Axonal Propagation of Simple and Complex Spikes in Cerebellar Purkinje Neurons

Abstract

In cerebellar Purkinje neurons, the reliability of propagation of high-frequency simple spikes and spikelets of complex spikes is likely to regulate inhibition of Purkinje target neurons. To test the extent to which a one-to-one correspondence exists between somatic and axonal spikes, we made dual somatic and axonal recordings from Purkinje neurons in mouse cerebellar slices. Somatic action potentials were recorded with a whole-cell pipette, and the corresponding axonal signals were recorded extracellularly with a loose-patch pipette. Propagation of spontaneous and evoked simple spikes was highly reliable. At somatic firing rates of ϳ200 spikes/sec, Ͻ10% of spikes failed to propagate, with failures becoming more frequent only at maximal somatic firing rates (ϳ260 spikes/sec). Complex spikes were elicited by climbing fiber stimulation, and their somatic waveforms were modulated by tonic current injection, as well as by paired stimulation to depress the underlying EPSCs. Across conditions, the mean number of propagating action potentials remained just above two spikes per climbing fiber stimulation, but the instantaneous frequency of the propagating spikes changed, from ϳ375 Hz during somatic hyperpolarizations that silenced spontaneous firing to ϳ150 Hz during spontaneous activity. The probability of propagation of individual spikelets could be described quantitatively as a saturating function of spikelet amplitude, rate of rise, or preceding interspike interval. The results suggest that ion channels of Purkinje axons are adapted to produce extremely short refractory periods and that brief bursts of forward-propagating action potentials generated by complex spikes may contribute transiently to inhibition of postsynaptic neurons.

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

“…Innervation of single DCN neurons by multiple Purkinje neurons is likely crucial for the alterations reported here to be consequential for the DCN firing given that, in individual neurons, axonal propagation of action potentials, particularly of spikelets, which are more often of stout stature, is unreliable at the high frequencies attained within complex spikes (Khaliq and Raman, 2005;Monsivais et al, 2005). Intriguingly, Kv3.3 channels thus far appear not to be enriched at nodes of Ranvier, in contrast to Kv3.1 (Chang et al, 2007), offering a potential explanation for the conduction failures and suggesting this is not the subcellular locus of Kv3.3 function.…”

Axonal bleb recording

“…The development of tight-seal axonal bleb recording was inspired by extracellular loose-patch recordings from the axons of cerebellar Purkinje cells [34,35] . Because of the surrounding myelin sheath, the membrane of axonal blebs was not accessible to patch pipettes and thus only extracellular spikes were detectable.…”

“…Because of the surrounding myelin sheath, the membrane of axonal blebs was not accessible to patch pipettes and thus only extracellular spikes were detectable. Using this axonal loose patch technique, two research groups [34,35] found that somatic simple spikes are faithfully transmitted along the axons of Purkinje cells, whereas the complex spike waveform cannot be faithfully propagated to distal axonal compartments.…”

Reliability and Heterogeneity of Calcium Signaling at Single Presynaptic Boutons of Cerebellar Granule Cells

“…In extracellular recordings of action potentials from axons of hippocampal CA3 pyramidal neurons, the maximum rate of reliable propagation of APs was ϳ160 Hz (Raastad and Shepherd, 2003;Meeks et al, 2005). In Purkinje cell axons, simple spikes propagated with a high success rate at up to 200 Hz but became unreliable at 300 Hz (Khaliq and Raman, 2005;Monsivais et al, 2005). Thus, in comparison with other classes of neurons in which high-frequency action potential propagation has been examined, granule cells are remarkable in their ability to reliably signal at up to 500 Hz.…”