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Gert Van Dijck
University of Cambridge

A solution to identifying neurones using extracellular activity in awake animals: a probabilistic machine-learning approach

Friday 19th of October 2012 at 11:00am
Evans 560

Electrophysiological studies over the last fifty years have been hampered by the difficulty of reliably assigning signals to identified cortical neurones. Previous studies have employed a variety of measures based on spike timing or waveform characteristics to tentatively classify other neurone types (Vos et al., Eur. J. Neurosci., 1999; Prsa et al., J. Neurosci., 2009), in some cases supported by juxtacellular labelling (Simpson et al., Prog. Brain Res., 2005; Holtzman et al., J. Physiol., 2006; Barmack and Yakhnitsa, J. Neurosci., 2008; Ruigrok et al., J. Neurosci., 2011), or intracellular staining and / or assessment of membrane properties (Chadderton et al., Nature, 2004; Jorntell and Ekerot, J. Neurosci., 2006; Rancz et al., Nature, 2007). Anaesthetised animals have been widely used as they can provide a ground-truth through neuronal labelling which is much harder to achieve in awake animals where spike-derived measures tend to be relied upon (Lansink et al., Eur. J. Neurosci., 2010). Whilst spike-shapes carry potentially useful information for classifying neuronal classes, they vary with electrode type and the geometric relationship between the electrode and the spike generation zone (Van Dijck et al., Int. J. Neural Syst., 2012). Moreover, spike-shape measurement is achieved with a variety of techniques, making it difficult to compare and standardise between laboratories.In this study we build probabilistic models on the statistics derived from the spike trains of spontaneously active neurones in the cerebellum and the ventral midbrain. The mean spike frequency in combination with the log-interval-entropy (Bhumbra and Dyball, J. Physiol.-London, 2004) of the inter-spike-interval distribution yields the highest prediction accuracy. The cerebellum model consists of two sub-models: a molecular layer - Purkinje layer model and a granular layer - Purkinje layer model. The first model identifies with high accuracy (92.7 %) molecular layer interneurones and Purkinje cells, while the latter identifies with high accuracy (99.2 %) Golgi cells, granule cells, mossy fibers and Purkinje cells. Furthermore, it is shown that the model trained on anaesthetized rat and decerebrate cat data has broad applicability to other species and behavioural states: anaesthetized mice (80 %), awake rabbits (94.2 %) and awake rhesus monkeys (89 - 90 %).Recently, opto-genetics allow to obtain a ground-truth about cell classes. Using opto-genetically identified GABA-ergic and dopaminergic cells we build similar statistical models to identify these neuron types from the ventral midbrain.Hence, this illustrates that our approach will be of general use to a broad variety of laboratories.


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