Mechanisms of Spontaneous Electrical Activity in the Developing Cerebral Cortex – Subplate Zone

Abstract

In a developing brain, neurogenesis, migration, neurodifferentiation and synapse formation are regulated by spontaneous calcium and electrical activity. The aim of this work is to investigate the mechanisms contributing towards the generation of spontaneous electrical activity in the mammalian cortical mantle. We are focused on a group of neurons located in the subplate zone called the subplate (SP) neurons. One unique property of SP neurons, in both rodent and human cerebral cortex, is spontaneous electrical activity comprising of highly irregular plateau depolarizations crowned with action potentials (UP states). SP neurons govern the path-finding of incoming axonal projections and establishment of cortical connections and cortical columns. The selective disruption of SP neurons has been implicated in mental retardation and schizophrenia. We performed whole-cell recordings, immunolabeling and calcium imaging from positively identified SP neurons in acute brain slices obtained from the newborn mice pups (P01 – P06). The spontaneously-occurring outbursts of electrical activity (UP states) were challenged with drugs that block voltage-gated and ligand-gated membrane conductances. We found that the spontaneous activity in SP neurons was not exclusively mediated by glutamatergic, GABAergic, or glycinergic synaptic transmission. A significant portion of spontaneous depolarizing currents is linked to intact functioning of connexin-based pores and purinergic receptors. Our results suggest that spontaneous flickering of connexin hemichannels and release of ATP contribute to the generation of spontaneous electrical activity in the subplate zone of developing mammalian cerebral cortex. We think that connexin hemichannels located on both neurons and glia are involved.