Neuronal and Network-based Mechanisms of Spontaneous Synchronous Activity in the Developing Mouse Cortex

Thesis (Ph.D.)--University of Washington, 2014Spontaneous synchronous activity (SSA) that propagates as electrical waves is found in numerous CNS structures and is critical for normal development, but the mechanisms of generation of such activity are not clear. In previous work, we showed that the ventrolateral piriform cortex is uniquely able to initiate SSA in contrast to the dorsal neocortex which participates in but does not initiate SSA. In this study we used Ca2+ imaging of cultured E18-P2 coronal slices (E17 + 1-4 days in culture) of the mouse cortex to investigate the different activity patterns of individual neurons in these regions. In the piriform cortex where SSA is initiated, a higher proportion of neurons were active asynchronously between waves in comparison to the dorsal cortex. In addition, a larger number of groups of co-active cells were present in the ventral cortex than in the dorsal cortex. When we applied GABA and glutamate synaptic antagonists, asynchronous activity and cellular clusters remained while synchronous activity was eliminated, indicating that asynchronous activity is a result of cell-intrinsic properties that differ between these regions. To test the hypothesis that higher levels of cell-autonomous activity in the piriform cortex underlie its ability to initiate waves, we constructed a conductance-based network model in which three layers differed only in the proportion of neurons able to intrinsically generate bursting behavior. Simulations using this model demonstrated that a gradient of intrinsic excitability was sufficient to produce directionally propagating waves that replicated key experimental features, indicating that the higher level of cell-intrinsic activity in the piriform cortex may provide a substrate for SSA generation