Comparison of glomerular activity patterns by fMRI and wide-field calcium imaging: Implications for principles underlying odor mapping

Functional imaging signals arise from distinct metabolic and hemodynamic events at the neuropil, but how these processes are influenced by pre- and post-synaptic activities need to be understood for quantitative interpretation of stimulus-evoked mapping data. The olfactory bulb (OB) glomeruli, spherical neuropil regions with well-defined neuronal circuitry, can provide insights into this issue. Optical calcium-sensitive fluorescent dye imaging (OICa(2+)) reflects dynamics of pre-synaptic input to glomeruli, whereas high-resolution functional magnetic resonance imaging (fMRI) using deoxyhemoglobin contrast reveals neuropil function within the glomerular layer where both pre- and post-synaptic activities contribute. We imaged odor-specific activity patterns of the dorsal OB in the same anesthetized rats with fMRI and OICa(2+) and then co-registered the respective maps to compare patterns in the same space. Maps by each modality were very reproducible as trial-to-trial patterns for a given odor, overlapping by ~80%. Maps evoked by ethyl butyrate and methyl valerate for a given modality overlapped by ~80%, suggesting activation of similar dorsal glomerular networks by these odors. Comparison of maps generated by both methods for a given odor showed ~70% overlap, indicating similar odor-specific maps by each method. These results suggest that odor-specific glomerular patterns by high-resolution fMRI primarily tracks pre-synaptic input to the OB. Thus combining OICa(2+) and fMRI lays the framework for studies of OB processing over a range of spatiotemporal scales, where OICa(2+) can feature the fast dynamics of dorsal glomerular clusters and fMRI can map the entire glomerular sheet in the OB.

[1]  G. Shepherd,et al.  Functional organization of rat olfactory bulb analysed by the 2‐deoxyglucose method , 1979, The Journal of comparative neurology.

[2]  T. Schormann,et al.  Functional mapping of human brain in olfactory processing: a PET study. , 2000, Journal of neurophysiology.

[3]  M. Leon,et al.  Modular representations of odorants in the glomerular layer of the rat olfactory bulb and the effects of stimulus concentration , 2000, The Journal of comparative neurology.

[4]  Peter Herman,et al.  Tactile and non-tactile sensory paradigms for fMRI and neurophysiologic studies in rodents. , 2009, Methods in molecular biology.

[5]  J Mertz,et al.  Odor-evoked calcium signals in dendrites of rat mitral cells. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[6]  K. Mori,et al.  Compensatory Rapid Switching of Binasal Inputs in the Olfactory Cortex , 2008, The Journal of Neuroscience.

[7]  J. White,et al.  Sniffing controls an adaptive filter of sensory input to the olfactory bulb , 2007, Nature Neuroscience.

[8]  Fahmeed Hyder,et al.  Cortical energy demands of signaling and nonsignaling components in brain are conserved across mammalian species and activity levels , 2013, Proceedings of the National Academy of Sciences.

[9]  David E. Hornung,et al.  A quantitative analysis of sniffing strategies in rats performing odor detection tasks , 1987, Physiology & Behavior.

[10]  R G Shulman,et al.  Dynamic mapping at the laminar level of odor-elicited responses in rat olfactory bulb by functional MRI. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Tom Misteli,et al.  In vivo imaging. , 2003, Methods.

[12]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[13]  C. Gall,et al.  Odors increase Fos in olfactory bulb neurons including dopaminergic cells. , 1995, Neuroreport.

[14]  Naoshige Uchida,et al.  Sensory-Evoked Intrinsic Optical Signals in the Olfactory Bulb Are Coupled to Glutamate Release and Uptake , 2006, Neuron.

[15]  L. Cohen,et al.  Presynaptic afferent inhibition of lobster olfactory receptor cells: reduced action-potential propagation into axon terminals. , 1998, Journal of neurophysiology.

[16]  Y. Lam,et al.  Odors Elicit Three Different Oscillations in the Turtle Olfactory Bulb , 2000, The Journal of Neuroscience.

[17]  R. Friedrich,et al.  Combinatorial and Chemotopic Odorant Coding in the Zebrafish Olfactory Bulb Visualized by Optical Imaging , 1997, Neuron.

[18]  Fahmeed Hyder,et al.  Odor maps of aldehydes and esters revealed by functional MRI in the glomerular layer of the mouse olfactory bulb , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Mickaël Tanter,et al.  Functional ultrasound imaging reveals different odor-evoked patterns of vascular activity in the main olfactory bulb and the anterior piriform cortex , 2014, NeuroImage.

[20]  Peter Herman,et al.  DYNAmic Multi‐coIl TEchnique (DYNAMITE) shimming of the rat brain at 11.7 T , 2014, NMR in biomedicine.

[21]  Fahmeed Hyder,et al.  Mapping at glomerular resolution: fMRI of rat olfactory bulb , 2002, Magnetic resonance in medicine.

[22]  L. Cohen,et al.  Representation of Odorants by Receptor Neuron Input to the Mouse Olfactory Bulb , 2001, Neuron.

[23]  Justus V. Verhagen,et al.  Retronasal odor concentration coding in glomeruli of the rat olfactory bulb , 2014, Front. Integr. Neurosci..

[24]  F. Helmchen,et al.  Simultaneous BOLD fMRI and fiber-optic calcium recording in rat neocortex , 2012, Nature Methods.

[25]  Gordon M Shepherd,et al.  An Energy Budget for the Olfactory Glomerulus , 2007, The Journal of Neuroscience.

[26]  Peter Herman,et al.  Oxidative Neuroenergetics in Event-Related Paradigms , 2009, The Journal of Neuroscience.

[27]  John S. Kauer,et al.  Contributions of topography and parallel processing to odor coding in the vertebrate olfactory pathway , 1991, Trends in Neurosciences.

