Control of neuronal firing by dynamic parallel fiber feedback:implications for electrosensory reafference suppression

Abstract

SUMMARY The cancellation of self-generated components of sensory inputs is a key function of sensory feedback pathways. In many systems, cerebellar parallel fiber feedback mediates this cancellation through anti-Hebbian plasticity,resulting in the generation of a negative image of the reafferent inputs. Parallel fiber feedback involves direct excitation and disynaptic inhibition as well as synaptic plasticity on multiple time scales. How the dynamics of these processes interact with anti-Hebbian plasticity to shape synaptic inputs and provide a cancellation mechanism remains unclear. In the present study, we investigated the influence of parallel fiber feedback onto pyramidal neurons of the electrosensory lateral line lobe (ELL) in weakly electric fish under open loop conditions. We mimicked naturalistic parallel fiber inputs in an ELL brain slice by implementing an experimentally based model of this synaptic pathway using dynamic clamp. We showed that as parallel fiber activity increases, the effective input to ELL pyramidal neurons changes from net excitation to net inhibition, resulting in a non-monotonic firing response. Using a model neuron, we found that this robust non-monotonic response is due to a shift from balanced excitation and inhibition at low parallel fiber input rates, to dominant inhibition at high input rates. We then showed that this non-monotonic response provides a simple basis for negative image generation. Through changes in the mean activation rate of parallel fibers, the feedback can switch roles between enhancement and suppression of sensory inputs in a manner that is directly determined by the slope of the non-monotonic response curve.

Burst-Induced Anti-Hebbian Depression Acts through Short-Term Synaptic Dynamics to Cancel Redundant Sensory Signals

“…The parallel fiber inputs consist of a direct excitatory component and a disynaptic inhibitory component. Previous studies have developed an experimentally based model of the dynamics underlying these inputs Maler, 2002a, 2004;Lewis et al, 2007). This original model described excitation in terms of the presynaptic dynamics as well as inhibition.…”

“…Here, we consider the effects of changing the postsynaptic excitatory conductance. A basic description of the model is provided in the following sections; the details, along with the motivation and associated data, can be found in previous studies Maler, 2002a, 2004;Lewis et al, 2007).…”

“…The total synaptic conductance G exc and G inh (and hence total synaptic current, I syn ) are due to the combined effects of 120 independent excitatory inputs and 120 independent inhibitory inputs, respectively. The presynaptic excitatory inputs also exhibit short-term facilitation ( F) and depression ( D) and are modeled using the following standard approach (Dayan and Abbott, 2001;Lewis et al, 2007):…”

“…We simulate the experimental conditions involved in the generation of a negative image by a sinusoidal rate modulation of the parallel fibers (Lewis et al, 2007). In doing so, we assume that a sinusoidal spatially global sensory input is represented accurately in the parallel fiber activity .…”

“…A negative image results when the pyramidal cell activity (variations in membrane potential or spike output) is out of phase with the input modulation. We quantify the neural responses in terms of the phase histogram and the vector strength Lewis et al, 2007). All simulations used an Euler integration method (time step ϭ 0.2 ms) and were implemented in Igor Pro (Wavemetrics).…”