Synaptic Input and ACh Modulation Regulate Dendritic Ca2+ Spike Duration in Pyramidal Neurons, Directly Affecting Their Somatic Output

Amir Dudai, Michael Doron, Idan Segev, Michael London*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Nonlinear synaptic integration in dendrites is a fundamental aspect of neural computation. One such key mechanism is the Ca2+ spike at the apical tuft of pyramidal neurons. Characterized by a plateau potential sustained for tens of milliseconds, the Ca2+ spike amplifies excitatory input, facilitates somatic action potentials (APs), and promotes synaptic plasticity. Despite its essential role, the mechanisms regulating it are largely unknown. Using a compartmental model of a layer 5 pyramidal cell (L5PC), we explored the plateau and termination phases of the Ca2+ spike under input current perturbations, long-step current-injections, and variations in the dendritic high-voltage-activated Ca2+ conductance (that occur during cholinergic modulation). We found that, surprisingly, timed excitatory input can shorten the Ca2+ spike duration while inhibitory input can either elongate or terminate it. A significant elongation also occurs when the high-voltage-activated Ca2+ channels (CaHVA) conductance is increased. To mechanistically understand these phenomena, we analyzed the currents involved in the spike. The plateau and termination phases are almost exclusively controlled by the CaHVA inward current and the Im outward K+ current. We reduced the full model to a single-compartment model that faithfully preserved the responses of the Ca2+ spike to interventions and consisted of two dynamic variables: the membrane potential and the K+-channel activation level. A phase-plane analysis of the reduced model provides testable predictions for modulating the Ca2+ spike and reveals various dynamical regimes that explain the robust nature of the spike. Regulating the duration of the Ca2+ spike significantly impacts the cell synaptic-plasticity window and, as we show, its input-output relationship.

Original languageAmerican English
Pages (from-to)1184-1195
Number of pages12
JournalJournal of Neuroscience
Volume42
Issue number7
DOIs
StatePublished - 16 Feb 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 the authors

Keywords

  • Ca spike
  • dendrites
  • phase plane
  • synaptic perturbation

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