scholarly journals Functional microstructure of CaV-mediated calcium signaling in the axon initial segment

2020 ◽  
Author(s):  
Anna M Lipkin ◽  
Margaret M Cunniff ◽  
Perry WE Spratt ◽  
Stefan M Lemke ◽  
Kevin J Bender
Keyword(s):  
Calcium Channels ◽  
Action Potential ◽  
High Speed ◽  
Initial Segment ◽  
Laser Scanning ◽  
Pyramidal Neurons ◽  
Calcium Influx ◽  
Axon Initial Segment ◽  
Spatiotemporal Resolution ◽  
Sodium Potassium

ABSTRACTThe axon initial segment (AIS) is a specialized neuronal compartment in which synaptic input is converted into action potential output. This process is supported by a diverse complement of sodium, potassium, and calcium channels (CaV). Different classes of sodium and potassium channels are scaffolded at specific sites within the AIS, conferring unique functions, but how calcium channels are functionally distributed within the AIS is unclear. Here, we utilize conventional 2-photon laser scanning and diffraction-limited, high-speed spot 2-photon imaging to resolve action potential-evoked calcium dynamics in the AIS with high spatiotemporal resolution. In mouse layer 5 prefrontal pyramidal neurons, calcium influx was mediated by a mix of CaV2 and CaV3 channels that differentially localized to discrete regions. CaV3 functionally localized to produce nanodomain hotspots of calcium influx that coupled to ryanodine-dependent stores, whereas CaV2 localized to non-hotspot regions. Thus, different pools of CaVs appear to play distinct roles in AIS function.

Control of Neuronal Output by Inhibition at the Axon Initial Segment

1990 ◽  
Vol 2 (3) ◽  
pp. 283-292 ◽  
Author(s):  
Rodney J. Douglas ◽  
Kevan A. C. Martin
Keyword(s):  
Visual Cortex ◽  
Action Potential ◽  
Initial Segment ◽  
Compartmental Model ◽  
Pyramidal Neurons ◽  
Axon Initial Segment ◽  
Synaptic Current ◽  
Basket Cells ◽  
Excitatory Synaptic Current ◽  
Neuronal Output

We examine the effect of inhibition on the axon initial segment (AIS) by the chandelier (“axoaxonic”) cells, using a simplified compartmental model of actual pyramidal neurons from cat visual cortex. We show that within generally accepted ranges, inhibition at the AIS cannot completely prevent action potential discharge: only small amounts of excitatory synaptic current can be inhibited. Moderate amounts of excitatory current always result in action potential discharge, despite AIS inhibition. Inhibition of the somadendrite by basket cells enhances the effect of AIS inhibition and vice versa. Thus the axoaxonic cells may act synergistically with basket cells: the AIS inhibition increases the threshold for action potential discharge, the basket cells then control the suprathreshold discharge.

scholarly journals Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

2016 ◽  
Vol 113 (51) ◽  
pp. 14841-14846 ◽  
Author(s):  
Mustafa S. Hamada ◽  
Sarah Goethals ◽  
Sharon I. de Vries ◽  
Romain Brette ◽  
Maarten H. P. Kole
Keyword(s):  
Action Potential ◽  
Initial Segment ◽  
Pyramidal Neurons ◽  
Dendritic Tree ◽  
Apical Dendrite ◽  
Axial Current ◽  
Axon Initial Segment ◽  
Output Code ◽  
The Face ◽  
Dendritic Complexity

In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies.

scholarly journals Activity-dependent mismatch between axo-axonic synapses and the axon initial segment controls neuronal output

2015 ◽  
Vol 112 (31) ◽  
pp. 9757-9762 ◽  
Author(s):  
Winnie Wefelmeyer ◽  
Daniel Cattaert ◽  
Juan Burrone
Keyword(s):  
Action Potential ◽  
Hippocampal Neurons ◽  
Initial Segment ◽  
Pyramidal Neurons ◽  
Neuronal Cell ◽  
Axon Initial Segment ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Auditory Nucleus

The axon initial segment (AIS) is a structure at the start of the axon with a high density of sodium and potassium channels that defines the site of action potential generation. It has recently been shown that this structure is plastic and can change its position along the axon, as well as its length, in a homeostatic manner. Chronic activity-deprivation paradigms in a chick auditory nucleus lead to a lengthening of the AIS and an increase in neuronal excitability. On the other hand, a long-term increase in activity in dissociated rat hippocampal neurons results in an outward movement of the AIS and a decrease in the cell’s excitability. Here, we investigated whether the AIS is capable of undergoing structural plasticity in rat hippocampal organotypic slices, which retain the diversity of neuronal cell types present at postnatal ages, including chandelier cells. These interneurons exclusively target the AIS of pyramidal neurons and form rows of presynaptic boutons along them. Stimulating individual CA1 pyramidal neurons that express channelrhodopsin-2 for 48 h leads to an outward shift of the AIS. Intriguingly, both the pre- and postsynaptic components of the axo-axonic synapses did not change position after AIS relocation. We used computational modeling to explore the functional consequences of this partial mismatch and found that it allows the GABAergic synapses to strongly oppose action potential generation, and thus downregulate pyramidal cell excitability. We propose that this spatial arrangement is the optimal configuration for a homeostatic response to long-term stimulation.

