Developmental biology - Buiding the Brain|
Synapses control migration of neurons
Whether neurons do or do not communicate when migrating during brain development affects how our future brain works...
Synapses connect neurons. In mature neurons, synapses are critical in neuron to neuron communication, and essential in virtually all neural functions. But, synapses being critical to the migration of neurons in the fetal brain — well that was unexpected.
In this study, a research team has found that neurons forming the subplate of the fetal brain make transient synapses between newborn neurons, pulsing them forward on their migration into becomming the neocortex.
The human cerebral neocortex is responsible for higher brain function, conscious thought and language. Located at the topmost and front of our skull, neocortex neurons somehow precisely self-arrange into a 6-layered structure. This sandwiched structure is formed from billions of neurons migrating in sequenced waves towards our upper skull.
"Subplate neurons" are one of the first types of neurons born to the neocortex. They exist transiently during fetal development and disappear when development is complete. We found that a special type of subplate neuron controls migration of newborn neurons through communication by synapses. We were really surprised by this as synapses are thought to be structures used by mature neurons. This is the first time that synapses have been found so early in development."
Chiaki Ohtaka-Maruyama PhD, Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Japan; Lab Director and lead author.
These research results appeared in Science magazine, April 20, 2018.
• During neocortical development in the fetus, neurons are born deep within the brain from repeated cell divisions of neural progenitor cells.
•Subplate neurons are the first neurons born in the neocortex, and they form a layer called the subplate layer. Below: MRI images of fetal subplate (dark grey) at 23 and 27 weeks post gestation:
• After generation of subplate neurons, neural progenitor cells next generate enormous numbers of excitatory neurons, which then migrate en masse toward the brain surface, where they form the different layers of the neocortex.
• When excitatory neurons are first born, they are star-shaped, or multipolar, and migrate in a slow, meandering manner without a set direction. This type of migration is referred to as multipolar migration.
• At some point, multipolar neurons suddenly change into a spindle shape with two protrusions, and begin migrating quickly towards the brain surface in a process called locomotion or radial neuronal migration. The mechanism regulating this switch had been unknown.
As Ohtaka-Maruyama observed newborn neurons switch from multipolar migration to radial neuronal migration along the subplate layer, she and her team hypothesized these subplate neurons might be affecting the organization of this migration. Subplate neurons actively extend processes, much like psuedopodia, which communicate to other subplate neurons through synapses. Preventing subplate neuron communication prevents their migration. In fact, spritzing newborn neurons with the neurotransmitter glutamate, which mimics synaptic activity, increases radial migration. Cortical excitability reflects a balance between excitation and inhibition. Glutamate is the main excitatory stimulus and GABA the main inhibitory neurotransmitter in our mammalian cortex (from: GABA and Glutamate in the Human Brain).
Various mental disorders such as autism and schizophrenia are associated with defects in locomotion during radial neuron migration. Therefore, these observations help explain how some mental disorders might have orginated as well as how our complex human neocortex evolved.
The neocortex exhibits a six-layered structure that is formed by radial migration of excitatory neurons, for which the multipolar-to-bipolar transition of immature migrating multipolar neurons is required. Here, we report that subplate neurons, one of the first neuron types born in the neocortex, manage the multipolar-to-bipolar transition of migrating neurons. By histochemical, imaging, and microarray analyses on the mouse embryonic cortex, we found that subplate neurons extend neurites toward the ventricular side of the subplate and form transient glutamatergic synapses on the multipolar neurons just below the subplate. NMDAR (N-methyl-D-aspartate receptor)–mediated synaptic transmission from subplate neurons to multipolar neurons induces the multipolar-to-bipolar transition, leading to a change in migration mode from slow multipolar migration to faster radial glial-guided locomotion. Our data suggests that transient synapses formed on early immature neurons regulate radial migration.
Authors: Chiaki Ohtaka-Maruyama, Mayumi Okamoto, Kentaro Endo, Minori Oshima, Noe Kaneko, Kei Yura, Haruo Okado, Takaki Miyata, Nobuaki Maeda
From: University of Oxford/Oxford Talks:
During the formation of mammalian six-layered neocortical structure, newborn neurons depart the ventricular zone and migrate toward the pial surface. At a middle stage of cortical development, newly differentiated postmitotic neurons show multipolar shape (MP), and move non-radially in the intermediate zone (multipolar migration). When these multipolar neurons pass through the subplate (SP) layer, they show dynamic morphological changes and adopt bipolar shape (BP). Then, they migrate toward the pial surface (locomotion). Many KO mice with radial migration defects show abnormal MP-BP conversion at the SP suggesting that the interaction between migrating neurons and SP layer plays critical roles in switching the migration mode. SP neurons are known to help thalamocortical innervation during early stage of neural circuit formation, but their roles in radial neuronal migration remain to be elucidated. Our present working hypothesis is that MP neurons receive certain signals from the SP to change their morphology and migration mode. To test our hypothesis, we are analyzing the interaction between migrating young neurons and SP in many aspects. In this context, we examined neuronal activity of SP neurons by Ca2+-imaging using GCaMP3, and observed that they exhibited calcium oscillations at E15. Moreover, we found that suppression of neuronal activities of SP neurons by electroporation of inward-rectifier potassium ion channel Kir2.1 led to the impairment of radial migration. This suggests that neuronal activity of SP neurons is critical for radial migration. I will also discuss the evolutionally aspect of this study.
About the Tokyo Metropolitan Institute of Medical Science
The Tokyo Metropolitan Institute of Medical Science is a public interest foundation funded by the Tokyo metropolitan government. Its goal is to pursue medical and basic research to improve the health and well-being of the people of Tokyo and worldwide. The Institute contains 35 research laboratories, and was ranked as the top research institute in life sciences in Japan by Nature Index 2018 Japan.
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May 1, 2018 Fetal Timeline Maternal Timeline News News Archive
Mature nerve cell extending one axon to right of image.