Periodic Reporting for period 1 - PlastiMap (Multi-dimensional mapping of the interplay between stability and plasticity in the adult visual pathway)
Reporting period: 2021-09-01 to 2023-08-31
Our brains are incredible organs that constantly adapt to the world around us. They strike a delicate balance between staying stable enough to work properly throughout our lives and being flexible enough to learn new things and adjust to changes. This balance is crucial for learning new skills, training our senses, and recovering from injuries or damage to our brains.
We know that certain parts of our brains, like the visual system, can change in response to experiences. For example, when we lose vision or have changes in what we see, the areas of our brain that process visual information can also change. These changes are especially strong during childhood when our brains are still developing, but they can also happen in adulthood, although to a lesser extent. However, understanding exactly how and when these changes happen in the adult brain is still unknown. One reason for this is that most studies focus on small parts of the brain or individual neurons, which might not give us the whole picture. To really understand how our brains change and adapt, we need better ways to look at the whole brain and see how different brain areas interact over time. We also need methods that can give us detailed information about how neurons are working and how they change over time. By doing this, we can gain a clearer understanding of how our brains adapt and learn, both when we're young and as we grow older.
In PlastiMap, we used the latest technology in brain imaging and advanced computer models to study how the visual system adapts in response to environmental changes. In particular we investigated the following research questions: Can the brain change even after it's fully developed? Is visual experience driving brain plasticity? How long does it take for brain changes to happen? Do changes in one part of the brain affect other parts too?
We know that certain parts of our brains, like the visual system, can change in response to experiences. For example, when we lose vision or have changes in what we see, the areas of our brain that process visual information can also change. These changes are especially strong during childhood when our brains are still developing, but they can also happen in adulthood, although to a lesser extent. However, understanding exactly how and when these changes happen in the adult brain is still unknown. One reason for this is that most studies focus on small parts of the brain or individual neurons, which might not give us the whole picture. To really understand how our brains change and adapt, we need better ways to look at the whole brain and see how different brain areas interact over time. We also need methods that can give us detailed information about how neurons are working and how they change over time. By doing this, we can gain a clearer understanding of how our brains adapt and learn, both when we're young and as we grow older.
In PlastiMap, we used the latest technology in brain imaging and advanced computer models to study how the visual system adapts in response to environmental changes. In particular we investigated the following research questions: Can the brain change even after it's fully developed? Is visual experience driving brain plasticity? How long does it take for brain changes to happen? Do changes in one part of the brain affect other parts too?
To address these questions, we tracked changes in neural activity and characterized its timing properties along the entire visual pathway in healthy and plasticity-inducing animal models. First, we developed a novel set-up to display contextual information in animal scanners, and a set-up to acquire simultaneously fMRI and calcium signals (Objective 1). Second, we will harness our unique setup to characterize brain topography and cortical circuitry in the healthy rodent visual pathway (Objective 2). Third, we tracked plasticity changes (brain remapping and changes in function specialization) over several months in a chronic model of visual deprivation (Objective 3).
We used a model in which rodents are born and raised in the dark until adulthood, well past the critical period of plasticity. Consequently, the brains of these animals had not yet undergone the key processes required for visual specialisation. The animals were then exposed to light for the first time inside the MRI scanner. This allowed us to observe the brain’s response to its first encounter with visual stimuli, but also to study how it might adapt to this delayed exposure, yielding two pivotal insights. First, when the animals were exposed to light for the first time during the initial MRI scan, their brains displayed no organised response to visual information. Instead, their nerve cells across different areas reacted to a broad range of visual details, from fine to coarse. Moreover, the receptive field sizes of neurons – the specific area of the visual field that they respond to – was also larger in visually deprived rats compared to the control group. Together, these findings suggested that the visual pathway in the light-deprived rats lacked specialisation. Second, after exposure to light, the animals’ brains began to change. Even
within a week, visual responses became more organised, such that neighbouring neurons began to respond to nearby positions in the visual field, and the cells started to react more to specific visual characteristics. The receptive fields of the neurons also became smaller and more spatially selective. After a month, the animals’ brains looked much like those of healthy controls. 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 studies.
We used a model in which rodents are born and raised in the dark until adulthood, well past the critical period of plasticity. Consequently, the brains of these animals had not yet undergone the key processes required for visual specialisation. The animals were then exposed to light for the first time inside the MRI scanner. This allowed us to observe the brain’s response to its first encounter with visual stimuli, but also to study how it might adapt to this delayed exposure, yielding two pivotal insights. First, when the animals were exposed to light for the first time during the initial MRI scan, their brains displayed no organised response to visual information. Instead, their nerve cells across different areas reacted to a broad range of visual details, from fine to coarse. Moreover, the receptive field sizes of neurons – the specific area of the visual field that they respond to – was also larger in visually deprived rats compared to the control group. Together, these findings suggested that the visual pathway in the light-deprived rats lacked specialisation. Second, after exposure to light, the animals’ brains began to change. Even
within a week, visual responses became more organised, such that neighbouring neurons began to respond to nearby positions in the visual field, and the cells started to react more to specific visual characteristics. The receptive fields of the neurons also became smaller and more spatially selective. After a month, the animals’ brains looked much like those of healthy controls. 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 studies.
We are 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. 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.
Furthermore, the techniques from this study are extendable to other animal disease models, including, for example, Parkinson’s Disease. As there are known early, subtle visual problems in Parkinson’s, the method could be applied to track differences in visual system responses over time, possibly revealing new insights into disease progression and treatment options in animal models. In addition, 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.
Furthermore, the techniques from this study are extendable to other animal disease models, including, for example, Parkinson’s Disease. As there are known early, subtle visual problems in Parkinson’s, the method could be applied to track differences in visual system responses over time, possibly revealing new insights into disease progression and treatment options in animal models. In addition, 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.