Introduction: Purkinje Cell (PC) output displays a complex firing pattern consisting of high frequency sodium spikes and low frequency calcium spikes, and disruption in this firing behavior may contribute to cerebellar ataxia. Riluzole, neuroprotective agent, has been demonstrated to have neuroprotective effects in cerebellar ataxia. Here, the spectral analysis of PCs firing in control, 3-acetylpyridine (3-AP), neurotoxin agent, treated alone and riluzole plus 3-AP treated were investigated to determine changes in the firing properties. Difference in the power spectra of tonic and burst firing was assessed. Furthermore, the role of calcium-activated potassium channels in the power spectra was evaluated.
Methods: Analysis was performed using Matlab. Power spectral density (PSD) of PCs output were obtained. Peak frequencies were extracted from the spectrum and statistical comparisons were done. In addition, a multi-compartment computational model of a Purkinje cell was used. This computational stimulation allowed us to study the changes in the power spectral density of the PC output as a result of alteration in ion channels.
Results: Spectral analysis showed that in the spectrum of tonic and burst firing pattern only high sodium frequency and low calcium frequency was seen, respectively. In addition, there was a significant difference between the frequency components of PCs firing obtained from normal, ataxia and riluzole treated rats. Results indicated that sodium firing frequency of normal, ataxic and treated PCs occurred in approximate frequency of 22.53±5.49, 6.46±0.23, and 31.34±4.07 Hz, respectively; and calcium frequency occurred in frequency of 4.22±2.02, 1.52±1.19, and 3.88±1.37 Hz, respectively. The simulation results demonstrated that blockade of calciumactivated potassium channels in the PC model changed the PSD of the PC model firing activity. This change was similar to PSD changes in ataxia condition.
Conclusion: These alterations in the spectrum of PC output may be a basis for developing possible new treatment strategies to improve cerebellar ataxia.