Precise mapping of functional somatotopy in sensorimotor cortex

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Recent innovations in live animal imaging permit real-time measurement of cellular signalling in the intact brain and visualization of the microscopic structure of the neurons that form the framework for brain function. By combining these cellular imaging techniques with regional functional imaging and measures of brain anatomy, this research will precisely map the function, connectivity, and adaptive changes the cortex associated with limb sensation in mice and rats. Regional imaging maps the cortical areas responsive to sensory stimulation, while cellular imaging of sensory-evoked calcium signals enables simultaneous assessment of spiking activity and the precise three-dimensional organization of hundreds to thousands of optically-recorded neurons. Using stimuli that deliver precise mechanical stimulation to discrete regions of the fore- or hind-paw, these imaging techniques will precisely map the borders between regions of cortex responding to stimulation of different areas of the limbs. Moreover, calcium indicators can be administered in a manner that permits calcium imaging with subcellular resolution to single axons and synapses. As such, our imaging approach can define precise three-dimensional functional organization not possible through any other method. Targeted injections of neuronal tracers, compounds that allow one to identify the individual neurons that project to or receive projections from the injection site, will also be made within these functional maps such that the organization of the projections to and from these discrete somatosensory regions can be described. Finally, to assess how the shape of the functional representations, the activity of individual neurons, and their anatomical connections are altered by behavioural experience, the imaging and tract tracing techniques described above will be performed in rats undergoing environmental enrichment, voluntary endurance exercise, or skilled-reaching training. Combined, the proposed studies combine innovative imaging techniques with established protocols for neuronal tract tracing to define the neuronal organization and experience-dependent plasticity of the rodent sensorimotor cortex.