Efficient spike-sorting of multi-state neurons using inter-spike intervals information.

We demonstrate the efficacy of a new spike-sorting method based on a Markov chain Monte Carlo (MCMC) algorithm by applying it to real data recorded from Purkinje cells (PCs) in young rat cerebellar slices. This algorithm is unique in its capability to estimate and make use of the firing statistics as well as the spike amplitude dynamics of the recorded neurons. PCs exhibit multiple discharge states, giving rise to multi-modal inter-spike interval (ISI) histograms and to correlations between successive ISIs. The amplitude of the spikes generated by a PC in an "active" state decreases, a feature typical of many neurons from both vertebrates and invertebrates. These two features constitute a major and recurrent problem for all the presently available spike-sorting methods. We first show that a hidden Markov model with three log-normal states provides a flexible and satisfying description of the complex firing of single PCs. We then incorporate this model into our previous MCMC based spike-sorting algorithm [Pouzat C, Delescluse M, Viot P, Diebolt J. Improved spike-sorting by modeling firing statistics and burst-dependent spike amplitude attenuation: a Markov chain Monte Carlo approach. J Neurophysiol 2004;91:2910-28] and test this new algorithm on multi-unit recordings of bursting PCs. We show that our method successfully classifies the bursty spike trains fired by PCs by using an independent single unit recording from a patch-clamp pipette.