Wednesday, January 22, 2025
1/22/2025
Project Summary Experience shapes cortical sensory representations in a remarkable manner during development, but after maturation capacity for plasticity becomes limited. The tightly regulated plasticity of the mature cortex enables learning but impedes the brain’s capacity to regain appropriate function after injury, stroke or prolonged sensory loss. Studying mechanisms that underlie perceptual learning in the adult stage will advance our understanding of perception and will provide the foundation to develop novel approaches that promote plasticity in the adult brain. Recent studies in the tree shrew (tupaia belangeri), a highly visual mammal that shares cortical organization features with primates, show that learning a reward-based orientation discrimination task leads to long lasting changes in excitatory responses that increase discriminability between task relevant stimuli in the mature primary visual cortex (V1). However, we lack a clear understanding of the underlying circuit mechanisms that are responsible for these changes. I will combine my previous experience studying mechanisms of synaptic plasticity with new training focused on expanding my technical expertise in cutting edge optical approaches to uncover the mechanisms underlying perceptual learning in the tree shrew. Preliminary data suggest that a transient and feature specific decrease in the inhibitory network response precedes changes in the excitatory neuronal population associated with enhanced performance, showing that the learning process in tree shrew V1 layer 2/3 is a precise one where circuit elements are engaged with both feature and temporal specificity. I will employ chronic 2-photon imaging in combination with novel genetic enhancers and precise RNAscope technology to determine changes in the response properties of V1 inhibitory neural subpopulations during perceptual learning (Aim 1). Additionally, I will define changes in the functional synaptic architecture of excitatory neurons that undergo learning-related changes (Aim 2) by applying calcium imaging of dendritic spines through the learning process. Finally, I will establish the spatiotemporal recruitment of acetylcholine release during discrimination learning (Aim 3) by taking advantage of a recently developed cholinergic sensor that can be imaged chronically through learning stages. This project capitalizes on the functional organization of the tree shrew V1 area as a unique model to address how perceptual learning is implemented in highly structured cortical networks akin to those found in the primate cortex. The studies will take place in a collaborative environment at Max Planck Florida Institute for Neuroscience (MPFI) known for developing innovative approaches to address fundamental questions about neural circuits and hosting one of the few tree shrew colonies in the world. Completion of these aims and training plan will lead to a comprehensive framework describing the progression of learning-related plasticity in a functionally structured cortex upon which I will build an independent research program in the future.
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