Neural Circuit and Cognitive Development: Comprehensive Developmental Neuroscience

640 Pages·2020·45.552 MB·English

by  John Rubenstein (editor), Pasko Rakic (editor), Bin Chen (editor), Kenneth Y. Kwan (editor)

Neural Circuit and Cognitive
Development
Comprehensive Developmental Neuroscience
Second Edition
Senior Editors-in-Chief
John Rubenstein
Department of Psychiatry & Weill Institute for Neurosciences
University of California, San Francisco, San Francisco, CA, United States
Pasko Rakic
Department of Neuroscience & Kavli Institute for Neuroscience
Yale School of Medicine, New Haven, CT, United States
Editors-in-Chief
Bin Chen
Department of Molecular, Cell & Developmental Biology
University of California, Santa Cruz, Santa Cruz, CA, United States
Kenneth Y. Kwan
Michigan Neuroscience Institute & Department of Human Genetics
University of Michigan, Ann Arbor, MI, United States
Section Editors
Hongkui Zeng
Allen Institute for Brain Science, Seattle, WA, USA
Helen Tager-Flusberg
Department of Psychological and Brain Sciences & Center for Autism Research Excellence Boston
University, Boston, MA, USA
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Contributors
ArielAguero,UniversityofNotreDame,NotreDame,IN, ElysiaPoggiDavis,DepartmentofPsychology,University
United States of Denver, Denver, CO, United States; Department of
Psychiatry and Human Behavior, University of Cali-
NatachaA.Akshoomoff,CenterforHumanDevelopment,
fornia Irvine, Irvine, CA, United States
University of California, San Diego, La Jolla, CA,
United States; Department of Psychiatry, University of Jean Decety, Department of Psychology, Department of
California, San Diego, La Jolla, CA, United States Psychiatry and Behavioral Neuroscience, The Univer-
sity of Chicago, Chicago, IL, United States; The Child
Fabrice Ango, INM, University of Montpellier, CNRS,
Neurosuite, The University of Chicago, Chicago, IL,
INSERM, Montpellier, France
United States
Patricia J. Bauer, Department of Psychology, Emory
Jenalee R. Doom, Department of Psychology, University
University, Atlanta, GA, United States
of Denver, Denver, CO, United States; Center for Hu-
L. Bayet, American University, Washington, DC, United
manGrowthandDevelopment,UniversityofMichigan,
States
Ann Arbor, MI, United States
Adriene M. Beltz, University of Michigan, Ann Arbor,
Jessica A. Dugan, Department of Psychology, Emory
MI, United States
University, Atlanta, GA, United States
Sheri A. Berenbaum, The Pennsylvania State University,
Anne Engmann, Department of Stem Cell and Regener-
University Park, PA, United States
ative Biology, and Center for Brain Science, Harvard
Stefanie C. Bodison, Chan Division of Occupational Sci- University, Cambridge, MA, United States
enceandOccupationalTherapy,UniversityofSouthern Daniel E. Feldman, Department of Molecular & Cell
California (USC), Los Angeles, CA, United States;
Biology, Helen Wills Neuroscience Institute, UC Ber-
Keck School of Medicine of USC, Department of
keley, Berkeley, CA, United States
Pediatrics, Los Angeles, CA, United States
Kayla H. Finch, Department of Psychological & Brain
S.D. Burton, Department of Neurobiology and Anatomy,
Sciences,BostonUniversity,Boston,MA,UnitedStates
University of Utah, Salt Lake City, UT, United States;
N.A. Fox, University of Maryland, College Park, MD,
Department of Neurobiology, University of Pittsburgh,
United States
Pittsburgh, PA, United States
Charles R. Gerfen, Intramural Research Program, NIMH,
G.A. Buzzell, University of Maryland, College Park, MD,
Bethesda, MD, United States
United States
Aryn H. Gittis, Department of Biological Sciences and
