Rethinking Rigidity: The Surprising Plasticity of Adult Vision

Rethinking Inflexibility: The Unexpected Malleability of Adult Vision

A new approach has been developed by researchers to introduce intricate visual stimuli to rodents within an MRI scanner, offering insights into the adaptability of adult brain visual pathways. Image Credit: Hedi Young

Importance of Adult Adaptability

Much like how young children quickly grasp languages during their early years, our visual system also undergoes a “critical period” in its initial developmental phase marked by rapid progress. However, beyond this stage, the capacity for adaptation diminishes, following the adage, “You can’t teach an old dog new tricks.”

Indeed, numerous treatments designed to restore vision, including those addressing congenital cataracts or “lazy eye,” are effective only before the age of 7. As various established and emerging techniques to restore adult vision, such as gene therapy, bionic eyes, and surgeries, emerge, it becomes crucial to ascertain whether the adult brain can process novel visual signals.

Noam Shemesh, the senior author of the study, notes, “If the adult brain lacks such plasticity or adaptability, treatments targeting the eyes may prove futile if the brain is unable to interpret the incoming information. Interestingly, there are examples in nature, like birds rewiring their brains seasonally or humans experiencing a brief window of plasticity after a stroke, which show that adaptation in adults is possible in certain circumstances.”

Hence, the central inquiry of this study was to investigate whether the adult mammalian brain retains the ability to reorganize its visual pathways and adapt even after the critical developmental period has elapsed.

Innovations in Science and Technology

With the help of a groundbreaking technical achievement, researchers discovered that when rodents, raised in darkness from birth, were exposed to light during adulthood – well after the critical period had concluded – their brains underwent notable reorganization and adaptation, showcasing a remarkable level of plasticity. These findings not only provide evidence that the adult brain maintains significant plasticity, challenging previous notions of its rigidity, but also pave the way for new prospects in visual rehabilitation treatments.

Noam Shemesh underscores the challenges faced in reaching these insights. “Our lead researcher, Joana Carvalho, encountered numerous obstacles and skepticism from prominent laboratories worldwide, who deemed her endeavor impossible. But Joana’s persistence paid off. Without her determination and creativity, we wouldn’t have reached this point. I truly credit Joana for that.”

Carvalho had to surmount the unprecedented challenge of fitting a screen inside the confined space of a rodent MRI scanner to project images onto it. “Due to limitations in space and materials due to the ultra-high magnetic field,” Carvalho explains, “previous rodent studies only presented flashes of light. Our method allows us to extract more intricate information compared to simple flashing visual stimuli.”

The Experiment

Using their novel functional MRI (fMRI) setup, the team exposed the animals to complex, patterned stimuli and non-invasively mapped brain-wide properties that were previously accessible only through invasive techniques. Carvalho elaborates, “Initially, the challenge was to project images into a confined space filled with obstacles, ensuring the mouse could view them unhindered. The extremely high magnetic field of the MRI, capable of lifting a train, posed another significant challenge. We had to devise solutions within these constraints, utilizing mirrors and specialized hardware to deliver the images to their intended locations. The fact that the rats were sedated, minimizing their spontaneous eye movements and other motions, proved beneficial.”

Having conquered these obstacles, the researchers delved into the adaptability of the adult brain to visual signals. They employed a model in which rodents were born and raised in darkness until adulthood, well beyond the critical period of plasticity. Consequently, the brains of these animals hadn’t undergone the key processes necessary for visual specialization.

Subsequently, the rodents were exposed to light for the first time while inside the MRI scanner. This allowed the researchers not only to observe the brain’s response to its initial encounter with visual stimuli but also to explore how it might adapt to this delayed exposure, yielding two crucial insights.

Firstly, when the animals were subjected to light for the first time during the initial MRI scan, their brains didn’t exhibit an organized response to visual information. Instead, nerve cells across various regions reacted to a broad spectrum of visual details, ranging from fine to coarse. Additionally, the receptive fields of neurons – the specific visual field area they responded to – were larger in visually deprived rats compared to the control group. Collectively, these findings indicated a lack of specialization in the visual pathway of light-deprived rats.

