Navigation Links
New period of brain 'plasticity' created with transplanted embryonic cells
Date:3/25/2010

UCSF scientists report that they were able to prompt a new period of "plasticity," or capacity for change, in the neural circuitry of the visual cortex of juvenile mice. The approach, they say, might some day be used to create new periods of plasticity in the human brain that would allow for the repair of neural circuits following injury or disease.

The strategy which involved transplanting a specific type of immature neuron from embryonic mice into the visual cortex of young mice could be used to treat neural circuits disrupted in abnormal fetal or postnatal development, stroke, traumatic brain injury, psychiatric illness and aging.

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.

In the other study (Cell Stem Cell, vol. 6, issue 3, 2010), UCSF scientists reported the first use of MGEs to treat motor symptoms in mice with a condition designed to mimick Parkinson's disease. The finding was reported by the lab of Arnold Kriegstein, MD, PhD, UCSF professor of neurology and director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, in collaboration with Alvarez-Buylla and Krys Bankiewicz, MD, PhD, UCSF professor of neurological surgery.


'/>"/>

Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert

Related biology news :

1. Super atoms turn the periodic table upside down
2. Periodontitis and myocardial infarction: A shared genetic predisposition
3. Study finds genetic links to age of first menstrual period and menopause
4. In vitro antibody production enables HIV infection detection in window period -- key to safer blood
5. Prevent periodontitis to reduce the risk of head and neck cancer
6. Algae and pollen grains provide evidence of remarkably warm period in Antarcticas history
7. Overweight adults age 70 or older are less likely to die over a 10-year period
8. Were short warm periods typical for transitions between interglacial and glacial epochs?
9. Invasion of the brain tumors
10. HIV is a double hit to the brain
11. AIDS interferes with stem cells in the brain
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/1/2016)... , June 1, 2016 Favorable ... Election Administration and Criminal Identification to Boost Global Biometrics ... recently released TechSci Research report, " Global Biometrics Market ... Competition Forecast and Opportunities, 2011 - 2021", the global ... by 2021, on account of growing security concerns across ...
(Date:5/12/2016)... WearablesResearch.com , a brand of Troubadour Research & ... Q1 wave of its quarterly wearables survey. A particular ... a program where they would receive discounts for sharing ... "We were surprised to see that so many ... CEO of Troubadour Research, "primarily because there are segments ...
(Date:4/28/2016)... , April 28, 2016 First quarter ... (139.9), up 966% compared with the first quarter of 2015 ... totaled SEK 589.1 M (loss: 18.8) and the operating margin was ... (loss: 0.32) Cash flow from operations was SEK 249.9 ... 2016 revenue guidance is unchanged, SEK 7,000-8,500 M. The ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... 2016 , ... Newly created 4Sight Medical Solutions ... healthcare market. The company's primary focus is on new product introductions, to include ... are necessary to help companies efficiently bring their products to market. , The ...
(Date:6/27/2016)... -- Liquid Biotech USA , Inc. ... Research Agreement with The University of Pennsylvania ("PENN") ... patients.  The funding will be used to assess ... outcomes in cancer patients undergoing a variety of ... to support the design of a therapeutic, decision-making ...
(Date:6/24/2016)... , June 24, 2016  Regular discussions on a range ... place between the two entities said Poloz. Speaking ... Ottawa , he pointed to the country,s inflation ... federal government. "In ... "Both institutions have common economic goals, why not sit down ...
(Date:6/24/2016)... NY (PRWEB) , ... June 24, 2016 , ... While ... machines such as the Cary 5000 and the 6000i models are higher end machines ... is the height of the spectrophotometer’s light beam from the bottom of the cuvette ...
Breaking Biology Technology: