New period of brain 'plasticity' created with transplanted embryonic cells
Like all regions of the brain, the visual cortex undergoes a highly plastic period during early life. Cells respond strongly to visual signals, which they relay in a rapid, directed way from one appropriate cell to the next in a process known as synaptic transmission. The chemical connections created in this process produce neural circuitry that is crucial for the function of the visual system. In mice, this critical period of plasticity occurs around the end of the fourth week of life.
The catalyst for the so-called critical period plasticity in the visual cortex is the development of synaptic signaling by neurons that release the inhibitory neurotransmitter GABA. These neurons receive excitatory signals from other neurons, thus helping to maintain the balance of excitation and inhibition in the visual system.
In their study, published in the journal Science (Vol. 327. no. 5969, 2010), the scientists wanted to see if the embryonic neurons, once they had matured into GABA-producing inhibitory neurons, could induce plasticity in mice after the normal critical period had closed.
The team first dissected the immature neurons from their origin in the embryonic medial ganglionic eminence (MGE) of the embryonic mice. Then they transplanted the MGE cells into the animals' visual cortex at two different juvenile stages. The cells, targeted to the visual cortex, dispersed through the region, matured into GABAergic inhibitory neurons, and made widespread synaptic connections with excitatory neurons.
The scientists then carried out a process known as monocular visual deprivation, in which they blocked the visual signals to one eye in each of the animals for four days. When this process is carried out during the critical period, cells in the visual cortex quickly become less responsive to the eye deprived of sensory input, and become more responsive to the non-deprived eye, creating alterations in the neural circuitry. This phenomenon, known as ocular dominance plasticity, greatly diminishes as the brain matures past this critical postnatal developmental period.
The team wanted to see if the transplanted cells would affect the visual system's response to the visual deprivation after the critical period. They studied the cells' effects after allowing them to mature for varying lengths of time. When the cells were as young as 17 days old or as old as 43 days old, they had little impact on the neural circuitry of the region. However, when they were 33-39 days old, their impact was significant. During that time, monocular visual deprivation shifted the neural responses away from the deprived eye and toward the non-deprived eye, revealing the state of ocular dominance plasticity.
Naturally occurring, or endogenous, inhibitory neurons are also around 33-39 days old when the normal critical period for plasticity occurs. Thus, the transplanted cells' impact occurred once they had reached the cellular age of inhibitory neurons during the normal critical period.
The finding, the team says, suggests that the normal critical period of plasticity in the visual cortex is regulated by a developmental program intrinsic to inhibitory neurons, and that embryonic inhibitory neuron precursors can retain and execute this program when transplanted into the postnatal cortex, thereby creating a new period of plasticity.
"The findings suggest it ultimately might be possible to use inhibitory neuron transplantation, or some factor that is produced by inhibitory neurons, to create a new period of plasticity of limited duration for repairing damaged brains," says author Sunil P. Gandhi, PhD, a postdoctoral fellow in the lab of Michael Stryker, PhD, professor of physiology and a member of the Keck Center for Integrative Neurosciences at UCSF. "It will be important to determine whether transplantation is equally effective in older animals."
Likewise, "the results raise a fundamental question: how do these cells, as they pass through a specific stage in their development, create these windows of plasticity?" says author Derek G. Southwell, PhD, a student in the lab of Arturo Alvarez-Buylla, PhD, Heather and Melanie Muss Professor of Neurological Surgery and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.
The findings could be relevant to understanding why learning certain behaviors, such as language, occurs with ease in young children but not in adults, says Alvarez-Buylla. "Grafted MGE cells may some day provide a way to induce cortical plasticity and learning later in life."
The findings also complement two other recent UCSF studies using MGE cells to modify neural circuits. In a collaborative study among the laboratories of Scott Baraban, PhD, professor of neurological surgery; John Rubenstein, MD, PhD, professor of psychiatry, and Alvarez-Buylla, the cells were grafted into the neocortex of juvenile rodents, where they reduced the intensity and frequency of epileptic seizures. (Proceedings of the National Academy of Science, vol. 106, no. 36, 2009). Other teams are exploring this tactic, as well.
