Investigating Layer-Specific Mechanisms Underlying Progression of Cortical Plasticity and Tactile Performance using Rodent MRI Model – LSMCP_MRI

It is well-known that the brain can be modified, or is plastic, through lifetime, even in adults. Brain and body injuries can result in life-changing, even devastating physical disability. Previous clinical and basic research studies have shown that the brain can undergo many self-organization processes following brain trauma or body injury, and lead to behavioral and perceptual impairments. However the mechanisms underlying brain plasticity remain largely unknown. There are very important questions that remain unclear in the field of brain plasticity. For example, how fast does plasticity occur' How does plasticity develop over time' Do different cortical layers express plasticity differently' What are the roles of cortical layers in shaping plasticity of other layers' What initiates these changes' What happens to perception and behavioral performance after plasticity occurs' And how can plasticity be regulated' Our research goal aims to address these important questions. A translational animal imaging model can help to bridge the gap between basic and clinical research. In this research proposal, we will utilize rodent MRI, in combination with different neuroscience approaches to study the activity (or experience) determinants of brain plasticity. Using an animal MRI model is critical because it allows investigating mechanistic questions using more invasive manipulations which are not feasible in human studies. Yet, since the same methodology is applied, knowledge obtained from animal fMRI experiments can be directly translated to human research. In addition, we will employ electrophysiology recordings to study neuronal properties, and use neuroanatomy to study neuronal connections because they have been considered the long-held, gold standard approaches to interpret brain functions. The aims of our research are to (1) understand how input activity contributes to cortical-layer specific brain plasticity, (2) investigate the development of brain plasticity, (3) evaluate the functional outcomes of brain plasticity, and (4) formulate strategies to regulate brain plasticity based on our understanding of these mechanisms. A better understanding of the mechanisms underlying brain plasticity is critical to formulate remedial therapy strategies in order to restore brain functions and to improve behavioral performance. To achieve these goals, we will first establish an animal model to study brain plasticity longitudinally. We will employ a multidisciplinary approach, including functional and anatomical MRI, electrophysiology, neuroanatomy and behavior to study altered brain functions and their accompanying perceptual and behavioral outcomes. We will study brain functions with functional MRI and electrophysiology. Particularly, we will examine whether different cortical layers express and maintain plasticity differently, and investigate the interactions between cortical layers and between cortical regions during the plasticity processes. Furthermore, to study the anatomical and cellular basis of these functional changes, we will employ a novel MRI visible tract-tracing compound and various histological staining methods to investigate whether these functional changes are accompanied by anatomical rewiring, and to examine the cellular mechanisms underlying these changes. After gaining a better understanding of the mechanisms underlying brain plasticity, we will perturb neuronal activity to understand the specific role of cortical layers and anatomical connections in mediating plasticity, and will formulate strategies for regulating cortical plasticity by 'turning-on' or 'silencing' the functions of anatomical pathways. Finally we will evaluate animals' behavioral performance after brain plasticity. The completion of this research proposal will yield a better understanding of the principles of brain dynamics, which is critical for developing therapeutic strategies to promote the recovery of cortical functions.