[Show abstract][Hide abstract] ABSTRACT: Recent studies have demonstrated that the membrane potential of Purkinje cells is bi-stable and that this phenomenon underlies bi-modal simple spike firing. Membrane potential alternates between a depolarized state, that is associated with spontaneous simple spike firing (up state), and a quiescent hyperpolarized state (down state). A controversy has emerged regarding the relevance of bi-stability to the awake animal, yet recordings made from behaving cat Purkinje cells have demonstrated that at least 50% of the cells exhibit bi-modal firing. The robustness of the phenomenon in vitro or in anaesthetized systems on the one hand, and the controversy regarding its expression in behaving animals on the other hand suggest that state transitions are under neuronal control. Indeed, we have recently demonstrated that synaptic inputs can induce transitions between the states and suggested that the role of granule cell input is to control the states of Purkinje cells rather than increase or decrease firing rate gradually. We have also shown that the state of a Purkinje cell does not only affect its firing but also the waveform of climbing fiber-driven complex spikes and the associated calcium influx. These findings call for a reconsideration of the role of Purkinje cells in cerebellar function. In this manuscript we review the recent findings on Purkinje cell bi-stability and add some analyses of its effect on the regularity and variability of Purkinje cell activity.
[Show abstract][Hide abstract] ABSTRACT: The recently described bi-stability of Purkinje cells and the state-dependence of the complex spike waveform suggest that calcium currents may play a pivotal role in both the complex spike waveform and the state of the membrane voltage. Here we used Ca2+ imaging to record the changes in intracellular [Ca2+] that are elicited by either spontaneous or climbing fiber-evoked activity in rat Purkinje cells. We show that a continuous somatic Ca2+ influx occurs during an "UP" state. Furthermore Ca2+ transients that are evoked by climbing fiber stimulation are state-dependent. Somatic transients are smaller following an "UP" state, while dendritic transients are smaller following a "DOWN" state. The state-dependence of these signals should affect the intrinsic firing of Purkinje cells as well as plastic processes that modulate synaptic strength.
[Show abstract][Hide abstract] ABSTRACT: In a recent report we demonstrated that stimulation of cerebellar mossy fibers synchronously activates Purkinje cells that are located directly above the site of stimulation. We found that the activated Purkinje cells are arranged in a radial patch on the cerebellar surface and that this organization is independent of the integrity of the inhibitory system. This arrangement of activity is counterintuitive. The anatomical structure with the extensive parallel fiber system implies that mossy fiber stimulation will activate Purkinje cells along a beam of parallel fibers. In this short review we highlight this discrepancy between anatomical structure and functional dynamics and suggest a plausible underlying mechanism.
Frontiers in Neuroscience 01/2009; 2(2):192-8. DOI:10.3389/neuro.01.036.2008 · 3.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The olivo-cerebellar system has been implicated in temporal coordination of task components. Here, we propose a novel model that enables the olivo-cerebellar system to function as a generator of temporal patterns. These patterns could be used for timing of motor, sensory and cognitive tasks. The proposed mechanism for the generation of these patterns is based on subthreshold oscillations in a network of inferior olivary neurons and their control by the cerebellar cortex and nuclei. Our model, which integrates a large body of anatomical and physiological observations, lends itself to simple, testable predictions and provides a new conceptual framework for olivo-cerebellar research.
Trends in Neurosciences 11/2008; 31(12):617-25. DOI:10.1016/j.tins.2008.09.005 · 13.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The lattice-like structure of the cerebellar cortex and its anatomical organization in two perpendicular axes provided the foundations for many theories of cerebellar function. However, the functional organization does not always match the anatomical organization. Thus direct measurement of the functional organization is central to our understanding of cerebellar processing. Here we use voltage sensitive dye imaging in the isolated cerebellar preparation to characterize the spatio-temporal organization of the climbing and mossy fiber (MF) inputs to the cerebellar cortex. Spatial and temporal parameters were used to develop reliable criteria to distinguish climbing fiber (CF) responses from MF responses. CF activation excited postsynaptic neurons along a parasagittal cortical band. These responses were composed of slow ( approximately 25 ms), monophasic depolarizing signals. Neither the duration nor the spatial distribution of CF responses were affected by inhibition. Activation of MF generated responses that were organized in radial patches, and were composed of a fast ( approximately 5 ms) depolarizing phase followed by a prolonged ( approximately 100 ms) negative wave. Application of a GABA(A) blocker eliminated the hyperpolarizing phase and prolonged the depolarizing phase, but did not affect the spatial distribution of the response, thus suggesting that it is not the inhibitory system that is responsible for the inability of the MF input to generate beams of activity that propagate along the parallel fiber system.
Frontiers in Systems Neuroscience 02/2007; 1:1. DOI:10.3389/neuro.06.001.2007
[Show abstract][Hide abstract] ABSTRACT: Localizing the seizure focus is difficult and frequently, multiple sites are found. This reflects our poor understanding of the fundamental mechanisms of seizure generation and propagation. We used multisite electrophysiological recordings in two seizure models and voltage-sensitive dye imaging, to spatiotemporally characterize the initiation and propagation of seizures in an intact epileptogenic brain region, the isolated hippocampus. In low-magnesium perfusate, seizures always originated in the temporal region, and propagated along the septotemporal axis to the septal region. After the seizure spread across the hippocampus, the bursts within a seizure became bidirectional, with different propagation patterns at different frequencies. When the intact hippocampus was separated along the septotemporal axis, independent bidirectional activity was observed in the two halves, and region-specific cuts to the tissue reveal that the CA3 region is critical for seizure generation and propagation. In a second seizure model, using focal tetanic stimulation of the septal and temporal CA3 region, seizures always originated at the stimulated site with bidirectionality later developing at different frequencies, as noted in the low magnesium model, behavior compatible with coupled neuronal network oscillators. These data provide novel insights into the dynamic multifocality of seizure onset and propagation, revealing that the current concept of a single seizure "focus" is complex.
Neurobiology of Disease 09/2006; 23(2):312-28. DOI:10.1016/j.nbd.2006.03.014 · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Department for neurobiology, the Hebrew university Unlike many areas of the cerebral cortex, the cerebellum is a structure whose exact function is very difficult to define. It is usually considered as part of the motor system, but has also been suggested to participate in sensory and even cognitive tasks (Bower, 1997; Ito, 2000, 2008). In contrast to its complex function, its anatomy and connectivity are strikingly simple. Therefore our understanding of cerebellar function relies heavily on our understanding of its circuit physiology. Indeed in many cerebellar theories it is the cerebellar network properties that are the basis for the suggested function (Braitenberg & Atwood, 1958; Marr, 1969; Albus, 1971). During the last decades, the physiological properties of almost all neurons in this system were systematically studied. However, recent evidence suggest that some basic notions in the classical view of cerebellar physiology are in need for revision. Here I describe two sets of observations that challenge the classical view of cerebellar function, demonstrating the need for a conceptual revision. The first deals with the spatio-temporal organization of cerebellar cortical responses to mossy fiber input, and the second deals with the biophysics of Purkinje cells and the way they respond to granule cell input. Figure 1. The cerebellar cortical circuitry: Black -Purkinje cells, blue, -granule cells, green – Golgi cells, red and orange – stellate and basket cells, magenta – climbing fiber, brown – mossy fiber.