Dataset Information

Kv3.3 channels at the Purkinje cell soma are necessary for generation of the classical complex spike waveform.

ABSTRACT: Voltage-gated potassium channel subunit Kv3.3 is prominently expressed in cerebellar Purkinje cells and is known to be important for cerebellar function, as human and mouse movement disorders result from mutations in Kv3.3. To understand these behavioral deficits, it is necessary to know the role of Kv3.3 channels on the physiological responses of Purkinje cells. We studied the function of Kv3.3 channels in regulating the synaptically evoked Purkinje cell complex spike, the massive postsynaptic response to the activation of climbing fiber afferents, believed to be fundamental to cerebellar physiology. Acute slice recordings revealed that Kv3.3 channels are required for generation of the repetitive spikelets of the complex spike. We found that spikelet expression is regulated by somatic, and not by dendritic, Kv3 activity, which is consistent with dual somatic-dendritic recordings that demonstrate spikelet generation at axosomatic membranes. Simulations of Purkinje cell Na+ currents show that the unique electrical properties of Kv3 and resurgent Na+ channels are coordinated to limit accumulation of Na+ channel inactivation and enable rapid, repetitive firing. We additionally show that Kv3.3 knock-out mice produce altered complex spikes in vitro and in vivo, which is likely a cellular substrate of the cerebellar phenotypes observed in these mice. This characterization presents new tools to study complex spike function, cerebellar signaling, and Kv3.3-dependent human and mouse phenotypes.

SUBMITTER: Zagha E

PROVIDER: S-EPMC2657222 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Kv3.3 channels at the Purkinje cell soma are necessary for generation of the classical complex spike waveform.

Zagha Edward E Lang Eric J EJ Rudy Bernardo B

The Journal of neuroscience : the official journal of the Society for Neuroscience 20080201 6

Voltage-gated potassium channel subunit Kv3.3 is prominently expressed in cerebellar Purkinje cells and is known to be important for cerebellar function, as human and mouse movement disorders result from mutations in Kv3.3. To understand these behavioral deficits, it is necessary to know the role of Kv3.3 channels on the physiological responses of Purkinje cells. We studied the function of Kv3.3 channels in regulating the synaptically evoked Purkinje cell complex spike, the massive postsynaptic ...[more]

PMID: 18256249

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Project description:Traditionally, the key step before decoding motor intentions from cortical recordings is spike sorting, the process of identifying which neuron was responsible for an action potential. Recently, researchers have started investigating approaches to decoding which omit the spike sorting step, by directly using information about action potentials' waveform shapes in the decoder, though this approach is not yet widespread. Particularly, one recent approach involves computing the moments of waveform features and using these moment values as inputs to decoders. This computationally inexpensive approach was shown to be comparable in accuracy to traditional spike sorting. In this study, we use offline data recorded from two Rhesus monkeys to further validate this approach. We also modify this approach by using sums of exponentiated features of spikes, rather than moments. Our results show that using waveform feature sums facilitates significantly higher hand movement reconstruction accuracy than using waveform feature moments, though the magnitudes of differences are small. We find that using the sums of one simple feature, the spike amplitude, allows better offline decoding accuracy than traditional spike sorting by expert (correlation of 0.767, 0.785 vs. 0.744, 0.738, respectively, for two monkeys, average 16% reduction in mean-squared-error), as well as unsorted threshold crossings (0.746, 0.776; average 9% reduction in mean-squared-error). Our results suggest that the sums-of-features framework has potential as an alternative to both spike sorting and using unsorted threshold crossings, if developed further. Also, we present data comparing sorted vs. unsorted spike counts in terms of offline decoding accuracy. Traditional sorted spike counts do not include waveforms that do not match any template ("hash"), but threshold crossing counts do include this hash. On our data and in previous work, hash contributes to decoding accuracy. Thus, using the comparison between sorted spike counts and threshold crossing counts to evaluate the benefit of sorting is confounded by the presence of hash. We find that when the comparison is controlled for hash, performing sorting is better than not. These results offer a new perspective on the question of to sort or not to sort.

Dataset Information

Kv3.3 channels at the Purkinje cell soma are necessary for generation of the classical complex spike waveform.

Publications

Kv3.3 channels at the Purkinje cell soma are necessary for generation of the classical complex spike waveform.

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