Neuron type-selective effects of activin on development of the hippocampus

Activin is a member of the transforming growth factor-β superfamily and affects the viability of hippocampal neurons during postnatal neurogenesis. We used primary hippocampal neuron to study the actions of activin on developing neurons. Continuous treatment of hippocampal cultures with activin suppressed the emergence of GAD67⁺ neurons, which are a subtype of GABAergic interneurons, and increased the percentage of Prox1⁺ neurons, which are dentate granule cells. The effects of activin were abolished by co-treatment with follistatin, which is a direct inhibitor of activin. In contrast, follistatin treatment alone increased the percentage of GAD67⁺ neurons and decreased the percentage of Prox1⁺ neurons. These results indicate that changes in activin signaling during postnatal neural development alter the composition of the neural circuitry and suggest that alterations in the ratio of excitatory to inhibitory neurons may be responsible for changes in the spontaneous and evoked-reactivity of these neurons to other neural inputs.