Claire E.J. Cheetham,University of Pittsburgh School of
Center for the Neural Basis of Cognition, Carnegie
Medicine, Pittsburgh, PA, United States
Mellon University, Pittsburgh, PA, United States
HughesClaire,NewnhamCollege,CambridgeUniversity,
L.V. Goodrich, Harvard Medical School, Boston, MA,
Cambridge, United Kingdom; Centre for Family
United States
Research, Cambridge University, Cambridge, United
Kingdom Megan R. Gunnar, Institute of Child Development, Uni-
versity of Minnesota, Minneapolis, MN, United States
John B. Colby, Department of Radiology and Biomedical
Imaging, University of California, San Francisco, CA, Frank Haist, Center for Human Development, University
United States of California, San Diego, La Jolla, CA, United States;
DepartmentofPsychiatry,UniversityofCalifornia,San
A. Conejero, Mind, Brain and Behavior Research Center
Diego, La Jolla, CA, United States
(CIMCYC), University of Granada, Granada, Spain
xv
xvi Contributors
RichardHawkes,DepartmentofCellBiology&Anatomy Amanda N. Noroña, Department of Psychology, Univer-
and Hotchkiss Brain Institute, Cumming School of sityofDenver,Denver,CO,UnitedStates;Department
Medicine, University of Calgary, Calgary, Alberta, of Psychiatry, University of Colorado Anschutz Medi-
Canada cal Campus, Aurora, CO, United States
BryanM.Hooks,DepartmentofNeurobiology,University Abdulkadir Ozkan, Department of Stem Cell and
of Pittsburgh School of Medicine, Pittsburgh, PA, Regenerative Biology, and Center for Brain Science,
United States Harvard University, Cambridge, MA, United States
Mark H. Johnson, Department of Psychology, University MichelePignatelli,RIKEN-MITCenterforNeuralCircuit
of Cambridge, Cambridge, United Kingdom Genetics at the Picower Institute for Learning and
Memory, Department of Biology and Department of
Scott P. Johnson, University of California, Los Angeles,
Brain and Cognitive Sciences, Massachusetts Institute
CA, United States
ofTechnology,Cambridge,MA,UnitedStates;Howard
Masanobu Kano, Department of Neurophysiology, Grad-
Hughes Medical Institute, Massachusetts Institute of
uate School of Medicine, The University of Tokyo,
Technology, Cambridge, MA, United States
Tokyo, Japan
Hilary Richardson, Department of Brain and Cognitive
P.O. Kanold, Johns Hopkins University, Baltimore, MD,
Sciences, MIT, Cambridge, MA, United States
United States; University of Maryland, College Park,
Kathleen S. Rockland, Department of Anatomy and
MD, United States
Neurobiology, Boston University School of Medicine,
DominicP.Kelly,UniversityofMichigan,AnnArbor,MI,
Boston, MA, United States
United States
Benjamin A. Rowland, Department of Neurobiology &
Taehyeon Kim, University of Pittsburgh School of Medi-
Anatomy, Wake Forest School of Medicine,
cine, Pittsburgh, PA, United States WinstoneSalem, NC, United States
A. Lahat, University of Toronto, Toronto, ON, Canada
M.R. Rueda, Department of Experimental Psychology,
Jill Lany, University of Liverpool, Liverpool, United University of Granada, Granada, Spain; Mind, Brain
Kingdom and Behavior Research Center (CIMCYC), University
of Granada, Granada, Spain
G. Lepousez, Perception and Memory Unit, Institut Pas-
teur, Centre National de la Recherche Scientifique, Vibhu Sahni, Department of Stem Cell and Regenerative
Paris, France Biology, and Center for Brain Science, Harvard Uni-
versity, Cambridge, MA, United States; Burke Neuro-
P.-M. Lledo, Perception and Memory Unit, Institut Pas-
teur, Centre National de la Recherche Scientifique, logical Institute, Weill Cornell Medicine, White Plains,
NY, United States; Feil Family Brain and Mind
