Abstract
Mammals are born with immature sensory systems which develop postnatally. Despite their continuing maturation, developing sensory systems provide crucial inputs for neonatal mammalian development, the maturation of neural circuits and adult behavior. Rodents are born with functional olfactory, somatosensory, as well as gustatory systems, which continue to develop postnatally. However, the auditory and visual systems are only functional at P11 and P14, respectively. Therefore, rodent early sensory experience largely depends on olfaction and somatosensation. This dissertation is dedicated to understanding the developmental long-range corticocortical communication and its impact in brain dynamics and sensory maturation using the mouse as a model system. My first doctoral project focused on the development of the whisker somatosensory system of mice. Specifically, I studied the development of the functional connectivity and interaction between the primary and secondary whisker somatosensory cortex (wS1 and wS2, respectively). The second main project of my thesis focused on the developmental interaction of the whisker somatosensory with the olfactory system. During my doctoral studies I also contributed to other projects, with one being the output connectivity of subdomains within wS1, barrels versus septal to wS2 and primary motor cortex (M1), as well as the local interneuron distribution within these same domains. The first project focuses on the developmental engagement of wS2 and communication from wS1 to wS2. Using in vivo wide-field calcium imaging and multi-electrode recording techniques, we discovered the wS2 developmental timeline of bottom-up input from the thalamus and cortico-cortical input from wS1. wS2 processes bottom-up information from the thalamus from birth, while it begins to receive wS1 input only at the end of the first postnatal week and switches to more inhibitory inputs after the second postnatal week. Here we uncovered a developmental window when information transfer between wS1 and wS2 reaches mature function. The second project is about olfaction and somatosensation. We reveal that olfactoryevoked activity propagates to a large part of the cortex during the first postnatal week in mice and enhances whisker-evoked activity in wS1. This odor-enhancement effect is only observed in neonatal mice and disappears in adult mice due to the loss of neonatal excitatory connectivity from the olfactory cortex to wS1. By olfactory-depriving the neonatal mice and performing electrophysiological and behavioral experiments in adults, we find olfactory information provides important transient regulation of wS1 sensory driven neural dynamics and somatosensation. Our work discovered a critical window for somatosensory functional maturation regulated by olfaction. The third project studied the anatomical output of wS1 barrel vs septa domains to downstream S2 and M1 as well as their interneuron distribution. By using the retrograde virus tracing technique, CLARITY and 3D light-sheet imaging, we quantified the cell numbers in the barrel and septal domains across all the layers. We found the differential distribution and projection between L4 barrel and septal neurons. With three different projects using wS1 as a sensory modal to study the development of mammal sensory systems, we discovered critical windows before the second postnatal week which are related to other late-developed sensory systems (auditory and visual systems) coming online. The timing of all the sensory systems working together affects deeply the brain’s developmental states.
Cai, Linbi