognitive performance in healthy older individuals. These results highlight the impact of structural connectivity changes on the reorganisation of functional connectivity associated with the preservation of cognitive function, and provide a mechanistic understanding of the concepts of brain maintenance and compensation with aging. Investigation of the link between structure and function could thus represent a new marker of individual variability, and of pathological changes.