[28]  Afonso C. Silva,et al.  Spatiotemporal Evolution of the Functional Magnetic Resonance Imaging Response to Ultrashort Stimuli , 2011, The Journal of Neuroscience.

[29]  Matt Wachowiak,et al.  Distributed and concentration-invariant spatial representations of odorants by receptor neuron input to the turtle olfactory bulb. , 2002, Journal of neurophysiology.

[30]  Dustin Scheinost,et al.  Unified Framework for Development, Deployment and Robust Testing of Neuroimaging Algorithms , 2011, Neuroinformatics.

[31]  J. Karbowski Constancy and trade-offs in the neuroanatomical and metabolic design of the cerebral cortex , 2014, Front. Neural Circuits.

[32]  Shree Hari Gautam,et al.  Evidence that the sweetness of odors depends on experience in rats. , 2010, Chemical senses.

[33]  S. Charpak,et al.  What Does Local Functional Hyperemia Tell about Local Neuronal Activation? , 2011, The Journal of Neuroscience.

[34]  Gilles Laurent,et al.  Estimating Firing Rates from Calcium Signals in Locust Projection Neurons in Vivo , 2007, Frontiers in neural circuits.

[35]  Matt Wachowiak,et al.  Correspondence between odorant-evoked patterns of receptor neuron input and intrinsic optical signals in the mouse olfactory bulb. , 2003, Journal of neurophysiology.

[36]  Bradley J. Baker,et al.  Wide-field and two-photon imaging of brain activity with voltage- and calcium-sensitive dyes , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[37]  A. Grinvald,et al.  A tandem-lens epifluorescence macroscope: Hundred-fold brightness advantage for wide-field imaging , 1991, Journal of Neuroscience Methods.

[38]  N. Logothetis,et al.  Neurophysiology of the BOLD fMRI Signal in Awake Monkeys , 2008, Current Biology.

[39]  R G Shulman,et al.  Assessment and discrimination of odor stimuli in rat olfactory bulb by dynamic functional MRI. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Justus V. Verhagen,et al.  Direct Behavioral Evidence for Retronasal Olfaction in Rats , 2012, PloS one.

[41]  Naoshige Uchida,et al.  Odor maps in the mammalian olfactory bulb: domain organization and odorant structural features , 2000, Nature Neuroscience.

[42]  Fahmeed Hyder,et al.  Reproducibility of odor maps by fMRI in rodents , 2006, NeuroImage.

[43]  Karl J. Friston,et al.  A direct quantitative relationship between the functional properties of human and macaque V5 , 2000, Nature Neuroscience.

[44]  L C Katz,et al.  Symmetry, Stereotypy, and Topography of Odorant Representations in Mouse Olfactory Bulbs , 2001, The Journal of Neuroscience.

[45]  M. Lauritzen,et al.  Relationship of Spikes, Synaptic Activity, and Local Changes of Cerebral Blood Flow , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[46]  Richard D. Hoge,et al.  Calibrated fMRI , 2012, NeuroImage.

[47]  Bo Li,et al.  Complex relationship between BOLD-fMRI and electrophysiological signals in different olfactory bulb layers , 2014, NeuroImage.

[48]  Fahmeed Hyder,et al.  Quantitative fMRI and oxidative neuroenergetics , 2012, NeuroImage.

[49]  Seong-Gi Kim,et al.  Layer-dependent BOLD and CBV-weighted fMRI responses in the rat olfactory bulb , 2014, NeuroImage.

[50]  Michael Leon,et al.  Focal 2-DG uptake persists following olfactory bulb lesions , 1995, Brain Research Bulletin.

[51]  F. Hyder,et al.  Cerebral energetics and spiking frequency: The neurophysiological basis of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[52]  J. Fahrenkrug,et al.  Nasal swell-bodies and cyclic changes in the air passage of the rat and rabbit nose. , 1971, Journal of anatomy.

[53]  Matt Wachowiak,et al.  Presynaptic inhibition of olfactory receptor neurons in crustaceans , 2002, Microscopy research and technique.

[54]  M. Ducros,et al.  The Relationship between Blood Flow and Neuronal Activity in the Rodent Olfactory Bulb , 2007, The Journal of Neuroscience.

[55]  Fahmeed Hyder,et al.  Adaptation in the rodent olfactory bulb measured by fMRI , 2005, Magnetic resonance in medicine.

[56]  L. C. Katz,et al.  Optical Imaging of Odorant Representations in the Mammalian Olfactory Bulb , 1999, Neuron.

[57]  Peter Herman,et al.  Energetics of neuronal signaling and fMRI activity , 2007, Proceedings of the National Academy of Sciences.

[58]  V. Murthy,et al.  Coupling of Neural Activity to Blood Flow in Olfactory Glomeruli Is Mediated by Astrocytic Pathways , 2008, Neuron.

[59]  Matt Wachowiak,et al.  Optical Dissection of Odor Information Processing In Vivo Using GCaMPs Expressed in Specified Cell Types of the Olfactory Bulb , 2013, The Journal of Neuroscience.

[60]  E. Yaksi,et al.  Reconstruction of firing rate changes across neuronal populations by temporally deconvolved Ca2+ imaging , 2006, Nature Methods.

[61]  Matt Wachowiak,et al.  In Vivo Imaging of Neuronal Activity by Targeted Expression of a Genetically Encoded Probe in the Mouse , 2004, Neuron.

[62]  I. Fried,et al.  Coupling Between Neuronal Firing, Field Potentials, and fMRI in Human Auditory Cortex , 2005, Science.

[63]  John S. Kauer,et al.  Local sites of activity-related glucose metabolism in rat olfactory bulb during olfactory stimulation , 1975, Brain Research.