Distinct nonuniform cable properties optimize rapid and efficient activation of fast-spiking GABAergic interneurons

Abstract

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.cable models | dendrites | hippocampus | basket cell F ast-spiking, parvalbumin-expressing basket cells (BCs) play an important role in feedforward and feedback inhibition, providing rapid control over the frequency and timing of action potential initiation in principal neuron ensembles (1-6). Although inhibition comprises several steps, including activation of excitatory input synapses on BCs, dendritic integration of excitatory postsynaptic potentials (EPSPs), action potential initiation and propagation, and GABA release from output synapses, the kinetics of disynaptic inhibition can be very rapid, with ≈2 ms total onset time at physiologic temperature (3, 7). Several synaptic specializations contribute to the remarkable speed of feedforward and feedback inhibition. At the glutamatergic input synapses of BCs, the fast clearance of transmitter from the synaptic cleft and the expression of molecularly specialized L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) contribute to rapid signaling (8, 9). At the GABAergic output synapses of BCs, the use of rapidly gated P/Qtype Ca 2+ channels and the tight coupling of these channels to the Ca 2+ sensors of exocytosis may serve a similar function (10, 11). Thus, functional specializations at both input and output synapses maximize the speed of BC-mediated disynaptic inhibition.Synaptic location, dendritic structure, and electrical cable properties will also contribute to rapid signaling in GABAergic interneurons. For example, the proximal location of excitatory synapses may promote rapid activation of BCs. The significance of this factor, however, is unclear, because many glutamatergic synapses terminate on distal dendrites of BCs (12). Furthermore, rapid signaling could be promoted by the extensive axon, which may accelerate the somatic EPSP decay time course by ge...

Developmental pruning of excitatory synaptic inputs to parvalbumin interneurons in monkey prefrontal cortex

“…Second, we excluded sampling of synapses on the dendrites of PV interneurons in monkey DLPFC due to the lack of PV immunoreactivity within these structures. Although PV neurons receive excitatory inputs more frequently on their dendrites than cell bodies (54), somal excitatory inputs produce much stronger depolarization in PV neurons than dendritic excitatory inputs (55,56). Moreover, the densities of excitatory inputs to the dendrites (44) and the cell bodies (28) of PV neurons both similarly predict activity-dependent PV levels and are similarly affected by ErbB4 expression in the current study.…”

Strength and duration of perisomatic GABAergic inhibition depend on distance between synaptically connected cells

“…How can both distance-dependent signaling mechanisms emerge in the dentate gyrus network? The density of PII axonal collaterals declines with tangential distance from the PII soma in the granule cell layer (18,19). Here, we demonstrate that this drop in axon density with distance directly translates into a smaller connection probability (Fig.…”

“…In fact, quantitative analysis of the PII axon morphology shows a gradual decline in axon collateral density with distance from the soma (17)(18)(19) frequently interpreted as a reduction in connection probability at larger distances (20,21), comparable to observations from excitatory glutamatergic neurons in the neocortex (22,23). However, conclusive physiological data on the functional properties of output synapses from one PII to several postsynaptic partners are lacking.…”

A supercritical density of fast Na+ channels ensures rapid propagation of action potentials in GABAergic interneuron axons

“…2; see Ref 14). Confocally targeted subcellular patch-clamp recording from BCs allowed us to measure absolute voltage changes in the axon with microsecond temporal resolution at defined locations up to 418 μm from the soma, covering a major part of the axonal arborization of these GABAergic interneurons 9 .…”

“…Simulation of AP initiation and propagation was performed using NEURON 7.1 61 9 (cell 2; 1017 sections total, or other cells from the sample as indicated). Neurons had been filled with biocytin during recording, stained with 3,3′-diaminobenzidine, and fully reconstructed (including soma, dendrites, and entire axon) using a Neurolucida reconstruction system, as described in the previous publication 9 .…”