Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Neuroscience
First Advisor
Cardin, Jessica
Abstract
The cerebral cortex is essential to the processing and integration of sensory information, allowing us to perceive and interact with the world around us. Cortical function is subserved by specialized neural circuits comprised of excitatory and inhibitory neurons. Inhibitory GABAergic interneurons regulate the activity of excitatory pyramidal neurons to determine the output of cortical circuits across the entire brain. Interneurons are an extremely diverse population, but somatostatin-expressing interneurons play unique roles in cortical processing and function. In primary visual cortex, somatostatin interneurons exhibit robust visual responses, are broadly tuned for visual features such as stimulus size, and are modulated by arousal states including locomotion. However, the developmental trajectory of these specialized interneurons and their role within developing visual circuits during key postnatal windows remains unknown. To address this gap in our knowledge, we first used slice electrophysiology and in vivo 2-photon calcium imaging to assess the developmental trajectory of somatostatin neurons and pyramidal neurons in the developmental period following eye-opening in mice. Eye-opening is a major developmental milestone in mice, occurring two weeks after birth and precipitating a profound visual experience-dependent rewiring of their cortical circuits. Our results show contrasting developmental timelines for somatostatin and pyramidal neurons in primary visual cortex. We found that pyramidal neurons exhibit mature visual- and state-dependent responses immediately following eye-opening, whereas somatostatin interneurons progressively gain visual sensitivity, stimulus size selectivity, and state-dependent modulation. In parallel, these changes are supported by rapid increases in excitatory synaptic input to somatostatin cells within days of eye-opening. Next, we sought to characterize the functional relationship between somatostatin interneurons and pyramidal neurons, their primary synaptic targets. Using simultaneous optogenetic manipulation of somatostatin neurons and 2-photon calcium imaging of pyramidal neurons, we found that somatostatin neurons exert little influence over pyramidal neurons during early postnatal development but gradually provide greater inhibitory impact as animals age. Our results thus reveal functional connectivity between somatostatin and pyramidal neurons but limit the potential for somatostatin neurons to mediate surround suppression in pyramidal neurons early in postnatal development. Collectively, the findings in this thesis shed light on a previously unknown period of somatostatin interneuron development in primary visual cortex. Our results highlight inhibitory-excitatory interactions in developing cortex and deepen our understanding of experience-dependent cortical circuit formation as a whole.
Recommended Citation
Wang, Alex, "Emergence of Inhibitory Circuitry in the Developing Cortex" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1274.
https://elischolar.library.yale.edu/gsas_dissertations/1274
