Mild neonatal hypoxia disrupts adult hippocampal learning and memory and is associated with CK2-mediated dysregulation of synaptic calcium-activated potassium channel KCNN2 DOI

Art Riddle,

Taasin Srivastava, Kang Wang

et al.

Published: July 16, 2024

Abstract Objective Although nearly half of preterm survivors display persistent neurobehavioral dysfunction including memory impairment without overt gray matter injury, the underlying mechanisms neuronal or glial dysfunction, and their relationship to commonly observed cerebral white injury are unclear. We developed a mouse model test hypothesis that mild hypoxia during equivalence is sufficient persistently disrupt hippocampal maturation related adult cellular learning memory. Methods: Neonatal (P2) mice were exposed (8%O 2 ) for 30 min evaluated acute responses survived until adulthood assessment neurodevelopment. Results resulted in clinically relevant oxygen desaturation tachycardia bradycardia was not accompanied by injury. exposure cause deficits abnormal CA1 neurons persisted into adulthood. This reduced CA3-CA1 synaptic strength LTP activity calcium-sensitive SK2 channels, key regulators spike timing dependent neuroplasticity, LTP. Structural illumination microscopy revealed density, but intact localization at synapse. Persistent loss mediated altered casein kinase (CK2) signaling. Interpretation Clinically hypoxic neonatal produce morphometric functional disturbances independently Additionally, we describe novel mechanism potassium channel dysregulation after hypoxia. Collectively our findings suggest an unexplored explanation broad spectrum neurobehavioral, cognitive disabilities paradoxically persist birth.

Language: Английский

Tuning cohesin trajectories enables differential readout of the Pcdhα cluster across neurons DOI
Lea Kiefer, Simon Gaudin, Sandy M. Rajkumar

et al.

Science, Journal Year: 2024, Volume and Issue: 385(6707)

Published: July 25, 2024

Expression of Protocadherin (Pcdh) genes is critical to the generation neuron identity and wiring nervous system. Pcdhα are arranged in clusters exhibit a range expression profiles, from stochastic deterministic. Because promoters have high sequence share distal enhancers, how distinct neurons choose which gene express remains unclear. We show that interplay between multiple epigenetics, genome folding orchestrates differential readouts locus across neurons. The probability promoter choice depends on enhancer/promoter encounters catalyzed by cohesin, whose extrusion trajectories determine likelihood an individual can "escape" heterochromatin-mediated silencing. propose tunable locus-specific regulatory elements cell type-specific cohesin activity underlie cellular diversity Pcdh genes.

Language: Английский

Citations

8
Proteomic Study on the Mechanism of Arsenic Neurotoxicity in the Rat Cerebral Cortex and the Protective Mechanism of Dictyophora Polysaccharides against Arsenic Neurotoxicity DOI
Xinglai Zhang, Hongmei Yang, Yi Wang

et al.

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(12), P. 2302 - 2319

Published: June 5, 2023

Arsenic (As) is a toxic element, and long-term exposure to As can cause neurotoxicity. The bioactive natural compound Dictyophora polysaccharide (DIP) from edible plants has been reported reduce the toxicity of As. In this study, poisoning was simulated by feeding As-containing feed, followed proteomic analysis after one month DIP treatment. showed that 145, 276, 97 proteins were differentially expressed between As-treated rats control (As/Ctrl group), DIP-treated + (DIP As/As As/Ctrl respectively. (DEPs) in groups mainly related apoptosis, synapses, energy metabolism, nervous system development, mitochondria. After treatment, expression dysregulated group restored or reversed, 12 them reversed proteins. These results suggest metabolism disorder, mitochondrial dysfunction, development injury, synaptic oxidative stress may be key pathological mechanisms As-induced nerve injury rats. restore reverse proteins, which main mechanism its intervention poisoning.

Language: Английский

Citations

15
Critical state of energy-efficient firing patterns with different bursting kinetics in temperature-sensitive Chay neuron DOI
Lulu Lu, Ming Yi,

Zhuoheng Gao

et al.

Nonlinear Dynamics, Journal Year: 2023, Volume and Issue: 111(17), P. 16557 - 16567

Published: July 24, 2023

Language: Английский

Citations

15
Neurons exploit stochastic growth to rapidly and economically build dense radially oriented dendritic arbors DOI Creative Commons
Xiaoyi Ouyang, Sabyasachi Sutradhar, Olivier Trottier

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Dendrites grow by stochastic branching, elongation, and retraction. A key question is whether such a mechanism sufficient to form highly branched dendritic morphologies. Alternatively, are signals from other cells or the topological hierarchy of growing network necessary for dendrite geometry? To answer these questions, we developed mean-field model in which branch dynamics isotropic homogenous (i.e., no extrinsic instruction) depends only on average lengths densities branches. Branching modeled as density-dependent nucleation so there tree structures topology. Despite its simplicity, predicted several morphological properties class IV Drosophila sensory dendrites, including exponential distribution lengths, parabolic scaling between number length densities, tight spacing meshwork (which required minimal total length), radial orientation Stochastic growth also accelerated overall expansion rate arbor. Therefore, an economical rapid space-filling building arbors without external guidance hierarchical branching mechanisms. Our provides general theoretical framework understanding how macroscopic patterns emerge microscopic dynamics.