Paris, France
Research Institute, Weill Cornell Medicine, New York,
Jeffrey D. Macklis, Department of Stem Cell and Regen-
NY, United States
erative Biology, and Center for Brain Science, Harvard
Rebecca Saxe, Department of Brain and Cognitive Sci-
University, Cambridge, MA, United States; Bauer
ences, MIT, Cambridge, MA, United States
Laboratory, Cambridge, MA, United States
Constantino Sotelo, Sorbonne Universités, UPMC Uni-
Kalina J. Michalska, Department of Psychology, Uni-
versité Paris 06, INSERM, CNRS, Institut de la Vision
versity of California, Riverside, CA, United States
Paris, France; Instituto de Neurociencias de Alicante,
Zoltán Molnár, Department of Physiology, Anatomy and
UMH-CSIC, Universidad Miguel Hernández de Elche,
Genetics, University of Oxford, Oxford, United
Alicante, Spain
Kingdom
Elizabeth R. Sowell, Keck School of Medicine of USC,
C.A. Nelson, III, Harvard Medical School, Boston, MA,
Department of Pediatrics, Los Angeles, CA, United
UnitedStates;BostonChildren’sHospital,Boston,MA,
States; Developmental Cognitive Neuroimaging Labora-
United States; Harvard Graduate School of Education, tory,Children’sHosiptal,LosAngeles,CA,UnitedStates
Cambridge, MA, United States
Contributors xvii
Terrence R. Stanford, Department of Neurobiology & Helen Tager-Flusberg, Department of Psychological &
Anatomy, Wake Forest School of Medicine, BrainSciences,BostonUniversity,Boston,MA,United
WinstoneSalem, NC, United States States
BarryE. Stein, Department ofNeurobiology &Anatomy, Abbie Thompson, Valparaiso University, Valparaiso, IN,
WakeForestSchoolofMedicine,WinstoneSalem,NC, United States
United States
M.Wachowiak,DepartmentofNeurobiologyandAnatomy,
Joan Stiles, Department of Cognitive Science, University University of Utah, Salt Lake City, UT, United States
of California, San Diego, La Jolla, CA, United States;
MasahikoWatanabe,Department ofAnatomy,Hokkaido
Center for Human Development, University of Cali-
University Graduate School of Medicine, Sapporo,
fornia, San Diego, La Jolla, CA, United States
Japan
Chapter 1
Neural circuits of the mammalian main
olfactory bulb
S.D. Burton1,3, G. Lepousez2, P.-M. Lledo2 and M. Wachowiak1
1DepartmentofNeurobiologyandAnatomy,UniversityofUtah,SaltLakeCity,UT,UnitedStates;2PerceptionandMemoryUnit,InstitutPasteur,
CentreNationaldelaRechercheScientifique,Paris,France;3DepartmentofNeurobiology,UniversityofPittsburgh,Pittsburgh,PA,UnitedStates
Chapter outline
1.1. Introduction 3 1.2.4. Modulationofsensoryprocessing 14
1.2. Synapticorganizationofthemainolfactorybulb 4 1.2.4.1. Localcircuitsandcentrifugalinnervation 14
1.2.1. Organizationofsensoryinputs 4 1.2.4.2. Brainstateandcontext 16
1.2.2. Synapticmicrocircuits 6 1.3. Plasticityinthemainolfactorybulb 17
1.2.2.1. Glomerularlayermicrocircuits 8 1.3.1. Adultneurogenesis 17
1.2.2.2. Externalplexiformlayermicrocircuits 9 1.3.1.1. Regenerationofsensoryinput 17
1.2.3. Neuralcomputation 11 1.3.1.2. Adult-borninterneurons 18
1.2.3.1. Contrastenhancement 11 1.3.2. Circuitandsynapticplasticity 20
1.2.3.2. Slowtimescaledecorrelation 12 1.4. Concludingremarks 21
1.2.3.3. Fasttimescalesynchronization 13 Acknowledgments 21
1.2.3.4. Downstreamdecoding 14 References 21
1.1 Introduction
Sensory systems are specialized biological devices by which organisms perceive their external sensory space. The
mammalian brain harnesses several sophisticated sensory systems that operate according to a specific set of rules to
transform sensory information from one dimension to another. For the chemical senses, such as olfaction, this trans-
