Biology subjects

Adel, M.

Publications and source records attributed to Adel, M..

8 recordsLinked to original sources

bioRxiv2026

Subicular Plateaus Signal Reward Locations during Goal-Directed Behavior

The hippocampus is essential for spatial learning, yet how its principal output structure, the subiculum, encodes behaviorally relevant information during navigation remains poorly understood. Because subicular neurons exhibit prominent burst firing, elucidating how this bursting is generated during behavior is critical. Using in vivo whole-cell recordings from dorsal subiculum neurons in head-fixed mice performing a goal-directed navigation task, we show that many bursts correspond to plateau events consisting of a series of action potentials riding on a large ([~]20-30 mV) sustained subthreshold depolarization. Subicular plateaus were synaptic in origin and required NMDA receptor activation. Organizing plateaus by the membrane potential preceding their onset revealed distinct behavioral associations. Plateaus initiated from relatively hyperpolarized membrane potentials preferentially clustered near reward locations, whereas plateaus initiated from more depolarized membrane potentials were more spatially distributed and showed weaker reward specificity. Reward-related clustering required a fixed, learned reward location and dynamically rearranged during learning of a new reward location. Together, our findings identify subicular plateaus as a prominent cellular substrate of hippocampal bursting output and demonstrate that intracellular membrane potential state organizes the behavioral associations of subicular plateaus during goal-directed learning.

neuroscience↗

bioRxiv2024

Tensor Kernel Learning for Classification of Alzheimer's Conditions using Multimodal Data

Early, timely, and accurate assessment of Alzheimers disease (AD), particularly at its earlier stage - mild cognitive impairment (MCI) -, is central to detecting, managing, and potentially treating the disease. The biological underpinnings of AD, however, is multifaceted, from genetic variations, abnormal protein accumulation, to irregular brain functions and structure. A joint analysis of these data, therefore, may offer potentially new insights about AD-related biomarkers and AD prediction. But such explorations must confront the complexity of these data: heterogeneity, multimodality and high-dimensionality. Here, to address these challenges, we propose a new machine-learning method, namely the tensor kernel learning (TKL), leveraging tensor methods and kernel learning, to enhance AD assessment by enhancing multi-modal data integration. More specifically, TKL first uses CP/PARAFAC decomposition and graph diffusion to fuse multiple kernels learned from four complementary data modalities (MRI, PET, CSF, and SNP data). We then used a supervised kernel for a kernel SVM classifier to identify potential patients. To evaluate the effectiveness of TKL, we apply it to data from the Alzheimers Disease Neuroimaging Initiative (ADNI; the sample size n = 331 subjects), including cognitively normal individuals (CN), MCI subjects, and AD patients. TKL improves AD classification performance in both linear and nonlinear combinations, achieving accuracies of 91.31% for CN vs. AD, 81.45% for CN vs. MCI, and 78.27% for AD vs. MCI, compared to 85.48%, 70.89%, and 73.51% using the best single modality. Additionally, TKL reveals clearer, more structured patterns in the data, enhancing interpretation and understanding of the relationships among different modalities. Detailed implementation details of our method can be found at: https://github.com/thanhvd18/Tensor-Kernel-Learning-matlab.

neuroscience↗

bioRxiv2023

Pleiotropic contribution of rbfox1 to psychiatric and neurodevelopmental phenotypes in a zebrafish model

RBFOX1 is a highly pleiotropic gene that contributes to several psychiatric and neurodevelopmental disorders. Both rare and common variants in RBFOX1 have been associated with several psychiatric conditions, but the mechanisms underlying the pleiotropic effects of RBFOX1 are not yet understood. Here we found that, in zebrafish, rbfox1 is expressed in spinal cord, mid- and hindbrain during developmental stages. In adults, expression is restricted to specific areas of the brain, including telencephalic and diencephalic regions with an important role in receiving and processing sensory information and in directing behaviour. To investigate the effect of rbfox1 deficiency on behaviour, we used rbfox1sa15940, a rbfox1 loss-of-function line. We found that rbfox1sa15940 mutants present hyperactivity, thigmotaxis, decreased freezing behaviour and altered social behaviour. We repeated these behavioural tests in a second rbfox1 loss-of-function line with a different genetic background, rbfox1del19, and found that rbfox1 deficiency affects behaviour similarly in this line, although there were some differences. rbfox1del19 mutants present similar thigmotaxis, but stronger alterations in social behaviour and lower levels of hyperactivity than rbfox1sa15940 fish. Taken together, these results suggest that rbfox1 deficiency leads to multiple behavioural changes in zebrafish that might be modulated by environmental, epigenetic and genetic background effects, and that resemble phenotypic alterations present in Rbfox1-deficient mice and in patients with different psychiatric conditions. Our study thus highlights the evolutionary conservation of rbfox1 function in behaviour and paves the way to further investigate the mechanisms underlying rbfox1 pleiotropy on the onset of neurodevelopmental and psychiatric disorders.