Secondly, following exposure to light, the animals’ brain responses began to change. Even within a week, visual responses became more organized, with neighboring neurons beginning to respond to adjacent positions in the visual field, and the cells displaying increased reactions to specific visual attributes. The receptive fields of neurons also became smaller and more precise. After a month, the brains of the animals resembled those of healthy control subjects.

Shemesh comments, “Surprisingly, in less than a month, the structure and function of the visual system in the visually deprived animals became similar to the controls. While plasticity has been observed in humans, deciphering it remains highly challenging. What we’re observing here in rodents, which offer insights into brain mechanisms not easily attainable through human studies, is a phenomenon that hasn’t been witnessed before: extensive plasticity in the adult brain across the entire visual pathway, rather than being localized to specific brain regions, as previous studies have shown.”

Prior investigations had employed electrophysiology and calcium imaging, which focus on isolated brain areas, and lack a comprehensive view of the complete pathway. Although these methods offer direct measures of neural activity, they are invasive and potentially introduce confounding factors. Additionally, monitoring the same cells at different times using these techniques might lead to detecting unrelated changes, unrelated to actual plasticity.

While lacking the specificity of single-cell measurements and indirectly reflecting neuronal activity, fMRI allows the non-invasive and longitudinal measurement of entire visual regions simultaneously, with very high precision.

Carvalho notes, “As a result, we were able to observe an intriguing detail. The superior colliculus, a part of the visual pathway, appeared to adapt more slowly in visually deprived animals compared to other areas like the cortex. This is an avenue we’d love to explore further. It emphasizes the importance of considering the entire system integratively in the same animal over multiple time points.”

Potential Clinical Significance and Future Prospects

Shemesh remarks, “We’re now in a position to investigate whether we can predict which animals might experience improved or deteriorated vision based on the MRI responses of their visual system. In animals with impaired vision, we aim to identify those most likely to benefit from specific therapeutic interventions. Presently, determining from an MRI scan whether a patient’s brain will respond to a given treatment is challenging for medical practitioners, leading to needless suffering and wasted time. Through preclinical imaging, we can begin to chart treatment responses in rats, deepening our understanding of treatment effects and expediting treatment development in humans. Additionally, this can guide clinicians on the necessary scans for their patients.”

Moreover, the techniques pioneered in this study can be extended to other animal disease models, such as Parkinson’s Disease, which is also under investigation in the Shemesh Lab. Since subtle visual issues are known to occur early in Parkinson’s Disease, the method could be employed to track alterations in visual system responses over time, potentially revealing novel insights into disease progression and treatment avenues in animal models.

Shemesh adds, “Within the preclinical context, this technique could assist in pinpointing the optimal timing for visual restoration and rehabilitation procedures, enhancing the effectiveness of treatments like retinal stem cell transplantation.”

Meanwhile, the research team continues to make strides. Carvalho is eager to delve into the neural mechanisms behind the adaptation of the visual system in light-deprived rats, particularly focusing on excitatory-inhibitory balances and the role of long-range connections.

Shemesh plans to build upon Carvalho’s innovations to conduct experiments in awake, non-sedated rats. However, this will necessitate overcoming further challenges, such as extended training to acclimatize the animals to scanner noises and maintaining a fixed gaze to prevent distortions induced by eye movements. The Champalimaud Foundation’s acquisition of an 18 Tesla MRI scanner, the most potent horizontal scanner globally, will undoubtedly facilitate their endeavors to comprehend and enhance plasticity in adult humans, and perhaps one day, even in elderly dogs.

Frequently Asked Questions (FAQs) about neural plasticity

More about neural plasticity

• Study: Extensive topographic remapping and functional sharpening in the adult rat visual pathway upon first visual experience
• Champalimaud Foundation
• Noam Shemesh Lab
• MRI Imaging
• Neural Plasticity
• Visual Rehabilitation