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

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.