genetics↗

bioRxiv2022

Local translation provides the asymmetric distribution of CaMKII required for associative memory formation

How compartment-specific local proteomes are generated and maintained is inadequately understood, particularly in neurons, which display extreme asymmetries. Here we show that local enrichment of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in axons of Drosophila mushroom body neurons is necessary for cellular plasticity and associative memory formation. Enrichment is achieved via enhanced axoplasmic translation of CaMKII mRNA, through a mechanism requiring the RNA-binding protein Mub and a 23-base Mub-recognition element in the CaMKII 3UTR. Perturbation of either dramatically reduces axonal, but not somatic, CaMKII protein without altering the distribution or amount of mRNA in vivo and both are necessary and sufficient to enhance axonal translation of reporter mRNA. Together, these data identify elevated levels of translation of an evenly distributed mRNA as a novel strategy for generating subcellular biochemical asymmetries. They further demonstrate the importance of distributional asymmetry in the computational and biological functions of neurons.

neuroscience↗

bioRxiv2022

Pairing-dependent plasticity in a dissected fly brain is input-specific and requires synaptic CaMKII enrichment and nighttime sleep

In Drosophila, in vivo functional imaging studies revealed that associative memory formation is coupled to a cascade of neural plasticity events in distinct compartments of the mushroom body (MB). In-depth investigation of the circuit dynamics, however, will require an ex vivo model that faithfully mirrors these events to allow direct manipulations of circuit elements that are inaccessible in the intact fly. The current ex vivo models have been able to reproduce the fundamental plasticity of aversive short-term memory, a potentiation of the MB intrinsic neurons (Kenyon cells; KCs) responses after artificial learning ex vivo. However, this potentiation showed different localization and encoding properties from those reported in vivo and failed to generate the previously reported suppression plasticity in the mushroom body output neurons (MBONs). Here, we develop an ex vivo model using the female Drosophila brain that recapitulates behaviorally evoked plasticity in the KCs and MBONs. We demonstrate that this plasticity accurately localizes to the MB 3 compartment and is encoded by a coincidence between KCs activation and dopaminergic input. The formed plasticity is input-specific, requiring pairing of the conditioned stimulus (CS) and unconditioned stimulus (US) pathways; hence we name it pairing-dependent plasticity (PDP). PDP formation requires an intact CaMKII gene and is blocked by previous-night sleep deprivation but is rescued by rebound sleep. In conclusion, we show that our ex vivo preparation recapitulates behavioral and imaging results from intact animals and can provide new insights into mechanisms of memory formation at the level of molecules, circuits, and brain state. Significance StatementThe mammalian ex vivo LTP model enabled in-depth investigation of the hippocampal memory circuit. We develop a parallel model to study the Drosophila mushroom body (MB) memory circuit. Pairing activation of the conditioned stimulus and unconditioned stimulus pathways in dissected brains induces a potentiation pairing-dependent plasticity (PDP) in the axons of {beta} Kenyon cells and a suppression PDP in the dendrites of their postsynaptic MB output neurons, localized in the MB 3 compartment. This PDP is input-specific and requires the 3 untranslated region of CaMKII. Interestingly, ex vivo PDP carries information about the animals experience before dissection; brains from sleep deprived animals fail to form PDP while those from animals who recovered 2 hours of their lost sleep form PDP.

neuroscience↗

bioRxiv2022

Characterization of a novel peptide mined from the Red Sea brine pools and modified to enhance its anticancer activity

