Old brains, new tricks: Researchers have documented a new brain activity never seen before
The way young children rapidly pick up languages in their formative years mirrors the “critical period” in our visual system during our early life. Beyond this phase, adaptability slows down, reflecting the saying, “You can’t teach an old dog new tricks.”
Vision restoration treatments, such as those for congenital cataracts or “lazy eye”, tend to work only before age 7. Given the emergence of methods like gene therapy, artificial eyes, and surgical procedures to improve vision in mature individuals, it’s essential to determine the adult brain’s capacity to handle fresh visual inputs.
Noam Shemesh, the lead author, comments, “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.
But nature offers clues. Birds alter their brain structures seasonally, and humans show temporary flexibility after events like strokes. The study aimed to discern if the adult mammalian brain can still adjust its visual systems post the vital growth phase.
Innovative Approach and Discoveries
Leveraging groundbreaking techniques, the team discovered that rodents, which were deprived of light since birth, showed considerable brain adaptation and restructuring when exposed to light in their mature years, well past their primary developmental phase. This significant finding suggests that the mature brain retains a high level of adaptability, defying earlier notions of its inflexibility and paving the way for innovative visual treatment methods.
Noam Shemesh highlights the technical challenges faced during this research. ““Joana Carvalho, our lead researcher, faced numerous challenges and even doubts from some of the world’s leading labs who thought her endeavour was impossible. But Joana’s perseverance paid off.”
Carvalho had the intricate task of fitting a display in the limited space of a rodent MRI scanner. Carvalho remarks, “Due to space limitations and material constraints due to the ultrahigh magnetic field, previous studies in rodents only displayed flashes of light. Our method enables us to extract more detailed information compared to simple flashing visual stimuli.”
The Study in Depth
Using their innovative fMRI technology, the researchers presented the animals with complex visual patterns, enabling a non-invasive examination of comprehensive brain characteristics that were formerly studied only through intrusive methods. Carvalho detailed the initial challenges: Initially, the challenge was to project images into a confined space riddled with obstructions, ensuring the mouse could view them without hindrance. The extremely high magnetic field of the MRI, capable of lifting a train, posed another substantial hurdle. We had to work around these constraints, using mirrors and specialized hardware, to get the images to where they needed to be. It helped that the rats were sedated, keeping their spontaneous eye movements and other motions to a minimum.”
Overcoming these hurdles, the team delved into investigating the adaptability of the mature brain to visual cues. They studied rodents that had been kept in darkness since birth, surpassing their prime adaptability phase. As these rodents’ brains hadn’t experienced the essential phases for visual development, their first exposure to light within the MRI scanner was enlightening. The team could analyze not just the brain’s immediate response to new visual stimuli, but also its potential adaptability after such a belated encounter, which led to two key discoveries.
Initially, during their debut exposure to light, the animals’ brains didn’t show any systematic reaction to visual input. The neurons, across varied regions, responded to a wide spectrum of visual nuances, from the intricate to the obvious. Additionally, the area of the visual spectrum the neurons responded to was noticeably larger in these light-deprived rats than in their counterparts. This data hinted at a lack of specialization in the visual pathways of these deprived rodents.
However, post-light exposure, transformations in the rodents’ brains commenced. Within a week, there was a more structured response to visual stimuli. Neurons responded to adjacent positions in the visual spectrum and became more receptive to distinct visual features. The area each neuron responded to also grew more defined and restricted. A month later, these rats’ brain structures closely mirrored those of regular rodents.
Shemesh commented, “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, interpreting it remains very difficult. What we are seeing here in rodents, which offer insights into brain mechanisms unattainable in human studies, is a phenomenon that has not been observed before: large-scale plasticity in the adult brain across the entire visual pathway, not just localised to a specific brain area as shown in previous papers.”
Historically, research relied on electrophysiology and calcium imaging, focusing on individual brain sections, limiting a holistic understanding of the entire system. Although they provided direct neural activity feedback, they were intrusive and had the possibility of misinterpretations due to the challenge of consistently observing the same neurons.
Contrastingly, while fMRI doesn’t offer cellular-level precision and provides indirect feedback on neural activity, it enables a detailed, non-invasive examination of complete visual regions at once. Carvalho shared a captivating observation: “One segment of the visual route, the superior colliculus, seemed to have a prolonged adaptation in light-deprived rodents than other sections, such as the cortex. It’s a phenomenon we’re eager to delve deeper into, underscoring the value of observing the complete system in a single animal across varied timelines.
Future Prospects and Further Studies
“We’re now in a position to start exploring whether we can predict which animals may have improved or deteriorated vision based on the MRI responses of their visual system”, Shemesh commented. “In animals with impaired vision, we’d like to determine which ones will benefit most from certain therapeutic interventions. Currently, it’s challenging for medical doctors to determine from an MRI scan whether a patient’s brain will respond to a particular treatment, leading to unnecessary suffering and lost time. Through preclinical imaging, we can begin to chart treatment responses in rats, which could not only deepen our understanding of the treatment’s effects but also accelerate the pace of treatment development in humans, as well as guide clinicians on the necessary scans for their patients.”
Moreover, the methodologies derived from this research can be applied to other animal models of diseases, including disorders like Parkinson’s Disease, a subject of study in the Shemesh Lab. Given the early and subtle visual disturbances noted in Parkinson’s, this approach might help monitor changes in visual responses over time, potentially shedding light on the course of the illness and possible treatment paths in animal settings.
Shemesh added, “within the preclinical setting, 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.”
The research group remains steadfast in its pursuit. Carvalho is enthusiastic about investigating the neural underpinnings behind the adaptability of the visual system in rats kept in the dark, emphasizing aspects like excitatory-inhibitory dynamics and the significance of expansive neural connections. Shemesh is eager to expand on Carvalho’s groundwork, planning experiments with alert, non-anesthetized rats.
This endeavor will introduce new obstacles, such as the need for extended training to familiarize the animals with the scanner sounds and ensure their eyes remain steady to prevent distortions caused by eye movements.
With the Champalimaud Foundation’s recent acquisition of an 18 Tesla MRI scanner, the world’s most potent horizontal scanner, the team is undoubtedly in a better position to delve into the mysteries of brain adaptability in adults, possibly extending the insights to even the elderly canine population.
Source: 10.1371/journal.pbio.3002229
Image Credit: Getty