Other news from the department science
Start-up Colossal Biosciences Joins Biorescue In Its Mission To Save The Northern White Rhino From Extinction
Colossal will assist the rescue mission by leveraging genome sequencing and gene editing methods to save the endangered species
"For the first time, we have systematically measured the size and abundance of cells across all major tissues and organs"
What's that smell? New gut microbe produces smelly toxic gas but protects against pathogens
Taurine-degrading bacteria influence intestinal microbiome
Wastewater treatment plants as drivers for the energy transition
Technical add-on module can, in principle, turn any wastewater treatment plant into a CO2 sink and decentralized methane production plant
At which age we are at our happiest
An evaluation of over 400 samples shows how subjective well-being develops over the course of a lifespan
New approach to testing for long Covid
Blood vessels in the eye altered with persistent coronavirus symptoms
Researchers create pioneering approaches for the detection of viral antigens
Sybodies: a revolution in biological recognition
New SARS-CoV-2 variant Eris on the rise
SARS-CoV-2 lineage EG.5.1 has an advantage at evading neutralizing antibodies
Does the human brain have an Achilles heel that ultimately leads to Autism?
CHOOSEn fate: one brain organoid’s tale on Autism
Co-crystal improves the water-solubility of ASA
This could benefit patients diagnosed with suspected acute myocardial infarction
Observing nanoparticles with unprecedented precision
Illuminated: Researchers investigate new physical phenomena on the nanoscale with microstructured fibers
Falling Walls announces Science Breakthrough of the Year 2023 laureates
“These outstanding breakthroughs will change the face of the world and impressively prove what ingenuity, curiosity and courage can achieve”
Most read news
Cells with an ear for music release insulin
For the first time, researchers are using music, including Queen's global hit "We will rock you," to stimulate insulin release from cells
"Anti-obesity drugs" normalises brain in obesity
Anti-obesity drug improves associative learning in people with obesity
Microbe of the Year 2023: Bacillus subtilis – for health and technology
Already, Bacillus subtilis is indispensable in many industries, and many more innovations are expected
Younger generation gets sick earlier and more often than older generation
In spite of their advanced age, they are in the middle of life, healthy, active and mentally alert – they are referred to as the “young old”
How sleep deprivation can harm the brain
Sleep deprivation decreases the amount of a factor that protects neurons
A whole new order of bacteria could hold the key to improving biogas production
The discovery was made by researchers from Germany, Spain and the Netherlands
How to inactivate common cold viruses
In the cold season, cold viruses are everywhere. But we can do something about it
New approach to testing for long Covid
Blood vessels in the eye altered with persistent coronavirus symptoms
How minimal genetic differences can turn healthy food into a deadly danger
You are what you eat - this old saying could take on a new dimension according to latest research results
More news from our other portals
Major breakthrough in the development of electric vehicle batteries
New study finds ways to suppress lithium plating in automotive batteries for faster charging electric vehicles
Blender Bites launches at Walmart USA
The products are to be introduced in about 1,600 stores across the country
Benchtop NMR spectroscopy can accurately analyse pyrolysis oils
More accessible analysis could help develop the potential of bio-oils as an alternative to fossil fuels
Clean water from fog
A property known as photocatalytic memory ensures that this also functions when skies are overcast and at night
Research shows table salt could be the secret ingredient for better chemical recycling
Table salt as the key to the plastics recycling revolution?
Green, sweet and crisp - New apple variety Pia41 approved
The apple bred at the Julius Kühn Institute receives variety protection
Graphene discovery could help generate hydrogen cheaply and sustainably
Microscopic insights into electrochemical interfaces
Sugar: Small increase in production despite record prices
EU sugar market more than in need of reform to keep medium-sized processing companies competitive
Scientists use quantum device to slow down simulated chemical reaction 100 billion times
What happens in femtoseconds in nature can now be observed in milliseconds in the lab
Green methanol for shipping and industry: € 10.4 Mio. for the "Leuna100" project
A consortium of two Fraunhofer institutes, DBI-Gastechnologisches Institut Freiberg, Technical University of Berlin and C1 makes industrial history at the Leuna site
Stanford study shows how the meat and dairy sector resists competition from alternative animal products
New battery holds promise for green energy
Redox-flow battery eliminates costly and inefficient membrane
Fondant under the magnifying glass
New insights into the properties of sweet coating: The results could be used to optimize the industrial production process in the future
Leipzig-based start-up converts CO₂ into green chemicals with patented plasma catalysis
CO₂ recycling as a useful complement to carbon capture and storage
A microchip for Parmigiano Reggiano cheese
Consorzio del Parmigiano Reggiano, p-Chip Corporation, and Kaasmerk Matec Partner to Launch Breakthrough in Food-Safe Digital Tracking Technology
Cleaning water with ‘smart rust’ and magnets
New method for pollutants such as crude oil, glyphosate, microplastics and hormones
A Second Life for Electric Car Batteries
Scientists develop a decision model for retired lithium-ion batteries