Emergence of somatostatin interneuron function in the developing visual cortex

项目总结:

PROJECT SUMMARY: 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, whereas the role of cortical SST-INs in adult animals has been well characterized, their function in developing cortical circuits is unknown. Indeed, the organization of functional 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 juvenile viral injection, advanced behavioral state analysis, optogenetic manipulations, and 2-photon monitoring of neuronal signaling. We will test the following hypotheses: (1) The development of the visual response properties of SST-INs directly influences the development of local and large- scale cortical circuits during the postnatal period. (2) The maturation of these circuits contributes to the developmental emergence of state-dependent modulation of spontaneous and visually evoked activity in the visual cortex. 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.