Spatial Embryonic Origin Delineates GABAergic Hub Neurons Driving Network Dynamics in the Developing Entorhinal Cortex

Abstract

Coordinated neuronal activity is essential for the development of cortical circuits. GABAergic hub neurons that function in orchestrating early neuronal activity through a widespread net of postsynaptic partners are therefore critical players in the establishment of functional networks. Evidence for hub neurons was previously found in the hippocampus, but their presence in other cortical regions remains unknown. We examined this issue in the entorhinal cortex, an initiation site for coordinated activity in the neocortex and for the activity-dependent maturation of the entire entorhinal-hippocampal network. Using an unbiased approach that identifies "driver hub neurons" displaying a high number of functional links in living slices, we show that while almost half of the GABAergic cells single-handedly influence network dynamics, only a subpopulation of cells born in the MGE and composed of somatostatin-expressing neurons located in infragranular layers, spontaneously operate as "driver" hubs. This indicates that despite differences in the origin of interneuron diversity, the hippocampus and entorhinal cortex share similar developmental mechanisms for the establishment of functional circuits.

Keywords: GABA hub neuron; developing network dynamics; entorhinal cortex; fate-mapping.