title: Computational modeling predicts the ionic mechanism of late-onset responses in unipolar brush cells.
abstract: Unipolar Brush Cells (UBCs) have been suggested to play a critical role in cerebellar functioning, yet the corresponding cellular mechanisms remain poorly understood. UBCs have recently been reported to generate, in addition to early-onset glutamate receptor-dependent synaptic responses, a late-onset response (LOR) composed of a slow depolarizing ramp followed by a spike burst (Locatelli et al., 2013). The LOR activates as a consequence of synaptic activity and involves an intracellular cascade modulating H- and TRP-current gating. In order to assess the LOR mechanisms, we have developed a UBC multi-compartmental model (including soma, dendrite, initial segment, and axon) incorporating biologically realistic representations of ionic currents and a cytoplasmic coupling mechanism regulating TRP and H channel gating. The model finely reproduced UBC responses to current injection, including a burst triggered by a low-threshold spike (LTS) sustained by CaLVA currents, a persistent discharge sustained by CaHVA currents, and a rebound burst following hyperpolarization sustained by H- and CaLVA-currents. Moreover, the model predicted that H- and TRP-current regulation was necessary and sufficient to generate the LOR and its dependence on the intensity and duration of mossy fiber activity. Therefore, the model showed that, using a basic set of ionic channels, UBCs generate a rich repertoire of bursts, which could effectively implement tunable delay-lines in the local microcircuit.
authors.affiliation: Neurophysiology Unit, Department of Brain and Behavioral Science, University of Pavia Pavia, Italy ; Consorzio Interuniversitario per le Scienze Fisiche della Materia (CNISM) Pavia, Italy.
authors.forename: Sathyaa
authors.initials: S
authors.lastname: Subramaniyam
authors.affiliation: Neurophysiology Unit, Brain Connectivity Center, Istituto Neurologico IRCCS C. Mondino Pavia, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Solinas
authors.affiliation: Neurophysiology Unit, Department of Brain and Behavioral Science, University of Pavia Pavia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Perin
authors.affiliation: Neurophysiology Unit, Department of Brain and Behavioral Science, University of Pavia Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Neurophysiology Unit, Department of Brain and Behavioral Science, University of Pavia Pavia, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Masetto
authors.affiliation: Neurophysiology Unit, Department of Brain and Behavioral Science, University of Pavia Pavia, Italy ; Neurophysiology Unit, Brain Connectivity Center, Istituto Neurologico IRCCS C. Mondino Pavia, Italy.
authors.forename: Egidio
authors.initials: E
authors.lastname: D'Angelo
keywords: biorealistic modeling; ionic channel regulation; slow synaptic responses; unipolar brush cells; vestibular cerebellum