Large Identified Pyramidal Cells in Macaque Motor and Premotor Cortex Exhibit “Thin Spikes”: Implications for Cell Type Classification

Since the pioneering work of Mountcastle, there has been great enthusiasm for the notion that single unit activity could be attributed to specific cell types based on extracellular spike waveforms. The current work by Lemon and Colleagues (Vigneswaran et al., 2011) highlights a previously unrecognized caveat of this approach by demonstrating that a subset of pyramidal cells have narrow spikes and could easily be misclassified as interneurons. Complicating matters further, we would point out an additional caveat, that a substantial proportion of interneurons have broad spikes and could conversely be misclassified as pyramidal cells. Recent results from our group obtained using unbiased techniques show that prior studies had underestimated the size of the interneuron population that is not fast-spiking, which we have found constitutes approximately 60% of the interneurons in mouse somatosensory cortex (Rudy et al., 2011). Intracellular recordings in awake behaving mice have demonstrated that some non-fast-spiking interneurons can not be distinguished from pyramidal cells based on spike waveform alone (Gentet et al., 2010), and although a similar in vivo study has not been performed in primates, intracellular slice recordings from primate cortex show similar broad spike waveforms for a large subset of interneurons (Zaitsev et al., 2009). Further complicating the picture, the proportion of GABAergic interneurons expressing narrow-spiking markers varies substantially between rodents and primates, as well as between different cortical areas (Constantinople et al., 2009). Hence as revealed by both the Vigneswaran et al. work and our own, unambiguous extracellular identification of neurons requires the use of other techniques, such as optogenetic stimulation (Lima et al., 2009). We therefore join the authors in encouraging the extracellular recording community to exercise caution when inferring cell type based on spike waveforms.

References:

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Conflict of Interest:

None declared