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Simultaneous imaging of structural and functional plasticity in the awake brain Podgorski, Kaspar Jan

Abstract

During learning, and particularly during development, neurons in the brain undergo structural and functional changes that are intricately interrelated. This plasticity is guided by patterns of activity that encode information about the environment, allowing the brain to adapt to an organism's specific experiences. Here I developed optical methods and analysis tools to measure and analyze sensory-evoked activity patterns in the awake brain, and track how sensory information guides plasticity. Several different methods and their applications are presented. I described models and analysis tools for nonlinear decoding of somatic activity patterns in populations of neurons, and used them to track functional reorganization of neural circuits during training. I identified a group of ultrabright and stable organic dyes that enable two-photon imaging deep within living tissue, and applied them to produce a sensitive intracellular label for excitatory synapses. I developed a random access microscope capable of tracking activity at all excitatory synapses on a neuron simultaneously, enabling the first comprehensive measurements of a single neuron's dendritic input and firing output within the awake brain. I used this microscope to track neurons' comprehensive activity and structural changes across plasticity-inducing training, and identified rules by which somatic and dendritic activity direct the detailed growth patterns of dendrites, producing spatially clustered input patterns along neurons' dendritic arbor. Throughout this work, I've taken advantage of the Xenopus laevis model system to observe rapid experience-dependent plasticity in the awake, developing brain. These results demonstrate ways in which specific experiences direct the detailed connectivity of developing neural circuits.

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Attribution-NonCommercial-NoDerivs 2.5 Canada