Calcium activity is a degraded estimate of spikes

Current Biology(2022)

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Recording action potentials extracellularly during behavior has led to fundamental discoveries regarding neural function—hippocampal neurons respond to locations in space, 1 O’Keefe J. Place units in the hippocampus of the freely moving rat. Exp. Neurol. 1976; 51: 78-109https://doi.org/10.1016/0014-4886(76)90055-8 Crossref PubMed Scopus (1174) Google Scholar motor cortex neurons encode movement direction, 2 Georgopoulos A.P. Kalaska J.F. Caminiti R. Massey J.T. On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex. J. Neurosci. 1982; 2: 1527-1537 Crossref PubMed Google Scholar and dopamine neurons signal reward prediction errors 3 Schultz W. Responses of midbrain dopamine neurons to behavioral trigger stimuli in the monkey. J. Neurophysiol. 1986; 56: 1439-1461https://doi.org/10.1152/jn.1986.56.5.1439 Crossref PubMed Scopus (297) Google Scholar —observations undergirding current theories of cognition, 4 Buzsáki G. Tingley D. 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However, while initial studies were grounded in prior unit recording work, it has become fashionable to assume that calcium is identical to spiking, even though the spike-to-fluorescence transformation is nonlinear, noisy, and unpredictable under real-world conditions. 10 Huang L. Ledochowitsch P. Knoblich U. Lecoq J. Murphy G.J. Reid R.C. de Vries S.E. Koch C. Zeng H. Buice M.A. et al. Relationship between simultaneously recorded spiking activity and fluorescence signal in GCaMP6 transgenic mice. eLife. 2021; 10: e51675https://doi.org/10.7554/eLife.51675 Crossref PubMed Scopus (55) Google Scholar It remains an open question whether calcium provides a high-fidelity representation of single-unit activity in awake, behaving subjects. Here, we have addressed this question by recording both signals in the lateral orbitofrontal cortex (OFC) of rats during olfactory discrimination learning. Activity in the OFC during olfactory learning has been well-studied in humans, 11 Zelano C. 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Our single-unit results replicated prior findings, whereas the calcium signal provided only a degraded estimate of the information available in the single-unit spiking, reflecting primarily reward value.
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orbitofrontal cortex,learning,electrophysiology,ensembles,calcium imaging,single unit,sensory,prediction,value,reward
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