BBB webinar: Hua Hu
Reverse engineering a cortical inhibitory interneuron axon
Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo
Cortical neuronal networks include both glutamatergic principal neurons and GABAergic (g-aminobutyric acid, GABA) interneurons. Although GABAergic interneurons contribute to less than 20% of the cortical neuronal population, they play an important role in a broad range of cortical functions. Here, I will present our research on parvalbumin-expressing fast-spiking basket cells (PV+-BCs) that represent a key type of GABAergic interneuron in the brain.
A hallmark feature of PV+-BCs is speed. These interneurons are capable of coupling action potential initiation in the proximal axon to the release of GABA from distal presynaptic terminals within less than a millisecond. This functional hallmark provides PV+-BCs with the ability to control the probability and precise timing of action potential initiation in principal neurons. With the subcellular patch-clamp method, we have identified a number of axonal signaling mechanisms that contribute to this remarkably fast synaptic inhibition. First, PV+-BC axons express an excessively high density of Na+ channels to increase conduction velocity of action potentials1. Second, the action potential mechanism in PV+-BC axons is tuned to conserve energy2. Third, an axon-specific distribution pattern of hyperpolarization-activated cyclic nucleotide-gated channels that catalyzes the fast action potential signaling in PV+-BC axons3. Collectively, these subcellular specializations allow PV+-BC axons to reliably transmit action potentials over long distances at high speed and with high metabolic efficiency.
- Hu H. and Jonas P. A supercritical density of Na+ channels ensures fast signaling in GABAergic interneuron axons. Nat. Neurosci. 17, 686-93 (2014)
- Hu H., Roth F.C., Vandael D. and Jonas P. Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron 98, 156-65 (2018)
- Roth F.C. and Hu H. An axon-specific expression of HCN channels catalyzes fast action potential signaling in GABAergic interneurons. Nat. Commun. 11, 2248 (2020)
Chairperson: Clive R. Bramham, Department of Biomedicine