title: Inhibition as a Binary Switch for Excitatory Plasticity in Pyramidal Neurons.
abstract: Synaptic plasticity is thought to induce memory traces in the brain that are the foundation of learning. To ensure the stability of these traces in the presence of further learning, however, a regulation of plasticity appears beneficial. Here, we take up the recent suggestion that dendritic inhibition can switch plasticity of excitatory synapses on and off by gating backpropagating action potentials (bAPs) and calcium spikes, i.e., by gating the coincidence signals required for Hebbian forms of plasticity. We analyze temporal and spatial constraints of such a gating and investigate whether it is possible to suppress bAPs without a simultaneous annihilation of the forward-directed information flow via excitatory postsynaptic potentials (EPSPs). In a computational analysis of conductance-based multi-compartmental models, we demonstrate that a robust control of bAPs and calcium spikes is possible in an all-or-none manner, enabling a binary switch of coincidence signals and plasticity. The position of inhibitory synapses on the dendritic tree determines the spatial extent of the effect and allows a pathway-specific regulation of plasticity. With appropriate timing, EPSPs can still trigger somatic action potentials, although backpropagating signals are abolished. An annihilation of bAPs requires precisely timed inhibition, while the timing constraints are less stringent for distal calcium spikes. We further show that a wide-spread motif of local circuits-feedforward inhibition-is well suited to provide the temporal precision needed for the control of bAPs. Altogether, our model provides experimentally testable predictions and demonstrates that the inhibitory switch of plasticity can be a robust and attractive mechanism, hence assigning an additional function to the inhibitory elements of neuronal microcircuits beyond modulation of excitability.
authors.affiliation: Department of Biology, Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany.|Bernstein Center for Computational Neuroscience, Berlin, Germany.
authors.forename: Katharina A
authors.initials: KA
authors.lastname: Wilmes
authors.affiliation: Bernstein Center for Computational Neuroscience, Berlin, Germany.|Technische Universität Berlin, Berlin, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Sprekeler
authors.affiliation: Department of Biology, Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany.|Bernstein Center for Computational Neuroscience, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D003198:Computer Simulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006801:Humans; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*