Cortical representations of olfactory input by trans-synaptic tracing

In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of ‘starter’ cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.

[1]  S. S. Winans,et al.  The differential projections of the olfactory bulb and accessory olfactory bulb in mammals , 1975, The Journal of comparative neurology.

[2]  E. G. Jones,et al.  The organization and postnatal development of the commissural projection of the rat somatic sensory cortex , 1976, The Journal of comparative neurology.

[3]  G. Shepherd.  The Synaptic Organization of the Brain , 1979 .

[4]  J. W. Scott,et al.  The organization of projections from the olfactory bulb to the piriform cortex and olfactory tubercle in the rat , 1980, The Journal of comparative neurology.

[5]  Esmail Meisami,et al.  A quantitative study of the effects of early unilateral olfactory deprivation on the number and distribution of mitral and tufted cells and of glomeruli in the rat olfactory bulb , 1981, Brain Research.

[6]  M. Luskin,et al.  The distribution of axon collaterals from the olfactory bulb and the nucleus of the horizontal limb of the diagonal band to the olfactory cortex, demonstrated by double retrograde labeling techniques , 1982, The Journal of comparative neurology.

[7]  F. Macrides,et al.  Topographic organization of connections between the main olfactory bulb and pars externa of the anterior olfactory nucleus in the hamster , 1984, The Journal of comparative neurology.

[8]  M. T. Shipley,et al.  the connections of the mouse olfactory bulb: A study using orthograde and retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase , 1984, Brain Research Bulletin.

[9]  E. Orona,et al.  Pattern of rat olfactory bulb mitral and tufted cell connections to the anterior olfactory nucleus pars externa , 1985, The Journal of comparative neurology.

[10]  A. Keller,et al.  Long-term potentiation in the motor cortex. , 1989, Science.

[11]  L. Rosselli-Austin,et al.  Enriched neonatal odor exposure leads to increased numbers of olfactory bulb mitral and granule cells. , 1990, Brain research. Developmental brain research.

[12]  R. Napper,et al.  Early postnatal alcohol exposure acutely and permanently reduces the number of granule cells and mitral cells in the rat olfactory bulb: A stereological study , 1992, The Journal of comparative neurology.

[13]  G. Felsenfeld,et al.  A 5′ element of the chicken β-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila , 1993, Cell.

[14]  Richard Axel,et al.  Topographic organization of sensory projections to the olfactory bulb , 1994, Cell.

[15]  Linda B. Buck,et al.  Information coding in the olfactory system: Evidence for a stereotyped and highly organized epitope map in the olfactory bulb , 1994, Cell.

[16]  G. Ugolini.  Specificity of rabies virus as a transneuronal tracer of motor networks: Transfer from hypoglossal motoneurons to connected second‐order and higher order central nervous system cell groups , 1995, The Journal of comparative neurology.

[17]  Richard Axel,et al.  Visualizing an Olfactory Sensory Map , 1996, Cell.

[18]  S. Segovia,et al.  Estradiol Masculinizes the Number of Accessory Olfactory Bulb Mitral Cells in the Rat , 1997, Brain Research Bulletin.

[19]  H. Markram,et al.  Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. , 1997, The Journal of physiology.

[20]  H. Hayashi,et al.  OCAM: A New Member of the Neural Cell Adhesion Molecule Family Related to Zone-to-Zone Projection of Olfactory and Vomeronasal Axons , 1997, The Journal of Neuroscience.

[21]  William Schroeder,et al.  The Visualization Toolkit: An Object-Oriented Approach to 3-D Graphics , 1997 .

[22]  Bahram Parvin,et al.  Surface reconstruction from sparse fringe contours , 1998, Proceedings Fourth IEEE Workshop on Applications of Computer Vision. WACV'98 (Cat. No.98EX201).

[23]  W M Cowan,et al.  The Emergence of Modern Neuroanatomy and Developmental Neurobiology , 1998, Neuron.

[24]  Carol M. Petito.  The Synaptic Organization of the Brain, 4th Ed , 1998 .

[25]  Prof. Dr. Dr. Valentino Braitenberg,et al.  Cortex: Statistics and Geometry of Neuronal Connectivity , 1998, Springer Berlin Heidelberg.

[26]  L. Buck,et al.  Combinatorial Receptor Codes for Odors , 1999, Cell.

[27]  Michael Davis,et al.  The amygdala , 2000, Current Biology.

[28]  M. T. Hasan,et al.  Exploring the sequence space for tetracycline-dependent transcriptional activators: novel mutations yield expanded range and sensitivity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[29]  D. Restrepo,et al.  Variability of position of the P2 glomerulus within a map of the mouse olfactory bulb , 2001, The Journal of comparative neurology.

[30]  L. Haberly,et al.  Parallel-distributed processing in olfactory cortex: new insights from morphological and physiological analysis of neuronal circuitry. , 2001, Chemical senses.

[31]  L. Luo,et al.  Representation of the Glomerular Olfactory Map in the Drosophila Brain , 2002, Cell.

[32]  Richard Axel,et al.  Spatial Representation of the Glomerular Map in the Drosophila Protocerebrum , 2002, Cell.

[33]  Caiying Guo,et al.  A cre recombinase transgene with mosaic, widespread tamoxifen‐inducible action , 2002, Genesis.

