GABAergic interneurons are central to the normal development and function of neocortical circuits. In particular, cells that express the peptide somatostatin (SST-INs) are thought to play critical roles in both spontaneous and sensory-evoked neuronal activity, primarily via their robust inhibition of the dendrites of excitatory pyramidal neurons. However, the functional roles of the diverse classes of SST-INs in deep cortical layers remain unknown. Furthermore, whereas the role of SST-INs in superficial cortical layers of adult animals has been well characterized, their function in developing cortical circuits is unknown. Indeed, the organization of synaptic connectivity of SST-INs at various developmental time points remains unexplored. Our preliminary data suggest the surprising finding that the circuit-level influence of SST-INs is not yet present at eye opening in juvenile mice, potentially revealing a critical developmental trajectory for the influence of these interneurons and their contribution to visual processing. To further explore this observation, we propose to combine a number of methodological approaches, including optogenetic manipulations, 2-photon and electrophysiological monitoring of neuronal signaling, and in vivo pharmacological manipulations. We will test the following hypotheses: (1) The extensive inputs to SST-INs and their influence on local and large-scale cortical circuits develop during the postnatal period. (2) SST-IN populations in superficial and deep layers of visual cortex are functionally distinct and differentially regulated by behavioral state. (3) The activity of SST-INs and their underlying excitatory and neuromodulatory synaptic drivers are strongly regulated by developmental age. Our results will provide an unprecedented level of insight into the development and function of SST-INs and their relationship to visual processing in the neocortex.
GABAergic interneurons play key roles in the development and maintenance of the neocortex. This proposal will determine how interneurons that express somatostatin (SST-INs) contribute to the maturation of circuits underlying spontaneous and sensory-evoked neuronal activity in mouse visual cortex. We expect our findings to provide important insights into the cellular underpinnings of cortical development and visual processing by the brain.
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