Intravital Imaging of Neocortical Heterotopia Reveals Aberrant Axonal Pathfinding and Myelination around Ectopic Neurons

Li, Alice M.; Hill, Robert A.; Grutzendler, Jaime

doi:10.1093/cercor/bhab090

Cited by 6 publications

(6 citation statements)

References 94 publications

(134 reference statements)

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“…The DTI sequence in MRI enables the demonstration of aberrant axonal projections in hemimegalencephaly 114,115 . Intravital imaging of neocortical heterotopia reveals aberrant axons around heterotopic neurons 116 . Microscopic examination of tissue sections of the brain, using immunocytochemical antibodies to demonstrate neuronal maturation and synaptogenesis, provides another means of demonstrating axonal projections in fetuses postmortem 117,118 .…”

Section: Axonal Projections In Cerebral Dysgenesismentioning

confidence: 99%

Axonal pathfinding during the development of the nervous system

Sarnat

2022

Annals of the Child Neurology Society

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Guidance of axons sprouting from maturing neuroblasts, during intermediate trajectories and in seeking target neurons for synaptogenesis, is a fundamental developmental process in central nervous system maturation. Axons but not dendrites sprout from neuroblasts during migration. The growth cone of the axonal tip projects constantly changing multiple veils and spikes (lamellipodia and filopodia) that contain microtubules, actin microfilaments, mitochondria, endosomes, and membrane receptor proteins. They are sensitive to changes in ionic calcium flux and may be impeded by perinatal hyper-or hypoglycemia. The growth of axonal membranes occurs mainly at the growth cone. Neurofilaments appear in the axonal tip as it approaches its target. Growth cones are attracted to or repelled by various extracellular matrix molecules that guide them, such as netrins and glycoproteins. Numerous genes are involved, some specific for only certain projections. Neurotransmitters later to be secreted are recognized in growing axons before their synthesis. Axonal fascicles are enveloped by extracellular keratan sulfate that ensures that fascicles contain axons of similar origin and destination and whose neurons secrete the same transmitter. Near their targets, axonal tips may ramify to form synapses on more than one neuron. Transitory pioneer axons provide supplementary mechanical guides to permanent axonal trajectories. Thalamus and olfactory bulb contain axonless neurons with dendrodendritic synapses. Chromaffin neurons of neural crest origin develop no neurites. Most cerebral malformations involve aberrant axonal pathfinding; in holoprosencephaly, keratan sulfate abnormally ensheathes individual axons. Axonal pathfinding to near or distant target neurons is primordial for synaptic circuitry subserving normal and abnormal neurological functions including epilepsy.I consider primitive nerve fibres to be protoplasmic outgrowths of the central nerve cell.

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Section: Axonal Projections In Cerebral Dysgenesismentioning

confidence: 99%

Axonal pathfinding during the development of the nervous system

Sarnat

2022

Annals of the Child Neurology Society

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“…This negative effect may be particularly true for very early lesions, in violation of the so-called Kennard Principle ( Schneider, 1979 ; Johnston, 2004 ; Elliott, 2020 ). In the case of the rat with the freezing lesion, the injury triggers plasticity in connections and in the cell composition of connectionally related areas ( Rosen et al, 1998 ; Li et al, 2021 ). In rats with shRNAi and in the knock-out mouse, epigenetic changes are triggered in other genes that are part of the injured gene’s network ( Che et al, 2014 , 2016 ).…”

Section: Animal Models Of Dyslexiamentioning

confidence: 99%

Animal models of developmental dyslexia

Galaburda

2022

Front. Neurosci.

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As some critics have stated, the term “developmental dyslexia” refers to a strictly human disorder, relating to a strictly human capacity – reading – so it cannot be modeled in experimental animals, much less so in lowly rodents. However, two endophenotypes associated with developmental dyslexia are eminently suitable for animal modeling: Cerebral Lateralization, as illustrated by the association between dyslexia and non-righthandedness, and Cerebrocortical Dysfunction, as illustrated by the described abnormal structural anatomy and/or physiology and functional imaging of the dyslexic cerebral cortex. This paper will provide a brief review of these two endophenotypes in human beings with developmental dyslexia and will describe the animal work done in my laboratory and that of others to try to shed light on the etiology of and neural mechanisms underlying developmental dyslexia. Some thought will also be given to future directions of the research.

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“…In the highlighted work, 8 demonstrate a novel method for targeted induction of molecular layer heterotopia in mouse neocortex. As with many great inventions, the technique was developed accidentally.…”

Section: Commentarymentioning

confidence: 99%