Faculty Bibliography

The olivo-cerebellar network is a key neuronal circuit that provides high-level motor control in the vertebrate CNS. Functionally, its network dynamics is organized around the oscillatory membrane potential properties of inferior olive (IO) neurons and their electrotonic connectivity. Because IO action potentials are generated at the peaks of the quasisinusoidal membrane potential oscillations, their temporal firing properties are defined by the IO rhythmicity. Excitatory inputs to these neurons can produce oscillatory phase shifts without modifying the amplitude or frequency of the oscillations, allowing well defined time-shift modulation of action potential generation. Moreover, the resulting phase is defined only by the amplitude and duration of the reset stimulus and is independent of the original oscillatory phase when the stimulus was delivered. This reset property, henceforth referred to as selfreferential phase reset, results in the generation of organized clusters of electrically coupled cells that oscillate in phase and are controlled by inhibitory feedback loops through the cerebellar nuclei and the cerebellar cortex. These clusters provide a dynamical representation of arbitrary motor intention patterns that are further mapped to the motor execution system. Being supplied with sensory inputs, the olivo-cerebellar network is capable of rearranging the clusters during the process of movement execution. Accordingly, the phase of the IO oscillators can be rapidly reset to a desired phase independently of the history of phase evolution. The goal of this article is to show how this selfreferential phase reset may be implemented into a motor control system by using a biologically based mathematical model.

Synaptotagmin (Syt) I, a ubiquitous synaptic vesicle protein, comprises a transmembrane region and two C2 domains. The C2 domains, which have been shown to be essential for both synaptic vesicle exocytosis and endocytosis, are also seen as the Ca(2+) sensors in synaptic vesicular release. In a previous study, we reported that a polyclonal antibody raised against the squid (Loligo pealei) Syt I C2B domain, while inhibiting vesicular endocytosis, was synaptic release neutral at the squid giant synapse. Recent reports concerning the C2B requirements for synaptic release prompted us to readdress the role of C2B in squid giant synapse function. Presynaptic injection of another anti-Syt I-C2B antibody (using recombinant whole C2B domain expressed in mammalian cell culture as an antigen) into the presynaptic terminal reproduced our previous results, i.e., reduction of vesicular endocytosis without affecting synaptic release. This set of results addresses the issue of the geometrical arrangement of the Ca(2+) sensor, allowing the C2B domain antibody to restrict Ca(2+)-dependent C2B self-oligomerization without modifying the Ca(2+)-dependent release process

The olivo-cerebellar system is one of the central networks organizing movement coordination in vertebrates. This system consists of three main anatomical structures: the inferior olive (10), the cerebellar nuclei, and the cerebellar cortex. Over the last four decades studies in many laboratories have contributed significantly to our understanding of the electrophysiology of 10 and cerebellar neurons. However, addressing the dynamic properties of olivo-cerebellar network requires information beyond the limits attainable using single cell recordings. Research at the neuronal network level is presently being implemented in order to determine the spatiotemporal activity profiles of ensemble neuronal activity using optical imaging of voltage-sensitive dye signals. We summarize here results of such type of study using the in vitro 10 slices. The dynamic characteristic of the system is addressed using the imaging results as well as mathematical modeling of the network, as a heuristic tool. A computer-based control system based on such biological findings is outlined

A model is presented that simulates the process of neuronal synchronization, formation of coherent activity clusters and their dynamic reorganization in the olivo-cerebellar system. Three coupled 2D lattices dealing with the main cellular groups in this neuronal circuit are used to model the dynamics of the excitatory feedforward loop linking the inferior olive (IO) neurons to the cerebellar nuclei (CN) via collateral axons that also proceed to terminate as climbing fiber afferents to Purkinje cells (PC). Inhibitory feedback from the CN-lattice fosters decoupling of units in a vicinity of a given IO neuron. It is shown that noise-sustained oscillations in the IO-lattice are capable to synchronize and generate coherent firing clusters in the layer accounting for the excitable collateral axons. The model also provides phase resetting of the oscillations in the IO-lattices with transient silent behavior. It is also shown that the CN-IO feedback leads to transient patterns of couplings in the IO and to a dynamic control of the size of clusters