Abstract
Spike generation in cortical neurons depends on the interplay between diverse intrinsic conductances. The phase response curve (PRC) is a measure of the spike time shift caused by perturbations of the membrane potential as a function of the phase of the spike cycle of a neuron. Near the rheobase, purely positive (type I) phase-response curves are associated with an onset of repetitive firing through a saddle-node bifurcation, whereas biphasic (type II) phase-response curves point towards a transition based on a Hopf-Andronov bifurcation. In recordings from layer 2/3 pyramidal neurons in cortical slices, cholinergic action, consistent with down-regulation of slow voltage-dependent potassium currents such as the M-current, switched the PRC from type II to type I. This is the first report showing that cholinergic neuromodulation may cause a qualitative switch in the PRCs type implying a change in the fundamental dynamical mechanism of spike generation.
Highlights
The ability of neurons to synchronize their spiking activity depends on their mutual synaptic connectivity and their intrinsic properties
The intrinsic properties can be revealed by the phase response curve (PRC) [1], defined as the spike time shift caused by a small perturbation of the membrane potential as a function of the time of the perturbation during the spike cycle
We have shown that cortical pyramidal neurons can switch their PRC type, and most likely the type of bifurcation leading to spiking in response to cholinergic neuromodulation
Summary
The ability of neurons to synchronize their spiking activity depends on their mutual synaptic connectivity and their intrinsic properties. The intrinsic properties can be revealed by the phase response curve (PRC) [1], defined as the spike time shift caused by a small perturbation of the membrane potential as a function of the time of the perturbation during the spike cycle. In neurons with a purely positive, or type I, PRC, perturbations at every phase of the oscillatory cycle cause a time-advance of the spike. For neuronal models with such purely positive PRCs measured at relatively low firing rates, the transition from rest to tonic spiking comes about generically through a saddle-node bifurcation [1]. The resulting dynamics imply a general absence of subthreshold oscillations and the onset frequency of firing is arbitrarily low. The firing frequency – injected current relationship is roughly linear and the action potentials are all-or-none and well separated from subthreshold responses. A large number of biophysical models of cortical pyramidal neurons has type I excitability [1,2,3]
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