scholarly journals Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nora Jamann ◽  
Dominik Dannehl ◽  
Nadja Lehmann ◽  
Robin Wagener ◽  
Corinna Thielemann ◽  
...  
Keyword(s):  
Action Potential ◽  
Initial Segment ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Barrel Cortex ◽  
Sensory Deprivation ◽  
Axon Initial Segment ◽  
Electrophysiological Recordings ◽  
Network States

AbstractThe axon initial segment (AIS) is a critical microdomain for action potential initiation and implicated in the regulation of neuronal excitability during activity-dependent plasticity. While structural AIS plasticity has been suggested to fine-tune neuronal activity when network states change, whether it acts in vivo as a homeostatic regulatory mechanism in behaviorally relevant contexts remains poorly understood. Using the mouse whisker-to-barrel pathway as a model system in combination with immunofluorescence, confocal analysis and electrophysiological recordings, we observed bidirectional AIS plasticity in cortical pyramidal neurons. Furthermore, we find that structural and functional AIS remodeling occurs in distinct temporal domains: Long-term sensory deprivation elicits an AIS length increase, accompanied with an increase in neuronal excitability, while sensory enrichment results in a rapid AIS shortening, accompanied by a decrease in action potential generation. Our findings highlight a central role of the AIS in the homeostatic regulation of neuronal input-output relations.

scholarly journals High-speed volumetric two-photon fluorescence imaging of neurovascular dynamics

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiang Lan Fan ◽  
Jose A. Rivera ◽  
Wei Sun ◽  
John Peterson ◽  
Henry Haeberle ◽  
...  
Keyword(s):  
Blood Flow ◽  
High Speed ◽  
Laser Scanning ◽  
Three Dimensional ◽  
Laser Scanning Microscopy ◽  
Fluorescence Signal ◽  
Imaging Method ◽  
Spatiotemporal Resolution ◽  
Two Photon

AbstractUnderstanding the structure and function of vasculature in the brain requires us to monitor distributed hemodynamics at high spatial and temporal resolution in three-dimensional (3D) volumes in vivo. Currently, a volumetric vasculature imaging method with sub-capillary spatial resolution and blood flow-resolving speed is lacking. Here, using two-photon laser scanning microscopy (TPLSM) with an axially extended Bessel focus, we capture volumetric hemodynamics in the awake mouse brain at a spatiotemporal resolution sufficient for measuring capillary size and blood flow. With Bessel TPLSM, the fluorescence signal of a vessel becomes proportional to its size, which enables convenient intensity-based analysis of vessel dilation and constriction dynamics in large volumes. We observe entrainment of vasodilation and vasoconstriction with pupil diameter and measure 3D blood flow at 99 volumes/second. Demonstrating high-throughput monitoring of hemodynamics in the awake brain, we expect Bessel TPLSM to make broad impacts on neurovasculature research.

scholarly journals Optical measurement of physiological sodium currents in the axon initial segment

2020 ◽  
Author(s):  
Luiza Filipis ◽  
Marco Canepari
Keyword(s):  
Temporal Resolution ◽  
Initial Segment ◽  
Pyramidal Neurons ◽  
Optical Measurement ◽  
Brain Slices ◽  
Axon Initial Segment ◽  
Neuron Models ◽  
Pixel Resolution ◽  
Fluorescence Measurements ◽  
Kinetics Of

ABSTRACTIn most neurons of the mammalian central nervous system, the action potential (AP) is triggered in the axon initial segment (AIS) by a fast Na+ current mediated by voltage-gated Na+ channels. The intracellular Na+ increase associated with the AP has been measured using fluorescent Na+ indicators, but with insufficient resolution to resolve the Na+ current in the AIS. In this article, we report the critical improvement in temporal resolution of the Na+ imaging technique allowing the direct experimental measurement of Na+ currents in the AIS. We determined the AIS Na+ current, from fluorescence measurements at temporal resolution of 100 µs and pixel resolution of half a micron, in pyramidal neurons of the layer-5 of the somatosensory cortex from brain slices of the mouse. We identified a subthreshold current before the AP, a fast inactivating current peaking during the rise of the AP and a persistent current during the AP repolarisation. We correlated the kinetics of the current at different distances from the soma with the kinetics of the somatic AP. We quantitatively compared the experimentally measured Na+ current with the current obtained by computer simulation of published NEURON models and we show how the present approach can lead to the correct estimate of the native behaviour of Na+ channels. Thus, it is expected that the present method will be adopted to investigate the function of different channel types under physiological or pathological conditions.

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