formationconcernsthewaysinwhichchemicalinformationgivesrisetospecificneuronalresponsesinadedicatedsensory
organ (Ache and Young, 2005). Several factors make the transformation of olfactory stimuli particularly complex and
computationallydemanding.Forexample,odorants(i.e.,volatilemoleculesactivatingtheterrestrialmainolfactorysystem)
are inherently high-dimensional, and thus cannot easily be classified along a single dimension (such as frequency for
auditory stimuli). Further, each natural odor (i.e., olfactory percept) is typically composed of numerous distinct odorants
(e.g., coffee comprises >900 distinct volatile organic compounds (Farah, 2012)) that are nevertheless integrated into a
single percept (a process called configural or synthetic perception) (Gottfried, 2010). In addition, olfactory perceptual
intensity, of which odorant concentration is only one contributing factor, can vary substantially without changes in
perceivedodorquality(Mainlandetal.,2014).Relatedly,navigatingtowardanodorsourceinnaturerequiressensingand
integratinginformationcontainedacrossdynamicallyfluctuatingplumesofhigh-andlow-concentrationodorantfilaments
(Baker et al., 2018). The neural architecture responsible for processing olfactory stimuli must thus harbor profound
flexibility and computational power.
Olfactorysystemsandchemosensationmoregenerallyhaveevolvedfromtheearliestknownlifeformstomeetcrucial
needs such as locating potential food sources, detecting dangers such as predators, and mediating social and sexual in-
teractions (Ache and Young, 2005). Despite these highly conserved functions, interest in other sensory modalities has
historicallydominatedneuroscience,inpartduetothecomparativeeaseofmanipulatinglowerdimensionalsensorystimuli
3
NeuralCircuitandCognitiveDevelopment.https://doi.org/10.1016/B978-0-12-814411-4.00001-9
Copyright©2020ElsevierInc.Allrightsreserved.
4 PART | I Circuit development
FIGURE 1.1 Centripetal and centrifugal projections of the main olfactory bulb. Schematic depiction of the main centripetal and centrifugal
projectionsofthemainolfactorybulb(MOB).TheMOBprocessessensoryinputreceivedfromthemainolfactoryepithelium,andtransmitsinformation
tomultiplebrainregionsthatcollectivelyformtheolfactorycortex(blue).Inturn,severalregionsoftheolfactorycortex,inadditiontomajorneuro-
modulatorycentersofthebrain(red),denselyinnervatetheMOBtomodulatesensoryprocessing.
suchaslight,andinpartduetothenowdebunkednotionthatthehumansenseofsmellispoororunimportant(Shepherd,
2011; McGann, 2017). Nevertheless, neuroscience has made considerable progress in understanding how the brain per-
ceives odors so precisely, propelled in large part by the discovery in 1991 of a multigene family of odorant-binding
G-protein-coupled receptors (GPCRs) that revealed the molecular underpinnings of peripheral odorant recognition
(Buck and Axel, 1991). This pivotal discovery - awarded the Nobel Prize in Physiology or Medicine in 2004 - together
withtherecentexplosioninadvancedmoleculartechniquesforlabeling,monitoring,andperturbingdistinctneurontypes
hasyieldedanincreasinglyclearpictureofhowchemicalinformationisprocessedthroughoutthemainolfactorysystem.
Below,wereviewhowchemicalinformationisencodedandprocessedatthefirstcentralprocessingstationofthemain
olfactorysystem,themainolfactorybulb(MOB)(Fig.1.1).InadditiontotheMOB,whichprocessesolfactoryinformation
detected by sensory neurons in the main olfactory epithelium, a related structure in many mammals called the accessory
olfactory bulb processes pheromonal information detected in the peripheral vomeronasal organ (Mohrhardt et al., 2018).