Language: Английский

Citations

0
Ultrastructural Contributions to Extrasynaptic Glutamatergic Signaling in Olfactory Bulb Glomeruli DOI
Jennifer N. Bourne, Nathan E. Schoppa

The Journal of Comparative Neurology, Journal Year: 2025, Volume and Issue: 533(3)

Published: March 1, 2025

ABSTRACT Olfactory bulb glomeruli have a complex organization that includes axodendritic synapses between olfactory sensory neurons (OSNs) and excitatory mitral cells (MCs) tufted (TCs), as well dendrodendritic MCs/TCs GABAergic periglomerular (PGCs). MCs also receive signals from one subclass of TCs, the external (eTCs). While these are driven by glutamate released eTC dendrites, they appear not to reflect direct > MC synaptic connections but rather “spill‐over” at PGC acting on nearby dendrites. Here, we used serial section electron microscopy images rat with biocytin‐labeled dendrites evaluate potential ultrastructural underpinnings “extrasynaptic” signaling. We compared environment around using several quantitative measures and, further point comparison, evaluated OSN synapses. Across four synapse types, unique feature was their much closer distance nearest (including MCs), averaging ∼160 nm. In contrast, astroglial processes were positioned quite far away synapses, mean ∼500 These values would suggest may access without interference glial transporters, thus providing an basis for extrasynaptic Our battery measures, which included brick analyses, supported long‐standing model in segregated into discrete compartments.

Language: Английский

Citations

0
Homeostatic plasticity in the retina DOI
Michael J. Fitzpatrick, Daniel Kerschensteiner

Progress in Retinal and Eye Research, Journal Year: 2022, Volume and Issue: 94, P. 101131 - 101131

Published: Oct. 13, 2022

Language: Английский

Citations

16
Role of a Pdlim5:PalmD complex in directing dendrite morphology DOI Creative Commons
Yogesh Srivastava, Maxsam Donta, Lydia L. Mireles

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 13, 2024

Neuronal connectivity is regulated during normal brain development with the arrangement of spines and synapses being dependent on morphology dendrites. Further, in multiple neurodevelopmental aging disorders, disruptions dendrite formation or shaping associated atypical neuronal connectivity. We showed previously that Pdlim5 binds delta-catenin promotes branching. report here interacts PalmD, a protein suggested by others to interact cytoskeleton (e.g., via adducin/spectrin) regulate membrane shaping. Functionally, knockdown PalmD rat primary hippocampal neurons dramatically reduces branching conversely, exogenous expression as does Pdlim5. we show each proteins’ effects are presence other. In summary, using reveal contributions novel Pdlim5:PalmD complex, composed functionally inter-dependent components responsible for

Language: Английский

Citations

3
Gamma-protocadherins regulate dendrite self-recognition and dynamics to drive self-avoidance DOI
Samantha Ing-Esteves, Julie L. Lefebvre

Current Biology, Journal Year: 2024, Volume and Issue: 34(18), P. 4224 - 4239.e4

Published: Aug. 29, 2024

Language: Английский

Citations

3
The kinetochore protein KNL-1 regulates the actin cytoskeleton to control dendrite branching DOI Creative Commons

Henrique Alves Domingos,

Mattie Green,

Vasileios R. Ouzounidis

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 224(2)

Published: Dec. 3, 2024

The function of the nervous system is intimately tied to its complex and highly interconnected architecture. Precise control dendritic branching in individual neurons central building structure system. Here, we show that kinetochore protein KNL-1 associated KMN (Knl1/Mis12/Ndc80 complex) network partners, typically known for their role chromosome-microtubule coupling during mitosis, dendrite Caenorhabditis elegans mechanosensory PVD neuron. restrains excess promotes contact-dependent repulsion events, ensuring robust sensory behavior preventing premature neurodegeneration. Unexpectedly, loss resulted significant alterations actin cytoskeleton alongside changes microtubule dynamics within dendrites. We modulates F-actin generate proper architecture N-terminus can initiate assembly. These findings reveal postmitotic neuronal acts shape developing by regulating provide new insight into mechanisms controlling

Language: Английский

Citations

3
A Role for Frizzled and Their Post-Translational Modifications in the Mammalian Central Nervous System DOI Creative Commons
Patricia Pascual Vargas, Patricia C. Salinas

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Aug. 3, 2021

The Wnt pathway is a key signalling cascade that regulates the formation and function of neuronal circuits. main receptors for Wnts are Frizzled (Fzd) mediate diverse functions such as neurogenesis, axon guidance, dendritogenesis, synapse formation, synaptic plasticity. These processes crucial assembly functional circuits required ranging from sensory motor tasks to cognitive performance. Indeed, aberrant Wnt–Fzd has been associated with defects during development in neurodegenerative conditions Alzheimer’s disease. New studies suggest localisation stability Fzd play role determining function. Post-translational modifications (PTMs) emerging an important mechanism these receptors. However, only phosphorylation glycosylation have described modulate central nervous system (CNS). In this review, we discuss circuit connectivity how PTMs contribute their We also other PTMs, not yet CNS, they might connectivity. could by affecting at plasma membrane resulting local effects signalling, feature particularly polarised cells neurons. Our review highlights importance further into on context

Language: Английский

Citations

20