Youthful Vigor Restored to Adult Brains

Reactivated plasticity points to new treatments for developmental disorders.

They say you can’t teach an old dog new tricks. The same can be said of the adult brain. Its connections are hard to change, while in children, novel experiences rapidly mold new connections during critical periods of brain development.

UC Irvine neurobiologist Sunil Gandhi and colleagues wanted to know whether the flexibility of the juvenile brain could be restored to the adult brain. Apparently, it can: They’ve successfully re-created a critical juvenile period in the brains of adult mice. In other words, the researchers have reactivated brain plasticity — the rapid and robust changes in neural pathways and synapses as a result of learning and experience.

And in doing so, they’ve cleared a trail for further study that may lead to new treatments for developmental brain disorders such as autism and schizophrenia. Results of their study appear online in Neuron.

The scientists achieved this by transplanting a certain type of embryonic neuron into the brains of adult mice. The transplanted neurons express GABA, a chief inhibitory neurotransmitter that aids in motor control, vision and many other cortical functions.

Much like older muscles lose their youthful flexibility, older brains lose plasticity. But in the Gandhi study, the transplanted GABA neurons created a new period of heightened plasticity that allowed for vigorous rewiring of the adult brain. In a sense, old brain processes became young again.

In early life, normal visual experience is crucial to properly wire connections in the visual system. Impaired vision during this time leads to a long-lasting visual deficit called amblyopia. In an attempt to restore normal sight, the researchers transplanted GABA neurons into the visual cortex of adult amblyopic mice.

“Several weeks after transplantation, when the donor animal’s visual system would be going through its critical period, the amblyopic mice started to see with normal visual acuity,” said Melissa Davis, a postdoctoral fellow and lead author of the study.

This shows brain cut in half.

Much like older muscles lose their youthful flexibility, older brains lose plasticity. The image is for illustrative purposes only.

These results raise hopes that GABA neuron transplantation might have future clinical applications. This line of research is also likely to shed light on the basic brain mechanisms that create critical periods.

“These experiments make clear that developmental mechanisms located within these GABA cells control the timing of the critical period,” said Gandhi, an assistant professor of neurobiology & behavior.

He added that the findings point to the use of GABA cell transplantation to enhance retraining of the adult brain after injury. Furthermore, this work sparks new questions as to how these transplanted GABA neurons reactivate plasticity, the answers to which might lead to therapies for currently incurable brain disorders.

About this neurology research

Dario Figueroa Velez, Roblen Guevarra, Michael Yang, Mariyam Habeeb and Mathew Carathedathu of UCI contributed to the study.

Funding: The research was supported by a National Institutes of Health Director’s New Innovator Award (DP2 EY024504-01), a Searle Scholars award, a Klingenstein Fellowship and a postdoctoral training grant from the California Institute for Regenerative Medicine (TG2-01152).

Source: Tom Vasich – UC Irvine
Image Source: Image is in the public domain
Original Research: Abstract for “Inhibitory Neuron Transplantation into Adult Visual Cortex Creates a New Critical Period that Rescues Impaired Vision” by Melissa F. Davis, Dario X. Figueroa Velez, Roblen P. Guevarra, Michael C. Yang, Mariyam Habeeb, Mathew C. Carathedathu, and Sunil P. Gandhi in Neuron. Published online April 30 2015 doi:10.1016/j.neuron.2015.03.062


Abstract

Inhibitory Neuron Transplantation into Adult Visual Cortex Creates a New Critical Period that Rescues Impaired Vision

Highlights
•Interneuron transplantation to adult cortex reactivates critical period plasticity
•Transplantation recovers visual cortical function in visually impaired mice
•Transplantation restores normal perception to visually impaired mice

Summary
The maturation of inhibitory circuits in juvenile visual cortex triggers a critical period in the development of the visual system. Although several manipulations of inhibition can alter the timing of the critical period, none have demonstrated the creation of a new critical period in adulthood. We developed a transplantation method to reactivate critical period plasticity in the adult visual cortex. Transplanted embryonic inhibitory neurons from the medial ganglionic eminence reinstate ocular dominance plasticity in adult recipients. Transplanted inhibitory cells develop cell-type-appropriate molecular characteristics and visually evoked responses. In adult mice impaired by deprivation during the juvenile critical period, transplantation also recovers both visual cortical responses and performance on a behavioral test of visual acuity. Plasticity and recovery are induced when the critical period would have occurred in the donor animal. These results reveal that the focal reactivation of visual cortical plasticity using inhibitory cell transplantation creates a new critical period that restores visual perception after childhood deprivation.

“Inhibitory Neuron Transplantation into Adult Visual Cortex Creates a New Critical Period that Rescues Impaired Vision” by Melissa F. Davis, Dario X. Figueroa Velez, Roblen P. Guevarra, Michael C. Yang, Mariyam Habeeb, Mathew C. Carathedathu, and Sunil P. Gandhi in Neuron. Published online April 30 2015 doi:10.1016/j.neuron.2015.03.062

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