On the Firing Rate Dependency of the Phase Response Curve of Rat Purkinje Neurons in Vitro

PLoS Comput Biol. 2015 Mar 16;11(3):e1004112. doi: 10.1371/journal.pcbi.1004112. eCollection 2015 Mar.

Abstract

Synchronous spiking during cerebellar tasks has been observed across Purkinje cells: however, little is known about the intrinsic cellular mechanisms responsible for its initiation, cessation and stability. The Phase Response Curve (PRC), a simple input-output characterization of single cells, can provide insights into individual and collective properties of neurons and networks, by quantifying the impact of an infinitesimal depolarizing current pulse on the time of occurrence of subsequent action potentials, while a neuron is firing tonically. Recently, the PRC theory applied to cerebellar Purkinje cells revealed that these behave as phase-independent integrators at low firing rates, and switch to a phase-dependent mode at high rates. Given the implications for computation and information processing in the cerebellum and the possible role of synchrony in the communication with its post-synaptic targets, we further explored the firing rate dependency of the PRC in Purkinje cells. We isolated key factors for the experimental estimation of the PRC and developed a closed-loop approach to reliably compute the PRC across diverse firing rates in the same cell. Our results show unambiguously that the PRC of individual Purkinje cells is firing rate dependent and that it smoothly transitions from phase independent integrator to a phase dependent mode. Using computational models we show that neither channel noise nor a realistic cell morphology are responsible for the rate dependent shift in the phase response curve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Computational Biology
  • Computer Simulation
  • Models, Neurological*
  • Purkinje Cells / physiology*
  • Rats
  • Rats, Wistar

Grant support

Financial support from the 7th Framework Programme of the European Commission (FP7-PEOPLE-ITN “C7,” contract no. 238214), the Interuniversity Attraction Poles Program (IUAP) of the Belgian Science Policy Office, and the University of Antwerp is kindly acknowledged. DL is a Postdoctoral Fellow of the Flanders Research Foundation (grant no. 12C9112N, http://www.fwo.be). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.