Bidirectional GABAergic control of action potential firing in newborn hippocampal granule cells

• Published in: Nature neuroscience Vol. 19; no. 2; pp. 263 - 270
• Main Authors: Heigele, Stefanie, Sultan, Sébastien, Toni, Nicolas, Bischofberger, Josef
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2016; Nature Publishing Group
• Subjects: 14/19; 631/378/368/2431; 631/378/548/1964; 64/110; 9/74; Action potential; Action Potentials - physiology; Analysis; Animal Genetics and Genomics; Animals; Animals, Newborn; Behavioral Sciences; Biological Techniques; Biomedicine; Cytoplasmic Granules; Electron microscopes; Excitatory Postsynaptic Potentials - physiology; Female; GABA; gamma-Aminobutyric Acid - physiology; Growth; Hippocampus - cytology; Hippocampus - physiology; In Vitro Techniques; Interneurons - physiology; Mice; Mice, Inbred C57BL; Nerve Net - cytology; Nerve Net - physiology; Neural circuitry; Neurobiology; Neurons; Neurons - physiology; Neurosciences; Patch-Clamp Techniques; Physiological aspects; Pregnancy; Proteins; Synapses - physiology; Transmitters; Switzerland
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.4218

Adult-born neurons are already contributing to learning and memory at immature developmental stages. Heigele et al . show that during the first 3 weeks after mitosis, the young cells fire action potentials generated by excitatory GABAergic synapses. Strong GABAergic synaptic activity, however, inhibits spiking, thereby generating a well-defined GABAergic excitation window. Newly generated young neurons in the adult hippocampus receive GABAergic synaptic inputs, which are crucial for activity-dependent survival and functional maturation between 1–3 weeks after mitosis. We found synaptically driven action potential (AP) firing in these newborn young cells in adult mice. Although glutamatergic synaptic inputs remained subthreshold, activation of GABAergic synaptic inputs depolarized young neurons and reliably evoked APs. Furthermore, pairing of subthreshold excitatory postsynaptic potentials or somatic current injection with brief bursts of GABAergic inputs revealed efficient GABAergic excitation at conductances of ∼1.5 nS, corresponding to the activity of only three or four interneurons. Stronger GABAergic inputs (>4 nS) effectively blocked AP firing via shunting inhibition, which might be important to dynamically control spiking output in both directions. Taken together, GABAergic interneurons differentially recruit newborn young granule cells by supporting either AP generation or shunting inhibition dependent on hippocampal network activity.