Peptide-based drugs have emerged as highly selective and potent cancer therapy. Cancer is one of the leading causes of death worldwide. Multiple approaches have been developed towards cancer treatment, including chemotherapy, radiation, and hormonal therapy; however, such procedures non-specificity, toxicity, and inefficiency present a hurdle. In this study, we developed a support vector machine (SVM) model to detect the potential anticancer properties of novel peptides through scanning the American University in Cairo Red Sea metagenomics library. Further, we performed in silico studies on a novel 37-mer antimicrobial peptide mined from SVM pipeline analysis. This peptide was further modified to enhance its anticancer activity, analyzed for gene oncology, and subsequently synthesized. The anticancer properties of this 37-mer peptide were evaluated via cellular viability and cell morphology of SNU449, HepG2, SKOV3, and HeLa cells, using MTT assay. Furthermore, we assessed the migration capability of SNU449 and SKOV3 via scratch wound healing assay. Moreover, the targeted selectivity of the peptide for cancerous cells was assessed by testing its hemolytic activity on human erythrocytes. The peptide caused a significant reduction in cellular viability and critically affected the morphology of hepatocellular carcinoma (SNU449 and HepG2), ovarian cancer (SKOV3), and to a limited extent, cervical cancer cell lines (HeLa), in addition to decreasing viability of human fibroblast cell line (1Br-hTERT). Peptide treatment significantly affected the proliferation and migration ability of SNU449 and SKOV3 cells. Annexin V assay was used to evaluate induced cell death upon peptide treatment, attributing programmed cell death (Apoptosis) as the main cause of cell death in SNU449 cells. Finally, we established broad-spectrum antimicrobial properties of the peptide on both gram-positive and gram-negative bacterial strains. Thus, these findings infer the novelty of the peptide as a potential anticancer and antimicrobial agent.

cancer biology↗

bioRxiv2021

Bantam regulates the adult sleep circuit in Drosophila

Sleep is a highly conserved feature of animal life characterized by dramatic changes in behavior, neural physiology and gene expression. The gene regulatory factors responsible for these sleep-dependent changes remain largely unknown. microRNAs are post-transcriptional modulators of gene expression which have been implicated in sleep regulation. Our previous screen identified 25 sleep-regulating microRNAs in Drosophila melanogaster, including the developmental regulator bantam (ban). Here we show that ban promotes early nighttime sleep through a population of glutamatergic neurons- the {gamma}5{beta}'2a/{beta}'2mp/{beta}'2mp_bilateral Mushroom Body Output Neurons (MBONs). We found that knockdown of ban in these neurons led to a reduction in early night sleep. The {gamma}5{beta}'2a/{beta}'2mp/{beta}'2mp_bilateral MBONs were previously shown to be wake-promoting, suggesting that ban acts to inhibit these neurons. GCaMP calcium imaging revealed that bantam inhibits the neural activity of the {gamma}5{beta}'2a/{beta}'2mp/{beta}'2mp_bilateral MBONs during the night but not the day. Blocking synaptic transmission in the {gamma}5{beta}'2a/{beta}'2mp/{beta}'2mp_bilateral MBONs rescued the effect of ban knockdown on sleep. Together these results suggest that ban promotes night sleep via the inhibition of the {gamma}5{beta}'2a/{beta}'2mp/{beta}'2mp_bilateral MBONs. RNAseq further revealed that bantam negatively regulates the wake-promoting mRNAs Kelch and CCHamide-2 receptor in the {gamma}5{beta}'2a/{beta}'2mp/{beta}'2mp_bilateral MBONs. These experiments establish bantam as an active regulator of sleep and neural activity within the fly brain.

neuroscience↗

bioRxiv2019

Organotypic slice culture model demonstrates interneuronal spreading of alpha-synuclein aggregates

Here we describe the use of an organotypic hippocampal slice model for studying -synuclein aggregation and inter-neuronal spreading initiated by injection of preformed -synuclein filaments (PFFs). PFF injection at dentate gyrus templates the endogenous -synuclein to form aggregates in axons and cell bodies that spread to CA3 and CA1 regions. Aggregates were insoluble and phosphorylated at serine 129, recapitulating Lewy pathology features found in Parkinsons disease and other synucleinopathies. The spreading of the aggregates were favoring the anterograde direction in the slice model. The model allowed development of slices expressing only serine-129 phosphorylation-deficient human -synuclein (S129G) using adeno-associated viral (AAV) vector in -synuclein knockout slices. Processes of aggregation and spreading of -synuclein were thereby shown to be independent of phosphorylation at serine 129. We provide methods and highlight crucial steps for PFF microinjection and characterization of aggregate formation and spreading. Slices derived from genetically engineered mice or manipulated by using viral vectors allow testing of hypotheses on mechanisms involved in formation of -synuclein aggregates and their prion-like spreading.

neuroscience↗