A5027043416- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Extracellular vesicles in disease
- Memory and Neural Mechanisms
- Alzheimer's disease research and treatments
- Neural and Behavioral Psychology Studies
- Neurogenesis and neuroplasticity mechanisms
- Long-Term Effects of COVID-19
- MicroRNA in disease regulation
- Visual perception and processing mechanisms
- Functional Brain Connectivity Studies
- RNA Research and Splicing
- Curcumin's Biomedical Applications
- Stroke Rehabilitation and Recovery
- Transcranial Magnetic Stimulation Studies
- EEG and Brain-Computer Interfaces
- Nicotinic Acetylcholine Receptors Study
- Sleep and Wakefulness Research
- Biochemical effects in animals
- S100 Proteins and Annexins
- Cell Image Analysis Techniques
- Barrier Structure and Function Studies
- Immune cells in cancer
- Peripheral Nerve Disorders
Boston University
2016-2025
Center for Systems Biology
2022-2024
Henry Ford Health System
2023
University School
2014-2021
Institute of Neurobiology
2020
Villa Maria Hospital
2019-2020
Department of Medical Sciences
2007-2012
Abstract Introduction Extracellular vesicles (EVs) from human Alzheimer's disease (AD) biospecimens contain amyloid beta (Aβ) peptide and tau. While AD EVs are known to affect brain pathobiology, their biochemical molecular characterizations remain ill defined. Methods were isolated the cortical gray matter of 20 18 control brains. Tau Aβ levels measured by immunoassay. Differentially expressed EV proteins assessed quantitative proteomics machine learning. Results Levels pS396 tau Aβ1–42...
Significance Phase separation of proteins is increasingly thought to play a fundamental role in biological processes. Recent studies show that tau protein phase separates, but the significance unknown since artificial crowding agents are typically used and resulting not toxic. We now demonstrate TIA1 potentiates RNA-mediated tau, thereby enabling process occurs at physiological concentrations also directs formation biologically active, highly neurotoxic oligomeric tau. Coordinated...
A principal challenge of systems neuroscience is to understand the unique characteristics cortical neurons and circuits that enable area- species-specific sensory encoding, motor function, cognition, behavior. To address this issue, we compared properties layer 3 pyramidal in 2 areas span a broad range function—primary (V1), cognitive (frontal)—in mouse rhesus monkey. Hierarchical clustering discriminant analyses 15 physiological 25 morphological variables revealed fundamental principles....
Cortical circuits are thought to contain a large number of cell types that coordinate produce behavior. Current in vivo methods rely on clustering specified features extracellular waveforms identify putative types, but these capture only small amount variation. Here, we develop new method (
Abstract Lateral prefrontal and intraparietal cortices have strong connectional functional associations but it is unclear how their common visuomotor, perceptual working memory functions arise. The hierarchical scheme of cortical processing assumes that cortex issues ‘feedback’ projections to parietal cortex. However, the architectonic heterogeneity these raises question whether distinct areas laminar‐specific interconnections underlying complex relationship. Using quantitative procedures,...
The prefrontal cortex selects relevant signals and suppresses irrelevant in behavior, as exemplified by its functional interaction with superior temporal cortices. We addressed the structural basis of this process investigating quantitatively relationship pathways to inhibitory interneurons Pathways were labeled neural tracers, two neurochemical classes parvalbumin (PV) calbindin (CB), which differ mode control. Both markers varied significantly systematically across areas. Calbindin neurons...
Dorsolateral prefrontal areas 46 and 10 are involved in distinct aspects of cognition. Area has a key role working memory tasks, frontopolar area is recruited complex multitask operations. Both innervated by the anterior cingulate cortex (ACC), region associated with emotions but also important for attentional control through unknown synaptic mechanisms. Here, we found that rhesus monkeys ( Macaca mulatta ) most axon terminals labeled from tracers injected into ACC 32 spines presumed...
Understanding commonalities and differences in glutamatergic synaptic signaling is essential for understanding cortical functional diversity, especially the highly complex primate brain. Previously, we have shown that spontaneous EPSCs differed markedly layer 3 pyramidal neurons of two specialized areas rhesus monkey, high-order lateral prefrontal cortex (LPFC) primary visual (V1). Here, used patch-clamp recordings confocal electron microscopy to determine whether these distinct responses...
Abstract The excitatory glutamatergic synapse is the principal site of communication between cortical pyramidal neurons and their targets, a key locus action many drugs, highly vulnerable to dysfunction loss in neurodegenerative disease. A detailed knowledge structure these synapses distinct areas across species prerequisite for understanding anatomical underpinnings specialization and, potentially, selective vulnerability neurological disorders. We used serial electron microscopy assess...
Maternal immune activation (MIA) disrupts the central innate system during a critical neurodevelopmental period. Microglia are primary cells in brain although their direct influence on MIA phenotype is largely unknown. Here we show that alters microglial gene expression with upregulation of cellular protrusion/neuritogenic pathways, concurrently causing repetitive behavior, social deficits, and synaptic dysfunction to layer V intrinsically bursting pyramidal neurons prefrontal cortex mice....
The effects of normal aging on morphologic and electrophysiologic properties layer 3 pyramidal neurons in rhesus monkey primary visual cortex (V1) were assessed with whole-cell, patch-clamp recordings vitro slices. In another cohort monkeys, the ultrastructure synapses layers 2–3 neuropil V1 was using electron microscopy. Distal apical dendritic branching complexity reduced aged neurons, as total spine density, due to specific loss mushroom spines from tree thin basal tree. There also an...
Several neural precursor populations contemporaneously generate neurons in the developing neocortex. Specifically, radial glial stem cells of dorsal telencephalon divide asymmetrically to produce excitatory neurons, but also indirectly via three types intermediate progenitor cells. Why so many are needed has not been established; whether different merely expand output glia or instead distinct is unknown. Here we use a novel genetic fate mapping technique simultaneously track multiple streams...
The lateral prefrontal cortex (LPFC) and anterior cingulate (ACC) of the primate play distinctive roles in mediation complex cognitive tasks. Compared with LPFC, integration information by ACC can span longer timescales requires stronger engagement inhibitory processes. Here, we reveal synaptic mechanism likely to underlie these differences using vitro patch-clamp recordings events multiscale imaging markers rhesus monkeys. Although excitatory signaling does not differ, level inhibition is...
Functional recovery after cortical injury, such as stroke, is associated with neural circuit reorganization, but the underlying mechanisms and efficacy of therapeutic interventions promoting plasticity in primates are not well understood. Bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), which mediate cell-to-cell inflammatory trophic signaling, thought be viable targets. We recently showed, aged female rhesus monkeys, that systemic administration MSC-EVs enhances...
Abstract The use of iPSC derived brain organoid models to study neurodegenerative disease has been hampered by a lack systems that accurately and expeditiously recapitulate pathogenesis in the context neuron-glial interactions. Here we report development system, termed AstTau, which propagates toxic human tau oligomers neuron-astrocyte assembloids. AstTau system develops much neuronal astrocytic pathology observed tauopathies including misfolded, phosphorylated, oligomeric, fibrillar tau,...
Fundamental differences in excitatory pyramidal cells across cortical areas and species highlight the implausibility of extrapolation from mouse to primate neurons networks. Far less is known about comparative regional species-specific features neurochemically distinct inhibitory interneurons. Here, we quantified density, laminar distribution, somatodendritic morphology interneurons expressing one or more calcium-binding proteins (CaBPs) (calretinin [CR], calbindin [CB], and/or parvalbumin...