title: Controlling the oscillation phase through precisely timed closed-loop optogenetic stimulation: a computational study.
abstract: Dynamic oscillatory coherence is believed to play a central role in flexible communication between brain circuits. To test this communication-through-coherence hypothesis, experimental protocols that allow a reliable control of phase-relations between neuronal populations are needed. In this modeling study, we explore the potential of closed-loop optogenetic stimulation for the control of functional interactions mediated by oscillatory coherence. The theory of non-linear oscillators predicts that the efficacy of local stimulation will depend not only on the stimulation intensity but also on its timing relative to the ongoing oscillation in the target area. Induced phase-shifts are expected to be stronger when the stimulation is applied within specific narrow phase intervals. Conversely, stimulations with the same or even stronger intensity are less effective when timed randomly. Stimulation should thus be properly phased with respect to ongoing oscillations (in order to optimally perturb them) and the timing of the stimulation onset must be determined by a real-time phase analysis of simultaneously recorded local field potentials (LFPs). Here, we introduce an electrophysiologically calibrated model of Channelrhodopsin 2 (ChR2)-induced photocurrents, based on fits holding over two decades of light intensity. Through simulations of a neural population which undergoes coherent gamma oscillations-either spontaneously or as an effect of continuous optogenetic driving-we show that precisely-timed photostimulation pulses can be used to shift the phase of oscillation, even at transduction rates smaller than 25%. We consider then a canonic circuit with two inter-connected neural populations oscillating with gamma frequency in a phase-locked manner. We demonstrate that photostimulation pulses applied locally to a single population can induce, if precisely phased, a lasting reorganization of the phase-locking pattern and hence modify functional interactions between the two populations.
authors.affiliation: Cognitive Neuroscience Department, German Primate Center, Bernstein Center for Computational Neuroscience, Max Planck Institute for Dynamics and Self-Organization Göttingen, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Witt
authors.forename: Agostina
authors.initials: A
authors.lastname: Palmigiano
authors.forename: Andreas
authors.initials: A
authors.lastname: Neef
authors.forename: Ahmed
authors.initials: A
authors.lastname: El Hady
authors.forename: Fred
authors.initials: F
authors.lastname: Wolf
authors.forename: Demian
authors.initials: D
authors.lastname: Battaglia
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D001683:Biological Clocks / Q000502:physiology*; D019295:Computational Biology / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D016571:Neural Networks, Computer; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation / Q000379:methods*; D011897:Random Allocation; D013997:Time Factors
keywords: closed-loop systems; functional connectivity; modeling; optogenetic stimulation; oscillations; phase response