A GABAergic projection from the zona incerta to cortex promotes cortical neuron development

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Science  30 Oct 2015:
Vol. 350, Issue 6260, pp. 554-558
DOI: 10.1126/science.aac6472

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Circuits for brain building

The brain is made up of circuits. Chen and Kriegstein analyzed how one particular circuit functions differently in developing and mature mouse brains (see the Perspective by Spitzer). This circuit connects the brain's diencephalon to the cortex. Early in development, the circuit is excitatory and affects how the cortical neurons it touches build their dendrites and synapses. Later on, after the fundamentals of brain construction are in place, the circuit switches to inhibitory functions, helping the brain resist epileptiform activity.

Science, this issue p. 554; see also p. 510


γ-Aminobutyric acid (GABA) is the major inhibitory transmitter in the mature brain but is excitatory in the developing cortex. We found that mouse zona incerta (ZI) projection neurons form a GABAergic axon plexus in neonatal cortical layer 1, making synapses with neurons in both deep and superficial layers. A similar depolarizing GABAergic plexus exists in the developing human cortex. Selectively silencing mouse ZI GABAergic neurons at birth decreased synaptic activity and apical dendritic complexity of cortical neurons. The ZI GABAergic projection becomes inhibitory with maturation and can block epileptiform activity in the adult brain. These data reveal an early-developing GABAergic projection from the ZI to cortical layer 1 that is essential for proper development of cortical neurons and balances excitation with inhibition in the adult cortex.

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