The Roles of Potassium and Calcium Currents in the Bistable Firing Transition

Fernando S. Borges, Paulo R. Protachevicz, Diogo L.M. Souza, Conrado F. Bittencourt, Enrique C. Gabrick, Lucas E. Bentivoglio, José D. Szezech, Antonio M. Batista, Iberê L. Caldas, Salvador Dura-Bernal, Rodrigo F.O. Pena

Research output: Contribution to journalArticlepeer-review

Abstract

Healthy brains display a wide range of firing patterns, from synchronized oscillations during slow-wave sleep to desynchronized firing during movement. These physiological activities coexist with periods of pathological hyperactivity in the epileptic brain, where neurons can fire in synchronized bursts. Most cortical neurons are pyramidal regular spiking (RS) cells with frequency adaptation and do not exhibit bursts in current-clamp experiments (in vitro). In this work, we investigate the transition mechanism of spike-to-burst patterns due to slow potassium and calcium currents, considering a conductance-based model of a cortical RS cell. The joint influence of potassium and calcium ion channels on high synchronous patterns is investigated for different synaptic couplings ((Formula presented.)) and external current inputs (I). Our results suggest that slow potassium currents play an important role in the emergence of high-synchronous activities, as well as in the spike-to-burst firing pattern transitions. This transition is related to the bistable dynamics of the neuronal network, where physiological asynchronous states coexist with pathological burst synchronization. The hysteresis curve of the coefficient of variation of the inter-spike interval demonstrates that a burst can be initiated by firing states with neuronal synchronization. Furthermore, we notice that high-threshold ((Formula presented.)) and low-threshold ((Formula presented.)) ion channels play a role in increasing and decreasing the parameter conditions ((Formula presented.) and I) in which bistable dynamics occur, respectively. For high values of (Formula presented.) conductance, a synchronous burst appears when neurons are weakly coupled and receive more external input. On the other hand, when the conductance (Formula presented.) increases, higher coupling and lower I are necessary to produce burst synchronization. In light of our results, we suggest that channel subtype-specific pharmacological interactions can be useful to induce transitions from pathological high bursting states to healthy states.

Original languageEnglish (US)
Article number1347
JournalBrain Sciences
Volume13
Issue number9
DOIs
StatePublished - Sep 2023
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience

Keywords

  • bistability
  • burst synchronization
  • firing pattern transition
  • hysteresis
  • ion channels

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