Radial glia, the neuronal stem cells of the embryonic cerebral cortex, reside deep within the developing brain and extend radial fibres to the pial surface, along which embryonic neurons migrate to reach the cortical plate. Here we show that the gap junction subunits connexin 26 (Cx26) and connexin 43 (Cx43) are expressed at the contact points between radial fibres and migrating neurons, and acute downregulation of Cx26 or Cx43 impairs the migration of neurons to the cortical plate. Unexpectedly, gap junctions do not mediate neuronal migration by acting in the classical manner to provide an aqueous channel for cell-cell communication. Instead, gap junctions provide dynamic adhesive contacts that interact with the internal cytoskeleton to enable leading process stabilization along radial fibres as well as the subsequent translocation of the nucleus. These results indicate that gap junction adhesions are necessary for glial-guided neuronal migration, raising the possibility that the adhesive properties of gap junctions may have an important role in other physiological processes and diseases associated with gap junction function.

Neurons have long held the spotlight as the central players of the nervous system, but we must remember that we have equal numbers of astrocytes and neurons in the brain. Are these cells only filling up the space and passively nurturing the neurons, or do they also contribute to information transfer and processing? After several years of intense research since the pioneer discovery of astrocytic calcium waves and glutamate release onto neurons in vitro, the neuronal-glial studies have answered many questions thanks to technological advances. However, the definitive in vivo role of astrocytes remains to be addressed. In addition, it is becoming clear that diverse populations of astrocytes coexist with different molecular identities and specialized functions adjusted to their microenvironment, but do they all belong to the umbrella family of astrocytes? One population of astrocytes takes on a new function by displaying both support cell and stem cell characteristics in the neurogenic niches. Here, we define characteristics that classify a cell as an astrocyte under physiological conditions. We will also discuss the well-established and emerging functions of astrocytes with an emphasis on their roles on neuronal activity and as neural stem cells in adult neurogenic zones.

The development of a balance between excitatory and inhibitory synapses is a critical process in the generation and maturation of functional circuits. Accumulating evidence suggests that neuronal activity plays an important role in achieving such a balance in the developing cortex, but the mechanism that regulates this process is unknown. During development, GABA, the primary inhibitory neurotransmitter in adults, excites neurons as a result of high expression of the Na. Using NKCC1 RNA interference knockdown in vivo, we show that GABA-induced depolarization is necessary for proper excitatory synapse formation and dendritic development of newborn cortical neurons. Blocking NKCC1 with the diuretic bumetanide during development leads to similar persistent changes in cortical circuitry in the adult. Interestingly, expression of a voltage-independent NMDA receptor rescues the failure of NKCC1 knockdown neurons to develop excitatory AMPA transmission, indicating that GABA depolarization cooperates with NMDA receptor activation to regulate excitatory synapse formation. Our study identifies an essential role for GABA in the synaptic integration of newborn cortical neurons and suggests an activity-dependent mechanism for achieving the balance between excitation and inhibition in the developing cortex.