Due to space constraints, however, we focus exclusively on the main olfactory system, with a predominant focus on the
rodent experimental preparation and MOB. In the further interest of space, recent comprehensive reviews (in addition to
key representative studies) are cited where possible to provide direction for more thorough exploration of topics.
1.2 Synaptic organization of the main olfactory bulb
The main olfactory system is responsible for encoding sensory information from thousands to millions of different
odorants.Toaccomplishthiscomplextask,sensoryinformationisprocessedthroughdistinctunits.Ateachoftheseunits,
a modified representation of the sensory information is generated. Following a bottomeup approach, we will start our
description from the olfactory sensory organ located in the nasal cavity.
1.2.1 Organization of sensory inputs
As our knowledge about theneurobiology of olfaction grows, it isbecoming increasinglyevident that themainolfactory
systems of animals in disparate phyla share many strikingly parallel features. In particular, virtually all olfactory systems
require odorant interaction with specific receptors expressed on the dendritic cilia of peripheral sensory neurons; this
interactionistransducedbyanintracellularsecondmessengersignalingcascadeintoneuralactivity,whichthenpropagates
Neuralcircuitsofthemammalianmainolfactorybulb Chapter | 1 5
alongsensoryneuronaxonstoanatomicalstructurescalledglomeruliinthefirstcentralprocessingstationoftheolfactory
system (Ache and Young, 2005). If these common features represent adaptive mechanisms that have evolved indepen-
dently, then their study will likely bring valuable knowledge about the way the nervous system extracts olfactory infor-
mation from the environment.
Inmammals,olfactionbeginswiththeactivationofperipheralolfactorysensoryneurons(OSNs),whichlinethemain
olfactory epithelium (Fig. 1.2A,B). Each OSN of the mouse typically expresses a single odorant-binding receptor type,
mostofwhichbelongtothew1,000functionalGPCRodorantreceptor(OR)typesfirstcharacterizedbyBuckandAxel.
TheseORsevolutionarilysubdivideintothefish-likeClassIORsandterrestrial-likeClassIIORs(MoriandSakano,2011;
Bear et al., 2016). In addition to these classical ORs, recent research has further uncovered the trace amine-associated
receptors (TAARs), a second class of odorant-binding GPCRs that, while few in number (mice express 15 functional
TAAR types), interact with volatile and ethologically relevant amines capable of triggering innate behavioral responses
(Liberles and Buck, 2006). Each OR and TAAR interacts with a specific subset of odorants and, as with any molecular
receptor, these interactions are governed in a concentration-dependent manner according to receptor/ligand binding af-
finities. Increasing odorant concentrations therefore not only increase activation of receptors highly sensitive to those
odorants, but also activate additional receptors less sensitive to those odorants (Mainland et al., 2014).
AllOSNsexpressingthesameORorTAARprojecttheiraxonscentrallytoone(orsometimesafew)glomeruliineach
medial and lateral half of the ipsilateral MOB, forming roughly mirror-symmetric glomerular maps within each MOB
(Fig.1.2AeE)(MoriandSakano,2011;Liberles,2015).Eachglomerulusisalargesphericalneuropilstructure(w100mm
diameterinmice)whereinOSNsreleaseglutamatetoactivatediverseneurontypes.Sensoryinformationpropagatingfrom
the peripheral epithelium to a glomerulus is thereby processed by multiple local circuit interactions before being trans-
mittedtohigherbraincentersviatheMOBprojectionneurons(Fig.1.1).ThecoalescenceofOSNaxonsintoaglomerulus
is coordinated by a host of guidance cues and molecular interactions, including the odorant-binding receptor itself,
and represents one of the most exquisitely specific anatomical substrates in the brain (Mori and Sakano, 2011).
