TY - JOUR AB - Fast-spiking, parvalbumin-expressing GABAergic interneurons (PV+-BCs) express a complex machinery of rapid signaling mechanisms, including specialized voltage-gated ion channels to generate brief action potentials (APs). However, short APs are associated with overlapping Na+ and K+ fluxes and are therefore energetically expensive. How the potentially vicious combination of high AP frequency and inefficient spike generation can be reconciled with limited energy supply is presently unclear. To address this question, we performed direct recordings from the PV+-BC axon, the subcellular structure where active conductances for AP initiation and propagation are located. Surprisingly, the energy required for the AP was, on average, only ∼1.6 times the theoretical minimum. High energy efficiency emerged from the combination of fast inactivation of Na+ channels and delayed activation of Kv3-type K+ channels, which minimized ion flux overlap during APs. Thus, the complementary tuning of axonal Na+ and K+ channel gating optimizes both fast signaling properties and metabolic efficiency. Hu et al. demonstrate that action potentials in parvalbumin-expressing GABAergic interneuron axons are energetically efficient, which is highly unexpected given their brief duration. High energy efficiency emerges from the combination of fast inactivation of voltage-gated Na+ channels and delayed activation of Kv3 channels in the axon. AU - Hu, Hua AU - Roth, Fabian AU - Vandael, David H AU - Jonas, Peter M ID - 320 IS - 1 JF - Neuron TI - Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons VL - 98 ER - TY - JOUR AB - The success story of fast-spiking, parvalbumin-positive (PV+) GABAergic interneurons (GABA, γ-aminobutyric acid) in the mammalian central nervous system is noteworthy. In 1995, the properties of these interneurons were completely unknown. Twenty years later, thanks to the massive use of subcellular patch-clamp techniques, simultaneous multiple-cell recording, optogenetics, in vivo measurements, and computational approaches, our knowledge about PV+ interneurons became more extensive than for several types of pyramidal neurons. These findings have implications beyond the “small world” of basic research on GABAergic cells. For example, the results provide a first proof of principle that neuroscientists might be able to close the gaps between the molecular, cellular, network, and behavioral levels, representing one of the main challenges at the present time. Furthermore, the results may form the basis for PV+ interneurons as therapeutic targets for brain disease in the future. However, much needs to be learned about the basic function of these interneurons before clinical neuroscientists will be able to use PV+ interneurons for therapeutic purposes. AU - Hu, Hua AU - Gan, Jian AU - Jonas, Peter M ID - 2062 IS - 6196 JF - Science TI - Fast-spiking parvalbumin^+ GABAergic interneurons: From cellular design to microcircuit function VL - 345 ER - TY - JOUR AB - Fast-spiking, parvalbumin-expressing GABAergic interneurons, a large proportion of which are basket cells (BCs), have a key role in feedforward and feedback inhibition, gamma oscillations and complex information processing. For these functions, fast propagation of action potentials (APs) from the soma to the presynaptic terminals is important. However, the functional properties of interneuron axons remain elusive. We examined interneuron axons by confocally targeted subcellular patch-clamp recording in rat hippocampal slices. APs were initiated in the proximal axon ∼20 μm from the soma and propagated to the distal axon with high reliability and speed. Subcellular mapping revealed a stepwise increase of Na^+ conductance density from the soma to the proximal axon, followed by a further gradual increase in the distal axon. Active cable modeling and experiments with partial channel block revealed that low axonal Na^+ conductance density was sufficient for reliability, but high Na^+ density was necessary for both speed of propagation and fast-spiking AP phenotype. Our results suggest that a supercritical density of Na^+ channels compensates for the morphological properties of interneuron axons (small segmental diameter, extensive branching and high bouton density), ensuring fast AP propagation and high-frequency repetitive firing. AU - Hu, Hua AU - Jonas, Peter M ID - 2228 IS - 5 JF - Nature Neuroscience SN - 10976256 TI - A supercritical density of Na^+ channels ensures fast signaling in GABAergic interneuron axons VL - 17 ER - TY - JOUR AB - CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel–mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. AU - Kim, Sooyun AU - Guzmán, José AU - Hu, Hua AU - Jonas, Peter M ID - 3258 IS - 4 JF - Nature Neuroscience SN - 1546-1726 TI - Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons VL - 15 ER - TY - JOUR AB - Fast-spiking, parvalbumin-expressing basket cells (BCs) play a key role in feedforward and feedback inhibition in the hippocampus. However, the dendritic mechanisms underlying rapid interneuron recruitment have remained unclear. To quantitatively address this question, we developed detailed passive cable models of BCs in the dentate gyrus based on dual somatic or somatodendritic recordings and complete morphologic reconstructions. Both specific membrane capacitance and axial resistivity were comparable to those of pyramidal neurons, but the average somatodendritic specific membrane resistance (R(m)) was substantially lower in BCs. Furthermore, R(m) was markedly nonuniform, being lowest in soma and proximal dendrites, intermediate in distal dendrites, and highest in the axon. Thus, the somatodendritic gradient of R(m) was the reverse of that in pyramidal neurons. Further computational analysis revealed that these unique cable properties accelerate the time course of synaptic potentials at the soma in response to fast inputs, while boosting the efficacy of slow distal inputs. These properties will facilitate both rapid phasic and efficient tonic activation of BCs in hippocampal microcircuits. AU - Norenberg, Anja AU - Hua Hu AU - Vida, Imre AU - Bartos, Marlene AU - Peter Jonas ID - 3831 IS - 2 JF - PNAS TI - Distinct nonuniform cable properties optimize rapid and efficient activation of fast-spiking GABAergic interneurons VL - 107 ER - TY - JOUR AB - Fast-spiking, parvalbumin-expressing basket cells (BCs) are important for feedforward and feedback inhibition. During network activity, BCs respond with short latency and high temporal precision. It is thought that the specific properties of input synapses are responsible for rapid recruitment. However, a potential contribution of active dendritic conductances has not been addressed. We combined confocal imaging and patch-clamp techniques to obtain simultaneous somatodendritic recordings from BCs. Action potentials were initiated in the BC axon and backpropagated into the dendrites with reduced amplitude and little activity dependence. These properties were explained by a high K+ to Na+ conductance ratio in BC dendrites. Computational analysis indicated that dendritic K+ channels convey unique integration properties to BCs, leading to the rapid and temporally precise activation by excitatory inputs. AU - Hua Hu AU - Martina, Marco AU - Peter Jonas ID - 3830 IS - 5961 JF - Science TI - Dendritic mechanisms underlying rapid synaptic activation of fast-spiking hippocampal interneurons VL - 327 ER -