Institutt for biomedisin

BBB webinar: Hua Hu

Reverse engineering a cortical inhibitory interneuron axon


Hua Hu
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.


  1. Hu H. and Jonas P. A supercritical density of Na+ channels ensures fast signaling in GABAergic interneuron axons. Nat. Neurosci. 17, 686-93 (2014)
  2. 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)
  3. 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