FIGURE1.2 Glomerularorganizationofsensoryinputtothemainolfactorybulb.(A)Sagittalwholemountviewofthemedialglomerulusformed
by OSNs expressing the P2 odorant receptor (OR). Dashed line: MOB outline. Arrowhead: glomerulus. (B,C) Magnification of the OSNs (B) and
glomerulus(C)in(A).Inset:magnificationoftwofluorescentlylabeledOSNsinthemainolfactoryepithelium.Arrowhead:dendrites.Arrow:axons.(D)
DorsalwholemountviewofmedialandlateralglomeruliformedbyOSNsexpressingtraceamine-associatedreceptor(TAAR)3(green)andTAAR4
(red).Dashedline:bilateralMOBoutlines.Arrowheadandarrow:lateralandmedialglomeruli,respectively,ofleftMOB.(E)Magnificationoftheboxed
regionin(D),showingthepreciseconvergenceofthousandsofaxonstoneighboringglomeruli.(F)Dorsalwholemountviewofglomeruliformedby
OSNsexpressingClassIORs(yellow),ClassIIORs(red),andTAARs(cyan),formingDomainI,DomainII,andtheTAARDomainofthedorsalMOB.
(G)SchematicdorsolateralviewofthedomainorganizationofglomeruliintheMOB.Dashedblackline:approximateborderbetweenthedorsaland
ventralMOB.Dashedgrayline:accessoryolfactorybulboutline.D,dorsal;M,medial;P,posterior.(AeC)AdaptedfromMombaerts,P.,Wang,F.,
Dulac, C., Chao, S.K., Nemes, A., Mendelsohn, M., Edmondson, J., Axel, R., 1996. Visualizing an olfactory sensory map. Cell 87, 675e686, with
permission;(Binset,DeF)AdaptedfromPacifico,R.,Dewan,A.,Cawley,D.,Guo,C.,Bozza,T.,2012.Anolfactorysubsystemthatmediateshigh-
sensitivity detection of volatile amines. Cell Rep. 2, 76e88, with permission; (G) Adapted from Bear, D.M., Lassance, J.M., Hoekstra, H.E., Datta,
S.R.,2016.Theevolvingneuralandgeneticarchitectureofvertebrateolfaction.Curr.Biol.26,R1039eR1049,withpermission.
6 PART | I Circuit development
Eachglomerulusisformedbytheaxonalconvergenceofw2,000e40,000OSNs(Fig.1.2AeE)(Bresseletal.,2016)onto
theapicaldendritesofw30projectionneuronsonaverage(Schwarzetal.,2018),yieldingaconvergenceratioof102e3:1.
The convergence of so many OSNs is thought to not only broaden the dynamic range of the net sensory input to each
glomerulus,butmayalsoalloweachMOBprojectionneurontointegrateinputfromnumerousOSNs,heighteningsignal-
to-noise ratios and ensuring the detection of even faint sensory input (Mainland et al., 2014).
OSNs expressing each OR or TAAR are randomly distributed within one of a few dorsoventral zones of the main
olfactory epithelium, and this zonal distribution is conserved in the MOB glomerular map (Fig. 1.2F,G). OSNs in the
ventral epithelium express Class II ORs and project their axons to glomeruli in the ventral MOB. In dorsal zones of the
epithelium, intermixed OSNs express Class I ORs, Class II ORs, and TAARs, and interestingly segregate their axonal
projections to glomeruli in the anterodorsal Domain I, posterodorsal Domain II, and mediodorsal TAAR Domain of the
MOB, respectively (Mori and Sakano, 2011; Pacifico et al., 2012; Liberles, 2015). Within these domains, glomerular
positions are roughly conserved between bilateral MOBs, across animals, and even across species (Soucy et al., 2009).