[34]  P. Mombaerts,et al.  A Contextual Model for Axonal Sorting into Glomeruli in the Mouse Olfactory System , 2004, Cell.

[35]  Peter C. Brunjes,et al.  A field guide to the anterior olfactory nucleus (cortex) , 2005, Brain Research Reviews.

[36]  Hannah Monyer,et al.  Connexin36 Mediates Spike Synchrony in Olfactory Bulb Glomeruli , 2005, Neuron.

[37]  Hitoshi Sakano,et al.  Continuous and Overlapping Expression Domains of Odorant Receptor Genes in the Olfactory Epithelium Determine the Dorsal/Ventral Positioning of Glomeruli in the Olfactory Bulb , 2005, The Journal of Neuroscience.

[38]  Zhengyou Zhang,et al.  Iterative point matching for registration of free-form curves and surfaces , 1994, International Journal of Computer Vision.

[39]  L. Luo,et al.  Mosaic Analysis with Double Markers in Mice , 2005, Cell.

[40]  Ronald L. Davis,et al.  Olfactory memory formation in Drosophila: from molecular to systems neuroscience. , 2005, Annual review of neuroscience.

[41]  Z. Mainen,et al.  Early events in olfactory processing. , 2006, Annual review of neuroscience.

[42]  Lawrence C Katz,et al.  Synaptic Integration of Olfactory Information in Mouse Anterior Olfactory Nucleus , 2006, The Journal of Neuroscience.

[43]  Kevin M. Franks,et al.  Strong Single-Fiber Sensory Inputs to Olfactory Cortex: Implications for Olfactory Coding , 2006, Neuron.

[44]  Ian R. Wickersham,et al.  Monosynaptic Restriction of Transsynaptic Tracing from Single, Genetically Targeted Neurons , 2007, Neuron.

[45]  L. Luo,et al.  Modeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM) , 2007, Proceedings of the National Academy of Sciences.

[46]  L. Luo,et al.  Comprehensive Maps of Drosophila Higher Olfactory Centers: Spatially Segregated Fruit and Pheromone Representation , 2007, Cell.

[47]  Allan R. Jones,et al.  Genome-wide atlas of gene expression in the adult mouse brain , 2007, Nature.

[48]  S. Itohara,et al.  Innate versus learned odour processing in the mouse olfactory bulb , 2007, Nature.

[49]  Zeger Debyser,et al.  Comparative analysis of adeno-associated viral vector serotypes 1, 2, 5, 7, and 8 in mouse brain. , 2007, Human gene therapy.

[50]  Ian R. Wickersham,et al.  Retrograde neuronal tracing with a deletion-mutant rabies virus , 2007, Nature Methods.

[51]  R. Insausti,et al.  Segregated pathways to the vomeronasal amygdala: differential projections from the anterior and posterior divisions of the accessory olfactory bulb , 2007, The European journal of neuroscience.

[52]  K. Svoboda,et al.  Genetic Dissection of Neural Circuits , 2008, Neuron.

[53]  Minmin Luo,et al.  Precise Circuitry Links Bilaterally Symmetric Olfactory Maps , 2008, Neuron.

[54]  Gilles Laurent,et al.  Testing Odor Response Stereotypy in the Drosophila Mushroom Body , 2008, Neuron.

[55]  J. Isaacson,et al.  Odor Representations in Olfactory Cortex: “Sparse” Coding, Global Inhibition, and Oscillations , 2009, Neuron.

[56]  Dan D. Stettler,et al.  Representations of Odor in the Piriform Cortex , 2009, Neuron.

[57]  L. Luo,et al.  Uncoupling Dendrite Growth and Patterning: Single-Cell Knockout Analysis of NMDA Receptor 2B , 2009, Neuron.

[58]  Kristina D. Micheva,et al.  Visualizing the Distribution of Synapses from Individual Neurons in the Mouse Brain , 2010, PloS one.

[59]  J. Bekkers,et al.  Inhibitory neurons in the anterior piriform cortex of the mouse: Classification using molecular markers , 2010, The Journal of comparative neurology.

[60]  G. Ugolini,et al.  Advances in viral transneuronal tracing , 2010, Journal of Neuroscience Methods.

[61]  Massimo Scanziani,et al.  Pyramidal Cells in Piriform Cortex Receive Convergent Input from Distinct Olfactory Bulb Glomeruli , 2010, The Journal of Neuroscience.

[62]  Kristina J. Nielsen,et al.  Targeting Single Neuronal Networks for Gene Expression and Cell Labeling In Vivo , 2010, Neuron.

[63]  Ian R. Wickersham,et al.  Production of glycoprotein-deleted rabies viruses for monosynaptic tracing and high-level gene expression in neurons , 2010, Nature Protocols.

[64]  Jeffry S. Isaacson,et al.  From Dendrite to Soma: Dynamic Routing of Inhibition by Complementary Interneuron Microcircuits in Olfactory Cortex , 2010, Neuron.

[65]  C. Poo,et al.  Odor representations in olfactory cortex , 2010 .

[66]  Marco Tripodi,et al.  Monosynaptic Rabies Virus Reveals Premotor Network Organization and Synaptic Specificity of Cholinergic Partition Cells , 2010, Neuron.

[67]  Allan R. Jones,et al.  A robust and high-throughput Cre reporting and characterization system for the whole mouse brain , 2009, Nature Neuroscience.