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 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.

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 Neural excitability increases with axonal resistance between soma and axon initial segment

2021 ◽  
Vol 118 (33) ◽  
pp. e2102217118
Author(s):  
Aurélie Fékété ◽  
Norbert Ankri ◽  
Romain Brette ◽  
Dominique Debanne
Keyword(s):  
Initial Segment ◽  
Compartmental Model ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Experimental Studies ◽  
Theoretical Work ◽  
Axon Initial Segment ◽  
Neural Excitability ◽  
Axial Resistance

The position of the axon initial segment (AIS) is thought to play a critical role in neuronal excitability. Previous experimental studies have found that a distal shift in AIS position correlates with a reduction in excitability. Yet theoretical work has suggested the opposite, because of increased electrical isolation. A distal shift in AIS position corresponds to an elevation of axial resistance Ra. We therefore examined how changes in Ra at the axon hillock impact the voltage threshold (Vth) of the somatic action potential in L5 pyramidal neurons. Increasing Ra by mechanically pinching the axon between the soma and the AIS was found to lower Vth by ∼6 mV. Conversely, decreasing Ra by substituting internal ions with higher mobility elevated Vth. All Ra-dependent changes in Vth could be reproduced in a Hodgkin–Huxley compartmental model. We conclude that in L5 pyramidal neurons, excitability increases with axial resistance and therefore with a distal shift of the AIS.

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