A striking exception to these general properties of the main olfactory system is the recently discovered family of
membrane-spanning, 4-pass A odorant-binding receptors (MS4ARs) (Bear et al., 2016; Greer et al., 2016). In contrast to
ORsandTAARs,eachofthe12functionalMS4ARtypesinmiceisanon-GPCRthattransducesodorantbindingthrough
distinct and still unknown signaling cascades. Further, while each OR and TAAR type is expressed singularly by OSNs
randomlydistributedthroughoutoneofthedorsoventralepithelialzones,MS4ARexpressionisveryspecificallylocalized
to OSNs within the epithelial recesses (or “cul-de-sacs”), where each OSN further expresses multiple different MS4AR
types. Axons of the MS4AR-expressing OSNs selectively terminate in the few dozen necklace glomeruli of the posterior
MOB,whichanatomicallyringtheaccessoryolfactorybulb(Fig.1.2G).LikeTAARs(andlikeodorant-bindingreceptors
within olfactory subsystems outside of the main olfactory system), MS4AR types are few in number and yet critically
involved in driving specific olfactory-guided behaviors (Munger et al., 2009).
Aseachodorant-bindingreceptor(referredtobelowasolfactoryreceptor)respondstoaspecificsetofodorantsandis
expressed by OSNs projecting to conserved domains and approximate positions in the MOB, the glomerular layer (GL)
forms an approximate two-dimensional anatomical representation or map of the receptor repertoire (Wachowiak and
Shipley,2006;MoriandSakano,2011).Uponbindinginaconcentration-dependentmannerwithoftenmultipleolfactory
receptor types, odorants are thus first encoded as sensory information in the main olfactory system by the combinatorial
map of OSN activation and glutamate release within MOB glomeruli. These input maps directly reflect the anatomical
domain organization of the MOB; for example, distinct acid and ketone odorants activate Class I and Class II ORs and
evokeOSNactivationandinputtoglomeruliwithinDomainsIandII,respectively(Bozzaetal.,2009).However,whether
thereexistsatopographicalrelationshipbetweenglomerularpositionandOSNtuningtospecificodorantphysicochemical
propertiesatscalesfinerthanthelevelofgrossdomainsremainsunclear(Soucyetal.,2009;Maetal.,2012;Chaeetal.,
2019).Thislackofobviousfine-scaletopographycontrastswiththedirecttopographicalmappingofstimuluspropertiesto
neural space in other sensory systems, but is perhaps unsurprising given the high dimensionality of olfactory stimuli
(Cleland,2010).Irrespectiveofthedegreeoftopographicalorganization,however,theprecisemapofOSNinputdirectly
impacts olfactory processing and perception: odorants evoking more similar maps are more difficult to perceptually
discriminate (Linster et al., 2001).
Beyondspatialpatternsofsensoryinput,olfactoryinformationisalsoencodedbythetemporalpatternofOSNactivity,
whichisheavilysculptedbytheactivesamplingofodorantsviarepetitivesniffing.Indeed,ratherthansimplestaticmaps
of combinatorial OSN activation and input to glomeruli, odorants trigger bursts of activity in OSNs with onset latencies
distributedthroughouteachsniff(Wachowiak,2011).Suchsniff-drivenpacingnotonlyemergesthroughchemosensation
of odorants by olfactory receptors, but further arises through mechanosensory activation of ORs by nasal airflow
(Grosmaitreetal.,2007;Chenetal.,2012;Connellyetal.,2015).Thesechemo-andmechanosensorytemporalpatternsof
OSNactivityarethenpropagatedtodownstreamMOBcircuits suchthatneuralactivityisbroadlydistributedthroughout
the duration of each sniff (Shusterman et al., 2011; Iwata et al., 2017), providing a unique temporal framework for the
processing of sensory information (Wachowiak, 2011). Collectively, the spatiotemporal glomerular patterns of sensory
inputthataredrivenandshapedbysniffingarethenmodulatedonbothintra-andinterglomerularscalesbylocalcircuits
within the MOB, further increasing the coding and consequent perceptual capacity of the main olfactory system.
1.2.2 Synaptic microcircuits
Becauseofitslaminarorganizationandaccessiblelocationinrodents,theMOBisanidealmodelsystemforinvestigating
the principles underlying network processing of sensory information. With the application of in vitro slice recordings,
togetherwithrecentadvancesinmoleculartechniquesforlabeling,monitoring,andperturbingdistinctneurontypeswithin