The Making of a Complex Spike: Ionic Composition and Plasticity

Abstract

Climbing fiber (CF) activation evokes a large all‐or‐nothing electrical response in Purkinje cells (PCs), the complex spike. It has been suggested that the role of CFs (and thus complex spikes) is that of a “teacher” in simple learning paradigms such as associative eyeblink conditioning. An alternative hypothesis describes the olivocerebellar system as part of a timing device and denies a role of the CF input in learning. To date, neither of these hypotheses nor others can definitively be verified or discounted. Similarly, the complex spike evades a clear understanding when it comes to the cellular events underlying complex spike generation. What is known, however, is that complex spikes are associated with large dendritic calcium signals that are required for the induction of long‐term depression (LTD) at the parallel fiber (PF)‐PC synapse. PF‐LTD is a form of long‐term synaptic plasticity that has been suggested to underlie certain forms of cerebellar motor learning. In contrast to the PF input, the CF input has been considered invariant. Our recent discovery of LTD at the CF input shows that complex spikes are less static than previously assumed. In addition to depression of CF‐evoked excitatory postsynaptic currents, long‐lasting, selective reduction of slow complex spike components could be observed after brief CF tetanization. To understand the functional implications of CF‐LTD, it is crucial to know the types of currents constituting the specific complex spike components. Here we review the “anatomy” of the complex spike as well as our observations of activity‐dependent complex spike waveform modifications. In addition, we discuss which properties CF‐LTD might add to the circuitry of the cerebellar cortex.

Purkinje-Cell-Restricted Restoration of Kv3.3 Function Restores Complex Spikes and Rescues Motor Coordination inKcnc3Mutants

“…A climbing fiber-triggered complex spike consists of a largeamplitude sodium spike followed by several spikelets of smaller amplitudes (Schmolesky et al, 2002). The frequency of spikelets within a complex spike may reach Ͼ500 Hz, a discharge rate that requires fast-repolarizing potassium currents likely mediated by Kv3-type channels (Rudy and McBain, 2001).…”

“…Superimposed on the tonic firing of simple spikes are complex spikes that occur at a low frequency of ϳ1 Hz (Schmolesky et al, 2002). Each complex spike consists of a brief burst of spikes at a very high frequency (Ͼ500 Hz).…”

Axonal Propagation of Simple and Complex Spikes in Cerebellar Purkinje Neurons

“…These observations raise the additional question of whether the forward-propagating signals of complex spikes are also susceptible to modulation, thereby influencing the pattern of corticonuclear inhibition (Schmolesky et al, 2002;Foster and Regehr, 2004).…”

“…The informational role of the complex spike has been extensively studied, debated, and reviewed (Simpson et al, 1996;Schmolesky et al, 2002). In general, the signals that have been ascribed to complex spikes can be categorized as either long term or real time.…”

“…Simple spikes, which occur spontaneously, exceed 100 spikes/sec in response to excitation from parallel fibers (Thach, 1968;Gilbert and Thach, 1977;Kitazawa et al, 1998). Complex spikes, which are elicited by climbing fiber excitation, consist of a large-amplitude action potential followed by a series of spikelets having a frequency that approaches 500 Hz (Llinás and Sugimori, 1980;Schmolesky et al, 2002). Although action potentials forward-propagate reliably at low firing rates in several cell types (Mackenzie et al, 1996;Cox et al, 2000;Forti et al, 2000;Koester and Sakmann, 2000;Raastad and Shepherd, 2003) (but see Debanne et al, 1997), high firing rates can promote propagation failures (Debanne, 2004).…”